Yong PJ et al., 2026·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To provide health care professionals with an evidence-based approach to the management of endometriosis and its associated symptoms.
Women and gender-diverse individuals affected by endometriosis.
BENEFITS, HARMS, Timely and effective management of endometriosis has the potential to reduce pain, improve fertility and quality of life, and enhance long-term health outcomes. Early intervention may also help mitigate the financial and health system burdens associated with delayed diagnosis and treatment.
Published literature was retrieved through searches of PubMed, Ovid, Medline, Embase, Scopus, and the Cochrane Library from August 2010 through December 2025, using relevant MeSH heading and keywords. Results were restricted to systematic reviews, meta-analyses, randomized controlled trials/controlled clinical trials, observational studies, and clinical practice guidelines. Results were limited to English or French language materials. Evidence was supplemented with references from the 2010 Society of Obstetricians and Gynaecologists of Canada guideline No. 244.
The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations).
Health care providers involved in the care of individuals with endometriosis.
Early identification and management of endometriosis can significantly improve patient outcomes, reduce long-term health care costs and improve their quality of life.
RECOMMENDATIONS.
Santos da Silva A et al., 2026·Reproduction (Cambridge, England)·Free full text on PubMed Central
Endometriosis is an estrogen-dependent inflammatory disorder frequently associated with infertility and characterized by progesterone resistance and impaired endometrial receptivity. While ectopic lesions define the disease, accumulating evidence indicates that molecular abnormalities within the eutopic endometrium substantially contribute to infertility. In this study, we performed transcriptomic analysis of proliferative-phase eutopic endometrium from women with and without endometriosis and identified 44 dysregulated genes, including 13 upregulated and 31 downregulated genes, in women with endometriosis compared with controls. Among the significantly altered genes, YWHAZ (14-3-3 zeta) emerged as a prominently downregulated gene. Reduced YWHAZ expression was further validated at the protein level in both epithelial and stromal compartments of the endometrium from women with endometriosis. To investigate its physiological regulation, we examined YWHAZ expression during early pregnancy in mice and observed a dynamic, stage-specific pattern during the peri-implantation period, with strong expression at gestational days 3.5 and 4.5 and robust expression at the primary decidual zone at gestational day 5.5. Notably, YWHAZ expression was nearly abolished in uteri from progesterone receptor knockout and uterine signal transducer and activator of transcription 3 conditional knockout (Pgrcre/+Stat3f/f) mice, indicating that YWHAZ is dependent on intact progesterone receptor and STAT3 signaling. Together, these findings identify YWHAZ as a hormonally and transcriptionally regulated endometrial factor that is disrupted in endometriosis and tightly linked to implantation and decidual progression. This study highlights YWHAZ as a potential molecular node connecting progesterone resistance and STAT3 dysregulation to defective endometrial function and infertility in endometriosis.
Schliep KC et al., 2026·J Gynecol Obstet Hum Reprod·Free full text on PubMed Central
Endometriosis has been linked to cardiometabolic alterations, but whether these associations vary by disease severity or phenotype is unclear. We examined lipid profiles across endometriosis diagnosis, stage, and typology. Data came from 476 women in the NICHD ENDO cohort. Endometriosis was confirmed laparoscopically and staged using the rASRM criteria (I-IV). Typology was categorized as superficial endometriosis (SE), ovarian endometrioma (OE), deep infiltrating endometriosis (DE), and OE+DE. We compared endometriosis status, stage (I/II vs III/IV), and typology to no endometriosis using adverse lipid thresholds (total cholesterol ≥200 mg/dL, HDL <50 mg/dL, LDL ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, ApoA1 <125 mg/dL, and ApoB ≥120 mg/dL). Adjusted prevalence ratios (aPR) and 95 % CIs were estimated via generalized linear models, controlling for age, race/ethnicity, BMI, income, marital status, and serum cotinine. Endometriosis diagnosis alone was not associated with adverse lipid profiles. In contrast, moderate/severe disease showed higher prevalence of elevated triglycerides (aPR= 2.27; 95 % CI: 1.18,4.35) and VLDL (aPR= 2.41; 95 % CI: 1.50, 3.85). Typology revealed stronger patterns: OE and OE+DE were associated with adverse profiles across multiple markers (aPRs 1.59-4.09), particularly ApoB and triglycerides. Minimal/mild disease and SE were not associated. The metabolic signal was phenotype-driven rather than diagnosis-driven, with severe stage and OE/OE+DE showing clear associations with adverse lipid profiles. These findings suggest lipid profiles may serve as markers of phenotype severity or shared biological milieu. Replication in larger cohorts is needed.
Valenti M et al., 2026·Am J Obstet Gynecol·Free full text on PubMed Central
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; deep: -34.3%; 95% confidence interval, -56.2 to -1.4; superficial: -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
Fertility and Outcomes · Conception After Excision
Neutens S et al., 2026·Journal of Minimally Invasive Gynecology
To study whether bilateral nonpatency of fallopian tubes is correlated with a lower recurrence rate of endometriosis. Retrospective 2:1 matched case-control study. University hospital with a tertiary referral center for fertility and endometriosis surgery in Leuven, Belgium. All patients undergoing complete laparoscopic excision of any revised system of the American Society of Reproductive Medicine-stage endometriosis between 2010 and 2014 (n = 896). Comparison between patients with bilateral nonpatent or absent fallopian tubes and matched controls with at least 1 patent fallopian tube. MAIN Primary outcome was the recurrence rate, which was analyzed on 4 levels: overall recurrence, symptom recurrence, recurrence on imaging, and need for reintervention. Of 896 patients, 49 had bilateral nonpatent or absent fallopian tubes. These cases were compared with 98 matched controls with at least 1 patent fallopian tube. Symptoms recurred in 12.2% of the cases (n = 6) and 25.5% of the controls (n = 25) (p = .09). Recurrence was confirmed by imaging in 8% of the cases (n = 4) and 10.2% of the controls (n = 10) (p = .77). In 3 patients of the case group and 12 patients of the control group, there was a need for reintervention (p = .39). Within this subgroup, recurrence of endometriosis was histologically confirmed in none of the patients of the case group and 5 patients of the control group (p = .51). This study did not observe a statistically significant reduction in endometriosis recurrence in patients with bilateral occlusion/absence of the fallopian tubes after endometriosis surgery. A type II error may count for this result.
Olcha P et al., 2026·Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
This study evaluated the diagnostic potential of Fourier-transform infrared (FTIR) spectroscopy combined with machine learning for the detection of ovarian, bowel, and peritoneal endometriosis. The Boruta algorithm was applied to identify the most informative spectral intervals for each endometriosis type, revealing characteristic wave number ranges associated with molecular changes in endometriotic tissue. For ovarian endometriosis, key intervals included 741-748 cm-1, 984-993 cm-1, and 1125-1132 cm-1 bowel endometriosis, 1055-1063 cm-1, 1077-1079 cm-1, 1561-1572 cm-1, and 1717-1720 cm-1, and for peritoneal endometriosis, 917-919 cm-1, 1542-1547 cm-1, and 1573-1576 cm-1. Three machine learning algorithms, Deep Learning (DL), Support Vector Machine (SVM), and XGBoost, were tested using both the full spectral range and the Boruta-selected feature subsets. Across all endometriosis types, XGBoost consistently outperformed DL and SVM. Using the full spectrum, XGBoost achieved accuracies of 0.81, 0.77, and 0.78 for ovarian, bowel, and peritoneal endometriosis, respectively. Feature selection with Boruta significantly improved performance, increasing accuracies to 0.93, 0.88, and 0.90, respectively, and enhancing sensitivity, specificity, precision, F1 score, MCC, and ROC AUC across all datasets. DL models often exhibited high sensitivity but poor specificity, while SVM performance improved moderately with feature selection. Overall, these results demonstrate that targeted spectral feature selection enhances the diagnostic accuracy of machine learning models for endometriosis. XGBoost, in combination with Boruta-selected spectral intervals, provides the most reliable and balanced predictions, highlighting its potential for non-invasive detection and differentiation of ovarian, bowel, and peritoneal endometriotic lesions.
Fertility and Outcomes · Conception After Excision
Hsu JZ et al., 2025·Eur J Obstet Gynecol Reprod Biol
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Endometriosis is an estrogen-dependent, chronic inflammatory disorder characterized by the presence of endometrium-like tissue outside the uterus, affecting approximately 10% of individuals of reproductive age. It contributes to chronic pelvic pain, dysmenorrhea, and subfertility, resulting in substantial societal economic burdens. Genetic and environmental risk factors have been identified, and recent research suggests that endometriosis functions as a systemic disease affecting nonreproductive systems and increasing susceptibility to other health conditions. Various phenotypes-superficial peritoneal endometriosis, ovarian endometriomas, and deep endometriosis-may develop under different mechanisms, yet the relationship between these presentations remains unclear. Diagnosis relies on clinical evaluation, imaging, and surgical staging, and the advent of advanced ultrasonography and magnetic resonance imaging has helped to enhance accuracy. Although medical management focuses on hormonal modulation to alleviate symptoms, surgical intervention remains a critical tool for refractory symptoms. Postoperative care and patient education are essential to manage recurrence and to improve quality of life. Current research emphasizes the need for comprehensive, interdisciplinary approaches to endometriosis management, incorporating novel diagnostic tools, diverse therapeutic avenues, and patient-centered care models. Addressing disparities in treatment access is essential to improving outcomes. To achieve this, recruiting and analyzing data from racially, socioeconomically, and geographically diverse cohorts will reveal how disease presentation and treatment efficacy vary across populations. Continued efforts in research and health care policy are necessary to develop effective and personalized strategies in managing endometriosis.
Fertility and Outcomes · Conception After Excision
Somigliana E et al., 2025·Human Reproduction·Free full text on PubMed Central
The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression or recurrence. Women are therefore typically managed with long-term hormonal treatments, with or without surgery. However, this approach is unsuitable for those seeking natural pregnancy or undergoing IVF, as all hormonal treatments hinder conception. For women pursuing natural pregnancy, these treatments should be discontinued for about 1 year, the time needed to diagnose infertility. However, this suspension exposes women to the risk of recurrence or progression and is therefore clinically acceptable only if the woman has a reasonable likelihood of achieving pregnancy naturally. In women with endometriosis who are infertile and therefore require IVF, ovarian stimulation significantly raises estrogen levels-up to 10 times those of a natural cycle-potentially boosting the risk of endometriosis relapse. Evidence is reassuring on this issue even if some limited data suggest that ovarian stimulation may promote deep invasive endometriosis progression. Overall, physicians and patients must balance the chances of natural or ART-assisted pregnancy against the risk of disease recurrence or progression during treatment discontinuation or IVF. This choice is also complicated by the increased risk of severe pregnancy complications in women with endometriosis, possibly depending on the conception method. This review discusses the available evidence that can be helpful in guiding the decision-making process.
Chung HF et al., 2025·Hum Reprod·Free full text on PubMed Central
What is the association between endometriosis and the type and age of menopause? Women with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally. Endometriosis is associated with reduced ovarian reserve, but evidence on its relationship with the type of menopause (surgical vs natural) and timing (especially premature and early menopause) is limited. Women with endometriosis are more likely to undergo hysterectomy and/or oophorectomy (either unilateral or bilateral), but the average age of these surgeries remains unclear. STUDY DESIGN, SIZE, The study analysed individual-level data from 279 948 women in five cohort studies conducted in the UK, Australia, Sweden, and Japan between 1996 and 2022. PARTICIPANTS/MATERIALS, SETTING, Women whose menopause type and age could not be determined due to premenopausal hysterectomy with ovarian preservation or use of menopausal hormone therapy were excluded. Endometriosis was identified through self-reports and administrative data. Surgical menopause was defined as premenopausal bilateral oophorectomy. Fine-Gray subdistribution hazard models estimated hazard ratios (HRs) for surgical and natural menopause. Age at menopause was determined by the ages at the final menstrual period or bilateral oophorectomy. Linear regression assessed mean differences in menopause age, while multinomial logistic regression estimated odds ratios (ORs) for categorical menopause age: <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-54, and ≥55 years. Spontaneous premature ovarian insufficiency (POI) was defined as natural menopause before age 40 years. MAIN Endometriosis was identified in 3.7% of women. By the end of follow-up, 7.9% had surgical menopause and 58.2% experienced natural menopause. Using a competing risk model, women with endometriosis had a 7-fold increased risk of surgical menopause (HR: 7.54, 95% CI 6.84, 8.32) and were less likely to experience natural menopause (HR: 0.40, 95% CI 0.33, 0.49). On average, surgical menopause occurred 1.6 years (19 months) earlier (β: -1.59, 95% CI -1.77, -1.42) in women with endometriosis. Among women who experienced natural menopause, it was 0.4 years (5 months) earlier (β: -0.37, 95% CI -0.46, -0.28) for those with endometriosis. Women with endometriosis were twice as likely to experience premature surgical menopause (<40 years) (OR: 2.11, 95% CI 2.02, 2.20) or 1.4 times more likely to develop spontaneous POI (OR: 1.36, 95% CI 1.17, 1.59). They were also at increased odds of early surgical and natural menopause (40-44 years). LIMITATIONS, This study could not differentiate between subtypes and stages of endometriosis or assess treatments for ovarian endometrioma, which may impact ovarian reserve. Self-reported menopause type and age could introduce recall bias. Given the consistent findings across individual studies, our results are likely to be generalizable to different populations, highlighting the need for tailored management of endometriosis to prevent medically induced or premature menopause. Long-term monitoring of women with endometriosis is recommended, given their elevated risk of surgical menopause and premature or early menopause, which are associated with adverse health outcomes in later life. STUDY FUNDING/COMPETING INTEREST(S): The InterLACE Consortium is funded by the Australian National Health and Medical Research Council project grant (APP1027196) and Centres of Research Excellence (APP1153420). G.D.M. is funded by the Australian National Health and Medical Research Council Leadership Fellowship (APP2009577). This research is funded in part by the Japan Society for the Promotion of Science (JSPS 19KK0235, 23KK0167). The authors have no conflict of interest. Where authors are identified as personnel of the International Agency for Research on Cancer or WHO, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer or WHO. N/A.
Endometriosis, affecting 11% of reproductive-aged persons, is characterized by ectopic endometrial tissue and chronic inflammation. Prior research suggests those with endometriosis have higher cardiovascular disease risk, but mechanisms remain elusive. The objective of this study is to assess whether endometriosis diagnosis, staging, and typology (superficial endometriosis (SE), ovarian endometriomas (OE), and deep infiltrating endometriosis (DE)) are associated with serum interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-) concentrations. The study analyzed data from 395 premenopausal persons in Utah undergoing gynecologic laparoscopy who participated in the NICHD ENDO study (2007–2009). Post-operative reports determined endometriosis typology (SE, OE, DE) and staging (minimal, mild, moderate, severe) using Revised American Society for Reproductive Medicine classification. Elevated serum cytokine concentrations were defined as IL-6 ≥2pg/mL, IL-8 ≥3pg/mL, and TNF- ≥7.5pg/mL. Generalized linear models generated adjusted prevalence ratios (aPR) 95% CI controlling for age, BMI, marital status, race/ethnicity, and serum cotinine. Participants were on average 32 years (SD=7) at time of gynecologic laparoscopy/laparotomy, non-Hispanic white (79%), married (71%), mean BMI 28 (SD=8) and non-smokers (83% serum cotinine <10ng/mL). Forty-two percent (n=166) were diagnosed with incident endometriosis. We found no differences among those with, compared to without, endometriosis and elevated IL-6, 12% vs 10%, aPR: 1.01 (0.97, 1.10), IL-8, 5% vs 8%, aPR: 0.99 (0.94, 1.04); and TNF, 16% vs 13%, aPR: 1.00 (0.96, 1.04). While there were no statistically significant associations between endometriosis staging or typology and cytokines, those with moderate to severe endometriosis had nonsignificant lower IL-6 and IL-8 (aPR: 0.61 [0.15, 2.52] and aPR: 0.74 [0.17, 3.20]) but higher TNF- (aPR: 1.27 [0.56, 2.84]), compared to no endometriosis. Individuals with OE and DE had nonsignificant trends of IL-6 and Il-8 (aPR: 0.86 [0.11, 2.52] and aPR: 0.93 [0.14, 6.43]) but higher TNF- (aPR: 1.93 [0.77, 4.84]). In summary, this study found no clear correlation between endometriosis diagnosis, staging, typology and inflammatory markers IL-6, IL-8, and TNF-. Whether endometriosis severity or typology is associated with TNFshould be explored in future studies with adequate power and more representative samples.
Individuals with endometriosis, a gynecologic condition affecting approximately 11% of people with a uterus, may have an elevated risk for developing cardiovascular disease (CVD) later in life. However, the mechanisms underlying this association are not well understood. We investigated the association between incident endometriosis diagnosis, staging, and typology and lipid biomarkers measured at time of diagnostic surgery among women participating in the NICHD ENDO study (n=395). Endometriosis was categorized using the American Society for Reproductive Medicine staging (I−IV). Endometriosis typology was defined by lesion depth and location and categorized as superficial endometriosis (SE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DE). With no endometriosis as our reference, we evaluated the associations between endometriosis diagnosis, stage (I/II vs III/IV), and typology (SE, OE, DE, OE+DE) and dyslipidemia using standard clinical thresholds (total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, Apolipoprotein A-1 (APO-A1) <125 mg/dL, Apolipoprotein B (APOB) ≥120 mg/dL; APOB/APO-A1 ratio >0.78). We calculated adjusted prevalence ratios (aPR) and 95% CIs via generalized linear models, controlling for age, race/ethnicity, marital status, BMI, income (poverty level), and serum cotinine as a marker of smoking. At the time of gynecologic surgery, individuals were mean 32 years (SD: 7 years), non-Hispanic white (79%), married (71%), and mean BMI 28 (SD=8). While we found no differences in endometriosis diagnosis or endometriosis staging and dyslipidemia (
Figure 1; Table 1
), a pattern emerged regarding endometriosis typology (
Table 2
). Women with OE+DE, compared to no endometriosis, had increased prevalence of dyslipidemia: total cholesterol >200 mg/dL: 1.87 (0.99, 3.57); triglycerides
>
175 mg/dL: 2.48 (1.34, 4.57); VLDL ≥30 mg/dL: 2.08 (1.28, 3.38); and APOB mg/dL ≥120: 2.86 (1.22, 6.66). OE appeared to be driving this association. SE was not associated with dyslipidemia. The association between endometriosis, especially of more severe typology, and subsequent CVD may be through dyslipidemia, which may be detectable at the time of endometriosis diagnosis. Further research in larger, more representative samples is needed before definitive conclusions can be made.
Goodwin E et al., 2025·Journal of minimally invasive gynecology·Free to read
Endometriosis is a chronic and inflammatory condition that affects approximately 10% of the reproductive-age population. During the COVID-19 pandemic, there was a shift towards virtual care for endometriosis. Our aim was to evaluate the diagnostic and treatment outcomes of virtual-only care, compared to those who had both virtual and in-person visits.
Retrospective descriptive analysis of registry data.
This study was conducted in British Columbia, Canada, at a tertiary referral center for endometriosis and pelvic pain.
In this cohort (n = 389), we examined patients who received an initial virtual assessment followed by virtual care alone (Virtual Only group, n = 203) and those who had an initial virtual assessment followed by an in-person physical exam (Physical Exam group, n = 186).
Virtual care at the center during the COVID-19 pandemic.
The Physical Exam group was more likely to have surgery compared to the Virtual Only group (45.7% vs. 16%, p <.001). At the time of surgery, the groups did not differ based on type of surgery (e.g., excision of endometriosis and/or hysterectomy), endometriosis anatomic findings (e.g., stage and anatomic subtype), surgical complexity or surgical complications. At baseline, the two groups did not differ in their pain, mental health or quality of life scores. At 1-year follow-up, the two groups did not differ in these outcome measures.
There was a lower rate of surgery, but no differences in surgical findings or complications, nor in 1-year outcomes, after virtual only care for endometriosis compared to patients that had a virtual visit and then underwent a physical exam. These results support a hybrid model, where a virtual visit is the first contact and serves as a triage tool to determine whether a patient is appropriate for virtual only care or would benefit from a physical exam. Future research could incorporate population-based administrative data or qualitative approaches to understanding patient experiences and physician perspectives on virtual care for the treatment of endometriosis.
Tucker DR et al., 2025·Human reproduction (Oxford, England)·Free full text on PubMed Central
Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?
Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.
Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.
STUDY DESIGN, SIZE, This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.
PARTICIPANTS/MATERIALS, SETTING, PTEN and ARID1A loss was assessed using established immunohistochemistry (IHC) methods as proxies for somatic loss by two independent raters. PTEN and ARID1A status for each participant was defined as loss (loss in at least one sample for a participant) or retained (no loss in all samples for a participant). Primary analyses examined associations between PTEN and ARID1A loss and disease burden based on anatomic subtype (superficial peritoneal endometriosis (SUP), deep endometriosis (DE), ovarian endometrioma (OMA)) and rASRM stage (I-IV). Secondary analyses explored associations of PTEN and ARID1A loss with demographics, surgical difficulty, and pain scores (baseline and follow-up). Additionally, using previously published data on KRAS codon 12 mutations for this cohort, we investigated associations between variables in the primary and secondary analyses and acquiring two or more somatic events (PTEN loss, ARID1A loss, or KRAS mutation) in this cohort. The risk of reoperation over the 5-9 years was also examined.
MAIN PTEN loss (68.3%; 86 participants) exceeded ARID1A loss (24.6%; 31 participants). Inter-rater reliability was substantial for PTEN (k = 0.69; 95% CI: 0.62-0.77) and ARID1A (k = 0.64; 95% CI: 0.51-0.77). PTEN loss was significantly associated with more severe anatomic subtypes (P < 0.001; participants with SUP only = 46.4%; participants with DE only or OMA only = 72.7%; participants with mixed subtypes = 85.1%), and higher stages (P = 0.024; Stage I = 47.8%; Stage II = 73.7%; Stage III = 80.8%; Stage IV = 81.0%). Results were similar for ARID1A loss, albeit with smaller sample size limiting power. PTEN loss was further associated with non-White ethnicities (P = 0.017) and greater surgical difficulty (more frequent need for ureterolysis) (P = 0.02). There were no differences in pain scores (baseline or follow-up) based on PTEN or ARID1A status. Reoperation was uncommon (13.5% of the cohort), and patterns in reoperation rates based on the presence of somatic alterations did not reach statistical significance.
LIMITATIONS, Sequencing was not performed to determine the type of PTEN and ARID1A somatic mutations resulting in loss of expression.
These results demonstrate a link between PTEN somatic loss and greater endometriosis disease burden. These findings underscore the potential relevance of PTEN loss and other somatic driver mutations in a future molecular classification of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Canadian Institutes of Health Research (CIHR) project grant (MOP-142273 and PJT-156084). P.J.Y. was supported by a Health Professional Investigator award from Michael Smith Health Research BC, Canada, and a Canada Research Chair (Tier 2) in Endometriosis and Pelvic Pain. M.S.A. was supported by a Michael Smith Health Research BC Scholar award, and CIHR project grants (369990, 462997, and 456767). The sponsors did not play any role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to [truncated]
Schoeman EM et al., 2025·Human reproduction (Oxford, England)·Free full text on PubMed Central
Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis?
A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis.
Endometriosis poses intricate medical challenges for affected individuals and their physicians, yet diagnosis currently takes an average of 7 years and normally requires invasive laparoscopy. Consequently, the need for a simple, accurate non-invasive diagnostic tool is paramount.
STUDY DESIGN, SIZE, This study compared 805 participants across two independent clinical populations, with the status of all endometriosis and symptomatic control samples confirmed by laparoscopy. A proteomics workflow was used to identify and validate plasma protein biomarkers for the diagnosis of endometriosis.
PARTICIPANTS/MATERIALS, SETTING, A proteomics discovery experiment identified candidate biomarkers before a targeted mass spectrometry assay was developed and used to compare plasma samples from 464 endometriosis cases, 153 general population controls, and 132 symptomatic controls. Three multivariate models were developed: Model 1 (logistic regression) for endometriosis cases versus general population controls, Model 2 (logistic regression) for rASRM stage II to IV (mild to severe) endometriosis cases versus symptomatic controls, and Model 3 (random forest) for stage IV (severe) endometriosis cases versus symptomatic controls.
MAIN A panel of 10 protein biomarkers were identified across the three models which added significant value to clinical factors. Model 3 (severe endometriosis vs symptomatic controls) performed the best with an area under the receiver operating characteristic curve (AUC) of 0.997 (95% CI 0.994-1.000). This model could also accurately distinguish symptomatic controls from early-stage endometriosis when applied to the remaining dataset (AUCs ≥0.85 for stage I to III endometriosis). Model 1 also demonstrated strong predictive performance with an AUC of 0.993 (95% CI 0.988-0.998), while Model 2 achieved an AUC of 0.729 (95% CI 0.676-0.783).
LIMITATIONS, The study participants were mostly of European ethnicity and the results may be biased from undiagnosed endometriosis in controls. Further analysis is required to enable the generalizability of the findings to other populations and settings.
In combination, these plasma protein biomarkers and resulting diagnostic models represent a potential new tool for the non-invasive diagnosis of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S): Subject recruitment at The Royal Women's Hospital, Melbourne, was supported in part by funding from the Australian National Health and Medical Research Council (NHMRC) project grants GNT1105321 and GNT1026033 and Australian Medical Research Future Fund grant no. MRF1199715 (P.A.W.R., S.H.-C., and M.H.). Proteomics International has filed patent WO 2021/184060 A1 that relates to endometriosis biomarkers described in this manuscript; S.B., R.L., and T.C. declare an interest in this patent. J.I., S.B., C.L., D.I., H.L., K.P., M.D., M.M., M.R., P.T., R.L., and T.C. are shareholders in Proteomics International. Otherwise, the authors have no conflicts of interest.
N/A.
Schliep KC et al., 2025·F S Rep·Free full text on PubMed Central
To determine whether endometriosis typology, namely ovarian endometriomas (OE), deep infiltrating endometriosis (DIE), or superficial endometriosis (SE), correlates with fertility history.
Prospective cohort.
One of fourteen surgical centers in Salt Lake City, Utah (n = 5) or San Francisco, California (n = 9). A total of 473 women (18-44 years) with no prior endometriosis diagnosis, undergoing laparoscopies/laparotomies, irrespective of indication, in Utah or California (2007-2009). Exposure: Incident endometriosis. Before surgery, we queried women about time to become pregnant for prior planned pregnancies. Generalized linear models were used to calculate adjusted prevalence ratios (aPR) for association between endometriosis typology and infertility, defined as having ever tried >12 months (>6 months for women ≥35 years) to get pregnant. We also generated fecundability odds ratios (aFOR) to capture time to pregnancy. Twenty-five percent (n = 116) of women were diagnosed with SE only, 5% (n = 23) with OE, 6% (n = 29) with DIE, and 5% (n = 22) with OE + DIE, and 60% (n = 283) with no endometriosis. Compared with women with no endometriosis, women with SE had a 1.58 higher aPR (95% confidence interval [CI], 1.16-2.14), although women with OE and/or DIE had a 2.41 higher aPR for subfertility after adjusting for women's age, body mass index, and site. Compared with women with no endometriosis, women with OE and/or DIE had a 53% lower historic fecundability (aFOR, 0.47; 95% CI, 0.24-0.95); however, no association was found among women with SE (aFOR, 0.81; 95% CI, 0.49-1.33). Specific endometriosis typologies may be associated with fecundability, with OE and/or DIE associated with nearly a 150% higher prevalence of subfertility and over a 50% lower historic fecundability.
De Corte P et al., 2025·BJOG : an international journal of obstetrics and gynaecology·Free full text on PubMed Central
Endometriosis diagnosis reportedly faces delays of up to 10 years. Despite growing awareness and improved guidelines, information on the current status is limited. To systematically assess the published evidence on the status of time to diagnosis in individuals with endometriosis, with respect to the definition of time to diagnosis, geographical location and patient characteristics. MEDLINE (via PubMed) and Embase were searched for publications reporting time to diagnosing endometriosis since 2018. No restrictions to population or comparators were applied. All publications were screened by two independent reviewers. Search results were limited to primary publications of randomised controlled trials, non-randomised trials and observational studies. Case reports, secondary publications and grey literature were excluded. No restrictions were made regarding language, provided that an English title and abstract were available. Publications were assessed with respect to time to diagnosis, diagnostic methods, study type, study country and potential bias. The 17 publications eligible for inclusion in this literature review were all observational studies. The publications reported diagnosis times between 0.3 and 12 years, with variations depending on the definition of time to diagnosis (overall, primary, or clinical), geographical location and characteristics of the included study population. Evidence was of poor to good quality overall. Diagnostic delay is still present, primarily driven by physicians, and this review underscores the need for standardised definitions, increased awareness and targeted diagnostic interventions.
Salmanov AG et al., 2025·Wiadomosci lekarskie (Warsaw, Poland : 1960)
Aim this study was to evaluate the incidence of endometriosis in women with a recent history of surgical site infections (SSIs), and obstetric and gynecological surgical procedures.
Materials and A retrospective multicenter cohort was conducted on patients who have had obstetric or gynecological surgical procedures performer from January 2022 to December 2024 in 16 hospitals from six Ukrainian regions. Definitions of SSIs were adapted from the Centers for Disease Control and Prevention's National Healthcare Safety Network. The criteria for endometriosis were adapted from the ESHRE endometriosis guideline.
The study included 33,126 reproductive women with endometriosis who had 16,724 obstetric and 32,383 gynecologic surgical procedures. The incidence of endometriosis in women with history of obstetric and gynecologic surgical procedures, and SSIs was 25.5% [95% confidence interval (CI), 24.3-26.4], 33.3% (95% CI, 33.0-33.6), and 22,1% (20.8-24.2), respectively. Multivariate analysis identified SSIs, obstetric and gynecological surgical procedures as three factors positively associated with the risk of endometriosis. Factors that increased the odds of endometriosis was SSIs (adjusted odds ratio [AOR], 3.76; 95% CI, 2.29-6.20), and obstetric and gynecological surgical procedures (AOR, 7.91; 95% CI, 3.68-37.3). An SSIs and obstetric and gynecological surgery history increased the odds of an endometriosis >7-fold in the cohort (AOR, 7.96; 95% CI, 3.64-37.2).
Obstetric and gynecological surgical injury, and the inflammation resulting from SSIs may play a role in developing endometriosis.
Salmanov AG et al., 2025·Wiadomosci lekarskie (Warsaw, Poland : 1960)
To estimate the prevalence and risk factors associated with endometriosis in female evacuated from the Eastern Ukrainian military conflict regions.
Materials and A prospective multicenter cohort study was based on surveillance data for endometriosis. 982 women undergoing pelvic surgery were compared to 264 patients unexposed to surgery. The study cohort included women, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy in 2022-2024. Endometriosis among women was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging.
The prospective multicenter study included 1,246 women. The overall prevalence of endometriosis was 31.5%. Prevalence of the three types of endometrioses included peritoneal/superficial endometriosis, ovarian endometriotic cyst/endometrioma and deep infiltrating endometriosis was 13.8%, 9.8%, and 4.8%, respectively. Three hundred sixty-one women 36,8% in the surgical group and thirty-one women 13.3% in the community treatment group (unexposed to surgery, population cohort) were diagnosed with incident endometriosis. The pelvic pain, infertility and early age at menarche to be a consistent risk factor for endometriosis in both the operative and population cohorts. Data analysis showed that odds were decreased for gravidity, parity, and BMI. Factors that increased the odds of endometriosis diagnosis included dysmenorrhea, older age at first sex, pelvic pain as a surgical indication for laparoscopy, and higher education.
Our study findings demonstrate the high prevalence of endometriosis among women in Ukraine. The pelvic pain, infertility and early age at menarche to be a consistent risk factor for endometriosis in both the operative and population cohorts.
Salmanov AG et al., 2025·Wiadomosci lekarskie (Warsaw, Poland : 1960)·Free to read
To estimate the incidence of abdominal walls endometriosis in Ukraine and review the clinical findings, imaging results, and histopathology of patients who have had cesarean scar endometriosis.
Materials and We performed multicentre retrospective cohort study from January 2020 to December 2024. The study involved 27 hospitals from 10 regions of Ukraine and included 9,157 reproductive women who had a painful mass in their previous abdominal surgery scar area. Definitions of endometriosis were adapted from the WHO.
Among 9,157 patients, 387 (4.2%) abdominal walls endometriosis (AWE) were observed. Of all cases 82.2% women had cesarean scar endometriosis and 17.8% had scar endometriosis related to gynecologic surgical procedure. The incidence of AWE associated with history of cesarean section, gynecological abdominal hysterectomy and laparoscopic procedures was 6.3%, 2.3%, and 1.2%, respectively. The main symptoms of scar endometriosis were palpable abdominal mass (100%) and cyclic pain (86.8%). The latency period between cesarean section procedure and of cesarean scar endometriosis (CSE) symptom onset was 31.8 ± 23.6 months. The duration between the onset of symptoms of CSE and this surgery was 28.7 ± 25.4 months. The diagnosis of CSE was made through a histopathological examination.
In Ukraine abdominal wall endometriosis (AWE), is a relatively uncommon entity that usually develops at the site of a surgical scar that occurs after obstetric or gynecologic surgeries. In our study the most frequently of all AWE cases was cesarean scar endometriosis.
Yeung P et al., 2025·Acta Scientific Women's Health·Free to read
The primary purpose of this prospective cohort study was to determine if treating endometriosis with optimal excision surgery leads to lower rates of repeat surgery as compared to historical rates of repeat surgery by ablation. A secondary outcome was to examine whether the use of hormonal suppression differed before surgery, depending on the stage of endometriosis found at surgery. Optimal excision was defined as completely excising all areas of abnormal peritoneum, wherever found in the pelvis, having looked systematically with near contact laparoscopy. All surgeries were performed by a single surgeon specializing in optimal excision at a tertiary referral center. The rate of repeat surgery after optimal excision surgery for endometriosis was remarkably low (2.5%, 15/620) as compared to historical rates of repeat surgery by ablation. Additionally, the lack of significant evidence between hormonal suppression use and progression of stage of endometriosis provides implicit evidence that hormonal suppression does not prevent progression of the disease. Further controlled studies are needed to verify these findings.
Noar M et al., 2024·J Clin Med·Free full text on PubMed Central
Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by an absence of uniformly accurate, non-invasive diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers, unique to endometriosis, will allow non-invasive, uniformly accurate diagnosis or exclusion of endometriosis. Prospective open-label comparative study of 154 patients, age ≥ 18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically/histologically confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Non-invasive electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30 min post water load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and predictive probability or C-statistic used univariate, multivariate, linear, and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. The non-endometriosis cohort differed significantly from the endometriosis cohorts (p < 0.001) for median (IQR) and AUC percent frequency distribution of power at baseline, 10 min, 20 min, and 30 min post water load at all frequency ranges: 15-20 cpm, 30-40 cpm, and 40-50 cpm. The endometriosis cohorts were statistically similar (p > 0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV, and a C-statistic of >99%/98%, respectively, for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. EVG with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis-specific GIMA biomarkers threshold scoring.
Fertility and Outcomes · Conception After Excision
Zhang J et al., 2024·Eur J Obstet Gynecol Reprod Biol·Free to read
To analyze the factors that might influence the pregnancy rate in patients with infertility related to endometriosis (EMs) after undergoing laparoscopic surgery, providing guidance for our clinical diagnostic and therapeutic decision-making. A retrospective analysis was conducted on clinical records and 1-year postoperative pregnancy outcomes of 335 patients diagnosed with endometriosis-related infertility via laparoscopic surgery, admitted to our department from January 2018 to December 2020. The overall pregnancy rate for patients with endometriosis (EMs) related infertility 1-year post-surgery was 57.3 %, with the highest pregnancy rate observed between 3 to 6 months after surgery. Factors such as Body Mass Index (BMI) (P = 0.515), presence of dysmenorrhea (P = 0.515), previous pelvic surgery (P = 0.247), type of EMs pathology (P = 0.893), and preoperative result of serum carbohydrate antigen 125 (CA125)（P = 0.615）had no statistically significant effect on postoperative pregnancy rates. The duration of infertility (P = 0.029), coexistence of adenomyosis (P = 0.042), surgery duration (P = 0.015), intraoperative blood loss (P = 0.050), preoperative result of serum anti-Müllerian hormone (AMH) (P = 0.002) and age greater than 35 (P = 0.000) significantly impacted postoperative pregnancy rates. The post-surgery pregnancy rate in patients with mild (Stage I-II) EMs was notably higher than those with moderate to severe (Stage III-IV) EMs (P = 0.009). Age (P = 0.002), EMs stage (P = 0.018), intraoperative blood loss (P = 0.010) and adenomyosis (P = 0.022) were the factors that affected the postoperative live birth rate. For patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors.
Bendifallah S et al., 2024·European journal of obstetrics, gynecology, and reproductive biology
Patients with superficial peritoneal endometriosis (SPE) present with symptoms suggestive of endometriosis but clinical and imaging exams are inconclusive. Consequently, laparoscopy is usually necessary to confirm diagnosis. The present study aimed to evaluate the accuracy of microRNAs (miRNAs) to diagnose patients with SPE from the ENDOmiARN cohort This prospective study (NCT04728152) included 200 saliva samples obtained between January and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy and/or MRI to confirm the presence of endometriosis. Among the patients with endometriosis, two groups were defined: an SPE phenotype group of patients with peritoneal lesions only, and a non-SPE control group of patients with other endometriosis phenotypes (endometrioma and/or deep endometriosis). Data analysis consisted of two parts: (i) identification of a set of miRNA biomarkers using next-generation sequencing (NGS), and (ii) development of a saliva-based miRNA signature for the SPE phenotype in patients with endometriosis based on a Random Forest (RF) model.
Among the 153 patients with confirmed endometriosis, 10.5 % (n = 16) had an SPE phenotype. Of the 2633 known miRNAs, the feature selection method generated a signature of 89 miRNAs of the SPE phenotype. After validation, the best model, representing the most accurate signature had a 100 % sensitivity, specificity, and AUC.
This signature could constitute a new diagnostic strategy to detect the SPE phenotype based on a simple biological test and render diagnostic laparoscopy obsolete. PRéCIS: We generated a saliva-based signature to identify patients with superficial peritoneal endometriosis which is the most challenging form of endometriosis to diagnose and which is often either misdiagnosed or requires invasive laparoscopy.
Kiser AC et al., 2024·PLoS One·Free full text on PubMed Central
Endometriosis is a debilitating, chronic disease that is estimated to affect 11% of reproductive-age women. Diagnosis of endometriosis is difficult with diagnostic delays of up to 12 years reported. These delays can negatively impact health and quality of life. Vague, nonspecific symptoms, like pain, with multiple differential diagnoses contribute to the difficulty of diagnosis. By investigating previously imprecise symptoms of pain, we sought to clarify distinct pain symptoms indicative of endometriosis, using an artificial intelligence-based approach. We used data from 473 women undergoing laparoscopy or laparotomy for a variety of surgical indications. Multiple anatomical pain locations were clustered based on the associations across samples to increase the power in the probability calculations. A Bayesian network was developed using pain-related features, subfertility, and diagnoses. Univariable and multivariable analyses were performed by querying the network for the relative risk of a postoperative diagnosis, given the presence of different symptoms. Performance and sensitivity analyses demonstrated the advantages of Bayesian network analysis over traditional statistical techniques. Clustering grouped the 155 anatomical sites of pain into 15 pain locations. After pruning, the final Bayesian network included 18 nodes. The presence of any pain-related feature increased the relative risk of endometriosis (p-value < 0.001). The constellation of chronic pelvic pain, subfertility, and dyspareunia resulted in the greatest increase in the relative risk of endometriosis. The performance and sensitivity analyses demonstrated that the Bayesian network could identify and analyze more significant associations with endometriosis than traditional statistical techniques. Pelvic pain, frequently associated with endometriosis, is a common and vague symptom. Our Bayesian network for the study of pain-related features of endometriosis revealed specific pain locations and pain types that potentially forecast the diagnosis of endometriosis.
Lee CE et al., 2024·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain.
A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery.
Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy.
At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients.
Fertility and Outcomes · Conception After Excision
Nezhat C et al., 2024·J Clin Med·Free full text on PubMed Central
Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments. While biopsy remains the gold standard for diagnosis, emerging noninvasive screening methods are gaining prominence. These tests can indicate endometriosis in cases of unexplained infertility, offering valuable insights to patients and physicians managing both obstetric and non-obstetric conditions. In a retrospective cross-sectional study involving 215 patients aged 25 to 45 with unexplained infertility, diagnostic laparoscopy was performed after unsuccessful reproductive technology attempts. Pathology results revealed tissue abnormalities in 98.6% of patients, with 90.7% showing endometriosis, confirmed by the presence of endometrial-like glands and stroma. The study underscores the potential role of endometriosis in unexplained infertility cases. Although the study acknowledges selection bias, a higher than previously reported prevalence suggests evaluating endometriosis in patients who have not responded to previous reproductive interventions may be justified. Early detection holds significance due to associations with ovarian cancer, prolonged fertility drug use, pregnancy complications, and elevated post-delivery stroke risk.
Lu C et al., 2024·Int J Mol Sci·Free full text on PubMed Central
Studies have shown that the occurrence and development of endometriosis are closely linked to long-term psychological stress. The specific contribution of chronic stress to the metabolic adaptations in patients with endometriosis is still unknown. Lesions were removed from ten endometriosis patients during an operation, and the participants were divided into two groups using a psychological questionnaire. An mRNA Human Gene Expression Microarray analysis was applied to compare the mRNA expression profiles between the chronic stress group and the control group. In addition, the reliability of the mRNA Human Gene Expression Microarray analysis was verified by using research on metabolites based on both the liquid chromatography (LC-MS/MS) technique and quantitative reverse transcription polymerase chain reaction (RT-PCR). A microarray analysis of significantly up-regulated, differentially expressed genes between the chronic stress and the control groups showed genes that were principally related to metabolism-related processes and immune-related processes, such as the immune response process, negative regulation of T cell proliferation, the leucine metabolic process, and the L-cysteine metabolic process (p < 0.05). LC-MS showed that the differential metabolites were primarily concerned with arginine and proline metabolism, D-glutamine and D-glutamate metabolism, aspartate metabolism, glycine, serine metabolism, and tyrosine metabolism (p < 0.05). The possibility of chronic stress blocks the endometriosis immune response through metabolic reprogramming. Chronic stress reduces the supply of energy substrates such as arginine and serine, down-regulates T immune cell activation, and affects the anti-tumor immune response, thereby promoting the migration and invasion of endometriosis lesions in patients with chronic stress.
Dungate B et al., 2024·Women's health (London, England)·Free full text on PubMed Central
Endometriosis, a chronic condition characterized by the growth of endometrial-like tissue outside of the uterus, poses substantial challenges in terms of diagnosis and treatment. Artificial intelligence (AI) has emerged as a promising tool in the field of medicine, offering opportunities to address the complexities of endometriosis. This review explores the current landscape of endometriosis diagnosis and treatment, highlighting the potential of AI to alleviate some of the associated burdens and underscoring common pitfalls and challenges when employing AI algorithms in this context. Women's health research in endometriosis has suffered from underfunding, leading to limitations in diagnosis, classification, and treatment approaches. The heterogeneity of symptoms in patients with endometriosis has further complicated efforts to address this condition. New, powerful methods of analysis have the potential to uncover previously unidentified patterns in data relating to endometriosis. AI, a collection of algorithms replicating human decision-making in data analysis, has been increasingly adopted in medical research, including endometriosis studies. While AI offers the ability to identify novel patterns in data and analyze large datasets, its effectiveness hinges on data quality and quantity and the expertise of those implementing the algorithms. Current applications of AI in endometriosis range from diagnostic tools for ultrasound imaging to predicting treatment success. These applications show promise in reducing diagnostic delays, healthcare costs, and providing patients with more treatment options, improving their quality of life. AI holds significant potential in advancing the diagnosis and treatment of endometriosis, but it must be applied carefully and transparently to avoid pitfalls and ensure reproducibility. This review calls for increased scrutiny and accountability in AI research. Addressing these challenges can lead to more effective AI-driven solutions for endometriosis and other complex medical conditions.
Fertility and Outcomes · Conception After Excision
Salmanov AG et al., 2024·Wiadomosci lekarskie (Warsaw, Poland : 1960)
To estimate pregnancy outcomes associated with endometriosis in Ukraine.
Materials and We performed the multicentre prospective cohort study during the period from January 1st, 2019 to December 31st, 2021. The study included pregnant women aged ≥18 years hospitalized in 17 hospitals from 15 regions of Ukraine. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI).
Of the 27,558 women, 990 (3,6%) reported a diagnosis of endometriosis before pregnancy. In 990 deliveries, women with endometriosis had a higher risk of hypertension in pregnancy (OR 1.2, 95% CI 1.0-1.3), preeclampsia (OR 1.4, 95% CI 1.3-1.5), severe preeclampsia (OR 1.7, 95% CI 1.5-2.3), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0-2.5), placental abruption (OR 2.0, 95% CI 1.7-2.3), placenta previa (OR 3.9, 95% CI 3.5-4.3), premature rupture of membranes (OR 1.7, 95% CI 1.5-1.8), and retained placenta (OR 3.1, 95% CI 1.4-6.6). The neonates had increased risks of preterm birth before 28 weeks (OR 3.1, 95% CI 2.7-3.6), birth before 34 weeks (OR 3.2, 95% CI 2.8-3.6), being small for gestational age (OR 1.5, 95% CI 1.4-1.6), being diagnosed with congenital malformations (OR 1.3, 95% CI 1.3-1.4), and neonatal death (OR 1.8, 95% CI 1.4-2.1).
Pregnant women with endometriosis are at elevated risk for serious and important adverse maternal, fetal and neonatal outcomes. The magnitude of these complications calls for more intensive antenatal care of pregnant women with endometriosis.
Goodwin E et al., 2023·Women's health reports (New Rochelle, N.Y.)·Free full text on PubMed Central
Endometriosis patients have a high rate of co-occurring anxiety and depression. There is currently no literature investigating how this may affect endometriosis treatment and outcomes. This study examines the prevalence of depression and anxiety in a pathologically confirmed population-based endometriosis cohort and examines how endometriosis treatments and outcomes differ by the presence of co-occurring depression and/or anxiety.
This retrospective cohort study using population-based administrative data sets included pathologically confirmed endometriosis patients identified from the complete pathology records of Vancouver Coastal Health Authority (British Columbia, Canada) between 2000 and 2008. These data were linked with population-based health data for follow-up to 2017. Bivariate analyses assessed differences between patients with depression and/or anxiety and those without. Odds ratios (ORs) were calculated to assess the odds of binary postsurgical outcomes.
Our final cohort consisted of 3815 patients. There were 603 patients (15.8%) with depression and/or anxiety. They were more likely to visit a physician for pelvic pain, more likely to take some hormonal medications, and more likely to fill prescription-level analgesics, including opioids both before and after surgery. They also had a significantly higher risk of reoperation for their endometriosis than people without co-occurring depression and/or anxiety (OR 1.32, 95% confidence interval [CI]: 1.07-1.61).
Endometriosis patients with co-occurring depression and/or anxiety used more health services for pain, including prescription-level analgesics, and were more likely to have an endometriosis reoperation. We recommend that future study should aim to better understand the direction of this association between depression and/or anxiety and increased health services use.
Schliep KC et al., 2023·AJOG Glob Rep·Free full text on PubMed Central
Polycystic ovarian syndrome and endometriosis are 2 of the most common reproductive disorders among women but are thought to be unrelated. This study aimed to examine the overlap and common symptoms of polycystic ovarian syndrome and endometriosis. The study population included the Endometriosis, Natural History, Diagnosis, and Outcomes Study (2007-2009) operative cohort: 473 women, aged 18 to 44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 14 surgical centers located in Salt Lake City, Utah, or San Francisco, California, in addition to a population cohort composed of 127 women from the surgical centers' catchment areas. Age and site-adjusted multinomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals of reproductive history characteristics among women with endometriosis only, women with polycystic ovarian syndrome only, and women with both endometriosis and polycystic ovarian syndrome. Among the operative cohort, 35% had endometriosis only, 9% had polycystic ovarian syndrome only, and 5% had endometriosis and polycystic ovarian syndrome. Among the population cohort, 10% had endometriosis only, 8% had polycystic ovarian syndrome only, and 2% had endometriosis and polycystic ovarian syndrome. In the operative cohort, a history of subfertility was associated with a higher adjusted probability of having both conditions (adjusted prevalence ratio, 10.33; 95% confidence interval, 3.94-27.08), followed by having endometriosis only (adjusted prevalence ratio, 2.45; 95% confidence interval, 1.56-3.84) or polycystic ovarian syndrome only (adjusted prevalence ratio, 1.15; 95% confidence interval, 0.51-2.61), than having neither condition. In addition, experiencing chronic pelvic pain within the past 12 months was associated with a higher probability of having both conditions (adjusted prevalence ratio, 2.53; 95% confidence interval, 1.07-6.00) than having neither condition. Among a cohort of women undergoing gynecologic laparoscopy or laparotomy, our study found that nearly 1 in 20 women had both an incident endometriosis diagnosis and symptoms consistent with polycystic ovarian syndrome. Among a population cohort of women not seeking gynecologic care, polycystic ovarian syndrome and endometriosis overlap prevalence was approximately 1 in 50 women.
Latif S et al., 2023·J Clin Med·Free full text on PubMed Central
Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.
Wu Q et al., 2023·Reprod Biol Endocrinol·Free full text on PubMed Central
This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve. This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured. Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001). CONCLUSION(S): The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely.
Arangia A et al., 2023·Int J Mol Sci·Free full text on PubMed Central
A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.
Orr NL et al., 2023·The journal of pathology. Clinical research·Free full text on PubMed Central
The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p = 0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p = 0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR] = 1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR = 0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR = 1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.
Allaire C et al., 2023·CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne·Free full text on PubMed Central
[For a first-person account of endometriosis, see www.cmaj.ca/lookup/doi/10.1503/cmaj.230215][1] KEY POINTS Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside of the uterus, which can lead to estrogen-driven inflammation. The extent of disease can be
Anastasi E et al., 2023·International journal of environmental research and public health·Free full text on PubMed Central
Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.
Huang SJ et al., 2023·Frontiers in endocrinology·Free full text on PubMed Central
Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.
Blom JN et al., 2023·CMAJ open·Free full text on PubMed Central
Endometriosis, a prevalent condition among females of reproductive age, may be associated with increased risk of cardiovascular disease (CVD) through chronic inflammation and early menopause. The objective of this study was to estimate the association between endometriosis and subsequent risk of CVD. We conducted a population-based cohort study using administrative health data from Ontario residents from 1993 to 2015. We compared the incidence of CVD and cardiovascular health outcomes between females with endometriosis and 2 age-matched females without endometriosis. The primary outcome was hospital admission for CVD. Secondary outcomes included in-hospital CVD events of interest and emergency department visits for CVD. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) between endometriosis and CVD events. We identified 166 835 eligible patients with endometriosis and matched 333 706 patients without endometriosis. The mean age of those with endometriosis was 36.4 years. Patients with endometriosis had a higher incidence of hospital admission for CVD (195 admissions/100 000 person-years) compared with those without endometriosis (163 admissions/100 000 person-years). Similarly, the incidence of secondary CVD events was slightly higher among patients with endometriosis (292 cases/100 000 person-years) than among those without endometriosis (224 cases/100 000 person-years). Females with endometriosis had an increased risk of hospital admission (adjusted HR 1.14, 95% confidence interval [CI] 1.10-1.19) and secondary CVD events (adjusted HR 1.26, 95% CI 1.23-1.30). In this large, population-based study, endometriosis was associated with a small increased risk of CVD events. Future studies need to investigate potential etiological mechanisms and strategies to decrease long-term CVD risk in patients with endometriosis.
Cordeiro MR et al., 2022·Biomedicines·Free full text on PubMed Central
The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them in the spotlight for endometriosis research. The stem cell theory for endometriosis pathogenesis, supported by the consensual mechanism of retrograde menstruation, highlights the recognized importance that MenSC have gained by potentially being directly related to the genesis, development and maintenance of ectopic endometriotic lesions. Meanwhile, the differences observed between MenSC in patients with endometriosis and in healthy women underlines the applicability of these cells as a putative biomarker for the early diagnosis of endometriosis, as well as for the development of targeted therapies. It is expected that in the near future MenSC will have the potential to change the way we manage this complex disease, once their long-term safety and effectiveness are assessed.
Jiao HN et al., 2022·World J Clin Cases·Free full text on PubMed Central
Tubal endometriosis (TEM) is a category of pelvic endometriosis (EM) that is characterized by ectopic endometrial glands and/or stroma within any part of the fallopian tube. The fallopian tubes may be a partial source of ovarian endometriosis (OEM). TEM is difficult to diagnose during surgery and is usually detected by pathology after surgery. To provide a clinical basis for the diagnosis and treatment of TEM. In this study, the data of 30 patients who underwent laparoscopic salpingectomy due to various gynecological diseases and had pathological confirmation of TEM at our hospital were retrospectively analyzed, and the clinical basis for the diagnosis and treatment of TEM was evaluated. Among 1982 surgical patients, 30 met the study criteria. Among those, 6 patients had a history of infertility, 12 patients had a history of artificial abortion, 13 patients had a history of cesarean section, 1 patient had a history of tubal ligation, 4 patients had an intrauterine device, and 22 patients had hydrosalpinx. Sixteen patients (53.33%) conceived naturally and gave birth to healthy babies. Pathology showed that only 2 patients had TEM without any other gynecological diseases, while the others all had simultaneous diseases, including 26 patients with EM at other pelvic sites. The final diagnosis of TEM depends on pathological examination since there are no specific clinical characteristics. The rate of TEM combined with EM (especially OEM) was higher than that of other gynecological diseases, which indicates that TEM is related to OEM.
Farland LV et al., 2022·Stroke·Free full text on PubMed Central
Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥50 years), infertility history, body mass index (<25, ≥25 kg/m2), and menopausal status. We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.
Mercorio A et al., 2022·Front Endocrinol (Lausanne)·Free full text on PubMed Central
Endometriosis is a chronic, multifactorial, estrogen-dependent disease. The abnormal endocrine microenvironment of endometriosis lesions is considered a main feature and multiple enzymatic pathways leading to local increased synthesis of estrogens have been identified. However, the relevance of intracrinology in clinical practice is still lacking. Medline, Embase, Scopus database were systematically searched for studies reporting on local estrogens metabolism of endometriotic lesions. The main enzymatic pathways involved in the intracrinology of endometriosis such as aromatase (CYP19A1), 17β-hydroxysteroid dehydrogenase (HSD17B) type 1, type 2 and type 5, steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1) were assessed with a critical perspective on their role in disease endocrine phenotyping, drug resistance and as therapeutic targets. Overall, studies heterogeneity and missing clinical data affect the interpretation of the clinical role of these enzymes. Although the use of some drugs such as aromatase inhibitors has been proposed in clinical practice for two decades, their potential clinical value is still under investigation as well as their modality of administration. A closer look at new, more realistic drug targets is provided and discussed. Altered expression of these key enzymes in the lesions have far reaching implication in the development of new drugs aimed at decreasing local estrogenic activity with a minimal effect on gonadal function; however, given the complexity of the evaluation of the expression of the enzymes, multiple aspects still remains to be clarified. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311329, identifier CRD42022311329.
Sivajohan B et al., 2022·NPJ digital medicine·Free full text on PubMed Central
Endometriosis is a chronic, debilitating, gynecologic condition with a non-specific clinical presentation. Globally, patients can experience diagnostic delays of ~6 to 12 years, which significantly hinders adequate management and places a significant financial burden on patients and the healthcare system. Through artificial intelligence (AI), it is possible to create models that can extract data patterns to act as inputs for developing interventions with predictive and diagnostic accuracies that are superior to conventional methods and current tools used in standards of care. This literature review explored the use of AI methods to address different clinical problems in endometriosis. Approximately 1309 unique records were found across four databases; among those, 36 studies met the inclusion criteria. Studies were eligible if they involved an AI approach or model to explore endometriosis pathology, diagnostics, prediction, or management and if they reported evaluation metrics (sensitivity and specificity) after validating their models. Only articles accessible in English were included in this review. Logistic regression was the most popular machine learning method, followed by decision tree algorithms, random forest, and support vector machines. Approximately 44.4% (n = 16) of the studies analyzed the predictive capabilities of AI approaches in patients with endometriosis, while 47.2% (n = 17) explored diagnostic capabilities, and 8.33% (n = 3) used AI to improve disease understanding. Models were built using different data types, including biomarkers, clinical variables, metabolite spectra, genetic variables, imaging data, mixed methods, and lesion characteristics. Regardless of the AI-based endometriosis application (either diagnostic or predictive), pooled sensitivities ranged from 81.7 to 96.7%, and pooled specificities ranged between 70.7 and 91.6%. Overall, AI models displayed good diagnostic and predictive capacity in detecting endometriosis using simple classification scenarios (i.e., differentiating between cases and controls), showing promising directions for AI in assessing endometriosis in the near future. This timely review highlighted an emerging area of interest in endometriosis and AI. It also provided recommendations for future research in this field to improve the reproducibility of results and comparability between models, and further test the capacity of these models to enhance diagnosis, prediction, and management in endometriosis patients.
Mak J et al., 2022·Reprod Fertil·Free full text on PubMed Central
Endometriosis is a benign disease that can cause pain and infertility in women. Debate exists over how endometriosis should best be diagnosed. On one hand, endometriosis can be diagnosed by directly examining pelvic anatomy via a surgical procedure known as diagnostic laparoscopy. On the other hand, the disease can be diagnosed via non-surgical means such as using medical imaging, the symptoms described by the patient and whether the patient responds to non-surgical therapies such as medication. In this debate article, we argue in favour of diagnostic laparoscopy. We review the safety of the procedure, compare the ability of diagnostic laparoscopy vs medical imaging to detect endometriosis and consider the benefits of formally diagnosing or ruling out the condition.
Coccia ME et al., 2022·Int J Environ Res Public Health·Free full text on PubMed Central
Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions.
Fertility and Outcomes · Conception After Excision
Schliep KC et al., 2022·Paediatr Perinat Epidemiol·Free full text on PubMed Central
Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity. We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women. Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors. Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes. While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis.
Bendifallah S et al., 2022·Journal of clinical medicine·Free full text on PubMed Central
Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis.
We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm.
Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%.
The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.
Maksym RB et al., 2021·J Clin Med·Free full text on PubMed Central
Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.
Christ JP et al., 2021·American journal of obstetrics and gynecology
Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results. This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time. A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated. Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of <.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P<.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in 2015. The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data.
Leonardi M et al., 2020·Diagnostics (Basel, Switzerland)·Free full text on PubMed Central
We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools, including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team for complex cases that involve the urinary tract. While bladder deep endometriosis (DE) is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE, due to the serious health implications for women. When UTE exists, it is important to work within an interdisciplinary radiological and surgical team.
Qiu Y et al., 2020·Archives of gynecology and obstetrics
No consensus exists on the relationship between vitamin D status and endometriosis. The chief aim of our study was to evaluate the association between serum vitamin D levels and endometriosis. We searched for MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases for studies elucidated the circulating vitamin D levels in endometriosis. The standardized mean differences (SMDs) or odds ratios (ORs) with their 95% confidence interval (CIs) were calculated to evaluate the association between vitamin D levels and endometriosis. Nine studies were included in this meta-analysis. The pooled results indicated that women with endometriosis had lower vitamin D status than that in controls (SMD - 0.97 ng/mL, 95% CI - 1.80 to - 0.14; p = 0.02), and vitamin D status had a negative correlation with the severity of the disease (stage III-IV vs stage I-II: SMD - 1.33 ng/mL, 95% CI - 2.54 to - 0.12; p = 0.03). Although it was not statistically significantly different, hypovitaminosis D had a tendency to be associated with endometriosis (OR 2.77, 95% CI 0.85-6.08, p = 0.10). Heterogeneity was high among included studies. Subgroup analyses revealed that women with no hormone use had lower vitamin D status when compared with controls (SMD - 1.38 ng/mL, 95% CI - 2.59 to - 0.18; p = 0.02). For studies which sample size < 100, serum vitamin D levels were significantly lower in patients than that in controls (SMD - 0.65 ng/mL, 95% CI - 1.19 to - 0.11; p = 0.02). Women with endometriosis had lower vitamin D status when compared with controls, and a negative relationship between vitamin D levels and severity of endometriosis was observed. In addition, hypovitaminosis D was a potential risk factor for endometriosis.
Moustafa S et al., 2020·American journal of obstetrics and gynecology·Free to read
Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a noninvasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms.
The objective of the study was to validate the use of a microRNA panel as a noninvasive diagnostic method for detecting endometriosis.
This was a prospective study evaluating subjects with a clinical indication for gynecological surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms, and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs, miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p, and let-7b, were measured in serum by quantitative real-time polymerase chain reaction in a blinded fashion without knowledge of disease status. Receiver-operating characteristic analysis was performed on individual microRNAs as well as combinations of microRNAs. An algorithm combining the expression values of these microRNAs, built using machine learning with a random forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent data set of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance.
The mean age of women in the study population was 34.1 and 36.9 years for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n = 39). Subjects with endometriosis had significantly higher expression levels of 4 serum microRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum microRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual microRNAs had receiver-operating characteristic areas under the curve ranging from 0.68 to 0.92. A classifier combining these microRNAs yielded an area under the curve of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each microRNA based on revised American Society of Reproductive Medicine staging revealed that all microRNAs could distinguish stage I/II from control and stage III/IV from control but that the difference between stage I/II and stage III/IV was not significant. Subgroup analysis revealed that neither phase of the menstrual cycle or use of hormonal medication had a significant impact on the expression levels in the microRNAs used in our algorithm.
This is the first report showing that microRNA biomarkers can reliably differentiate between endometriosis and other gynecological pathologies with an area under the curve >0.9 across 2 independent studies. We validated the performance of an algorithm based on previously identified microRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis noninvasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated comorbidities, and health care costs.
Fertility and Outcomes · Conception After Excision
Schippert C et al., 2020·BMC Women's Health·Free full text on PubMed Central
Background Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility. Methods A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study. Results A total of 66.5% ( N = 137) of patients had stage III disease, and 33.5% ( N = 69) had stage IV disease. The average age was 37 years (17–59). A total of 63.1% ( N = 130) of surgeries were performed by laparoscopy, 21.8% ( N = 45) were performed by laparotomy and 15% ( N = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients ( N = 187). After surgery, 48.5% ( N = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% ( N = 192). The rate of recurrence was 21.8% ( N = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age < 35 ( p < 0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age < 35 ( p < 0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis ( p < 0.01). Conclusion We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the ‘gold standard’of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function.
Fertility and Outcomes · Conception After Excision
Yong PJ et al., 2020·Journal of minimally invasive gynecology
To systematically review and perform a meta-analysis of the risk of ectopic pregnancy in endometriosis.
MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO), and Cochrane Library to April 1, 2019. Inclusion criteria were cohort or case-control studies from 1990 onward. Exclusion criteria were cohort studies without controls, case reports or series, or no English full-text.
A total of 1361 titles/abstracts were screened after removal of duplicates, 39 full-texts were requested, and, after 24 studies were excluded, there were 15 studies in the meta-analysis.
TABULATION, INTEGRATION, Data were extracted using standardized spreadsheets with 2 independent reviewers, and conflicts were resolved by a third reviewer. We performed random effects calculation of weighted estimated average odds ratio (OR). Heterogeneity and publication bias were assessed with the I2 metric and funnel plots/Egger's test, respectively. The Ottawa-Newcastle Quality Assessment Scale was used with a cutoff of ≥7 for higher quality. There were 10 case-control studies (17 972 ectopic pregnancy cases and 485 266 nonectopic pregnancy controls) and 5 cohort studies (30 609 women with endometriosis and 107 321 women without endometriosis). For case-control studies, endometriosis was associated with increased risk of ectopic pregnancy with an OR of 2.66 (95% confidence interval [CI] = 1.14-6.21, p = .02). For cohort studies, the OR was 0.95 (95% CI = 0.29-3.11, p = .94), but after post hoc analysis of the studies with a Ottawa-Newcastle score ≥7, the OR was 2.16 (95% CI = 1.67-2.79, p <.001). For both case-control and cohort studies, there was high heterogeneity among studies (I2 = 93.9% and I2 = 96.6%, Q test p <.001) but no obvious evidence of systematic bias in the funnel plot, and Egger's test results were not significant (p = .35, p = .70), suggesting no strong publication bias. There were insufficient data to make any conclusions with respect to anatomic characteristics of endometriosis (e.g., stage) or mode of conception (e.g., assisted reproductive technology vs spontaneous).
Possible evidence of an association between endometriosis and ectopic pregnancy was observed (OR = 2.16-2.66). However, these results should be considered with caution, owing to high heterogeneity among studies. Continued research is needed to delineate the pregnancy implications of endometriosis.
Fertility and Outcomes · Conception After Excision
Farland LV et al., 2019·Obstetrics & Gynecology·Free full text on PubMed Central
To investigate the relationship between endometriosis and adverse pregnancy outcomes. Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman. Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45). We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.
Bulun SE et al., 2019·Endocr Rev·Free full text on PubMed Central
Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Nezhat C et al., 2019·JSLS : Journal of the Society of Laparoendoscopic Surgeons·Free full text on PubMed Central
Endometriosis is characterized by the presence of endometrial-like glands and stroma outside the uterine cavity and is believed to affect 6%-10% of reproductive-age women. Endometriosis within the lung parenchyma or on the diaphragm and pleural surfaces produces a range of clinical and radiological manifestations. This includes catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules, resulting in an entity known as thoracic endometriosis syndrome (TES). Computerized searches of MEDLINE and PubMed were conducted using the key words "thoracic endometriosis," "catamenial pneumothorax," "catamenial hemothorax," and "catamenial hemoptysis." References from identified sources were manually searched to allow for a thorough review. TES can produce incapacitating symptoms for some patients. Symptoms of TES are nonspecific, so a high degree of clinical suspicion is warranted. Medical management represents the first-line treatment approach. When this fails or is contraindicated, definitive surgical treatment for cases of suspected TES uses a combined video laparoscopy performed by a gynecologic surgeon and video-assisted thoracoscopic surgery performed by a thoracic surgeon. Postoperative hormonal suppression may further reduce disease recurrence.
Williams C et al., 2019·Journal of minimally invasive gynecology
To investigate ethnic differences for moderate-to-severe endometriosis.
Analysis of a prospective registry (Canadian Task Force classification II-2).
Tertiary referral center.
A total of 1594 women with pelvic pain and/or endometriosis.
None On logistic regression, adjusting for potential confounders, East/South East Asians were 8.3 times more likely than whites to have a previous diagnosis of stage III/IV endometriosis before referral (adjusted odds ratio [aOR], 8.33; 95% confidence interval [CI], 3.74-18.57), 2.7 times more likely to have a palpable nodule (aOR, 2.66; 95% CI, 1.57-4.52), 4.1 times more likely to have an endometrioma on ultrasound (aOR, 4.10; 95% CI, 2.68-6.26), and 10.9 times more likely to have stage III/IV endometriosis at the time of surgery at our center (aOR, 10.87; 95% CI, 4.34-27.21).
Moderate-to-severe endometriosis was more common in women with East or South East Asian ethnicity in our tertiary referral center. This could be explained by East/South East Asians with minimal to mild disease being less likely to seek care or genetic/environmental differences that increase the risk of more severe disease among East/South East Asians. (ClinicalTrials.gov, NCT02911090.).
Fertility and Outcomes · Conception After Excision
To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).
Cross-sectional analysis nested in a retrospective observational study (n = 940).
Hospitals and associated private practices. PATIENT(S): Previously pregnant women (n = 268) within reproductive age in matched pairs. INTERVENTION(S): Retrospective analysis of surgical reports and self-administered questionnaires. MAIN OUTCOME MEASURE(S): Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months' time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis). RESULT(S): The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%-42.0%]) compared with CW (22.0% [16.7%-27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41-2.75). This remained significant in subfertile WwE (50.0% [40.7%-59.4%]) vs. CW (25.8% [8.5%-41.2%]) but not in fertile WwE (24.5% [16.3%-31.6%]) vs. CW (21.5% [15.9%-26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%-51.4%] vs. rASRM III/IV 30.8% [22.6%-38.7%], compared with 22.0% [16.7%-27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%-53.9%]) compared with ovarian endometriosis (28.6% [17.7%-38.7%]) and deep infiltrating endometriosis (33.9% [21.2%-46.0%]) compared with CW (22.0% [16.7%-27.0%]). CONCLUSION(S): Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage. TRIAL NCT02511626.
Fertility and Outcomes · Conception After Excision
To evaluate the effect of endometriosis on pregnancy outcomes. Systematic review and meta-analysis. Not applicable. PATIENT(S): Women with or without endometriosis. INTERVENTION(S): Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included. MEAN OUTCOME MEASURE(S): Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI). RESULT(S): Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia. CONCLUSION(S): Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.
Fertility and Outcomes · Conception After Excision
Minebois H et al., 2017·Gynécologie Obstétrique Fertilité & Sénologie
In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriage. The aim of this study is to evaluate the association between endometriosis and miscarriage in spontaneous pregnancy. We searched the Cochrane Library, Medline of eligible studies from inception to December 2016, without any restriction. We selected studies that compared endometriosis-affected pregnant women to disease-free pregnant women. To ensure the quality of the methodology, the PRISMA criteria have been met at all stages of the development of this meta-analysis. The primary adverse pregnancy outcomes studied was miscarriage. Three reviewers independently extracted the studies' characteristics and outcome data. Of 225 identified abstracts, 4 primary studies met our inclusion criteria by comparing spontaneous pregnant patients with endometriosis to disease-free women. Miscarriage rate was higher in the endometriosis group (OR 1.77 [CI 95% 1.13-2.78]). In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriages (almost 80% increased risk). Further prospective studies are needed to confirm these results in order to establish the exact impact of endometriosis on spontaneous pregnancy course.
Patel BG et al., 2017·Acta obstetricia et gynecologica Scandinavica
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.
Parasar P et al., 2017·Current obstetrics and gynecology reports·Free full text on PubMed Central
Endometriosis is a disease of adolescents and reproductive-aged women characterized by the presence of endometrial tissue outside the uterine cavity and commonly associated with chronic pelvic pain and infertility. Here we review the epidemiology of endometriosis as well as potential biomarkers for detection and with the goal of highlighting risk factors that could be used in combination with biomarkers to identify and treat women with endometriosis earlier.. Early age at menarche, shorter menstrual length, and taller height are associated with a higher risk of endometriosis while parity, higher body mass index (BMI) and smoking are associated with decreased risk. Endometriosis often presents as infertility or continued pelvic pain despite treatment with analgesics and cyclic oral contraceptive pills. Despite a range of symptoms, diagnosis of endometriosis is often delayed due to lack of non-invasive, definitive and consistent biomarkers for diagnosis of endometriosis. Hormone therapy and analgesics are used for treatment of symptomatic endometriosis. However, the efficacy of these treatments are limited as endometriosis often recurs. In this review, we describe potential diagnostic biomarkers and risk factors that may be used as early non-invasive in vitro tools for identification of endometriosis to minimize diagnostic delay and improve reproductive health of patients.
To report on the presence and rate of endometriosis in hydatid cysts of Morgagni found at the time of excision surgery for endometriosis and to describe any association of endometriosis in hydatid cysts of Morgagni with preoperative or operative factors.
A retrospective cohort study (Canadian Task Force Classification II-2).
The Center for Endometriosis at Saint Louis University, a tertiary referral center for endometriosis. Women who underwent optimal excision surgery for suspected endometriosis because of chronic pelvic pain and/or infertility and who also had hydatid cysts of Morgagni removed at the time of surgery when found. Preoperative and operative data were collected prospectively. The rate of endometriosis in hydatid cysts of Morgagni. Secondary measures included are the rate of hydatid cysts of Morgagni in patients with pelvic pain or infertility with and without endometriosis in the cysts. The overall prevalence of endometriosis in hydatid cysts of Morgagni was 11.3%. Patients with pelvic pain had a higher rate (although not statistically significant) of hydatid cysts of Morgagni compared with those without pain (21.1% vs 12.5 %, p = .54). Patients with infertility had a higher rate of hydatid cysts of Morgagni compared with those without infertility (38.1% vs 16.7%, p < .001), and there was a higher rate of endometriosis in the hydatid cysts of Morgagni in patients with infertility compared with those without (11.1% vs 0.0%, p < .001). This study is the first known report of endometriosis found within hydatid cysts of Morgagni. With a rate of 11.3% of cysts of Morgagni having endometriosis within them, this study supports a practice of removing hydatid cysts of Morgagni at the time of surgery in order to achieve optimal excision of endometriosis. The rates of hydatid cysts of Morgagni and of endometriosis found within hydatid cysts of Morgagni were higher in patients with infertility. Further studies are needed to evaluate whether excising cysts of Morgagni affects clinical outcomes.
Background/aims: To estimate the prevalence of diagnosed endometriosis (DE) in women in the United States and assess the associated symptomatic burden. An online, cross-sectional survey of women aged 18-49 years was conducted from August 6, 2012, through November 14, 2012. Survey data (weighted by age, race, education, income, geographical distribution, and propensity score) were used to estimate the prevalence and symptomatic burden of DE in women in the United States. Weighted logistic regressions were used to assess differences in symptom burden between women with and without endometriosis. The prevalence of DE was estimated at 6.1% (2,922 of 48,020 women surveyed); 52.7% of women were 18-29 years of age when they were diagnosed with endometriosis. Most (86.2%) women experienced symptoms before diagnosis. More women with (vs. without) DE had menstrual pelvic pain/cramping (52.7 vs. 45.2%), non-menstrual pelvic pain/cramping (36.7 vs. 14.3%), infertility (11.6 vs. 3.4%), and dyspareunia (29.5 vs. 13.4%). Women with endometriosis were also more likely to report severe symptoms (OR (95% CI) 2.7 (2.3-3.1) for menstrual pelvic pain/cramping, 2.2 (1.7-2.9) for non-menstrual pelvic pain/cramping, and 2.4 (1.8-3.2) for dyspareunia). The prevalence of DE among US women is notable, and affected women experience a substantial symptom burden.
Miller JE et al., 2016·Oncotarget·Free full text on PubMed Central
Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.
Fertility and Outcomes · Conception After Excision
Buck Louis GM et al., 2016·J Womens Health (Larchmt)·Free full text on PubMed Central
Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs ResultsApproximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently ConclusionsWomen with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment.
Yeung PP Jr et al., 2016·Front Public Health·Free full text on PubMed Central
The purpose of this study was to examine if deep retraction pockets (DRPs) in the posterior cul-de-sac and uterosacral ligaments could be a manifestation of endometriosis and if excision of these pockets improves pain symptoms and quality of life. Prospective cohort study Canadian Task Force Classification, II-3. Preoperative data, operative data, and follow-up data were collected prospectively at the Center for Endometriosis at Saint Louis University, a referral center for the surgical management of endometriosis. The 107 consecutive patients who presented with preoperative deep dyspareunia were included in the study, and the median postoperative follow-up was 13 months. Endometriosis was confirmed histologically in any location excised in 88/107 (82.2%) of the women, and 31 DRPs were excised from 25 women with DRPs in the posterior cul-de-sac or uterosacral ligaments, of which 15/31 (48.4%) had endometriosis. Of the 10 DRPs without visible surface lesions, 3 (30.0%) had endometriosis on histology. Pain symptoms and quality of life significantly improved after excision surgery, whether or not DRPs were present. Women who had endometriosis in their DRP also had significant improvement in deep dyspareunia and chronic pelvic pain and quality of life. Results did not differ when patients who took postoperative hormonal suppression were removed from the analyses. Patients had significantly improved pain symptoms and quality of life after excision surgery, whether or not DRPs were present. This study demonstrated that a DRP may be a manifestation of endometriosis (even with a clear surface of the pocket), so that DRPs should be excised to achieve optimal excision of endometriosis.
Mu F et al., 2016·Circulation. Cardiovascular quality and outcomes·Free full text on PubMed Central
Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD). We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis. In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD.
Fertility and Outcomes · Conception After Excision
Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. No external funding was used for this study. The authors have no conflicts of interest to declare.
Medical Management · Hormonal Suppression Outcomes
Sanghera S et al., 2016·BMJ open·Free full text on PubMed Central
Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.
While the incidence of endometriosis is up to 40-60% in women with severe dysmenorrhea/chronic pelvic pain, patients with subfertility carries a risk up to 20-30%. In symptomatic patients, although medical therapy is preferred in women with endometriosis, surgery might be needed in nonresponders or patients with an endometrioma. Following the surgery, recurrence of the disease and/or symptoms might be still noticed which will progressively increase as times goes by. Nevertheless, some risk factors have been identified for the risk of recurrence that decreases the success of the procedure. Those risk factors might be classified as patient-disease related and surgery-associated variables. Herein, we will address about the management of endometriosis regarding the risk factors for relapse, mechanisms of recurrence and potential biomarkers to predict the event.
Agostinis C et al., 2015·Mediators Inflamm·Free full text on PubMed Central
To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.
Kvaskoff M et al., 2015·Hum Reprod Update·Free full text on PubMed Central
Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients.
Gogacz M et al., 2015·Ginekologia polska·Free to read
Endometriosis is a sex hormone-dependent and successively progressing gynecological disease, characterized by the presence of endometrial tissue outside the uterus. The etiology of endometriosis is known to be multifactorial, and its growth depends on immunological, hormonal, genetic and environmental factors. Angiogenesis plays a key role in implantation and growth of endometriotic lesions, as well as in adhesion formation. Physiologically angiogenesis is responsible for neoangiogenesis and recruitment of new capillaries from the already existing capillaries. It is well-documented that altered angiogenesis provokes improper follicular maturation, infertility recurrent miscarriages, ovarian hyperstimulation syndrome, and carcinogenesis. Factors stimulating angionesis include angiogenin, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF).
The aim of the study was to analyze angiogenic factor concentration (angiogenin, VEGF, FGF) in blood serum and peritoneal fluid in patients with diagnosed endometriosis and idiopathic infertility.
A total of 39 patients were recruited for the study including 19 patients (study group) diagnosed with endometriosis during the laparoscopic procedure and 20 patients (control group) with idiopathic infertility and no morphologic changes within the pelvis revealed during the laparoscopic procedure. All patients underwent laparoscopy during the follicular phase of the menstrual cycle. Vein blood sample was obtained before the procedure and during laparoscopy the entire peritoneal fluid was aspirated for further measurement of VEGF, FGF and angiogenin concentrations.
Angiogenin concentration in peritoneal fluid was statistically higher in patient with idiopathic infertility in comparison to endometriosis (p<0.05). Higher angiogenin concentration was detected also in blood serum of patients with idiopathic infertility as compared to patients with endometriosis, but no statistical significance was found. VEGF and FGF concentration in blood serum and peritoneal fluid was similar in both groups (p>0.05). There were no significant differences between serum and peritoneal fluid in case of VEGF FGF and angiogenin in any of the groups.
Angiogenic factors concentration (VEGF FGF agiogenin) in the peritoneal fluid and blood serum during the follicular phase of the menstrual cycle is not a diagnostic criterion for endometriosis.
Fertility and Outcomes · Conception After Excision
Fadhlaoui A et al., 2015·Front Surg·Free full text on PubMed Central
Endometriosis is defined as the presence of endometrial-like tissue (glands or stroma) outside the uterus, which induces a chronic inflammatory reaction. Although endometriosis impairs fertility, it does not usually completely prevent conception. The question of evidence based-medicine guidelines in endometriosis-associated infertility is weak in many situations. Therefore, we will highlight in this issue where the challenges are.
Dun EC et al., 2015·JSLS : Journal of the Society of Laparoendoscopic Surgeons·Free full text on PubMed Central
Women with endometriosis often report onset of symptoms during adolescence; however, the diagnosis of endometriosis is often delayed. The aim of this study was to describe the experience of adolescents who underwent laparoscopy for pelvic pain and were diagnosed with endometriosis: specifically, the symptoms, time from onset of symptoms to correct diagnosis, number and type of medical professionals seen, diagnosis, treatment, and postoperative outcomes. We reviewed a series of 25 females ≤21 years of age with endometriosis diagnosed during laparoscopy for pelvic pain over an 8-year period. These patients were followed up for 1 year after surgery. The mean age at the time of surgery was 17.2 (2.4) years (range, 10-21). The most common complaints were dysmenorrhea (64%), menorrhagia (44%), abnormal/irregular uterine bleeding (60%), ≥1 gastrointestinal symptoms (56%), and ≥1 genitourinary symptoms (52%). The mean time from the onset of symptoms until diagnosis was 22.8 (31.0) months (range, 1-132). The median number of physicians who evaluated their pain was 3 (2.3) (range, 1-12). The adolescents had stage I (68%), stage II (20%), and stage III (12%) disease. Atypical endometriosis lesions were most commonly observed during laparoscopy. At 1 year, 64% reported resolved pain, 16% improved pain, 12% continued pain, and 8% recurrent pain. Timely referral to a gynecologist experienced with laparoscopic diagnosis and treatment of endometriosis is critical to expedite care for adolescents with pelvic pain. Once the disease is diagnosed and treated, these patients have favorable outcomes with hormonal and nonhormonal therapy.
Endometriosis, an underdiagnosed and undertreated condition, affects 1 in 10 women and is associated with pain and infertility. Preoperative evaluation should include testing and management of other causes of pelvic pain. Ultrasonography can aid in surgical planning. Hormonal suppression improves symptoms, but should not be used to diagnose endometriosis, and is not shown to be effective in preventing disease recurrence nor in improving fertility. The goal of surgical management should be optimal removal or treatment of disease and should include measures for adhesion prevention. Rates of recurrence of endometriosis depend on the surgical completeness of removing the disease.
The purpose of this study was to assess the prevalence of endometriosis in women with premenstrual spotting and to determine the predictive value of this symptom in the diagnosis of endometriosis. We conducted a retrospective cohort study of 80 consecutive women who presented to the infertility clinic for evaluation and who subsequently underwent laparoscopic assessment for infertility with or without pelvic pain. Our main outcome measure was the presence or absence of histologically confirmed endometriosis in women with and without premenstrual spotting. Endometriosis was significantly more prevalent in subfertile women who reported premenstrual spotting for ≥2 days relative to women without this symptom (89% [34/38 women] vs 26% [11/42 women]; P < .0001). Multinomial logistic regression analysis demonstrated the presence of premenstrual spotting for ≥2 days to be associated significantly with the presence of endometriosis (odds ratio, 16; 95% confidence interval, 3.9-65.4; P < .01) and red vesicular lesion type (odds ratio, 52.6; 95% confidence interval, 8.6-323.1; P < .001). In this cohort of women with infertility, premenstrual spotting of ≥2 days was associated strongly with histologically confirmed endometriosis and a better predictor than dysmenorrhea or dyspareunia of finding endometriosis at laparoscopy. Premenstrual spotting of at least 2 days was also associated strongly with both higher stage disease and the red vesicular peritoneal endometriosis phenotype.
Is there any occurrence of hidden (occult) endometriotic lesions in normal peritoneum of women with and without visible endometriosis? We detected a slightly higher occurrence of occult microscopic endometriosis (OME) in normal peritoneum of women with visible endometriosis than in control women. Based on a small number of cases, the concept of invisible microscopic endometriosis in visually normal peritoneum has been reported for more than a decade but there is controversy regarding their tissue activity and clinical significance. STUDY DESIGN, SIZE, This case-controlled research study was conducted with prospectively collected normal peritoneal samples from 151 women with and 62 women without visible endometriosis. PARTICIPANTS/MATERIALS, SETTING, Normal peritoneal biopsy specimens from different pelvic sites of were collected during laparoscopy. A histological search of all peritoneal biopsy specimens for the detection of invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker). Tissue expression of estrogen/progesterone receptors (ER/PR) and cell proliferation marker, Ki-67, was performed by immunohistochemistry to identify tissue activity. MAIN Three different patterns of OME were detected based on (I) the presence of typical gland/stroma, (II) reactive hyperplastic change of endometrioid epithelial cells with surrounding stroma and (III) single-layered epithelium-lined cystic lesions with surrounding stroma. A higher tendency toward the occurrence of OME was found in women with visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P = 0.06, χ(2) test). The epithelial cells and/or stromal cells of OME lesions were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR expression was observed in all patterns of OME lesions. Ki-67 index was significantly higher in pattern I/II OME lesions than in pattern III OME lesions (P< 0.05 for each). LIMITATIONS, Bias in the incidence rate of OME lesions in this study cannot be ignored, because we could not analyze biopsy specimens from the Pouch of Douglas of women with revised classification of the American Society of Reproductive Medicine Stage III-IV endometriosis due to the presence of adhesions in the pelvis. We re-confirmed a decade long old concept of invisible (occult) endometriosis in visually normal peritoneum of women with visible endometriosis. The existence of a variable amount of tissue activity in these occult lesions may contribute to the recurrence/occurrence of endometriosis or persistence/recurrence of pain manifestation in women even after successful ablation or excision of visible lesions by laparoscopy. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science. There is no conflict of interest related to this study. Not applicable.
Yang J et al., 2014·International journal of clinical and experimental medicine·Free full text on PubMed Central
The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus, and, however, may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem cells in the etiology of endometriosis. All these data can have clinical implications and provide a basis for new potential therapeutic applications.
Brosens I et al., 2013·Human reproduction (Oxford, England)
We elaborate on a new theory to explain pelvic endometriosis, including endometriosis in premenarcheal girls, based on the finding that the neonatal endometrium can display secretory activity immediately after birth and, in some cases, changes analogous to those seen at menstruation in adults. The neonatal uterus is therefore capable of shedding its endometrium. Indeed, occult vaginal bleeding occurs in a majority of neonates, although overt bleeding is estimated to occur in only 5% of neonates. This may be due to functional plugging of the endocervical canal in the neonate, which in turn would promote retrograde flux of endometrial cells contained in menstrual debris. Ectopic endometrial implantation in a newborn with hydrometrocolpos has been documented. These data, coupled with the observation of a significantly increased risk of endometriosis in adolescents with cervical outflow obstruction and patent Fallopian tubes, indicate that endometriosis, especially in children and young adolescents, may originate from retrograde uterine bleeding soon after birth.
Yeung PP Jr et al., 2013·JSLS·Free full text on PubMed Central
To serve as a pilot feasibility study for a randomized study of excision versus ablation in the treatment of endometriosis by (1) estimating the magnitude of change in symptoms after excision only at multiple referral centers and (2) determining the proportion of women willing to participate in a randomized trial. We performed a multicenter prospective study of women undergoing excision for endometriosis (Canadian Task Force class II-3) at Duke University Center for Endometriosis Research & Treatment (currently the Saint Louis University Center for Endometriosis), Center for Endometriosis Care, Northshore University Health System, Memorial University (Canada), and Florida Hospital. The study comprised 100 female patients, aged 18 to 55 years, with endometriosis-suspected pelvic pain. The intervention was laparoscopic excision only of the abnormal peritoneum suspicious for endometriosis. The main outcome measures were quality of life, pelvic pain, dysmenorrhea, dyspareunia, and bowel and bladder symptoms. The mean follow-up period was 8.5 months. Excision of endometriosis showed a significant reduction in all pain scores except bowel symptoms, as well as significant improvement in quality of life. Of the patients, 84% were willing to participate in a randomized study. Quality of life is a needed primary outcome for any randomized study comparing excision versus ablation. A multicenter comparative trial is feasible, although quality assurance would have to be addressed. Patients were willing to be randomized even at surgical referral centers.
Peterson CM et al., 2013·Am J Obstet Gynecol·Free full text on PubMed Central
We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an ageand residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.
Whitehill K et al., 2012·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
Endometriosis is a known contributor to infertility, but the gold standard for its diagnosis is surgical. Therefore, it is important for clinicians to be able to predict which women with infertility are at high risk for endometriosis and thus should be offered laparoscopy. We sought to identify the clinical predictors of endometriosis in the infertility population.
We conducted a retrospective review of patients at an academic infertility centre. The primary outcome was identification of endometriosis at laparoscopy, and we used logistic regression to test clinical variables for their ability to predict endometriosis.
Primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity were significant independent predictors of finding endometriosis at laparoscopy. Other clinical variables (including hysterosalpingogram findings) were not independent predictors of endometriosis, and physicians with an endometriosis-focused practice were more likely to diagnose endometriosis at laparoscopy.
Key predictors of endometriosis in the infertility population are primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity. These results will be used to develop and validate a formal clinical prediction model for endometriosis in infertile women.
Delgado-Rosas F et al., 2011·Reproduction (Cambridge, England)
Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 μg/kg per day oral Cb2, or 50 or 200 μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.
Chapron C et al., 2011·Human reproduction (Oxford, England)
The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.
Buck Louis GM et al., 2011·Fertil Steril·Free full text on PubMed Central
To estimate the incidence of endometriosis in an operative cohort of women seeking clinical care and in a matched population cohort to delineate more fully the scope and magnitude of endometriosis in the context of and beyond clinical care.
Matched-exposure cohort design.
Surgical centers in the Salt Lake City, Utah, and San Francisco, California, areas. PATIENT(S): The operative cohort comprised 495 women undergoing laparoscopy/laparotomy between 2007 and 2009, and the population cohort comprised 131 women from the surgical centers' catchment areas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of endometriosis by diagnostic method in the operative cohort and by pelvic magnetic resonance imaged (MRI) disease in the population cohort. RESULT(S): Endometriosis incidence in the operative cohort ranged by two orders of magnitude by diagnostic 0.7% for only histology, 7% for only MRI, and 41% for visualized disease. Endometriosis staging was skewed toward minimal (58%) and mild disease (15%). The incidence of MRI-diagnosed endometriosis was 11% in the population cohort. CONCLUSION(S): Endometriosis incidence is dependent on the diagnostic method and choice of sampling framework. Conservatively, 11% of women have undiagnosed endometriosis at the population level, with implications for the design and interpretation of etiologic research.
To determine long-term outcomes after complete laparoscopic excision done at a tertiary referral center in a teenager population, who were not specifically advised to take postoperative hormonal suppression. Prospective observational case series (Canadian Task Force II-3). A tertiary referral center that specializes in the laparoscopic treatment of endometriosis. PATIENT(S): Teenagers with symptoms suspicious for endometriosis who consented and were prospectively recruited to participate in the study. INTERVENTION(S): All patients underwent diagnostic laparoscopy and complete excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Patients were not specifically advised to take postoperative hormonal suppression. MAIN OUTCOME MEASURE(S): Rate of recurrent (or persistent) endometriosis. RESULT(S): Twenty teenagers underwent complete laparoscopic excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Seventeen patients had endometriosis confirmed by histology at initial surgery. Follow-up was up to 66 months (average 23.1 months). There was a statistically significant improvement in most pain symptoms, including bowel-related symptoms, during this time period. The rate of repeat surgery was 8 of 17 patients (47.1%), but the rate of endometriosis (diagnosed visually or histologically) found at surgery was zero. Only one-third of patients took postoperative hormonal suppression for any length of time. CONCLUSION(S): Complete laparoscopic excision of endometriosis in teenagers--including areas of typical and atypical endometriosis--has the potential to eradicate disease. These results do not depend on postoperative hormonal suppression. These data have important implications in the overall care of teenagers, regarding pain management, but also potentially for fertility. Further large comparative trials are needed to verify these results.
Bulletti C et al., 2010·J Assist Reprod Genet·Free full text on PubMed Central
Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
Maroun P et al., 2009·The Australian & New Zealand journal of obstetrics & gynaecology
Endometriosis commonly presents with a range of symptoms none of which are particularly specific for the condition, often resulting in misdiagnosis or delay in diagnosis. To investigate gastrointestinal symptoms in women with endometriosis and compare their frequency with that of the classical gynaecological symptoms. Systematic exploration of symptoms in a consecutive series of 355 women undergoing operative laparoscopy for suspected endometriosis. Endometriosis was confirmed by histology in 290 women (84.5%). Bowel lesions were present in only 7.6%. Ninety per cent of women had gastrointestinal symptoms, of which bloating was the most common (82.8%), but 71.3% also had other bowel symptoms. All gastrointestinal symptoms were similarly predictive of histologically confirmed endometriosis. Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed. Gastrointestinal symptoms are nearly as common as gynaecological symptoms in women with endometriosis and do not necessarily reflect bowel involvement.
To provide a comprehensive review of the best evidence available in the laparoscopic management of endometriosis for pain and/or fertility and to provide practical recommendations based on this information.
Review article of randomized controlled trials. Women with endometriosis. A systematic search was performed of the Cochrane Library and MEDLINE database for randomized controlled trials relating only to laparoscopic management of endometriosis. The information from 7 Cochrane review articles and 35 original randomized trials is presented in a clinically relevant question-and-answer format. Awareness of endometriosis as a disease with substantial morbidity is vitally important. Laparoscopic treatment of endometriosis is beneficial for reducing pain and improving fertility. Laparoscopic presacral neurectomy, but not laparoscopic uterosacral nerve ablation, is a useful adjunct to conservative surgery for endometriosis in patients with a midline component of pain. Preoperative hormonal suppression with gonadotropin-receptor hormone analogue may be helpful in decreasing endometriosis disease scores. Postoperative hormonal suppression with either a gonadotropin-receptor hormone analogue or progestin (including the levonorgestrel intrauterine system) may be helpful in reducing pain and increasing time to recurrence of symptoms. Excisional cystectomy is the preferred method to treat endometrial cysts for both pain and fertility and may be aided by the use of mesna and initial circular excision. An absorbable adhesion barrier (Interceed), 4% icodextrin solution (Adept), and a viscoelastic gel (Oxiplex/AP, FzioMed, Inc., San Luis Obispd, CA; not available in the United States) are safe and effective products to help prevent adhesions in laparoscopic surgery to treat endometriosis.
Pugsley Z et al., 2007·Br J Gen Pract·Free full text on PubMed Central
The prevalence of endometriosis is estimated to be around 10%. Diagnosis is through visualisation of the lesions, mostly via laparoscopy. Studies reveal that there is an average delay in the diagnosis of endometriosis of between 8 and 12 years. Little is known about the reasons for delays in diagnosis women's experiences of primary care prior to diagnosis. To investigate women's experiences of endometriosis from first presentation to diagnosis. Retrospective analysis of data collected from primary care records in four general practices. General practice in south-east England. Women with a Read Code diagnosis of endometriosis were recruited to the study. Details of consultations, investigations, and referrals related to endometriosis were recorded from the notes. Data were analysed using descriptive statistics. The prevalence of endometriosis in women aged over 16 years was 1.44%. A third of women had consulted their GP six or more times before being diagnosed. Ultrasound was frequently requested by GPs, but was helpful in diagnosing endometriosis in only 10.6% of women who underwent a scan. Thirty-nine per cent of women were referred to gynaecologists two or more times before a positive diagnosis was made. The median time from first presentation with symptoms to diagnosis was 9.0 years (interquartile range = 4.5-13.5 years). Repeated consultations and negative investigations contribute to a median delay of 9.0 years before diagnosis of endometriosis. Further research into GPs' interpretation of symptoms and patients' experiences of negative investigations and consultations may lead to a more positive outcome for women with this condition.
Fertility and Outcomes · Conception After Excision
We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia. A retrospective case-control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies. The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7-33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis. We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility.
Endometriosis is an oestrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, multiple operations, and infertility. New findings on the genetics, the possible roles of the environment and the immune system, and intrinsic abnormalities in the endometrium of affected women and secreted products of endometriotic lesions have given insight into the pathogenesis of this disorder and serve as the background for new treatments for disease-associated pain and infertility. Affected women are at higher risk than the general female population of developing ovarian cancer, and they also may be at increased risk of breast and other cancers as well as autoimmune and atopic disorders. Clinicians should assess and follow up affected women for these and other associated disorders. There will probably be a new repertoire of approaches for treatment and perhaps cure of this enigmatic disorder in the near future.
Fertility and Outcomes · Conception After Excision
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Endometriosis impairs fertility through direct mechanical distortion of pelvic anatomy, peritoneal inflammatory mediators, and hormonal micro-environment alterations that reduce implantation potential, making thorough surgical excision critical to restoring fertility rather than bypassing it. The PEARS classification system, used in NaProTECHNOLOGY surgical practice, enables standardized documentation of endometriotic disease extent and correlates operative findings with postoperative reproductive outcomes.
Hilgers TW et al., 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Endometriotic implants are catalogued across their full morphological spectrum—classic powder-burn lesions, red flame lesions, clear vesicles, white fibrotic plaques, and subtle vascular changes—with photographic documentation guiding surgical recognition. Familiarity with atypical implant appearances is essential because underrecognition of non-pigmented lesions leads to incomplete excision and persistent symptomatology.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
CO2 laser vaporization technique for peritoneal and superficial ovarian endometriotic implants is described in detail, covering power density settings, spot size, vaporization depth control, and recognition of adequate treatment endpoints. Complete destruction of all visible implants, facilitated by the near-contact survey, is necessary to achieve durable symptom relief and improvement in fertility outcomes.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
The PEARS (Pelvic Endoscopic Adhesion-Related Surgery) procedure for peritoneal and ovarian endometriosis combines near-contact laser vaporization, adhesiolysis, and ovarian cystectomy under strict anti-adhesion protocols to achieve comprehensive disease eradication while preserving ovarian reserve. Outcomes data demonstrate superior fertility and pain resolution compared to incomplete surgical approaches, establishing PEARS as the operative standard within NaProTECHNOLOGY.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Deep infiltrating endometriosis involving the rectosigmoid, appendix, and small bowel is addressed through gynecologist-performed PEARS techniques that include superficial disc excision, appendectomy, and coordinated bowel resection when full-thickness involvement requires it. Recognition of intestinal endometriosis at laparoscopy and command of the relevant surgical steps allow the NaProTECHNOLOGY surgeon to treat the complete disease burden in a single operative setting.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Bowel endometriosis involving the rectosigmoid, appendix, and small intestine requires specialized resection and repair techniques that fall within the competency of a general surgeon collaborating with the NaProTECHNOLOGY surgical team. Addressing bowel involvement is essential to achieving complete excision of endometriotic disease, which underpins the PEARS philosophy of restoring normal pelvic anatomy and maximizing reproductive potential.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
Endometriosis recurrence after surgical excision remains a clinical reality driven by residual ectopic implants, persistent hormonal milieu favoring re-seeding, and incomplete initial resection. NaProTECHNOLOGY addresses recurrence risk through postoperative hormone normalization guided by CrMS biomarkers, with repeat PEARS reserved for symptomatic or fertility-impairing recurrence confirmed by clinical and laparoscopic assessment.
To present a case of recurrent catamenial pneumothorax and diaphragmatic endometriosis that was managed thoracoscopically. A review of the literature is also presented. A-28-year-old woman presented with bloody stools, chronic constipation, and chest pain. A review of systems was positive for monthly chest pain associated with her menses. A preoperative chest x-ray revealed a right pneumothorax. Colonoscopy revealed biopsy proven endometriosis of the sigmoid colon. A pelvic computed tomography scan revealed bilateral complex, cystic and solid adenexal lesions. A right thoracoscopy was performed. A lesion on the right hemidiaphragm was excised and confirmed to be endometriosis. A wedge section of lung tissue containing a bleb was resected and also contained endometriosis. Three months later, the patient underwent laparoscopic excision of her pelvic endometriosis, including a low anterior rectal resection. Five months later, she presented again with right-sided chest pain. A thoracoscopic right total pleurectomy was performed for recurrent pneumothorax. Pullmonary endometriosis may present as chest pain, shortness of breath, or hemoptysis associated with menstrual cycles. This case emphasizes the importance of a careful review of systems in patients with known endometriosis. Management now includes an endoscopic alternative and all of its known benefits.
This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.
Although numerous studies have attempted to elucidate the implication of endometriosis for infertility, this matter still remains unexplained. Diverse clinical approaches based on assisted reproduction techniques have produced conflicting results on this issue. Nevertheless, impairment of implantation and pregnancy rates seems to affect women who suffer from endometriosis. Whether this effect is due to alteration of the oocyte/embryo or the endometrium still remains to be elucidated, although actual data allude to deficiencies in both. Infertility due to poor quality embryos derived from impaired oocytes obtained from malfunctioning ovaries have been described by some groups. Endometrial defects have been argued by others. Adding more confusion to this topic, the influence of peritoneal fluid in women with endometriosis and/or mixed causes also needs to be considered. The aim of this review is to describe the current situation in the endometriosis-related infertility literature.
Endometriosis is an estrogen-dependent condition that affects 5 million American women; however, its etiology is not fully understood. The development of the baboon model of endometriosis provides an extremely powerful tool to investigate the development and progression of endometriosis from the early invasive phase to the advanced established disease. The inflammatory reaction that occurs in the peritoneal cavity at the site of endometriotic lesions does not clear the refluxed endometrial fragments. Moreover, this reaction appears to promote the survival of the tissue and the development of the disease. Exploration of the interactions between peritoneal macrophages and cytotoxic T cells and endometrial cells will determine whether their ability to scavenge and induce apoptosis is altered. Determining the mechanism(s) that induces the expression of estrogen and its receptor (ERbeta) is crucial to our understanding of the progression of the disease. The effects of ERbeta activation in endometriotic lesions should be investigated. It is important to determine the effects of estrogen on the function of the immune cells, either directly or indirectly. Finally, determining the effect of events at sites of ectopic endometrium on the eutopic endometrium may elucidate the mechanism(s) of infertility associated with endometriosis.
Fertility and Outcomes · Conception After Excision
There are many arguments to support the hypothesis that there is a causal relationship between the presence of endometriosis and subfertility. These arguments are reviewed in this article and include: (1) an increased prevalence of endometriosis in subfertile women compared with women of proven fertility; (2) a reduced monthly fecundity rate (MFR) in baboons with mild to severe (spontaneous or induced) endometriosis compared with those with minimal endometriosis or a normal pelvis; (3) a trend toward a reduced MFR in infertile women with minimal to mild endometriosis compared with women with unexplained infertility; (4) a dose-effect relationship: a negative correlation between the r-AFS stage of endometriosis and the monthly fecundity rate and crude pregnancy rate; (5) a reduced monthly fecundity rate and cumulative pregnancy rate after donor sperm insemination in women with minimal-mild endometriosis compared with those with a normal pelvis; (6) a reduced MFR after husband sperm insemination in women with minimal to mild endometriosis compared with those with a normal pelvis; (7) a reduced implantation rate per embryo after IVF in women with moderate to severe endometriosis compared with women with a normal pelvis; and (8) an increased monthly fecundity rate and cumulative pregnancy rate after surgical removal of minimal to mild endometriosis.
Laparoscopy is the standard method to visually identify endometriotic lesions under magnification within and outside the minor pelvis. The aim of this study was to analyze the accuracy of laparoscopic visualization in diagnosing the various endometriotic sites as confirmed histologically. Presumed endometriotic sites were observed in 164 patients operated on under the clinical suspicion of endometriosis. Targeted biopsies were performed for histologic corroboration, comparing the laparoscopic findings and diagnosis to the histological results. The histological reports of the biopsies confirmed the presence of endometriosis in 138 patients (84.1%), but in 26 patients (15.9%), no evidence of endometriosis was observed. 100% of "red" lesions, 92% of "black" lesions, and 31% of "white" lesions turned out to be endometriosis. Of the 264 various suspected endometriotic sites observed, 142 (53.8%) were confirmed histologically. The most accurate diagnosis was in lesions on the parietal peritoneum of the pelvis, confirmed in 9/9 cases (100%); the ovarian fossa, confirmed in 8/12 cases (66.7%); and the uterosacral ligaments and posterior surface of the broad ligament, confirmed in 83/138 cases (60.1%). As for the other sites, the histologic confirmation rates in the ovarian surface, bowel serosa, and vesicouterine fold of the peritoneum were 48%, 40%, and 13%, respectively. Endometriosis has a multiple appearance, and the lesions may be confused with nonendometriotic lesions. It is clear that a nonhistology-based diagnosis may lead to unnecessary prolonged medical treatment and operations and may delay the proper treatment measures from being applied. Therefore, a meticulous histological confirmation should still be the first step in the laparoscopic diagnosis and treatment of suspected endometriosis.
Buchweitz O et al., 2003·J Am Assoc Gynecol Laparosc
To evaluate the reliability of diagnosing minimal and mild endometriosis under routine conditions, and to determine to what extent disease activity is taken into account. Retrospective analysis (Canadian Task Force classification II-2). University teaching hospital. Laparoscopy. One hundred eighteen consecutive women with minimal and mild endometriosis undergoing routine surgery between 1994 and 1999. MAIN Analytic parameters were the total number of endometriotic lesions; intraoperative description of pigmented, nonpigmented, and nondefined lesions; and number of extirpated lesions and histologic detection rate. In 118 patients, 311 suspected endometriotic lesions were documented. Nonpigmented lesions were reported in only 27% of women. In 51% of surgical reports no importance was attached to disease morphology or activity. Only 1.2 biopsies/patient were taken. The histologic detection rate was 56%. In 49 patients the assumed intraoperative diagnosis was confirmed by histologic examination. Intraoperative description of endometriotic lesions is inadequate. Little attention is paid to the activity of the illness. There is room for improvement in the number of excisions and histologic detection, and an attempt should be made to find a way out of this diagnostic dilemma.
To report a case of acute hemoperitoneum due to erosion of the uterine artery by an endometriotic lesion of the left ovary. Case report and review of literature. University medical center. PATIENT(S): A 39-year-old nulliparous woman with stage 3 endometriosis. INTERVENTION(S): Operative laparoscopy followed by laparotomy, oophorectomy, and ligation of the bleeding uterine artery. RESULT(S): Patient is fully recovered and is attempting to conceive. CONCLUSION(S): An endometriotic lesion eroded the wall of the uterine artery, causing massive, acute hemoperitoneum. Such an event may be overlooked during laparotomy and attributed to the trauma of surgery.
In vitro studies demonstrated that implantation on membranes (peritoneum, amniotic membranes) can take place if there are defects on the surface of the membranes. If these mechanisms play a role for the development of endometriosis in vivo, then patients with surgical treatment of peritoneal endometriosis in the luteal phase must have a high recurrence rate. Retrospective analysis of operation charts and follow-up data. Department of gynecology, in a hospital-based endometriosis treatment center. PATIENT(S): Two hundred twenty premenopausal women. INTERVENTION(S): Laparoscopic treatment for peritoneal endometriosis, stage I and II by revised American Society for Reproductive Medicine guidelines. MAIN OUTCOME MEASURE(S): During the follow-up period of 2 years, symptoms and gynecological and sonographic findings were documented. In case of suspected recurrence a repeat laparoscopy with biopsy was performed to prove the recurrent endometriosis macroscopically and histologically. RESULT(S): The total recurrence rate after 2 years was 9.6%. The recurrence rate of group III (15%) was twice as high as those of group I (7%) and group II (8%), as indicated by subjective complaints, clinical findings, macroscopy, and histology; no differences were found between groups I and II. CONCLUSION(S): Endoscopic surgery for the treatment of peritoneal endometriosis should not be performed in the luteal phase.
To report a rare case of a patient with catamenial hemoptysis, secondary infertility, and endometriosis associated with a unicornuate uterus and noncommunicating rudimentary horn. Case report. University hospital. PATIENT(S): A 29-year-old woman who developed progressive catamenial hemoptysis and secondary infertility was evaluated at the University Hospital of Crete. INTERVENTION(S): The complete history, laboratory data, laparoscopic findings, and chest magnetic resonance image of this patient were analyzed. A GnRH agonist, leuprolide acetate, was successfully administered. MAIN OUTCOME MEASURE(S): Diagnosis and appropriate treatment of pulmonary endometriosis in a patient with rudimentary uterine horn. RESULT(S): Treatment with a GnRH agonist achieved suppression of both menstruation and hemoptysis. After 6 months of normal menstrual activity, the symptoms reappeared. The patient was again treated with leuprolide acetate (3.75 mg/mo IM) for 6 months and remained asymptomatic. In fact, the patient became pregnant after cessation of therapy. Finally, the patient was treated successfully with removal of the rudimentary uterine horn during cesarean section. Three-year follow-up showed disappearance of the chest symptoms. CONCLUSION(S): Pulmonary endometriosis and unicornuate uteri are rare. To our knowledge, this is the first case of catamenial hemoptysis with a congenital müllerian anomaly. We describe successful management using a combination of GnRH agonist and surgical resection of the rudimentary uterine horn.
Chapron C et al., 2002·J Am Assoc Gynecol Laparosc
To determine whether routine clinical examination is sufficient for the diagnosis and establishing the location of deeply infiltrating endometriosis (DIE). Retrospective analysis (Canadian Task Force classification II-2). University-affiliated hospital. Patients. One hundred sixty women with histologically proved deeply infiltrating endometriosis. MAIN Speculum examination allowed endometriotic lesions to be viewed in only 14.4% (23) of patients, and a classic, painful, spheric nodule was palpated in only 43.1% (69). Results of routine clinical examination varied significantly with location of DIE. Whereas a nodule was found in 80.0% (24) of patients with vaginal endometriosis, this rate dropped to only 35.3% (6) and 33.3% (34) in those with DIE of the digestive tract and uterosacral ligaments, respectively (p <0.0001). High locations of DIE lesions at the level of uterosacral ligaments, bottom of the pouch of Douglas, and upper one-third of the posterior vaginal wall explain why results of routine clinical examination are so poor. The term "deep endometriosis infiltrating the rectovaginal septum" is generally incorrect in the true anatomic sense.
Bulun SE et al., 2002·Annals of the New York Academy of Sciences
Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, that is, deficient 17beta-HSD type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.
To describe symptoms, surgical diagnosis and treatment, and long-term outcome of patients with symptomatic diaphragmatic endometriosis. Observational follow-up study. American tertiary referral center for the surgical treatment of endometriosis. PATIENT(S): Eight patients with diaphragmatic endometriosis causing severe or disabling symptoms. INTERVENTION(S): Laparoscopic diagnosis of diaphragmatic endometriosis followed by upper abdominal laparotomy for full-thickness resection of the diaphragm. MAIN OUTCOME MEASURE(S): Reduction of several symptoms as measured on a 5-point ranked ordinal scale administered by a phone survey up to 7 years after surgery. RESULT(S): Laparoscopy from an umbilical port may identify small "sentinel lesions" of endometriosis on the anterior or mid diaphragm. Eight symptomatic patients all had significant invasive disease with dimensions up to 5 cm across of the posterior right diaphragm, which could not always be seen from the umbilical port site. All such lesions can be seen by a laparoscope placed beneath the right costal margin. Laparoscopic treatment of symptomatic disease is not rational given the posterior placement of the disease out of sight behind the liver and the full-thickness nature of the disease in all eight patients. Laparotomy with full thickness resection of the diaphragm resulted in complete eradication of symptoms in seven of eight patients, and good symptomatic reduction in one. CONCLUSION(S): Treatment of diaphragmatic endometriosis by laparotomy results in a high rate of symptom relief. Laparoscopic treatment of diaphragmatic endometriosis will result in a high rate of incomplete diagnosis and incomplete treatment with a high rate of continuing symptoms.
Dmowski WP et al., 2001·J Am Assoc Gynecol Laparosc
Small bowel involvement by endometriosis occurs in about 0.5% of patients, but nodular endometriosis involving the entire wall of the terminal ileum is extremely rare. Endometriotic nodules protruding into the intestinal lumen may lead to chronic, partial, or acute complete small bowel obstruction and associated clinical changes. If obstruction is partial, preoperative diagnosis is difficult and seldom suspected, and no reliable diagnostic tests are available. At laparoscopic surgery, performed typically for associated pelvic endometriosis, bowel lesions may easily be overlooked, especially in women with abdominal adhesions from earlier surgery. Surgical injury, tension tears, or postoperative edema may contribute in such cases to the development of acute, complete small bowel obstruction, which may be difficult to differentiate from postoperative ileus. The patient may deteriorate rapidly and develop abdominal sepsis and multiple organ failure with high risk of mortality. Because of increased production of tumor necrosis factor-alpha by autologous monocytes, endometriosis may predispose to development of severe sepsis and septic shock. (J Am Assoc Gynecol Laparosc 8(1):161-166, 2001)
It is well known that certain aspects of endometriosis are similar to those of malignant disease. For example, like cancer, endometriosis can be both locally and distantly metastatic; it attaches to other tissues, invades, and damages them. Endometriosis is a common disease that does not create a cachectic or catabolic state, and is rarely fatal. There are, however, numerous reported cases of malignancy arising from endometriotic deposits and substantial histologic evidence that endometriosis is associated with endometrioid carcinoma and clear cell carcinoma of the ovary. A large review article by Mostoufizadeh and Scully investigated the association between endometriosis and endometrioid carcinoma, noting that women who had both diseases tended to be younger [1]. They found no association between endometriosis and serous or mucinous carcinoma of the ovary, and reported that malignant transformation of endometriosis was rare and associated with the use of exogenous estrogens. An epidemiological study of Swedish women reported a higher incidence of breast and ovarian cancer and non-Hodgkin's lymphoma in women with endometriosis compared with controls [2]. Vercellini and colleagues also reported a higher incidence of endometrioid and clear cell carcinoma in women with endometriosis compared with controls [3]. Mutations in genes associated with galactose metabolism have been identified as one possible mechanism for this association. These mutations are more common in ovarian cancer and have been reported to be more common in women with endometriosis. We compared 78 women with endometriosis with 248 controls and were unable to demonstrate an increased frequency of these mutations in any of these groups.
Perineal endometriosis with anal sphincter involvement is an infrequent occurrence. Wide excision is the best chance of cure of perineal endometriosis but may cause incontinence when the anal sphincter is involved. Conversely, narrow excision may result in incomplete removal, with increased recurrence rates and need of additional therapy. Wide excision with primary sphincteroplasty and narrow excision surgical techniques are reviewed. One case report of perineal endometriosis with anal sphincter involvement and previously reported cases were reviewed. Patients were compared based on type of resection (wide or narrow excision) and outcome. Since 1957 there have been seven reported cases of perineal endometriosis with anal sphincter involvement, with the present authors adding one additional case for a total of eight. The mean age was 33 (range, 22-47) years. Surgical treatment included wide excision with primary sphincteroplasty (2 cases), narrow excision (4 cases), and incomplete excision (1 case). One case spontaneously regressed after a subsequent pregnancy. There were two recurrences in the narrow excision group and no recurrences in the wide excision group. There were no complications reported for any of the procedures. Although follow-up time was variable and the numbers small, wide excision with primary sphincteroplasty for patients with perineal endometriosis with anal sphincter involvement seems to be the best chance of cure with good functional results. It should be considered particularly in younger patients to obviate the need of long-term subsequent hormonal therapy or re-excision for symptomatic recurrences. In contrast, patients closer to menopause (when endometriosis tends to regress) may be treated optimally by narrow excision to avoid the risks of significant anal sphincter resection.
Nackley AC et al., 2000·J Am Assoc Gynecol Laparosc
Ten women had endometriosis and pelvic peritoneal defects of the posterior leaf of the broad ligament, with the consistent finding of medial displacement of the ureter toward the uterosacral ligament. Ureterolysis at the time of surgery revealed the underlying course of the ureter and its proximity to the uterosacral ligament, making it susceptible to surgical injury. It is important for surgeons to be aware of this anatomic alteration associated with these specific peritoneal defects.
This is a case presentation of an usual nature, a 43-year-old Hispanic female, multigravida presenting with physical findings of massive ascites. In most instances, the presence of massive ascites is associated with malignancies, tuberculosis or perforated visous. In this case, the diagnosis of extensive endometriosis with ascites is reported as a very rare complication of the disease.
To assess the efficacy and diagnostic value of GnRH agonist (GnRH-a) therapy in cases of hidden sciatic nerve endometriosis. Case report. Academic tertiary referral center for endometriosis treatment. PATIENT(S): Three patients with cyclic, catamenial sciatica associated with pelvic endometriosis who had electromyographic evidence of sciatic nerve damage but negative computed tomography and magnetic resonance imaging findings. INTERVENTION(S): Monthly administration of the GnRH-a leuprolide acetate plus daily transdermal E2 (25 microg). MAIN OUTCOME MEASURE(S): Relief of pain symptoms and improvement in motor function. RESULT(S): All three patients had clear decreases in pain and partial amelioration of claudication. CONCLUSION(S): Endometriosis of the sciatic nerve may be hard to diagnose with the use of current imaging techniques but may be proved by clinical response to GnRH analogue treatment and may be more frequent than previously thought.
To describe a computerized pelvic mapping system for pelvic and intestinal endometriosis and preliminary insights gained from it with respect to the effects of ovarian disease. Contemporaneous computerized tabulation of pelvic and intestinal sites of biopsy-proved endometriosis. Tertiary referral center for the surgical treatment of endometriosis. PATIENT(S): One thousand nine hundred seventy-nine patients with endometriosis, 547 of whom had intestinal endometriosis. Patients with endometriosis with previous hysterectomy (n = 194) with or without castration were excluded from this total, leaving 1,785 patients for this study. INTERVENTION(S): Computer tabulation of sites of biopsy-proved pelvic and intestinal endometriosis. MAIN OUTCOME MEASURE(S): Extent of pelvic and intestinal endometriosis as reflected by number of pelvic or intestinal areas involved. Results were stratified by the presence or absence of ovarian endometriosis and by status of previous therapy. RESULT(S): Compared with patients without ovarian endometriosis, patients with ovarian endometriosis have more pelvic and intestinal areas involved by endometriosis. Patients with ovarian endometriosis and intestinal endometriosis are more likely to require full-thickness or segmental bowel resections for complete removal of intestinal disease. These findings persisted when adjusted for previous therapies or presence of superficial versus deep ovarian disease. Only 1.06% of patients had ovarian disease exclusively. CONCLUSION(S): Superficial or deep ovarian endometriosis is a marker for the presence of more extensive pelvic and intestinal disease. Surgeons diagnosing and treating only ovarian endometriosis may be underdiagnosing and undertreating their patients.
Henkel A et al., 1999·Eur J Obstet Gynecol Reprod Biol
According to the literature this is the first patient with the primary diagnosis of an endometriosis (EMT) based on the cardinal symptom of an uremia in combination with a colorectal ileus. Operative removal of EMT was possible after hormonal suppression with Dienogest.
To review the clinical presentations of and management options for diaphragmatic endometriosis. Retrospective review. Referral center. PATIENT(S): Twenty-four women with endometriosis of the diaphragm. INTERVENTION(S): Surgical management. MAIN OUTCOME MEASURE(S): Diagnostic accuracy and therapeutic feasibility of operative laparoscopy. RESULT(S): Operative findings in 17 patients included 2-5 spots of endometriosis on the diaphragm measuring <1 cm. Seven women had numerous lesions scattered across the diaphragm. Lesions were bilateral in 8 patients, limited to the right hemidiaphragm in 14 patients, and limited to the left hemidiaphragm in 2 patients. In 7 patients, six endometriosis lesions were directly in the line of the left ventricle and three lesions were adjacent to the phrenic nerve. Endometriosis was infiltrating into the muscular layer of the diaphragm in 7 patients. The symptoms in all 7 symptomatic patients decreased significantly after treatment, with a minimum follow-up period of 12 months. No postoperative complications occurred. CONCLUSION(S): The abdominal diaphragm can be involved with endometriosis and can be diagnosed and treated effectively with the use of videolaparoscopy.
Endometriosis, a benign gynecologic disorder, occurs in about 10% of women of reproductive age and in up to 50% of women with infertility. Endometriosis is defined as the presence of endometrial glandular and stromal cells outside their normal location in the uterus. Commonly affected areas in the abdominopelvic cavity include the ovaries, the cul-desac and other kinds of pelvic peritoneum, bowel and diaphragm. Rarely is it found in extraabdominal sites, including the pleura and pericardium. While it is not a malignant disorder, endometriosis exhibits cellular proliferation, cellular invasion and neoangiogenesis. The steroid hormone dependence of endometriosis is underscored by its appearance during the reproductive years. Furthermore, the progress of this enigmatic disease can be tempered by administration of antiestrogens, inhibitors of endogenous estradiol production, and hormonal and surgical castration. It is a disorder that markedly affects well-being and physical and emotional health in women. Research on the pathogenesis of endometriosis currently interfaces with four areas of basic research, including the fields of genetics, environmental science, cancer biology and immunology. Here we focus on current research in the latter two disciplines and their relevance to endometriosis research.
Fertility and Outcomes · Conception After Excision
Thornton JG et al., 1997·Eur J Obstet Gynecol Reprod Biol
To measure the relationship between laparoscopically detected pelvic pathology and pelvic pain or infertility. Women undergoing diagnostic laparoscopy either for the investigation of pelvic pain, for sterilisation or for the investigation of infertility were studied. The indication for surgery was recorded before laparoscopy. At operation a series of 35-mm slide photographs were taken of the pelvis and later scored by two independent assessors without knowledge of the indication for surgery. Satisfactory photographs were obtained in 298 women. Minimal endometriosis was not associated with pain (adjusted OR 1.3; 0.5-2.8), although moderate disease was non-significantly so (2.5; 0.4-7.1). Severe disease was significantly more common and never occurred in patients being sterilised (P = 0.02). The odds of pain were not increased in the presence of dilated veins > 9 mm diameter (OR 1.1; 0.4-3.2) or adhesions (OR 0.6; 0.2-4.7). The odds of infertility were non-significantly increased in the presence of minimal and moderate endometriosis (OR 2.0; 0.8-5.3, and OR 4.2; 0.6-25 respectively) and again significantly more common in the presence of advanced disease (P = 0.002). The odds of infertility tended to be lower in the presence of severely dilated veins (OR 0.2; 0.032-1.2). There was no clear effect of adhesions (OR 0.9; 0.1-5.9). The long established associations between severe endometriosis and pelvic pain, and between endometriosis in general and infertility are confirmed. However there is little or no association between minimal endometriosis, pelvic adhesions or dilated pelvic veins and pain. Previously reported associations may have been an artefact of the surgeon's knowledge of the indication for operation when assessing the pelvis.
To compare demographic, epidemiologic, and medical data and to evaluate diagnostic trends in women with endometriosis and chronic pelvic pain symptoms or endometriosis and infertility. Retrospective analysis. Institute for the Study and Treatment of Endometriosis. PATIENT(S): Six hundred ninety-three consecutive patients with endometriosis and chronic pelvic pain (n = 357) or endometriosis and infertility (n = 336). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and epidemiologic parameters, diagnostic trends. RESULT(S): Women with pelvic symptoms were younger, had less formal education, more frequent family history, and higher frequency and intensity of pelvic complaints. Mean ages at first symptom and diagnosis were lower in the pain group, but stage of endometriosis at first diagnosis was more advanced. The mean "diagnostic delay" was longer in the pelvic pain than in the infertile group (6.35 versus 3.13 years), but it decreased during three consecutive 5-year intervals in both groups, and there was also a gradual decrease in the frequency of advanced endometriosis at the time of first diagnosis. CONCLUSION(S): Demographic and epidemiologic parameters in women with endometriosis differ, depending whether chronic pelvic pain or infertility are the presenting symptoms. In the pain group, diagnostic delay is longer and endometriosis at diagnostic laparoscopy more advanced, indicating progressiveness of the disease. During the last 15 years, diagnostic delay steadily decreased and the frequency of advanced endometriosis at first diagnosis declined.
Chapron C et al., 1997·J Gynecol Obstet Biol Reprod (Paris)
The goal of this study is to assess the efficiency of laparoscopic surgical treatment of pain for patients presenting deep endometriosis located on the uterosacral ligaments. We analysed a continuous series of 36 patients treated by operative laparoscopy between January 1993 and April 1995. In all these cases treatment consisted of resection of all the uterosacral ligament(s) together with exeresis of all other endometriotic lesions. The results were assessed for all the patients with a minimum follow-up of one year. Patients who presented dysmenorrhea (29 cases) improved in 89.7% of cases (26 patients). Out of the 26 patients who presented deep dyspareunia, improvement was evident for 92.3% of cases (24 patients). The chronic pelvic pain suffered (17 cases) improved in 88.2% of cases (15 patients). Patients who benefited from an improvement rated it excellent or satisfactory in 80% of cases. These results demonstrate that provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of patients presenting painful symptoms related to deep endometriotic implants located on the uterosacral ligaments.
To evaluate the efficacy of the laparoscopic approach for the diagnosis and treatment of severe urinary tract endometriosis. Retrospective review of 28 cases of severe urinary tract endometriosis. Center for Special Pelvic Surgery, a tertiary referral center. PATIENT(S): Between October 1989 and September 1994, we treated 28 women who had deeply infiltrating urinary tract endometriosis (bladder, 7, ureter, 21). INTERVENTION(S): All procedures were performed laparoscopically. MAIN OUTCOME MEASURE(S): Postoperative urinary function, pain relief, and complications. RESULT(S): Those who had vesical endometriosis underwent partial cystectomy and primary repair. Partial ureteral obstruction was found in 17 women; 10 underwent ureterolysis and excision of endometriosis, and 7 had partial wall resection. Four patients with ureter involvement had complete obstruction. Three underwent partial resection and ureteroureterostomy, and one had ureteroneocystostomy. The rate of ureteral endometriosis in the present series is higher than that reported previously. CONCLUSION(S): Severe infiltrative endometriosis of the bladder and the ureter can present without specific symptoms and can cause silent compromise of renal function. We demonstrated that the laparoscopic approach is safe and effective in the diagnosis and treatment of this entity.
To describe a case of hepatic endometriosis. Case report. University hospital. A 34-year-old woman with a 2-year history of cyclic right subcostal pain. Gonadotropin-releasing hormone agonist (GnRH-a) therapy followed by surgical resection. Ultrasonography, computed tomography scan, and magnetic resonance imaging of the liver disclosed a 6-cm diameter mass. The GnRH-a therapy for 4 months led to clinical and radiologic improvement. Surgery performed to allow pregnancy confirmed the diagnosis of hepatic endometriosis. Hepatic endometriosis is uncommon. It may result from metaplasia of the peritoneum or from hematogenic or lymphatic spread.
Redwine DB, 1993·The Journal of the American Association of Gynecologic Laparoscopists
To determine if laparoscopic excision of endometriosis by electrosurgery is more rapid than by sharp dissection, a retrospective comparative study was made of operative times for the two procedures. Median operating times for laparoscopic electro-excision of endometriosis were 26% to 49% faster than excision by sharp dissection. A chi2 analysis of the frequency counts of surgical intervals, and disease stage revealed this difference to be statistically significant and not due to acquired experience or differences in extent of disease in the two groups. The reduction in operating time achieved with monopolar electro-excision seems primarily associated with a more rapid cutting action with simultaneous coagulation of bleeders.
To review and evaluate published studies that have examined the role of peritoneal fluid (PF) in the development of endometriosis. Important studies related to this topic have been identified through a computerized bibliographical search (MEDLINE), as well as by manually scanning the published literature of major reproductive journals over the last several years. Studies that examined the effect of PF or its components on the pathophysiology of endometriosis are discussed. These include reported effects on the histogenesis, maintenance and proliferation of endometriosis, as well as related actions on infertility. The majority of investigations into the role PF plays in the pathogenesis of endometriosis have evaluated how it may adversely affect fertility. Suggestive but inconclusive data in the literature indicate that degenerating endometrial tissue may release a biochemical factor(s) into the peritoneal environment that is capable of inducing ectopic endometrium formation. Peritoneal fluid itself contains growth factor that may play a role in the implantation and maintenance of the ectopic endometrium. The PF of women with endometriosis has been shown to contain angiogenic as well as other growth factors. These compounds may contribute to the proliferation of the ectopic endometrium.
To investigate the local natural killer (NK) activity of the peritoneal fluid mononuclear cells (PFMC). In a prospective way, the NK activity (K562-assay) was measured in peripheral blood (PB) and peritoneal fluid (PF) of 44 women who underwent a laparoscopy for infertility and/or pain at the University Hospital of Gasthuisberg, Leuven, Belgium. The NK activity of peripheral blood mononuclear cells and PFMC, the number and concentration of PFMC, the percentage of lymphocytes versus macrophages by May-Grünwald-Giemsa staining and the estradiol and progesterone concentration of the PF were correlated together and with the severity of endometriosis. We demonstrated that there is a significant NK activity in PF and that this activity is decreased in women with endometriosis. This defect was more pronounced in the follicular phase of the cycle compared with the postovulatory phase. In PB of the same 44 women, the decreased NK activity correlated with the severity of the disease. This confirms our previous report on another 34 women. The NK activity is decreased in women with endometriosis and correlated significantly with the severity of the disease in both the PB and PF of women with endometriosis.
Fertility and Outcomes · Conception After Excision
To investigate the effect of short-term glucocorticoid administration on embryotoxicity of sera from infertile patients with mild to moderate endometriosis. Prospective longitudinal study. SETTING, Eight infertile patients with mild to moderate endometriosis and a control group of eight infertile patients with tubal infertility were selected on the basis of laparoscopic examination. Basal (B) serum collection and day 1 (T1), day 3 (T2), day 6 (T3), and day 12 (T4) serum drawn after a 3-day glucocorticoid treatment in endometriosis patients. Embryotoxicity of endometriosis sera, before and after glucocorticoid treatment, was investigated using a bioassay performed on two-cell mouse embryos. Interleukin 1 alpha (IL-1 alpha) and antismooth muscle, antimitochondrial, and antinuclear autoantibodies were also tested in these sera. At 50% concentration, endometriosis serum is embryotoxic in comparison with control; 0% versus 61% of the embryos reached the blastocyst stage at 72 hours, respectively (basal versus control, P less than 0.001). However, this embryotoxicity significantly decreases 12 days after glucocorticoid treatment in comparison with untreated sera; 32.4% versus 0% of the embryos reached blastocyst stage at 72 hours, respectively (T4 versus basal, P less than 0.001), although they did not reach nontoxic levels (greater than 50%). Interleukin 1 alpha was undetectable in all samples analyzed. In endometriosis sera, antismooth muscle antibody was detected. At 50% concentration, serum from infertile patients with minimal to moderate endometriosis appears to be embryotoxic to the in vitro development of two-cell mouse embryos. However, this embryotoxicity significantly decreases 12 days after a 3-day treatment with glucocorticoids.
Fertility and Outcomes · Conception After Excision
Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity. The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid. The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable. These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis.
To determine the long-term outcome after laparoscopic excision of endometriosis. This longitudinal unmatched study evaluated surgical outcome using follow-up questionnaires and evaluation of reoperations with results presented in life table format. Surgery was performed by a private practitioner at a referral center. All 359 patients undergoing laparoscopic excision of endometriosis between December 12, 1980, and March 31, 1990, were studied. Endometriosis, including deeply invasive disease, was completely excised laparoscopically using 3-mm scissors and graspers. Adjunctive medical therapy was not used. Extent of disease present at reoperation and quarterly rates of reoperation and recurrent/persistent disease are used as indicators of efficacy of surgery. Interval rates of reoperation and recurrence/persistence of disease and extent or invasiveness of disease when found at reoperation did not increase with the passage of time after surgery. The maximum cumulative rate of recurrent or persistent disease was 19%, achieved in the 5th postoperative year. Laparoscopic excision of endometriosis results in a low rate of minimal persistent/recurrent disease. The natural history of endometriosis after surgery suggests a rather static nature of the disease.
The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.
In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain.
Perineal endometriosis was found unexpectedly in a 32-year-old woman with primary infertility. Since there had been no prior perineal trauma, the transport of endometrium through a venous or lymphatic route could have accounted for the location of the endometriosis.
Fertility and Outcomes · Conception After Excision
Pregnancy outcomes were evaluated retrospectively in 350 women to investigate the relationship between endometriosis and spontaneous abortions. The frequency of spontaneous abortions in women with endometriosis was significantly higher than in both a fertile nonendometriosis group and an infertile group with tubal disease. There was no correlation between the severity of the endometriosis and the frequency of spontaneous abortions. After treatment, the frequency of spontaneous abortions was significantly decreased in both the endometriosis and the tubal disease group, but these values were not significantly different from each other. We conclude that high spontaneous abortion rates are a characteristic of other subgroups of women with secondary infertility and not just in women with endometriosis, and that the majority of spontaneous abortions associated with endometriosis are not caused by the condition.
Since 1979, Dr Redwine has performed the near-contact laparoscopy for the removal of endometriosis on nearly 400 women. Data collected from Dr Redwine's follow-up studies indicate that 75% of his patients have experienced complete relief of symptoms, and 20% have experienced an improvement in their symptoms from disabling pain to minimal pain. The individualized perioperative care and the high success rate realized with the near-contact technique has attracted women seeking relief from the painful and sometimes debilitating effects of endometriosis.
A patient developed hypertension from unilateral hydronephrosis produced by endometriosis. Her blood pressure fell promptly after decompression of the involved kidney.
Endometriosis of the sciatic nerve is rare but must be included in the differential diagnosis of sciatic pain. Patients present with typical signs and symptoms of sciatica, which are cyclic in nature. Electromyography and computed tomographic scanning are useful in diagnosis. At laparoscopy or laparotomy, a characteristic "pocket sign" is frequently seen, and may be the only clue to the presence of endometriosis. The patient often requires definitive surgery with total abdominal hysterectomy and bilateral salpingo-oophorectomy. However, conservative surgery with excision of the endometriosis from the nerve can be successful in selected patients who wish to preserve reproductive function.
Endometriosis presents a large variety of color manifestations, most nonblack, and many easily missed unless meticulous inspection is used to identify small or nonhemorrhagic lesions. An evolution in appearance with age may occur, with resultant spurious effects on conclusions regarding the natural history of the disease. This study confirms and expands the concept of nonhemorrhagic appearances presented by Jansen and Russell.
Fertility and Outcomes · Conception After Excision
In this series of patients, endometriosis does not involve more pelvic areas in older age groups. Exposure to pregnancy is associated with slightly less pelvic involvement, although this effect is inconstant when age groups are studied individually.
High-volume intravenous urography was performed in 63 women with surgically proven endometriosis. Subtle abnormalities were found in 15.9% of these women. No patient had urologic symptoms, and there was no evidence of hydroureter or ureteral obstruction on the IVP. Long-term follow-up study will be required to determine whether or not these lesions will progress and cause ureteral obstruction.
Peritoneal fluid (PF) was studied for the presence of endometrial tissue in a consecutive series of 67 women (with documented tubal patency) undergoing diagnostic laparoscopy, tubal lavage, and hysteroscopy. PF was completely aspirated from the cul-de-sac both before and after uterine irrigation. The PF was then analyzed for the presence of endometrial tissue. In native PF no significant difference in the incidence of endometrial tissue between patients with (19%) and without (11%) endometriosis (P = 0.6) was observed. Refluxed PF, obtained after uterine irrigation, showed a significantly higher incidence of endometrial tissue in women with endometriosis (76%) as compared to controls (42%) (P = 0.03). We propose two models to explain the development of endometriosis. These are not mutually exclusive, may be independent of each other, and may represent two distinct pathophysiologic disease processes.
Fertility and Outcomes · Conception After Excision
It has been demonstrated that PF contains some factor or factors that interfere with effective gamete interaction as determined by an in vitro animal assay. PF from patients with mild endometriosis has an increased activity of this substance and/or additional inhibitory factors. In endometriosis, this peritoneal fluid factor or factors appear to be filterable and to a significant degree heat-labile. This observation may be of importance in explaining subfertility associated with early stages of endometriosis.
Fertility and Outcomes · Conception After Excision
The purpose of this study was to evaluate the effect of peritoneal fluid (PF) on in vitro cleavage of 2-cell mouse embryos. PF was aspirated from the posterior cul-de-sac at laparoscopy and centrifuged, and the cell-free supernatant was heat-inactivated at 56 degrees C for 30 minutes and filtered (0.22 micron). Five percent PF in Ham's F-10 media was prepared and eight to ten 2-cell mouse embryos cultured for 72 hours. There were two study groups, one consisting of 10 PF samples from infertile patients with no endometriosis (PF-NE) and 18 from infertile patients with endometriosis (PF-E). Each sample was assayed along with a control consisting of media only. At 72 hours, greater than 50% of the embryos in the control groups reached the blastocyst and hatching stages. Individual PF samples in both study groups were classified as toxic if less than 50% of the embryos reached the blastocyst and hatching stages at 72 hours. Eight of the 10 samples in the PF-NE group were nontoxic and 14 of the 18 samples in the PF-E group were toxic (P less than 0.01). For evaluation of the overall effect of PF, all results in the PF-E group were pooled (162 embryos) and compared by the Mann-Whitney U test to pooled results in the PF-NE group (100 embryos). The embryonic stages in the PF-NE group were significantly more advanced than those in the PF-E group (P less than 0.001) at 24, 48, and 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
An 83-year-old man with an endometrioma of the lower abdominal wall has been reported. This occurred following the administration of 25 mg of TACE for a period of about 10 years for what was thought to be carcinoma of the prostate. A second transurethral resection done by Dr. R. C. Thompson proved to be adenocarcinoma. Subsequent to this he was continued on TACE. A review of the more commonly accepted theories of the development of endometriosis in the female has been presented. It is pointed out that the separation between the male and female urogenital systems occurs in the embryo between the eighth week and the fourth month. There is always a possibility for remnants of the opposite sex to remain in individuals. No such was seen in the case which is herein reported. Normal phenotype male was demonstrated in the chromosomal evaluation. A review of the literature on endometriosis in the male reveals several cases which have occurred; the origin of which is though to be from the prostatic utricle which is a remnant of the uterus existing in the male. After a prolonged course the patient reported was followed until he died in 1979. There was no recurrence of the abdominal wall mass but persistent low grade carcinoma of the prostate remained. The terminal process was related to cardiovascular disease and not carcinoma of the prostate. There was delay in publication of this unusual case. The original plan was to await final confirmation of the exact pathologic nature of this condition; unfortunately this was never done since a postmortem examination was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Medical Management · Hormonal Suppression Outcomes
One case of extensive endometriosis with ascites in a young nulliparous woman is reported. The patient had been maintained on suppressive therapy with danazol for over two years, demonstrating the feasibility of conservative management in this extremely rare form of endometriosis. However, long-term efficacy and potential for fertility remain to be determined.
Fertility and Outcomes · Conception After Excision
There seems to be an association of first-trimester spontaneous abortion and untreated endometriosis. In this report, 52% of an untreated group of patients with endometriosis aborted. However, 12% of a second group of surgically treated patients and 7% of a third group of patients treated with danazol aborted. Therefore, either medical or surgical therapy for endometriosis lowers the abortion rate significantly.
Fertility and Outcomes · Conception After Excision
Two hundred sixty-three patients with a diagnosis of endometriosis or adenomyosis were studied in a retrospective fashion. The association between endometriosis resulted in a spontaneous abortion rate of 44.3%, Patients with adenomyosis spontaneously aborted 35.1% of their pregnancies. These figures are significantly increased in comparison to those pertaining to the general population. Uterine pathology occurring with endometriosis is discussed in relation to secondary infertility. Hypotheses that may explain the relationship between endometriosis and spontaneous abortion are discussed briefly.
Cell-mediated autoimmune responses were studied by means of in vivo and in vitro techniques in five rhesus monkeys with spontaneous endometriosis. The results were compared with similar data obtained from five normal rhesus monkeys without endometriosis. The in vivo studies included intrademal injection of autologous antigens prepared from uterine endometrium, ectopic endometrium, or peritoneum, or injection of the mitogen, phytohemagglutinin (PHA). Skin biopsies were obtained at 48 hours and evaluated under the light microscope for perivascular lymphocytic infiltration. The mean number of lymphocytes per high-power field after injection of the autologous endometrial antigen was significantly smaller in animals affected by endometriosis than in the control group. There was no significant difference in lymphocytic response to autologous peritoneal antigens between the groups. Animals of both groups responded readily to PHA with marked perivascular lymphocytic infiltration. Lymphocyte stimulation responses to the same autologous antigens or to PHA were evaluated by means of in vitro assays and micro-methods. Lymphocyte stimulation response to autologous endometrial antigens in the group with endometriosis was significantly less than in the control group. There was no significant difference in response to the peritoneal antigens between the groups, and the response to PHA was marked in all animals of both groups. The results of this study indicate that rhesus monkeys with spontaneous endometriosis have an altered cellular immune response to autologous antigens. Although the animals were immunologically competent, as judged by responses to PHA, both in vivo and in vitro studies indicated a decrease in the cell-mediated immune response to autologous endometrial antigens. These data suggest that endometrial cells translocated from their normal location may implant only in women with specific alteration in cell-mediated immunity. New light is thus shed on the cause of endometriosis.
Fertility and Outcomes · Conception After Excision
A homogeneous group of 214 infertile women with endometriosis treated at the Johns Hopkins Hospital from 1960 to 1979 received conservative surgery as the sole therapeutic modality. Among this group, 115 patients (54%) conceived following surgery; of these conceptions, 109 resulted in a living child. Among 49 patients with secondary infertility, the spontaneous abortion rate was reduced from 49% to 20% after conservative surgery (P less than or equal to 0.01). Three contemporary classification systems were utilized to categorize patients according to the sites and amount of endometriosis at the time of conservative surgery. Those systems suggested by Buttram (Fertil Steril 30:240, 1978) and by Kistner and coauthors (Fertil Steril 28:108, 1977) revealed differences among fecundability rates among the different categories (P less than or equal to 0.01); however, the system suggested by The American Fertility Society (AFS) (Fertil Steril 32:633, 1979) revealed significant differences only if categories were combined (mild plus moderate versus severe plus extensive, P less than or equal to 0.05). Nevertheless, the AFS system revealed that pregnancy success was significantly reduced if an ovarian endometrioma was greater than 3 cm or had ruptured (P less than or equal to 0.01).
Endometriosis was encountered in 66 of 140 patients (47%) who underwent laparoscopy for chronic pelvic pain at Boston Children's Hospital Medical Center. Pelvic pain associated with this diagnosis was both cyclic and acyclic and typically began 2.9 years after menarche. Other symptoms included irregular menses, gastrointestinal and bladder symptoms, and increased vaginal discharge. The diagnosis of endometriosis had not been made preoperatively in the majority of patients despite repeated pelvic examinations and thorough evaluation of the gastrointestinal and urinary tracts. Psychiatric referral had been recommended for 10 patients. The most constant physical finding preoperatively was tenderness with or without cul-de-sac nodularity. Eleven patients (17%) with biopsy-proved endometriosis has normal pelvic examinations. Fifty-eight percent of patients had early and minimal disease (stage I). In the remaining patients, the disease was more extensive, involving the ovaries, tubes, and/or adjacent pelvic structures (stages II-IV). Although in most instances the implants were typical in appearance, in 13 patients (20%) the disease was not recognizable grossly, but was confirmed morphologically. The regimens utilized as primary treatment were based on the stage of the disease and consisted of either ovulation suppression alone or surgery with or without subsequent ovulation suppression. A satisfactory outcome was achieved in 47 patients (71%). The remaining 19 patients (28%) who did not respond to primary treatment were either operated on or treated symptomatically and are being carefully followed.
Perforation of the sigmoid colon in a 28-year-old woman during the 37th week of pregnancy is reported. There was almost complete replacement of the bowel wall by endometriotic tissue showing extensive decidualization of its stroma. This appears to be a very rare complication of endometriosis and the effects of pregnancy upon endometriosis are briefly reviewed.
National Institute for Health and Care Excellence, 2026·National Institute for Health and Care Excellence
Second draft guidance (consultation 15 September to 5 October 2026; expected publication 21 January 2027). Recommendation 1.1: Endotest (Ziwig, saliva 109-microRNA signature, CE IVDR class C, ages 18 to 43, GBP 1,381 per test) can be used in the NHS during a 4-year evidence generation period as an option to diagnose endometriosis in primary care, only when clinical examination is normal and ultrasound is negative, inconclusive, declined or not suitable. Recommendation 1.5: more research is needed on DotEndo (DotLab blood microRNA, GBP 400), Endomkit (Camlab/apDia serum BDNF plus CA-125, GBP 28 to 199) and EndoSure (gastrointestinal myoelectrical activity, GBP 350) before NHS funding. Committee noted all peer-reviewed accuracy evidence came from secondary or tertiary care where prevalence is higher than in primary care; the developmental Endotest cohort was judged at high risk of bias and the external validation studies at unclear risk; DotEndo, Endomkit and EndoSure had no external validation studies; no study reported clinical outcomes; the technologies cannot distinguish types of endometriosis or determine severity; clinical experts stated a negative result should not be a reason to deny referral if endometriosis is still suspected; imaging does not identify all types, particularly superficial peritoneal endometriosis. Average time to diagnosis in the UK cited as 9 years 4 months.
Nowakowski Ł et al., 2026·Journal of clinical medicine·Free full text on PubMed Central
Background/Objectives: Female infertility represents a significant public health issue. Available evidence supports the hypothesis that the gut microbiota may play an essential role in women's reproductive health and may serve as a diagnostic or prognostic biomarker in specific gynecological disorders. A substantial part of current research concerns disturbed communication between the hypothalamic-pituitary-ovarian axis and the gut microbiota, providing the basis for analyzing this phenomenon as the gut-ovary axis or the gut-vagina-ovary axis. The primary aim of this scoping review was to map the available evidence on the relationship between gut microbiota composition and female infertility, with particular emphasis on polycystic ovary syndrome (PCOS, currently polyendocrine metabolic ovarian syndrome, PMOS) endometriosis, and uterine fibroids. The review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed, Scopus, and Google Scholar were searched using terms related to gut microbiota, female infertility, PCOS, endometriosis, and uterine leiomyomas. Peer-reviewed publications in English published between 2015 and 2025 were considered. The included studies were descriptively synthesized to identify recurring microbiota patterns and research gaps. The reviewed evidence indicates that gut dysbiosis may be associated with selected gynecological disorders affecting fertility, including PCOS, endometriosis, and uterine fibroids. The gut microbiome may have potential value as a biomarker supporting diagnosis, treatment selection, and prognosis. The gut microbiome represents a promising but still insufficiently validated area in the management of gynecological diseases associated with female infertility. Further high-quality clinical studies are needed to verify the effectiveness of microbiome-based therapies and to develop evidence-based guidelines for managing infertility associated with gut dysbiosis.
Vibert J et al., 2026·Human Reproduction Open·Free full text on PubMed Central
Does IVF worsen pelvic pain in women with endometriosis? Nearly half of women with endometriosis reported perceived worsening of pelvic pain after IVF. Prior studies generally suggested no IVF-related pain worsening, but few assessed delayed flares or longer-term trajectories. International cross-sectional study based on an online survey conducted between September 2024 and April 2025 including 546 respondents. PARTICIPANTS/MATERIALS Women aged ≥18 years with surgically or imaging-confirmed endometriosis and at least one completed IVF cycle. A 25-item questionnaire captured demographics, reproductive history, comorbidities, and patient-reported pain trajectories before, during, and after IVF. The primary outcome was perceived worsening of pelvic pain after IVF (patient-reported outcome measure; PROM). Secondary outcomes were worsening of dysmenorrhoea and dyspareunia. Group comparisons and exploratory multivariable logistic regressions were performed. Predictor analyses were exploratory. MAIN Among 546 respondents, 48.9% reported worsening pelvic pain after IVF, 49.1% reported worsening dysmenorrhoea, and 35.5% worsening dyspareunia. Current pain scores were significantly higher in women reporting worsening versus no worsening (all P < 0.001). In multivariable analyses, immediate post-cycle pain flare emerged as the strongest and most consistent predictor across all pain outcomes, independently associated with worsening of pelvic pain (adjusted odds ratio [aOR] 5.91, 95% CI 3.88-9.14), dysmenorrhoea (aOR 4.03, 95% CI 2.08-8.05), and dyspareunia (aOR 3.17, 95% CI 2.07-4.90) (all P < 0.001). For the primary outcome, reporting oocyte retrieval as the most painful IVF step (aOR 0.53, 95% CI 0.31-0.88; P = 0.016) and achieving a live birth after IVF (aOR 0.63, 95% CI 0.42-0.92; P = 0.020) were independently associated with lower odds of pelvic pain worsening. In secondary outcome models, live birth was associated with lower odds of dysmenorrhoea worsening, while bladder pain syndrome/interstitial cystitis independently predicted worsening of dyspareunia. A formal response rate could not be calculated due to open online dissemination without a known denominator. LIMITATIONS Self-reported, retrospective data are prone to recall and selection bias, and the cross-sectional design precludes causal inference. Recruitment via associations and social media without a denominator limits generalizability, absence of baseline pain scores impedes assessment of change, and incomplete capture of peri-IVF hormonal regimens may confound results. IVF may not be pain-neutral in endometriosis. Monitoring pain trajectories at key IVF milestones may help identify women at risk of long-term exacerbation. Prospective studies should test whether early monitoring combined with tailored interventions-optimized analgesia, psychological support, or adapted stimulation protocols-can mitigate chronic pain trajectories throughout the IVF journey and ultimately improve quality of life. No specific funding; authors declare no conflicts of interest. N/A.
Predictive tools are lacking for pain-related outcomes after endometriosis surgery. The objective of this study was to develop and validate a machine learning-based clinical model to predict poor pain-related quality of life after endometriosis surgery. Registry data from a prospective longitudinal cohort at a tertiary referral center (2013-2020) was used for model development and validation. Participants underwent an index endometriosis surgery, and completed the pain subscale of the Endometriosis Health Profile-30 (EHP-30) at baseline and 1-2-year follow-up. The outcome was poor pain-related quality of life defined as EHP-30 pain subscale above the 75th percentile for North America, at 1 to 2 years postsurgery. Thirty-two preoperative factors were evaluated, with final models retaining the top 10 most important predictors. Elastic net logistic regression, random forest (RF) and multilayer perceptron neural network models were developed. Internal validation was performed using 500 bootstrap samples, and a held-out test cohort. The study included 650 488 in the training cohort and 162 in a held-out test cohort. The RF model exhibited the most consistent discrimination, measured by the area under the receiver operating characteristic curve, between the training cohort (0.768; 95% CI: 0.690-0.837) and test cohort (0.766; 95% CI: 0.676-0.863, Δ = -0.002). The RF model also demonstrated the best integrated calibration index (0.029) and highest net benefit. Final preoperative predictors for the RF model included baseline EHP-30 score, surgery type (conservative fertility-sparing vs hysterectomy), anxiety scores, depression scores, pain catastrophizing scale scores, abdominal wall pain, pelvic floor myalgia, smoking status, back pain, and race/ethnicity. We present the RF model as the Endometriosis Pain Index to aid preoperative counselling for endometriosis surgery.
Shenoy-Bhangle AS et al., 2026·J Magn Reson Imaging
Endometriosis is a chronic multisystem disease caused by the presence of endometrium-like tissue outside the endometrial canal, inciting inflammation and fibrosis. Transvaginal ultrasound (TVUS) and MRI have replaced diagnostic laparoscopy as the noninvasive imaging modalities of choice for diagnosis and pre-surgical planning. Advanced disease in the pelvis can distort/obliterate anatomic planes and obscure the extent of pelvic organ involvement at laparoscopy. Unlike laparoscopy, MRI is not limited by anatomic distortion and provides accurate multi-compartment assessment of deep pelvic endometriosis involving the uterus and its ligaments, adnexa, bowel, distal ureters, urinary bladder, and pelvic nerves. Additionally, MRI can help detect extra-pelvic organ involvement in the same study. Use of a dedicated MRI protocol and structured reporting template improves multidisciplinary communication and provides a pre-surgical road map; helps patient counseling as well as assessing the need for additional intraoperative organ-specific expertise such as colorectal surgery or urology. Knowledge of MRI and laparoscopic correlation enhances recognition of the key MRI findings to include in the report for optimizing surgical outcomes. This article focuses on the role of MRI in the diagnosis and pre-surgical mapping of pelvic endometriosis, with correlation to laparoscopic findings. Evidence level: 1. Technical efficacy: 5.
Diagnosis of endometriosis is a challenge. The recent development of a saliva-based micro-ribonucleic acid (miRNA) signature for the diagnosis of endometriosis may enable a timelier and less invasive approach, but this requires external validation.
The prospective, multicenter validation of the salivary miRNA signature of endometriosis (ENDOmiRNA) study aimed to assess the diagnostic accuracy, validate the biological reproducibility, and evaluate the clinical utility of a saliva miRNA signature of endometriosis. The study population comprised patients 18 to 43 years of age with signs and symptoms suggestive of endometriosis, who were recruited from diverse medical settings. Patients received a diagnosis of endometriosis by imaging, laparoscopic procedure, or both. All patients who were determined to not have endometriosis were classified as controls (and all underwent laparoscopy). Assessment of endometriosis status based on the saliva miRNA signature was established blinded to patients' endometriosis status, as determined by imaging and/or laparoscopy and/or histology.
The external validation population was composed of 971 patients, including patients from a prior interim analysis, with an overall endometriosis prevalence of 77%. The saliva miRNA signature had an accuracy (defined as the probability of correct classification for both positive and negative results) of 96.6% (95% confidence interval [CI], 95.2 to 97.6%), a sensitivity of 97.3% (95% CI, 96.4 to 98.0%), a specificity of 94.1% (95% CI, 91.0 to 96.4%), a positive predictive value of 98.2% (95% CI, 97.3 to 98.9%), a negative predictive value of 91.3% (95% CI, 88.3 to 93.4%), a positive likelihood ratio of 16.6 (95% CI, 10.8 to 26.9), and a negative likelihood ratio of 0.03 (95% CI, 0.02 to 0.04). Among patients with surgical confirmation of the diagnosis, misclassification, underestimation, and overestimation rates were 4.6%, 2.4%, and 2.2%, respectively, for the saliva miRNA signature and 27.2%, 15.1%, and 12.2%, respectively, for imaging (either transvaginal ultrasound, magnetic resonance imaging, or both).
This prospective, multicenter external validation study demonstrated the accurate performance of a saliva-based miRNA signature for the diagnosis of endometriosis in this cohort. (Funded by Ziwig; ClinicalTrials.gov number, NCT05244668.).
Goodwin E et al., 2025·BMC women's health·Free full text on PubMed Central
Endometriosis is a chronic and inflammatory condition that often presents with chronic pelvic pain, dysmenorrhea, and dyspareunia, thus having important effects on quality of life. There are two proposed hypotheses to describe the known association between endometriosis and depression and anxiety: (1) the disease hypothesis, where the inflammatory nature of endometriosis is driving increased risk for depression and anxiety; and (2) the pain hypothesis, where it is the painful symptoms underlying the increased risk. We aimed to shed further light on these two hypotheses by assessing the risk for depression and/or anxiety in three groups of patients pathologically assessed for endometriosis: symptomatic endometriosis patients (Symp Endo), symptomatic patients with no pathological endometriosis diagnosis (Symp No Endo), and asymptomatic endometriosis patients (Asymp Endo).
This study included pathologically-confirmed endometriosis patients identified from the pathology records of Vancouver Coastal Health Authority between 2000 and 2008. These data were linked with population-based administrative health data for follow-up to 2017. Depression and anxiety were identified through diagnostics codes from health services use data and prescriptions for antidepressants. Bivariate analyses were performed to assess differences between groups. Cox proportional hazards models were run to generate hazard ratios for incident depression and/or anxiety between the groups.
There were 2729 people in Symp Endo, 585 in Symp No Endo, and 326 in Asymp Endo. Symp No Endo was more likely than Symp Endo to be visiting a physician for pelvic pain and to be taking prescription-level pain medications (p < 0.001). After adjusting for several covariates, Symp No Endo had a significantly higher risk of incident depression and/or anxiety (adjusted HR: 1.23, 95% CI: 1.06-1.41) compared to Symp Endo. There was no statistically significant difference in risk of depression and/or anxiety between Symp Endo and Asymp Endo (adjusted HR: 0.94, 95% CI: 0.76-1.17).
These results point toward the pain focused hypotheses as Symp No Endo patients were at higher risk for depression/anxiety than the Symp Endo group. However, the results also suggest the disease hypothesis is at play, because the Symp Endo and Asymp Endo groups were at the same level of risk for depression/anxiety.
Fayek B et al., 2025·Reproductive sciences (Thousand Oaks, Calif.)
Endometriosis contributes to 5-21% of hospital admissions for pelvic pain. While hormonal therapies are pivotal in managing endometriosis-related pain, no single hormonal treatment suits all patients. We aimed to assess the effectiveness and tolerability of hormonal therapies and factors influencing response in endometriosis-associated pain treatment. Additionally, to investigate adjuvant neuromodulatory drug usage in patients who have used hormonal therapy. This cross-sectional study examined endometriosis patients undergoing hormonal therapy for pelvic pain at a tertiary referral centre for endometriosis and chronic pelvic pain (CPP). We assessed the proportion of patients reporting ineffectiveness of hormonal therapy and rates of discontinuation attributed to side effects. We evaluated factors related to treatment ineffectiveness and discontinuation due to side effects. Lastly, we determined the rates of adjuvant neuromodulatory drug use among patients who used hormonal therapy. 1011 patients were included in the study. Most hormonal therapies' ineffectiveness was related to worse CPP (P < .05). Cul-de-sac obliteration was correlated with better response to cyclic CHCs, DNG, and GnRH agonist (OR = 0.55, 95% CI [0.36 - 0.84]; OR = 0.53, 95% CI [0.29 - 0.98]; OR = 0.26, 95% CI [0.14 - 0.91], respectively). Adjuvant neuromodulatory drugs were more frequently utilized by patients who found hormone therapy ineffective except for those who used norethisterone acetate (NETA). Endometriosis pain is associated with a high chance of failed hormonal therapy. Cul-de-sac obliteration correlated with improved hormonal therapy response, highlighting the multifactorial influence on treatment outcomes. Patients who found hormone therapy ineffective tended to use adjuvant neuromodulatory drugs more frequently.
Adhesion Prevention · Surgical Technique and Adhesions
Yeung P, 2025·J Restorative Reprod Med·Free to read
Restorative reproductive surgery has emerged to become an exciting and promising field of surgery that can transform the way that we treat patients, especially regarding fertility. As a prime example of this type of surgery, restorative reproductive surgery for endometriosis, a common and debilitating disease that can lead to infertility and pelvic pain, offers a root cause treatment to remove the actual disease and to optimize the reproductive anatomy, for best patient outcomes. Optimal excision of endometriosis and prevention of pelvic adhesions has been shown to lead to reduce symptoms, to lead to high natural fertility rates, and to lead to very low rates of the need for repeat surgery. Patients have improved symptoms and quality of life, in addition to improved fertility chances for one and subsequent pregnancies (if desired), demonstrating the link between wellness and fertility.
There is an urgent need for more resources, training, advocacy, research and publication for this exciting area of restorative reproductive surgery. Its time has come.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Prostaglandin E2 (PGE2) is a key driver of endometriosis pathogenesis. Vipoglanstat selectively inhibits mPGES-1 enzyme activity. A Phase I trial involved 72 healthy volunteers receiving single or repeated doses, while Phase II included 69 subjects with chronic inflammatory disease receiving daily treatment. Results demonstrated the compound was safe and well tolerated at therapeutic doses and achieved complete mPGES-1 inhibition while preserving protective prostacyclin production. A Phase II endometriosis trial is scheduled to begin in 2025, focusing on pain reduction and lesion assessment via imaging.
Female infertility from polycystic ovarian syndrome (PCOS) and endometriosis poses a challenge for both clinicians and women who are trying to conceive. The present clinical single case report aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in a woman with PCOS, endometriosis and low ovarian reserve. The observations helped to inform and establish the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; and (3) a healthy live birth. The case report concerns a female who failed to conceive naturally beyond five years and had experienced one unsuccessful IVF cycle. Case report of one female subject with infertility issues, which included failure to conceive naturally beyond five years. Previous conditions were recorded and then compared with outcomes from after the patient received a course of PBM treatments. PBM treatments were given at weekly and/or at two-week intervals over a 5-month period during the follicular stage of the menstrual cycle, using IR and NIR wavelengths between 600 and 1000 nm. After five months a spontaneous conception was achieved. The case resulted in a full-term pregnancy and the birth of a healthy baby. Improvements in reproductive health outcomes in this case give reason to suggest that PBM helped to alleviate PCOS and endometriosis which could have been associated with a low ovarian reserve. The case report indicates that a multiwavelength of red and NIR-PBM laser therapy could have positively contributed to a healthy live birth in a female diagnosed with PCOS, endometriosis and a low ovarian reserve. Extensive studies with large data are warranted to validate our PBM dosimetry and treatment protocols to assess the potential impact of PBM for treating endometriosis and PCOS. Subsequently, to understand the genetic and phenotype biomarkers would be an important step further to standardise a range of PBM light dosimetry.
Gentles A et al., 2024·Journal of clinical medicine·Free full text on PubMed Central
Endometriosis is an inflammatory chronic condition associated with nociceptive, neuropathic, and nociplastic pain. Central sensitization (CS) is the primary nociplastic pain mechanism. However, there are currently no standardized methods for detecting CS or nociplastic pain. This review aims to identify available tools for characterizing CS/nociplastic pain in endometriosis-related chronic pelvic pain. Following the PRISMA-P protocol, MEDLINE, Embase, Scopus, and PsychINFO databases were searched on 23 April 2024, for the terms "endometriosis", "central sensitization", "nociplastic pain", "widespread pain", and "assessment tools". Publications were selected if they mentioned tool(s) for detecting nociplastic pain or CS in endometriosis patients. Information was extracted on study demographics, assessment types, and the tools used for detection. Of the 379 citations retrieved, 30 papers met the inclusion criteria. When working to identify CS and nociplastic pain, fourteen studies exclusively used patient-reported questionnaires, six used quantitative sensory testing (QST), two used clinical assessments, and eight used multiple approaches combining patient-reported questionnaires and clinical assessment. This review illustrates the diversity of tools currently used to identify CS and nociplastic pain in endometriosis patients. Further research is needed to evaluate their validity and to standardize methods in order to improve the accuracy of nociplastic pain identification and guide treatment.
Ding A et al., 2024·The journal of sexual medicine·Free full text on PubMed Central
Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis.
To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization.
An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100).
Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no).
Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups.
Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis.
A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function.
Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.
Guidelines by Clinical Area · Gynecologic Guidelines
Singh SS et al., 2024·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To provide a contemporary approach to the understanding of the impact and methods for the diagnosis of endometriosis in Canada.
Individuals, families, communities, health care providers, and health care administrators who are affected by, care for patients with, or manage delivery of services for endometriosis.
The diagnosis of endometriosis is facilitated by a detailed history, examination, and imaging tests with providers who are experienced in endometriosis care. Surgical evaluation with pathology confirms a diagnosis of endometriosis; however, it is not required for those whose diagnosis was confirmed with imaging.
There is a need to address earlier recognition of endometriosis to facilitate timely access to care and support. Education directed at the public, affected individuals and families, health care providers, and health care administrators are essential to reduce delays in diagnosis and treatment.
BENEFITS, HARMS, Increased awareness and education about the impact and approach to diagnosis may support timely access to care for patients and families affected by endometriosis. Earlier and appropriate care may support a reduced health care system burden; however, improved clinical evaluation may require initial investments.
Each section was reviewed with a unique search strategy representative of the evidence available in the literature related to the area of focus. The literature searches for each section of this guideline are listed in Appendix A and include information from published systematic reviews described in the text.
The recommendations were developed following two rounds of review by a national expert panel through an iterative 2-year consensus process. Further details on the process are shared in Appendix B. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix C (Table C1 for definitions and Table C2 for interpretations of strong and conditional recommendations).
This guideline is intended to support health care providers and policymakers involved in the care of those impacted by endometriosis and the systems required to support them.
Endometriosis impact and diagnosis updated guidelines for Canadian health care providers and policymakers.
RECOMMENDATIONS.
Measurement and Statistics · Instrument Development and Validation
Lin T et al., 2024·Fertility and sterility·Free to read
The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies.
An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions.
N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics.
CONCLUSION(S): The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.
Salmanov AG et al., 2024·Wiadomosci lekarskie (Warsaw, Poland : 1960)
To evaluate the association between adverse pregnancy outcome, assisted reproductive technology (ART) and a previous diagnosis of endometriosis in Ukraine.
Materials and We conducted a multicentre retrospective cohort study was based on infertility surveillance data among women reproductive age from January 1st, 2017 to December 31st, 2021 in Ukraine. The patients from 10 Ukrainian regions who achieved singleton pregnancy by ART were included in this study. Linked hospital, pregnancy/birth and mortality data were used. Logistic regression analysis was performed to calculate odds ratios (OR) and 95 % confidence interval (CI) for the rates of adverse pregnancy outcomes.
During study period within the cohort of 11,271 singleton births, 94 women with endometriosis diagnosed before birth delivered 102 infants. Compared with women without endometriosis, women with endometriosis had higher risks of preterm birth [adjusted odds ratio 1.33, 95% confidence interval (CI), 1.23-1.44]. Women with endometriosis had higher risks of antepartal bleeding/placental complications, pre-eclampsia and Caesarean section. There was no association between endometriosis and risk of SGA-birth or stillbirth.
Endometriosis and ART use are both independently associated with increased risk of preterm birth, antepartum haemorrhage, placenta praevia and planned birth. These findings are clinically relevant to obstetricians for distinguishing high- and low-risk pregnancies. Pregnant women with endometriosis require increased antenatal surveillance.
Chen B et al., 2024·Frontiers in oncology·Free full text on PubMed Central
Previous studies have shown that the risk of malignant transformation of endometriosis in premenopausal women is approximately 1%, significantly impacting the overall well-being and quality of life of affected women. Presently, the diagnostic gold standard for endometriosis-associated ovarian cancer (EAOC) continues to be invasive laparoscopy followed by histological examination. However, the application of this technique is limited due to its high cost, highlighting the importance of identifying a non-invasive diagnostic approach. Therefore, there is a critical need to explore non-invasive diagnostic methods to improve diagnostic precision and optimize clinical outcomes for patients. This review presents a comprehensive survey of the current progress in comprehending the pathogenesis of malignant transformation in endometriosis. Furthermore, it examines the most recent research discoveries concerning the diagnosis of EAOC and emphasizes potential targets for therapeutic intervention. The ultimate objective is to improve prevention, early detection, precise diagnosis, and treatment approaches, thereby optimizing the clinical outcomes for patients.
Yeung PP Jr et al., 2023·Front Reprod Health·Free full text on PubMed Central
Pregnancy rates after the placement of expanded polytetrafluoroethylene (ePTFE, trade name Gore-Tex®) for adhesion prevention following cystectomy of endometriomas ≥3 cm and excision of endometriosis were analyzed in this pilot study. A prospective cohort study was performed at a single tertiary care center. 56 women qualified for the study and underwent surgery. Expanded polytetrafluoroethylene placement around affected ovaries was self-selected. Inclusion criteria for analysis were pathology-confirmed endometrioma ≥3 cm, no hysterectomy at time of surgery, ≥1 year of postoperative survey completion, and absence of strategies to avoid pregnancy. 18 women in the ePTFE group and 11 women in the control group met inclusion criteria for analysis. 16 of the 18 women in the ePTFE group and 7 of the 11 women in the control group were affected by infertility. Absolute pregnancy rates and cumulative 4-year pregnancy rates, which are based on survival analysis using lifetables and adjust for varying follow-up times, were calculated for all women as well as for women with infertility only. High cumulative 4-year pregnancy rates were observed for women with expanded polytetrafluoroethylene compared to women without (85% vs. 65%, p = 0.69). High cumulative 4-year pregnancy rates for women with infertility prior to surgery were observed for women with expanded polytetrafluoroethylene compared to women without (83% vs. 33%, p = 0.89). There are consistent trends, although not statistically significant, seen in pregnancy rates for women with ePTFE compared to women without, particularly in those with a history of infertility prior to ePTFE use. This is the first study examining how adhesion prevention strategy targeting the adnexa during surgery for endometriosis affects pregnancy rates. The trend towards increased pregnancy rates with expanded polytetrafluoroethylene use, particularly in patients with a history of infertility, is promising and warrants further study with larger groups.
Orr NL et al., 2023·JAMA network open·Free full text on PubMed Central
A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization.
To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes.
DESIGN, SETTING, This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022.
The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score (measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 [never, rarely, sometimes, often, and always, respectively]).
A total of 239 patients (mean [SD] age, 34 [7] years; 189 [79.1%] White [11 (5.8%) identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; P = .02), deep dyspareunia (OR, 1.03; 95% CI, 1.01-1.04; P = .004), dyschezia (OR, 1.03; 95% CI, 1.01-1.04; P < .001), and back pain (OR, 1.02; 95% CI, 1.00-1.03; P = .02) at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up (mean [SD] score, 43.8 [18.2] vs 41.7 [18.9]; P = .05); however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up.
In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery.
Genetic and Immune Testing · Karyotype and Genetic Panels
Ferrier C et al., 2023·BJOG : an international journal of obstetrics and gynaecology
To evaluate a saliva diagnostic test (Endotest®) for endometriosis compared with the conventional algorithm.
A cost-effectiveness analysis with a decision-tree model based on literature data.
France.
Women with chronic pelvic pain.
Strategy I is the French algorithm, representing the comparator. For strategy II, all patients have an Endotest®. For strategy III, patients undergo ultrasonography to detect endometrioma and patients with no endometrioma detected have an Endotest®. For strategy IV, patients with no endometrioma detected on ultrasonography undergo pelvic magnetic resonance imaging (MRI) to detect endometrioma and/or deep endometriosis. An Endotest® is then performed for patients with a negative result on MRI.
Costs and accuracy rates and incremental cost-effectiveness ratios (ICERs). Three analyses were performed with an Endotest® priced at €500, €750, and €1000. Probabilistic sensitivity analysis was conducted with Monte Carlo simulations.
With an Endotest® priced at €750, the cost per correctly diagnosed case was €1542, €990, €919 and €1000, respectively, for strategies I, II, III and IV. Strategy I was dominated by all other strategies. Strategies IV, III and II were, respectively, preferred for a willingness-to-pay threshold below €473, between €473 and €4670, and beyond €4670 per correctly diagnosed case. At a price of €500 per Endotest®, strategy I was dominated by all other strategies. At €1000, the ICERs of strategies II and III were €724 and €387 per correctly diagnosed case, respectively, compared with strategy I.
The present study demonstrates the value of the Endotest® from an economic perspective.
Long AJ et al., 2023·American journal of obstetrics and gynecology
More research is needed that compares the outcomes between those who underwent a hysterectomy for endometriosis with conservation of one or both ovaries and those who underwent a hysterectomy with bilateral salpingo-oophorectomy.
This study aimed to compare the rate and types of reoperations (primary outcome) and use of other pain-related health services (secondary outcomes) among people who underwent a hysterectomy with conservation of both ovaries, those who underwent a hysterectomy with unilateral salpingo-oophorectomy, and those who underwent a hysterectomy with bilateral salpingo-oophorectomy.
This was a population-based, retrospective cohort study of 4489 patients aged 19 to 50 years in British Columbia, Canada, who underwent a hysterectomy for endometriosis between 2001 and 2016. Index surgeries were classified as hysterectomy alone (conservation of both ovaries), hysterectomy with unilateral salpingo-oophorectomy, or hysterectomy with bilateral salpingo-oophorectomy. Reoperation rate was the primary outcome. Secondary outcomes (measured at 3-12 months and 1-5 years after hysterectomy) included physician visits for endometriosis and pelvic pain, prescriptions filled for opioids, and use of hormonal suppression medications and hormone replacement therapy.
Reoperation rates were low across all groups, with 89.5% of all patients remaining reoperation free by the end of follow-up (median of 10 years; interquartile range, 6.1-14.3 years). Patients who underwent a hysterectomy alone were more likely to undergo at least 1 reoperation when compared with those who underwent a hysterectomy with bilateral salpingo-oophorectomy (13% vs 5%; P<.0001), most commonly an oophorectomy or adhesiolysis. When oophorectomy as reoperation was removed in a sensitivity analysis, this difference was partially attenuated (6% of hysterectomy alone group vs 3% of hysterectomy with bilateral salpingo-oophorectomy group undergoing at least 1 reoperation). All groups were very similar in terms of rates of physician visits for endometriosis or pelvic pain and the number of days of opioid prescriptions filled. Furthermore, the rate of hormonal suppression medication use was similar among the groups, whereas the rate of prescriptions filled for hormone replacement therapy after hysterectomy with bilateral salpingo-oophorectomy was 60.6% of patients who filled at least 1 prescription at 3 to 12 months after index surgery.
Patients who underwent a hysterectomy with bilateral salpingo-oophorectomy had a lower reoperation rate than those who underwent a hysterectomy with conservation of one or both ovaries. However, there was little difference between the groups for the secondary outcomes measured, including physician visits for endometriosis and pelvic pain, opioid use, and use of hormonal suppression medications, suggesting that persistent pelvic pain after hysterectomy for endometriosis may not differ substantively based on ovarian conservation status. One limitation was the inability to stratify patients by stage of endometriosis or to determine the impact of endometriosis stage or the presence of adnexal disease or deep endometriosis on the outcomes. Moreover, hormone replacement therapy prescriptions was not filled by about 40% of patients after hysterectomy with bilateral salpingo-oophorectomy, which may have significant health consequences for these individuals undergoing premature surgical menopause. Therefore, strong consideration should be given to ovarian conservation at the time of hysterectomy for endometriosis.
DiVasta AD et al., 2021·F&S reports·Free full text on PubMed Central
To estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis. Randomized, double-blind, placebo-controlled pilot study. Tertiary care center. Women (n = 9) with surgically confirmed endometriosis. A random, double-blind assignment to either NETA (5 mg/day) + placebo twice weekly or cabergoline (0.5 mg) twice weekly + placebo daily for 6 months. We collected the measures of pelvic pain and laboratory parameters every 3 months. We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements than women treated with NETA. The serum measures of vascular endothelial growth factor receptor 1 declined over 6 months in those who received cabergoline. Cabergoline was well tolerated, and no serious adverse events occurred. Safe, effective adjunct treatments are lacking for patients with endometriosis who do not respond to standard care. Because the growth of endometriosis requires angiogenesis, blood vessel growth is an attractive therapeutic target. This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic pain due to endometriosis. Building upon this investigation, we will conduct larger, randomized trials of cabergoline, advancing research on the best treatments for endometriosis-particularly disease resistant to hormonal therapies. CLINICAL clinicaltrials.gov; registration number NCT02542410.
Wahl KJ et al., 2021·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
Endometriosis is an enigmatic, painful, complex disease that affects approximately 1 million people in Canada. The disease can involve multiple organ systems, often resulting in debilitating chronic pain and infertility. Social, medical, geographic, and other factors are implicated in years-long diagnostic delays and may limit access to care. An integrated approach from bench to bedside to community is urgently required. A pan-Canadian collaboration among patients, clinicians and researchers will improve endometriosis awareness, provide best practices, and link research across Canada.
Alfaraj S et al., 2021·Journal of minimally invasive gynecology
Endometriosis fertility index (EFI) is a robust tool to predict the pregnancy rate in patients with endometriosis who are attempting non-in vitro fertilization conception. However, EFI calculation requires laparoscopy. Newly established imaging techniques such as sliding sign, which is used to diagnose pouch of Douglas obliteration, could provide a promising alternative. The objective of this study was to investigate the practicality of using ultrasound data to predict a low EFI (score ≤6).
Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017.
Tertiary referral center at British Columbia Women's Hospital.
We analyzed data for 2583 participants from the Endometriosis Pelvic Pain Interdisciplinary Cohort. In this cross-sectional study, we included 86 women aged <40 years.
Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery.
Logistic regression was used to obtain receiver operating characteristic area under the curve (AUC) for the prediction models. Significance was p <.05. Patients with a negative sliding sign were older and had severe endometriosis and longer duration of infertility. Patients with a negative sliding sign had significantly lower total EFI scores and lower surgical factors scores than patients with a positive sliding sign. Logistic regression showed that a negative sliding sign and EFI historic factors score can predict an EFI score ≤6 (sensitivity = 87.9%, specificity = 81.1%, AUC = 0.93 [95% confidence interval, 0.88-0.98]). Adding the diagnosis of endometrioma to the previous prediction model resulted in AUC = 0.95 (95% confidence interval, 0.90-0.995), sensitivity = 84.8%, and specificity = 92.5%.
The sliding sign could be a potential alternative to the EFI surgical factors, and it could be used in combination with EFI historic factors and the diagnosis of endometrioma to predict an EFI score ≤6 for patients who are not scheduled for immediate surgery.
Allaire C et al., 2020·Seminars in reproductive medicine
Endometriosis-associated chronic pelvic pain can at times be a complex problem that is resistant to standard medical and surgical therapies. Multiple comorbidities and central sensitization may be at play and must be recognized with the help of a thorough history and physical examination. If a complex pain problem is identified, most endometriosis expert reviews and guidelines recommend multidisciplinary care. However, there are no specific recommendations about what should be the components of this approach and how that type of team care should be delivered. There is evidence showing the effectiveness of specific interventions such as pain education, physical therapy, psychological therapies, and pharmacotherapies for the treatment of chronic pain. Interdisciplinary team models have been well studied and validated in other chronic pain conditions such as low back pain. The published evidence in support of interdisciplinary teams for endometriosis-associated chronic pain is more limited but appears promising. Based on the available evidence, a model for an interdisciplinary team approach for endometriosis care is outlined.
Yong PJ et al., 2020·Human reproduction open·Free full text on PubMed Central
What are the use patterns and factors associated with combined hormonal contraception (CHC) ineffectiveness or discontinuation due to side-effects in patients with endometriosis and pelvic pain?
Worse chronic pelvic pain (CPP) severity and pelvic floor myalgia were associated with continuous CHC ineffectiveness, while poorer quality-of-life was associated with continuous CHC discontinuation due to side-effects.
CHC is a first line of therapy for endometriosis-associated pelvic pain in women. However, some patients state that CHC is ineffective for their pain, while others have to discontinue CHC due to side-effects.
Analysis of a prospective patient database from a tertiary care referral center for patients with endometriosis and pelvic pain between December 2013 and April 2015 was carried out.
PARTICIPANTS/MATERIALS A total of 373 patients of reproductive age with endometriosis from the database were included in the study. Data included patient self-reported questionnaires, physical examination findings and validated instruments. There were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). The primary outcome was CPP severity for the past 3 months (score of 0-10), and secondary outcomes were other pelvic pain scores, quality-of-life on the Endometriosis Health Profile 30 (EHP-30) and underlying conditions including irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia and depression, anxiety and pain catastrophizing.
MAIN Among the 373 cases in the dataset, prior cyclical CHC use was reported by 228 (61.1%) women, of which 103 (27.6%) stated it was ineffective for their pain and 94 (25.2%) stated they discontinued CHC due to side-effects. Previous continuous CHC use was reported by 175 (46.9%) women, of which 67 (18.0%) stated it was ineffective and 59 (15.8%) stated they discontinued due to side-effects. Worse CPP severity in the last 3 months was associated with a history of continuous CHC ineffectiveness (P < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects (P = 0.005). Among the underlying conditions, pelvic floor tenderness (as a marker of pelvic floor myalgia) was associated with CHC ineffectiveness.
LIMITATIONS This study involved patient recall and no longitudinal follow-up. Also, we do not have data on the type of side-effect that led to discontinuation. Medication ineffectiveness was reported subjectively by the patient rather than using standardized criteria. Finally, the diagnosis of endometriosis was based on previous surgery or a current nodule or endometrioma on examination/ultrasound; without prospective surgical data on all the patients, it was not possible to do a sub-analysis by current surgical features (e.g. stage).
In women with endometriosis, CHC ineffectiveness was associated with worse CPP and pelvic floor myalgia, which suggests myofascial or nervous system contributors to CPP that does not respond to hormonal suppression. A tender pelvic floor, as a sign of pelvic floor myalgia, may be a clinical marker of patients with endometriosis who are less likely to have an optimal response to hormonal suppression. For women who discontinue CHC due to side-effects, research is needed to help alleviate these side-effects as these patients report worse quality-of-life.
This work was supported by a Canadian Institutes of Health Research (CIHR) Transitional Open Operating Grant (MOP-142273) as well as BC Women's Hospital and the Women's Health Research Institute. PY is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB/CA has financial affiliations with Abbvie and Allergan; the other authors have no conflicts of interest.
Wahl KJ et al., 2020·Sexual medicine·Free full text on PubMed Central
Deep dyspareunia is a cardinal symptom of endometriosis, and as many as 40% of people with this condition experience comorbid superficial dyspareunia.
To evaluate the relationship between sexual pain and infertility concerns among women with endometriosis.
This is a cross-sectional study conducted at a university-based tertiary center for endometriosis. 300 reproductive-aged participants in the prospective Endometriosis Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov Identifier: NCT02911090) with histologically confirmed endometriosis were included (2013-2017).
The total score on the infertility concerns module of the Endometriosis Health Profile-30 categorized into 5 groups (0, 1-4, 5-8, 9-12, 13-16).
The odds of infertility concerns did not increase with severity of deep dyspareunia (odds ratio = 1.02, 95% CI: 0.95-1.09, P = .58). However, the odds of infertility concerns increased with severity of superficial dyspareunia (odds ratio = 1.09, 95% CI: 1.02-1.16, P = .011); this relationship persisted after adjusting for endometriosis-specific factors, infertility risk factors, reproductive history, and demographic characteristics (adjusted odds ratio [AOR] = 1.14, 95% CI: 1.06-1.24, P < .001). Other factors in the model independently associated with increased infertility concerns were previous difficulty conceiving (AOR = 2.09, 95% CI 1.04-4.19, P = .038), currently trying to conceive (AOR = 5.23, 95% CI 2.77-9.98, P < .001), nulliparity (AOR = 3.21, 95% CI 1.63-6.41, P < .001), and younger age (AOR = 0.94, 95% CI: 0.89-0.98, P = .005).
Severity of superficial dyspareunia, but not deep dyspareunia, was associated with increased odds of infertility concerns among women with endometriosis. Strengths of the study included the use of a validated measure of infertility concerns and disaggregation of sexual pain into deep and superficial dyspareunia. Limitations included the setting of a tertiary center for pelvic pain, which affects generalizability to fertility clinic and primary care settings. Women experiencing introital dyspareunia, who can have difficulties with achieving penetrative intercourse, may be concerned about their future fertility and should be counselled appropriately. Wahl KJ, Orr NL, Lisonek M, et al. Deep Dyspareunia, Superficial Dyspareunia, and Infertility Concerns Among Women With Endometriosis: A Cross-Sectional Study. Sex Med 2020;8:274-281.
Orr NL et al., 2020·The journal of sexual medicine
Deep dyspareunia, a common symptom in endometriosis, has previously been associated with bladder and/or pelvic floor tenderness (BPFT), which suggests a role for central nervous system sensitization. The Central Sensitization Inventory (CSI, 0-100) is a validated self-reported scale for patients with central sensitization.
The objective of this study was to phenotype deep dyspareunia using BPFT and the CSI.
The methods included cross-sectional analysis from a prospective registry from January 2018 to June 2018 at a tertiary center for endometriosis (ClinicalTrials.gov #NCT02911090). Included were women aged 18-50 years with endometriosis (previously surgically diagnosed, current visualized endometrioma on ultrasound, or current palpable or visualized nodule on ultrasound), who were newly or re-referred to the center. Severity of deep dyspareunia was self-reported using an 11-point numeric rating scale (0 = no pain; 10 = worst pain imaginable), categorized as no or low deep dyspareunia (0-4) and high deep dyspareunia (5-10). We identified the subgroup with high deep dyspareunia and presence of BPFT, where we hypothesized a central component of the sexual pain. This subgroup was compared with 2 other subgroups: no or low deep dyspareunia and high deep dyspareunia but no BPFT. The CSI was compared between the groups using analysis of variance, followed by post hoc testing (P < .05).
The main outcome measure was the CSI score ranging from 0 to 100.
Data from 163 women with endometriosis were analyzed. The mean age of this cohort was 36.4 ± 6.8 years, and the mean CSI score was 41.0 ± 18.6. 37 percent (61/163) had high deep dyspareunia and BPFT; 29% (47/163) had high deep dyspareunia and no BPFT; and 34% (55/163) had no or low deep dyspareunia. The CSI significantly differed between the 3 groups (analysis of variance: F = 22.4, P < .001). In post hoc testing, the CSI was higher in women with high deep dyspareunia and BPFT (51.3 ± 16.9), compared with women with no or low deep dyspareunia (30.9 ± 15.4, P < .001) and compared with women with high deep dyspareunia but no BPFT (39.4 ± 17.2, P = .001).
The CSI could be used to classify and phenotype patients with endometriosis-associated sexual pain.
Strengths include a prospective registry with integrated pain scores, validated questionnaires, and physical examination findings. Limitations include the lack of quantitative sensory testing for central sensitization.
In women with endometriosis, the subgroup with high deep dyspareunia and bladder and/or pelvic floor tenderness had a significantly higher score on the CSI than other subgroups, suggesting that this group may have a central component to their sexual pain. Orr NL, Wahl KJ,Noga H, et al. Phenotyping Sexual Pain in Endometriosis Using the Central Sensitization Inventory. J Sex Med 2020;17:761-770.
Gałczyński K et al., 2019·Journal of ovarian research·Free full text on PubMed Central
Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17-44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.
Mirabi P et al., 2019·JBRA Assist Reprod·Free full text on PubMed Central
The relation between excessive prolactin and endometriosis-related infertility is debatable. Anovulation or defective luteal phase occurs frequently due to hyperprolactinemia in subfertile women. In this investigation, we evaluated the association between serum prolactin levels and the severity of endometriosis. This retrospective cohort study carried out at the Babol Infertility Research Center looked into the baseline serum prolactin levels of 114 infertile women with endometriosis and compared them to the levels seen in 101 infertile women without endometriosis (controls). Statistical analysis included independent t-test, chi-square, Welch test and ROC curve analysis. Infertile women with endometriosis had significantly higher serum prolactin levels than infertile women without endometriosis (p=0.003). A significant difference was detected between controls and individuals with endometriosis stages III/IV (p-value=0.009). Prolactin was found to have diagnostic value to detect endometriosis stages III/IV vs. stages I/II in AUC=0.65, 95% CI (0.55, 0.76). Prolactin values with a cut off set at 20.08 ng/mL had a sensitivity of 0.74 and specificity of 0.54 in detecting disease stages III/IV vs. I/II. The prognostic capability of prolactin in detecting endometriosis in cases vs. controls by ROC curve analysis had an AUC=+0.67, 95% CI (0.60, 0.74). Prolactin values with a cut off set at 17.5 ng/mL had a sensitivity of 0.64 and specificity of 0.63 in segregating subjects with and without endometriosis. Higher prolactin levels were observed in infertile women with more severe endometriosis when compared to infertile women without endometriosis. Prolactin levels act as a probable prognostic biomarker to detect endometriosis stages III/IV vs. I/II and segregate infertile women with endometriosis from subjects without endometriosis.
Agarwal SK et al., 2019·American Journal of Obstetrics and Gynecology·Free to read
Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.
Wu CQ et al., 2019·Journal of minimally invasive gynecology
Controversy exists regarding surgical management of endometriomas in infertile women before in vitro fertilization (IVF) because growing evidence indicates that surgery may impair the ovarian response. The objective of the present systematic review and meta-analysis was to compare surgical and expectant management of endometriomas regarding IVF outcomes. Prospective and retrospective controlled studies were found via the Cochrane Library, Embase, and MEDLINE databases. Thirteen studies (1 randomized controlled trial and 12 observational studies, N = 2878) were pooled, and similar live birth rates were observed in the surgically and expectantly managed groups (odds ratio = 0.83; 95% confidence interval [CI], 0.56-1.22; p = .98). The clinical pregnancy rates (odds ratio = 0.83; 95% CI, 0.66-1.05; p = .86), the number of mature oocytes retrieved, and the miscarriage rates were not statistically different between study groups. However, the total number of oocytes retrieved was lower in the surgery group (mean difference = -1.51; 95% CI, -2.60 to -0.43; p = .02). Findings suggest that surgical management of endometriomas before IVF therapy yields similar live birth rates as expectant management. However, future properly designed randomized controlled trials are warranted.
Arion K et al., 2019·Journal of minimally invasive gynecology
To evaluate the point-of-care preoperative transvaginal ultrasound (TVUS) sliding sign in comparison with palpation of a nodule on digital pelvic examination for the prediction of pouch of Douglas (POD) obliteration.
Analysis of data from a prospective data registry (Canadian Task Force classification II-2).
A tertiary referral center.
Women with suspected endometriosis who had preoperative pelvic examination and point-of-care TVUS followed by laparoscopic surgery between August 2015 and December 2016.
Women were preoperatively assessed for the prediction of POD obliteration with pelvic examination for a nodule and point-of-care TVUS uterine/cervix sliding sign.
The study included 269 women, 15.2% (41/269) of whom had POD obliteration at the time of surgery. A preoperative negative sliding sign had a sensitivity of 73.2% (95% confidence interval, 57.1%-85.8%) and a specificity of 93.9% (95% CI, 89.9%-96.6%) in the prediction of POD obliteration compared with preoperative palpation of a nodule on pelvic examination, which had a sensitivity of 24.4% (95% CI, 12.4%-40.3%) and a specificity of 93.4% (95% CI, 89.4%-96.3%). The difference in sensitivity was statistically significant (McNemar test, p <.001). A negative sliding sign was also associated with longer operating times and more difficult surgery including the need for ureterolysis.
The point-of-care TVUS sliding sign showed significantly improved sensitivity compared with palpation of a nodule on pelvic examination for the prediction of POD obliteration. Therefore, the point-of-care TVUS sliding sign improves the preoperative assessment of POD disease and thus may lead to more optimal surgical planning in women with suspected endometriosis.
Yong PJ et al., 2018·The journal of sexual medicine
Deep dyspareunia is a common symptom in women, including in half of women with endometriosis, but little is known about its response to treatment and predictors of persistent deep dyspareunia over time.
To follow up deep dyspareunia severity over a 1-year prospective cohort at an interdisciplinary center, and to identify baseline predictors of more persistent deep dyspareunia at 1 year.
Prospective 1-year cohort study at a tertiary referral center for pelvic pain and endometriosis, where a range of interdisciplinary treatments are provided at a single center (surgical, hormonal, physical, and psychological therapies). Exclusion criteria were menopause, age >50 years, and never previously sexually active. Primary outcome (deep dyspareunia severity) and secondary outcome (sexual quality of life) were followed up over 1 year. Ordinal logistic regression was performed, controlling for baseline severity of deep dyspareunia, to identify baseline predictors of deep dyspareunia severity at 1 year.
Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale (0-10), categorized into absent-mild (0-3), moderate (4-6), and severe (7-10); secondary outcome was sexual quality of life measured by the Endometriosis Health Profile-30.
1-year follow-up was obtained for 278 subjects (56% response rate at 1 year; 278/497). Severity of deep dyspareunia improved over the 1 year (McNemar test, P < .0001): the proportion of patients in the severe category decreased from 55.0% to 30.4%, the moderate category remained similar from 17.7% to 25.0%, and the absent-mild category increased from 27.3% to 44.6%. Sexual quality of life also improved (56% to 43% on the sex subscale of the Endometriosis Health Profile-30) (Welch t test, P < .001). On ordinal regression, severity of deep dyspareunia at 1 year was independently associated with younger age (OR = 0.94, 95% CI = 0.91-0.97, P = .008), and with a higher baseline depression score on the Patient Health Questionnaire-9 (OR = 1.07, 95% CI = 1.03-1.11, P = .01).
Clinicians should consider employing an interdisciplinary approach for deep dyspareunia, and screening for and treating depression symptoms in these women.
Strengths of the study include its prospective nature, and assessment of deep dyspareunia specifically (as opposed to superficial dyspareunia). Limitations include non-randomized design, and the patients lost to follow-up over the 1 year.
Over 1 year in an interdisciplinary setting, improvements were observed in deep dyspareunia and sexual quality of life, but younger women and those with more severe depression at baseline had more persistent deep dyspareunia at 1 year. Yong PJ, Williams C, Bodmer-Roy S, et al. Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting. J Sex Med 2018;15:1765-1775.
Orr NL et al., 2018·The journal of sexual medicine
The etiology of endometriosis-associated deep dyspareunia may include direct endometriosis-specific factors (eg, stage or invasiveness of disease) and/or indirect contributors such as bladder/pelvic floor dysfunction (eg, related to myofascial mechanisms or nervous system sensitization).
This study aimed to determine whether bladder/pelvic floor tenderness and painful bladder syndrome were associated with severity of deep dyspareunia in women with endometriosis, regardless of Stage (I/II vs III/IV) or other endometriosis-specific factors.
Observational study from a prospective patient registry (January 2014 to December 2016) at a tertiary centre for endometriosis. Included were women aged 18 to 49 years who had surgical removal and histopathologic confirmation of endometriosis at the centre. Cases with Stage I/II vs Stage III/IV endometriosis were analyzed separately. Bivariate associations with the primary outcome (severity of deep dyspareunia) were tested for bladder/pelvic floor tenderness, painful bladder syndrome, as well as endometriosis-specific factors identified at the time of laparoscopic surgery (eg, deep infiltrating endometriosis) and demographic factors (eg, age). Multivariable ordinal logistic regression was carried out to adjust for factors associated with the primary outcome.
Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale, categorized as none/mild (0-3), moderate (4-6), and severe (7-10), from a preoperative self-reported questionnaire.
Overall, 411 women had surgically confirmed endometriosis: 263 had Stage I/II and 148 had Stage III/IV endometriosis. Among women with Stage I/II endometriosis, severity of deep dyspareunia was associated with both bladder/pelvic floor tenderness and painful bladder syndrome (AOR = 1.94, 95% CI: 1.11-3.38, P = .019 and AOR = 1.99, 95% CI: 1.15-3.44, P = .013, respectively), independent of endometriosis-specific factors or other factors associated with deep dyspareunia severity. Similar associations were found in women with Stage III/IV endometriosis (bladder/pelvic floor tenderness AOR =2.51, 95% CI: 1.25-5.02, P = .01, painful bladder syndrome: AOR = 1.90, 95% CI: 1.01-3.57, P = .048).
Myofascial or nervous system mechanisms may be important for deep dyspareunia in women with endometriosis, even in those with moderate-to-severe disease (Stage III/IV).
Strengths include the prospective registry, and histological confirmation of endometriosis and staging by experienced endometriosis surgeons. Limitations include assessment of only one pelvic floor muscle (levator ani).
In women with Stage I/II or Stage III/IV endometriosis, severity of deep dyspareunia was strongly associated with bladder/pelvic floor tenderness and painful bladder syndrome, independent of endometriosis-specific factors, which suggests the role of myofascial or sensitization pain mechanisms in some women with deep dyspareunia. Orr NL, Noga H, Williams C, et al. Deep Dyspareunia in Endometriosis: Role of the Bladder and Pelvic Floor. J Sex Med 2018;15:1158-1166.
Dawson A et al., 2018·Ecancermedicalscience·Free full text on PubMed Central
Endometriosis is a fascinating disease that we strive to better understand. Molecular techniques are shedding new light on many important aspects of this disease: from pathogenesis to the recognition of distinct disease variants like deep infiltrating endometriosis. The observation that endometriosis is a cancer precursor has now been strengthened with the knowledge that mutations that are present in endometriosis-associated cancers can be found in adjacent endometriosis lesions. Recent genomic studies, placed in context, suggest that deep infiltrating endometriosis may represent a benign neoplasm that invades locally but rarely metastasises. Further research will help elucidate distinct aberrations which result in this phenotype. With respect to identifying those patients who may be at risk of developing endometriosis-associated cancers, a combination of molecular, pathological, and inheritance markers may define a high-risk group that might benefit from risk-reducing strategies.
Gut and Inflammatory Bowel Disease · Irritable Bowel Syndrome
Lee CE et al., 2018·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
This study sought to examine factors associated with severity of irritable bowel syndrome (IBS) by using the Birmingham IBS symptom scale in patients presenting with endometriosis to a tertiary referral centre.
A prospective research cohort of patients presenting to a tertiary referral centre for endometriosis was evaluated for the presence and severity of IBS between December 2013 and April 2015. Patients with endometriosis had a diagnosis of IBS by using the Rome III criteria and were evaluated for severity of IBS symptoms by using the Birmingham IBS symptom scale. Multifactorial variables, including stage of endometriosis at the time of previous surgery, clinical examination findings, mood disorder questionnaire scores, and lifestyle factors, were evaluated using the t test and Spearman rank correlation test.
A total of 194 of 373 (52%) women with confirmed endometriosis had a diagnosis of IBS. Factors associated with severity of IBS symptoms in patients with endometriosis included lower-stage endometriosis (P = 0.004), presence of mood disorders (P <0.001), tenderness on physical examination (P ≤ 0.001), a history of sexual assault (P ≤ 0.02), and presence of sleep disturbance (P ≤ 0.01). Evaluation of the subscales of the Birmingham IBS symptom scale revealed a strong association between the previously identified factors and the pain subscale.
Using the Birmingham IBS symptom scale, our study revealed more severe IBS symptoms in patients with lower-stage endometriosis and identified other variables highly associated with severity of IBS. Continued research is required to characterize further the clinical importance of IBS symptoms in patients with endometriosis-associated pelvic pain.
Chronic Endometritis · Diagnosis of Chronic Endometritis
To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry. Case-control study. University hospital. PATIENT(S): Women with and without endometriosis who have undergone hysterectomy. INTERVENTION(S): Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis. MAIN OUTCOME MEASURE(S): CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells. RESULT(S): The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk. CONCLUSION(S): The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery.
Endometriosis is a common chronic disease affecting 1 in 10 women of reproductive age, with half of women with endometriosis experiencing deep dyspareunia. A review of research studies on endometriosis indicates a need for a validated question or questionnaire for deep dyspareunia. Moreover, placebo-controlled randomized trials have yet to demonstrate a clear benefit for traditional treatments of endometriosis for the outcome of deep dyspareunia. The reason some patients might not respond to traditional treatments is the multifactorial nature of deep dyspareunia in endometriosis, which can include comorbid conditions (eg, interstitial cystitis and bladder pain syndrome) and central sensitization underlying genito-pelvic pain penetration disorder. In general, there is a lack of a framework that integrates these multifactorial causes to provide a standardized approach to deep dyspareunia in endometriosis.
To propose a clinical framework for deep dyspareunia based on a synthesis of pain mechanisms with genito-pelvic pain penetration disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
Narrative review after literature search with the terms (endometriosis AND dyspareunia) OR (dyspareunia AND deep) and after analysis of placebo-controlled randomized trials.
Deep dyspareunia presence or absence or deep dyspareunia severity on a numeric rating scale or visual analog scale.
Four types of deep dyspareunia are proposed in women with endometriosis: type I that is directly due to endometriosis; type II that is related to a comorbid condition; type III in which genito-pelvic pain penetration disorder is primary; and type IV that is secondary to a combination of types I to III.
Four types of deep dyspareunia in endometriosis are proposed, which can be used as a framework in research studies and in clinical practice. Research trials could phenotype or stratify patients by each type. The framework also could give rise to more personalized care for patients by targeting appropriate treatments to each deep dyspareunia type. Yong PJ. Deep Dyspareunia in Endometriosis: A Proposed Framework Based on Pain Mechanisms and Genito-Pelvic Pain Penetration Disorder. Sex Med Rev 2017;5:495-507.
Anglesio MS et al., 2017·N Engl J Med·Free full text on PubMed Central
Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.
Yeung P et al., 2017·Journal of Endometriosis and Pelvic Pain Disorders
Introduction The aim of this manuscript is to present a systematic review of characteristics and management of endometriosis in adolescents in order to gain some relevant insight into the most appropriate clinical management of the disease. Methods The literature review was done using electronic database PubMed focusing on the terms ‘adolescents’, ‘endometriosis’, ‘teenagers’, ‘pain’, ‘infertility’, ‘quality of life’, ‘medical’ and ‘surgical management’ from 1980 onward and was limited to articles in English. Articles were only included if they reported original relevant research. Results The 24 studies selected for review included 1148 adolescents with laparoscopic proven endometriosis. The diagnosis of endometriosis was histologically confirmed in 39.02% (448/1148) of cases. The results from trials have been tabulated and main results presented in a question and answer format. Conclusions The majority of adolescent girls with chronic pelvic pain not responding to conventional medical therapy have endometriosis (up to 80%). Laparoscopy with biopsy is the only way to diagnose endometriosis in the adolescent population, and depends on recognition of atypical manifestations of the disease. Surgical management (especially by an expert surgeon) has been shown to be beneficial in reducing pain, improving infertility, and preventing progression or recurrence of disease. Postoperative hormonal suppression helps reduce pain symptoms and recurrence of endometriomas, but it does not seem to prevent disease recurrence or progression of peritoneal endometriosis, and has not been shown to improve future fertility. Postoperative suppression until pregnancy is based on expert opinion only. There is a need for good quality properly randomized trials.
Schliep KC et al., 2017·BJOG·Free full text on PubMed Central
To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially.
Inter-rater agreement study.
Five urban surgical centres. Population: Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study. Laparoscopies were diagnosed, digitally recorded, and reassessed. Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias-adjusted kappa values (κ) were calculated for diagnosis, and weighted κ values were calculated for staging. Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean κ = 0.67, range 0.61-0.69; mean κ = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports (n = 148; mean κ = 0.88, range 0.85-0.89; mean κ = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases. Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments. Tweetable Abstract: Endometriosis diagnosis and staging agreement between expert reviewers and operating surgeons was substantial.
Nisenblat V et al., 2016·The Cochrane database of systematic reviews·Free full text on PubMed Central
About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series.
To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision-making to undertake diagnostic surgery for endometriosis.
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions.
Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0
Nisenblat V et al., 2016·The Cochrane database of systematic reviews·Free full text on PubMed Central
About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.
To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.
Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work-up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single-marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high-throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut-off thresholds, and we could only perform meta-analyses on the data sets for anti-endometrial antibodies, interleukin-6 (IL-6), cancer antigen-19.9 (CA-19.9) and CA-125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA-125 was the only marker with sufficient data to reliably assess sources of heterogeneity.The mean sensitivities and specificities of anti-endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL-6, with a cut-off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).Studies assessed CA-125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut-off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut-off >
Mumford SL et al., 2015·Hum Reprod·Free full text on PubMed Central
What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication? Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Müllerian anomalies) or a normal pelvis. Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management. STUDY DESIGN, SIZE, The study population for these analyses includes the ENDO Study (2007-2009) operative cohort: 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded. PARTICIPANTS/MATERIALS, Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer-assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months. MAIN There was a high prevalence (≥30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post-operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis, reported more cyclic pelvic pain (49.5% versus 31.0% and 33.1%, P < 0.001). Additionally, women with endometriosis compared with women with a normal pelvis experienced more chronic pain (44.2 versus 30.2%, P = 0.04). Deep pain with intercourse, cramping with periods, and pain with bowel elimination were much more likely reported in women with versus without endometriosis (all P < 0.002). A higher percentage of women diagnosed with endometriosis compared with women with a normal pelvis reported vaginal (22.6 versus 10.3%, P < 0.01), right labial (18.4 versus 8.1%, P < 0.05) and left labial pain (15.3 versus 3.7%, P < 0.01) along with pain in the right/left hypogastric and umbilical abdominopelvic regions (P < 0.05 for all). Among women with endometriosis, no clear and consistent patterns emerged regarding pain characteristics and endometriosis staging or anatomic location. LIMITATIONS, Interpretation of our findings requires caution given that we were limited in our assessment of pain characteristics by endometriosis staging and anatomic location due to the majority of women having minimal (stage I) disease (56%) and lesions in peritoneum-only location (51%). Significance tests for pain topology related to gynecologic pathology were not corrected for multiple comparisons. Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed. Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests.
Franjoine SE et al., 2015·Minimally invasive surgery·Free full text on PubMed Central
Objective. To study the reproductive outcomes of modified laparoscopic fimbrioplasty (MLF), a surgical technique designed to increase the working surface area of the fimbriated end of the fallopian tube. We postulated that an improvement in fimbrial function through MLF will improve reproductive outcomes. Design. Retrospective cohort study. Setting. Academic tertiary-care medical center. Patients. Women with minimal endometriosis or unexplained infertility, who underwent MLF during diagnostic laparoscopy (n = 50) or diagnostic laparoscopy alone (n = 87). Intervention. MLF involved gentle, circumferential dilatation of the fimbria and lysis of fimbrial adhesions bridging the fimbrial folds. Main Outcome Measures. The primary outcome was pregnancy rate and the secondary outcome was time to pregnancy. Results. The pregnancy rate for the MLF group was 40.0%, compared to 28.7% for the control group. The average time to pregnancy for the MLF group was 13 weeks, compared to 18 weeks for the control group. The pregnancy rate in the MLF group was significantly higher for patients ≤35 ys (51.5% versus 28.8%), but not for those >35 ys (17.6% versus 28.6%). Conclusion. MLF was associated with a significant increase in pregnancy rate for patients ≤35 ys.
The relationship between ovarian cysts and infertility is a subject of debate, mainly because it is difficult to determine the real impact of the cyst and its treatment on later fertility. For a long time it was hoped that surgical treatment could prevent potential complications (such as rupture or malignancy). For presumed benign ovarian tumors, fertility sparing should be the main concern. The goal of this survey of current knowledge on the subject is to thoroughly explore the potential relationship between cysts, their treatment, and infertility. Our study is based on a review of the literature dealing with the epidemiology of ovarian cysts and the effects of their surgical management in relation to infertility. Analysis of the epidemiologic data, drawn mainly from comparative studies and cohorts, shows that the role of cysts in infertility is controversial and that the effects of surgical treatment are often more harmful than the cyst itself to the ovarian reserve. Surgery does not seem to improve pregnancy rates. When a surgical option is nonetheless chosen, a conservative laparoscopic approach is more suitable. Besides excision, sclerotherapy and plasma vaporization are promising, offering a greater preservation of the ovarian parenchyma, especially in endometriomas. These techniques must be better defined. The context of the infertility is essential, and surgeons and specialists in reproductive medicine should decide management jointly.
Yong PJ et al., 2013·Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology
The objective of this study was to determine if the combination of tenderness-guided endovaginal ultrasound and digital pelvic exam (i.e. EVUS-assisted exam) for preoperative pain mapping, in cases without nodules or endometriomas, increases sensitivity/specificity for laparoscopic findings. This was a retrospective review of women with chronic pelvic pain ± infertility with preoperative pain mapping exam prior to laparoscopy (n = 97, 2006-7). Predictor variables (EVUS-assisted exam vs digital pelvic exam alone, for pain mapping) were coded as tender vs non-tender. Primary outcome was findings on laparoscopy (e.g. endometriosis or adhesions) and was coded as abnormal vs normal. We found that EVUS-assisted exam had greater sensitivity (0.81, 95% CI: 0.70-0.89) for abnormal laparoscopy compared with digital pelvic exam alone (0.58, 95% CI: 0.46-0.69) (McNemar's test, p < 0.001). Specificity was limited for both types of pain mapping (0.22, 95% CI: 0.08-0.44 for EVUS-assisted; and 0.39, 95% CI: 0.20-0.61 for digital), with no significant difference (p = 0.13). In conclusion, in the absence of nodules or endometriomas, EVUS-assisted exam increases sensitivity, but with no benefit in specificity, for prediction of abnormal laparoscopy.
Supplements and Botanicals · Antioxidant Supplements
Porpora MG et al., 2013·Evid Based Complement Alternat Med·Free full text on PubMed Central
Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC) efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients-versus 1 within controls-cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases) or pregnancy (1 case). Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.
Measurement and Statistics · Research Tooling and Reproducibility
Schliep KC et al., 2012·Obstet Gynecol·Free full text on PubMed Central
To estimate the interrater and intrarater reliability of endometriosis diagnosis and severity of disease among gynecologic surgeons viewing operative digital images. The study population comprised a random sample (n=148 [36%]) of women who participated in the Endometriosis: Natural History, Diagnosis and Outcomes study. Four academic expert and four local, specialized expert surgeons reviewed the images, diagnosed the presence or absence of endometriosis for each woman, and rated severity using the revised American Society for Reproductive Medicine (ASRM) criteria. Interrater-level and intrarater-level agreement were calculated for both endometriosis diagnosis and staging. The interrater reliability for endometriosis diagnosis among the eight surgeons was substantial: Fleiss κ=0.69 (95% confidence interval [CI] 0.64-0.74). Surgeons agreed on revised ASRM endometriosis staging criteria after experienced assessment in a majority of cases (mean 61%, range 52-75%) with moderate interrater reliability: Fleiss κ=0.44 (95% CI 0.41-0.47). The intrarater reliability for experienced assessment compared with computer-assisted revised ASRM staging was almost perfect (mean weighted κ=0.95, range 0.89-0.99). Substantial reliability was found for revised ASRM endometriosis diagnosis, whereas moderate reliability was observed for staging. Almost perfect reliability was observed for surgeons' rating of disease severity compared with computerized-assisted, checklist-based staging. Findings suggest that reliability in endometriosis diagnosis is not greatly altered by location or composition of surgeons, supporting the conduct of multisite studies or compilation of endometriosis data across clinical centers. Although surgeons appear to be skilled at assessing endometriosis stage intuitively, how staging of disease burden correlates with clinical outcomes remains to be developed.
Somigliana E et al., 2012·J Minim Invasive Gynecol
Prevention of adhesions, whether de novo or by re-formation, is one of the most important and surprisingly neglected aspect of the treatment of endometriosis. Adhesions may cause infertility, dyspareunia, chronic pelvic pain but also intestinal obstruction and complications at subsequent surgery. They may play a role in the development of some forms of the disease such as ovarian endometriomas and possibly also deep invasive nodules. Three randomized controlled trials have been published documenting some partial success with Interceed, Oxiplex/AP gel or Adept solution in reducing adhesions extent at second look laparoscopy performed a few weeks after initial surgery. However, data on relevant long-term outcomes such as fertility, pelvic pain or disease recurrences or other adhesions-related complications is lacking. Noteworthy, endometriosis is a chronic inflammatory disorder and the insult causing adhesions is expected to persist after surgery. Therefore preventing adhesion formation with exclusively agents at the time of surgery may be insufficient. Future studies should focus on a 2-step strategy that includes measures applied at the time of surgery and subsequent administration of agents able to prevent the development of new adhesions.
To assess whether dopamine receptor 2 agonists reduced the size of peritoneal lesions in women with endometriosis and elucidate whether affectation of vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2)-dependent angiogenesis was mediating the observed effects. Proof-of-concept study. University hospital and a university-affiliated private IVF research center. PATIENT(S): Hyperprolactinemic patients (n = 9) with endometriosis requiring a first surgical intervention (L1) and benefiting from a second-look laparoscopy (L2) were evaluated. INTERVENTION(S): During L1, four to six peritoneal red lesions were identified. One-half of the lesions were removed and the remaining one-half were labeled with silk knot sutures. After L1, quinagolide was administered in a titrated manner (25-75 μg/d) for 18-20 weeks. During L2, the remaining lesions were surgically excised. MAIN OUTCOME MEASURE(S): Both L1 and L2 were video recorded to compare the effects of quinagolide treatment on lesion size. Lesions removed at L1 and L2 were compared by means of: 1) histologic analysis; 2) immunohistochemical quantitative analysis of angiogenesis; and 3) quantitative fluorescence polymerase chain reaction array analysis of 84 chemokines and pro-/antiangiogenic molecules. RESULT(S): Quinagolide induced a 69.5% reduction in the size of the lesions, with 35% vanishing completely. Histologic analysis showed tissue degeneration, which was supported by down-regulation of VEGF/VEGFR2, three proangiogenic cytokines (CCL2, RUNX1, and AGGF1) and plasminogen activator inhibitor (PAI) 1, a potent inhibitor of fibrinolysis in the L2 lesions. CONCLUSION(S): By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.
Measurement and Statistics · Instrument Development and Validation
To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception.
Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system--the endometriosis fertility index (EFI)--from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes.
Private reproductive endocrinology practice.
PATIENT(S): A total of 801 consecutively diagnosed and treated infertile patients with endometriosis.
INTERVENTION(S): Surgical diagnosis and treatment followed by non-IVF fertility management.
MAIN OUTCOME MEASURE(S): The EFI and life table PRs.
RESULT(S): A statistically significant variable used to create the EFI was the least function score (i.e., the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube, fimbria, and ovary on both sides). Sensitivity analysis showed that the EFI varies little, even with variation in the assignment of functional scores, and predicted PRs.
CONCLUSION(S): The EFI is a simple, robust, and validated clinical tool that predicts PRs after endometriosis surgical staging. Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses.
Aghajanova L et al., 2010·Seminars in reproductive medicine
Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has been implicated in several gynecologic disorders, including endometriosis, polycystic ovarian syndrome (PCOS), and endometrial hyperplasia. Although several investigators have analyzed eutopic endometrial expression of progesterone-target genes, the genesis and consequences of progesterone resistance remain unclear. We review evidence for progesterone resistance in endometrium of women with endometriosis, PCOS, and endometrial hyperplasia, and we identify possible mechanisms associated with reduced progesterone activity in endometrium of (some) women with these gynecologic disorders that have a significant impact on women's health and well-being.
This review will address the current understanding of the relationship between prolactin (PRL) and endometriosis-associated infertility. Although the exact mechanisms of action of hyperprolactinemia in patients with endometriosis-associated infertility have not been clearly established, this report reviews results from relevant studies in the literature. These include serum PRL levels in endometriosis-associated infertility, PRL receptors in ectopic endometriotic tissues, basal PRL levels after TSH and Danazol (isoxazolic derivative of the synthetic steroid 5alpha-ethinyl-testosterone) therapy, peritoneal fluid and nocturnal serum PRL levels in endometriosis, infertility, and luteal phase PRL concentrations in patients with endometriosis. Obstetricians & Gynecologists, Family Physicians. LEARNING After completion of this article, the reader should be able to explain the relationship between prolactinand endometriosis-associated infertility, relate endometriosis with infertility, and summarize two ways in which prolactin and endometriosis may be linked in the pathophysiology of infertility.
To investigate the reasons women experience delays in the diagnosis of endometriosis and the impact of this. A qualitative interview-based study of 32 women, 28 of whom were subsequently diagnosed with endometriosis. Southeast England. PATIENT(S): Women attending a pelvic pain clinic. INTERVENTION(S): Semistructured interviews. MAIN OUTCOME MEASURE(S): Women's reported experiences of being diagnosed with endometriosis. RESULT(S): Delays in the diagnosis of endometriosis occur at an individual patient level and a medical level, as both women and family doctors normalize symptoms, symptoms are suppressed through hormones, and nondiscriminatory investigations are relied upon. Women benefited from a diagnosis, because it provided a language in which to discuss their condition, offered possible management strategies to control symptoms, and provided reassurance that symptoms were not due to cancer. Diagnosis also sanctioned women's access to social support and legitimized absences from social and work obligations. CONCLUSION(S): Although recent guidelines for the management of chronic pelvic pain suggest that diagnostic laparoscopy may be considered a secondary investigation after the failure of therapeutic interventions, the present study highlights the importance of an early diagnosis for women who suffer at physical, emotional, and social levels when they remain undiagnosed.
To determine the positive predictive value of the combined symptoms of severe dysmenorrhea with the sign of tenderness and/or nodularity of the cul-de-sac and/or uterosacral ligament(s) in diagnosing endometriosis clinically. Material and In this prospective study, 116 patients with severe dysmenorrhea, after excluding urinary and gastrointestinal disease, underwent pelvic examination by the same investigator. Women having adnexal mass on pelvic examination were excluded Tenderness, and also nodularity, of the cul-de-sac, right and left uterosacral ligament were recorded separately. The laparoscopist did not know the findings of the pelvic examination. The diagnosis of endometriosis was made visually when lesions were typical and all other lesions were biopsied. The prevalence of endometriosis was 78.4%. Tenderness, nodularity, tenderness and nodularity, and also tenderness or nodularity of cul-de-sac and/or uterosacral ligament(s) were all statistically significantly associated with the presence of endometriosis (P = .048, .005, .004, and .004 respectively). The positive predictive values were 85.5%, 94.0%, 94.6% and 86.7%, respectively. The positive predictive value of severe dysmenorrhea with nodularity of the cul-de-sac and/or uterosacral ligament(s) was 94.0%.
Skrzypulec V et al., 2004·Wiadomosci lekarskie (Warsaw, Poland : 1960)
The aim of this study was to evaluate the influence of the treatment with oral doses of 50 mg GnRH analogue on the intensification of endometriosis symptoms and infertility amongst women with evident symptoms of endometriosis in comparison with placebo group. A group of 34 women at the age from 18 to 45 were introduced into the study. The inclusion criteria for investigated population contained: endometriosis symptoms, endometriosis diagnosed by laparoscopy, its surgical or pharmacological treatment, negative pregnancy test score and regular menses. The patients were divided into 2 groups: investigated group and control group. Women completed "Diary" every day in which they estimated main endometriosis symptoms: dysmenorrhea, dyspareunia, pelvic pain and vaginal bleeding (according to Pain Grading Scale). The intensification of dysmenorrhea and vaginal bleeding was reduced in the investigated group in comparison with control one. These differences were statistically significant. Although the extremity of dyspareunia was decreased in two groups, this correlation was statistically significant only in the investigated group. Pelvic pain evaluation showed that its level was lower in the investigated group (p > 0.05). It was found that 11 women (investigated group) and 5 women (control group) got pregnant after the period of 12-week treatment.
GnRH analogues have an efficient influence on the reduction of endometriosis symptoms. GnRH analogues could be used in the management of infertility.
Outcomes and Effectiveness · Outcomes by Diagnosis
To investigate the IVF outcome for patients with endometriosis. Meta-analysis. Academic research center. PATIENT(S): A MEDLINE search and review of the literature were performed. Patients were classified by level of endometriosis, and controls were classified according to the indication for IVF. INTERVENTION(S): Bivariate analysis and multivariate logistic regression was used to estimate overall effect and control for confounding. MAIN OUTCOME MEASURE(S): Pregnancy rates, fertilization rate, implantation rates, and numbers of oocytes retrieved. RESULT(S): Twenty-two published studies were included in the overall analysis. The chance of achieving pregnancy was significantly lower for endometriosis patients (odds ratio, 0.56; 95% confidence interval, 0.44-0.70) when compared with tubal factor controls. Multivariate analysis also demonstrated a decrease in fertilization and implantation rates, and a significant decrease in the number of oocytes retrieved for endometriosis patients. Pregnancy rates for women with severe endometriosis were significantly lower than for women with mild disease (odds ratio, 0.60; 95% confidence interval, 0.42-0.87). CONCLUSION(S): Patients with endometriosis-associated infertility undergoing IVF respond with significantly decreased levels of all markers of reproductive process, resulting in a pregnancy rate that is almost one half that of women with other indications for IVF. These data suggest that the effect of endometriosis is not exclusively on the receptivity of the endometrium but also on the development of the oocyte and embryo.
To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. Prospective study (study sample); retrospective record review (test sample). Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy. PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample). The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy. MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample. RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample. CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.
Corson SL et al., 2000·J Am Assoc Gynecol Laparosc
To determine the prevalence of reproductive pathology in a group of infertile women thought to be at low risk for altered pelvic anatomy. Retrospective chart review and follow-up (Canadian Task Force classification II-2). Academic-affiliated, private reproductive endocrinology practice. One hundred infertile women. Diagnostic and/or therapeutic laparoscopy. MAIN Of 100 patients with a negative reproductive work-up up to the point of laparoscopy, 68 had pathology of reproductive intrinsic tubal disease 24, peritubal adhesive disease 34, and endometriosis 43, some in combination. Laparoscopy was especially helpful in establishing treatment protocols for older women, who were referred for assisted reproductive techniques earlier than otherwise might have been the case. Women conceived after hormone therapy and after operative intervention. Although the hysterosalpingogram was read as normal in all women, tubal disease was diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2 having complete obstruction. Endometriosis stage I-II was found in 22 patients, stage III in 13, and stage IV in 6. Even in women thought to be at low risk for significant pelvic pathology affecting reproduction, the yield was high. Although some pregnancies were achieved after operative intervention, frequently laparoscopy was helpful in making a decision to go to assisted reproductive technology, particularly when infertility had been of long duration and in older women. Frequently the degree of pathology was such that a full operating suite was necessary to provide adequate instrumentation and anesthesia for operative intervention, which would not have been the case with office laparoscopy.
To assess the value of laparoscopy in infertile women with normal hysterosalpingograms, with and without risk factors suggesting pelvic disease. We retrospectively reviewed 1,022 consecutive charts from a tertiary infertility practice. In 265 women, laparoscopies were performed after normal hysterosalpingograms. Laparoscopies were normal in 136 (51%) women, whereas 129 (49%) had one or more abnormal laparoscopic findings, including minimal or mild endometriosis (n = 85), moderate or severe endometriosis (n = 11), adnexal adhesions (n = 27), subserosal myomas (n = 17), ovarian neoplasms (n = 5), distal phimosis (n = 1) and salpingitis isthmica nodosa (n = 1). Only 7% of cases had findings that might require standard operative laparoscopy or laparotomy, although not all were causally related to infertility. A history of dysmenorrhea or dyspareunia increased the likelihood of detecting endometriosis from 41% to 64% and 69%, respectively. The presence of both symptoms increased the likelihood to 83%. In the presence of a normal hysterosalpingogram, laparoscopy identified other pelvic disease in about half of patients. Because most abnormalities were mild, this knowledge can be used to plan a micro-laparoscopic approach for many women, reserving traditional or operative laparoscopy for women with an abnormal hysterosalpingogram or extensive disease following micro-laparoscopy. Alternately, knowledge of the nature and severity of the expected laparoscopic findings might lead to bypassing laparoscopy in favor of assisted reproduction when the perceived benefit of surgical intervention is small.
To evaluate and compare the safety and efficacy of leuprolide versus placebo in managing chronic pelvic pain in women with clinically suspected endometriosis. Women 18-45 years of age with moderate to severe pelvic pain of at least 6 months' duration underwent extensive, noninvasive diagnostic testing and laboratory evaluation, including pelvic ultrasound, complete blood count, determination of erythrocyte sedimentation rate, and endocervical cultures. Those with clinically suspected endometriosis were randomized to double-blind treatment for 3 months with depot leuprolide (3.75 mg/mo) or placebo. The accuracy of the clinical diagnosis of endometriosis was evaluated by posttreatment laparoscopy. Of 100 women randomized, 95 completed the study: 49 in the leuprolide group and 46 in the placebo group. Women in the leuprolide group had clinically and statistically significant (P < or = .001) mean improvements from baseline after 12 weeks of therapy in all pain measures. These mean improvements were significantly greater (P < or = .001) than those in the placebo group. At 12 weeks, mean decreases in physician-rated scores for dysmenorrhea, pelvic pain, and pelvic tenderness were 1.7, 1.0, and 0.8 points greater, respectively, in the leuprolide group than in the placebo group (on a four-point scale). Thirty-eight (78%) of 49 and 40 (87%) of 46 patients in the leuprolide and placebo groups, respectively, had laparoscopically confirmed endometriosis after 12 weeks of treatment. No women withdrew from the study because of adverse events. Depot leuprolide was effective and safe for treating patients with chronic pelvic pain and clinically suspected endometriosis, confirming the potential of its empiric use in these patients.
To evaluate the validity of transrectal ultrasonography in the assessment of rectovaginal endometriosis. We compared the findings of transrectal ultrasonographic examination performed before surgery with the operative and pathologic findings in 140 women who underwent laparoscopy or laparotomy for suspected endometriosis. The ultrasonographer was asked to investigate whether any deep endometriotic lesions were present in the rectovaginal septum and to define the lateral extension on the basis of involvement of the uterosacral ligaments. In addition, infiltration of the rectal and vaginal walls was evaluated. Thirty-four women had endometriosis infiltrating the rectovaginal septum confirmed by combined operative and pathologic findings. Ultrasonography showed a sensitivity and specificity of 97% and 96%, respectively, in the diagnosis of the presence of rectovaginal endometriosis. The sonographer identified infiltration of the rectal and vaginal walls correctly in all cases in whom it was present, but also reported rectal infiltration in three cases not confirmed by the surgeon and pathologist. The sensitivity and specificity in the diagnosis of uterosacral ligament infiltration were 80% and 97%, respectively. If our preliminary results are confirmed by a larger series, transrectal ultrasonography will be considered a valid diagnostic tool in the evaluation of rectovaginal endometriosis.
Diagnostic Criteria and Classification · Staging and Classification Systems
We investigated the length of time between the onset of pain symptoms and the surgical diagnosis of endometriosis in women from the UK and the USA. A total of 218 women with surgically confirmed disease, recruited through endometriosis self-help groups, completed a postal questionnaire. The mean +/- SD delay in diagnosis for women from the USA was 11.73 +/- 9.05 years, significantly higher than the equivalent delay of 7.96 +/- 7.92 years for women from the UK (P < 0.01). The stage of disease did not effect the length of time between the onset of symptoms and diagnosis. Therefore there is considerable delay in the diagnosis of endometriosis for women from both the UK and the USA. Efforts to reduce this delay are required to minimize the suffering of women with this disease.
A study was conducted to determine if the increased recognition of various forms of endometriosis might have increased the ability to correlate focal tenderness with lesions. The prospective study of 82 patients revealed a strong correlation between focal tenderness on examination with the presence of deep fibrotic endometriosis and other fibrotic pathology. The data suggested that focal tenderness and depth of infiltration may direct further study in women with endometriosis.
We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms.
Lumbar bone mineral density (BMD) was evaluated by dual photon absorptiometry (DPA) in 38 women with laparoscopically diagnosed and staged endometriosis. DPA was performed before and at the completion of 26 weeks of treatment with either gonadotropin releasing hormone agonist (GnRHa) or danazol. Twenty-five women received GnRHa either nasally or subcutaneously and 13 women received danazol 200 mg four times daily by mouth. During treatment amenorrhea and suppressed estradiol levels were observed in all patients. Each patient took a supplement of oral calcium 1 gm daily. DPA (reproducibility +/- 1.5%) was read by a single observer unaware of the treatment assignment of the patient. The mean (+/- standard error) of the entire group prior to treatment was 98.8% +/- 0.03% of a control population of women from the same geographic area matched for race, age, and weight. At the completion of treatment, BMD was slightly decreased in the GnRHa group and marginally increased in the danazol group but neither change was significant. Women with endometriosis have lumbar BMD in the normal range and ovarian suppression with either GnRHa or danazol produces no significant change in BMD.
Among 59 laparoscopically staged endometriosis patients, 28.8% tested positive for antinuclear antibody. Of 44 patients, 45.5% were lupus anticoagulant positive (greater than 1.3) and 20.5% were within a borderline range (1.2-1.3). Antinuclear antibody positivity was inversely related to stage of disease (P = .009); lupus anticoagulant positivity exhibited a similar trend, but did not reach statistical significance. Of 31 endometriosis patients, 64.5% exhibited immunoglobulin G (IgG) autoantibodies and 45.2% demonstrated IgM autoantibodies to at least one of 16 antigens investigated. Among IgG autoantibodies, those to phospholipids were most frequently detected, followed in order of frequency by antibodies to histones and nucleotides. The incidence of IgM autoantibodies was inverted, with antinucleotides appearing most frequently and antiphospholipids least frequently. A strong correlation was noted between the presence of lupus anticoagulant and antinuclear antibody with both IgG and IgM autoantibodies. These observations suggest that endometriosis is associated with abnormal polyclonal B cell activation, a classic characteristic of autoimmune disease. This contention is further supported in that immunoglobulin levels (particularly IgG) are elevated in patients with endometriosis, and more so in lupus anticoagulant-positive than lupus anticoagulant-negative endometriosis patients (P = .021).
The effectiveness of ovulation induction with clomiphene citrate or human menopausal gonadotropins was evaluated in 52 infertile women with stage I or stage II endometriosis and ovulatory dysfunction: anovulation or luteinized unruptured follicle (LUF) syndrome before (group I) and after (group II) danazol treatment. The incidence of anovulation and LUF in the endometriosis population was 9% and 34%, respectively. In group I, 10 of 36 patients (27.8%) conceived, with an average of 17.6 induction cycles per pregnancy. In group II, 21 of 30 patients (70%) conceived, with an average of 4.5 cycles per pregnancy (difference significant at P less than 0.001). There was no difference in the average number of ovulation induction cycles per patient between groups I and II (4.9 and 3.1, respectively). Of 14 patients who did not conceive in group I and crossed over to group II, 9 (64.3%) conceived (not different from group II). Spontaneous abortion rates were 20% in group I and 14% in group II. These results indicate that mild endometriosis may interfere with conception through mechanisms other than ovulatory dysfunction and that treatment with danazol appears to more than double the fertility rate.
Endometriosis has been associated with an increased incidence of spontaneous abortion, compared with the abortion rate of the general population. To assess whether a separate control group would affect these conclusions, we studied 139 consecutive infertility patients with laparoscopically proven endometriosis to determine the incidence of spontaneous abortion. Ninety-five of these patients underwent conservative surgical resection of endometriosis, and 44 patients opted for expectant management. There was no significant difference between these two groups in average age, duration of infertility, or proportion of patients with primary infertility. The average spontaneous abortion rate before diagnosis for all patients was 63.1%. After surgical treatment, the abortion rate dropped to 0% (P less than 0.000001) for all stages of disease. However, even in those patients who received expectant management only, the abortion rate fell to 16.7% and 21.4% for mild and moderate endometriosis, respectively (P less than 0.001). These results suggest that the spontaneous abortion rate in untreated endometriosis may not be as high as previously reported and may not be significantly different from the rate in the general population. The data also emphasize the need for well-defined control groups when assessing the effects of a treatment regimen.
More than 100 years after the first description of endometriosis, the pathophysiology of the disorder still remains an enigma. In addition to infertility, an increased frequency of clinically apparent spontaneous abortions (32% vs. 8-15% in the normal population and 19% in the infertile one) has been found in women with endometriosis and secondary infertility. Treatment of endometriosis with conservative surgery, danazol or both results in a frequency of spontaneous abortion within the range of the normal population's. Although the factors involved in the pathophysiology of endometriosis are probably multiple, abnormal corpus luteum function is a common mechanism that might explain both the infertility and the spontaneous abortions. Several studies suggested a relationship between endometriosis and corpus luteum function, which may be mediated by prostaglandins. However, not all the data have been supportive. We developed a hypothetical scheme (modified from Drake) that outlines possible mechanisms of endometriosis mediated by the adverse effects of increased prostaglandins. Further investigation of this scheme may provide new information about the pathophysiology of endometriosis.
Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients had evidence of blood in the pelvis. Also, 90% of patients with endometriosis and eight of nine women on oral contraceptives had bloody fluid during the menstrual period. The present observations indicate that retrograde menstruation through the fallopian tubes into the peritoneal cavity is a very common physiologic event in all menstruating women with patent tubes.
Luteinizing hormone (LH) receptor concentrations in ovarian follicles and corpora lutea were measured in 51 patients with histologically proven endometriosis and in 41 control patients. The LH receptor concentrations in cases of endometriosis were lower during the early (0.43 +/- 0.11 [mean +/- standard error] versus 1.31 +/- 0.27 fmol/mg protein; P less than 0.001) and late (0.48 +/- 0.10 versus 1.59 +/- 0.22 fmol/mg protein; P less than 0.001) follicular phase, and during the late luteal phase (2.62 +/- 0.55 versus 4.62 +/- 0.65 fmol/mg protein; P less than 0.05) of the cycle than in control patients. In contrast to the control patients, the LH receptor concentration during the follicular phase remained constant in endometriosis, being lower in patients with extensive or severe disease than in patients with moderate or mild disease (0.28 +/- 0.07 versus 0.61 +/- 0.21 fmol/mg protein; P less than 0.05). Endometriosis-associated infertility might be a consequence of a defect in the mechanism mediating LH action in the ovaries.
The cause of infertility has remained obscure in women with endometriosis in whom the tuboovarian relationship is unaltered. Abnormal corpus luteum function has been one mechanism implicated in the pathophysiology of endometriosis in infertilityl-3 and may also be a possible explanation for the high frequency of spontaneous abortions among women with untreated endometriosis.4 However, we have observed only an occasional occurrence of luteal phase deficiency in women with an ultimate diagnosis of endometriosis. In order to verify this observation, we examined the incidence of luteal phase defects (LPDs) in. our infertility population.