Santos da Silva A et al., 2026·Reproduction (Cambridge, England)
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.
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.
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
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.
Schoeman EM et al., 2025·Human reproduction (Oxford, England)
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.
Yeung P et al., 2025·Acta Scientific Women's Health·
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.
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·
Open Access
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.
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.
Wu Q et al., 2023·Reprod Biol Endocrinol·
Open Access
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.
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.
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·
Open Access
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.
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·
Open Access
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·
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
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.
Leonardi M et al., 2020·Diagnostics (Basel, Switzerland)
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.
Fertility and Outcomes · Conception After Excision
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.
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
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.
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.
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)·
Open Access
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.
Nisenblat V et al., 2016·The Cochrane database of systematic reviews·
Open Access
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 >
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.
Fertility and Outcomes · Conception After Excision
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.
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.
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.
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.
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.
Fertility and Outcomes · Conception After Excision
Bulletti C et al., 2010·J Assist Reprod Genet·
Open Access
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.
Yeung PP Jr et al., 2009·J Minim Invasive Gynecol·
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.
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.
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.
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, 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·
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.
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·
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.
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.
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.
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)
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.
Medical Management · Hormonal Suppression Outcomes
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.
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.
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.
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
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.
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.
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
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, and Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina
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)
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.
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.
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.
Valenti M et al., 2026·Am J Obstet Gynecol·
Open Access
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.
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.).
Adhesion Prevention · Surgical Technique and Adhesions
Yeung P, 2025·J Restorative Reprod Med·
Open Access
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.
Diagnostic Criteria and Classification · Staging and Classification Systems
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.
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.
De Corte P et al., 2025·BJOG : an international journal of obstetrics and gynaecology
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.
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.
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.
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·
Open Access
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.
Schliep KC et al., 2023·AJOG Glob Rep·
Open Access
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.
Outcomes and Effectiveness · Outcomes by Diagnosis
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.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
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.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
Anastasi E et al., 2023·International journal of environmental research and public health
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.
Case-based clinical presentation examining the role of mast cells in the pathophysiology of endometriosis and dysmenorrhea, presented by April Lind, MD (IFMCP, CFCMC, RHRI). Reviews mast-cell mediated inflammation, its relationship to endometriosis-associated pain and abnormal uterine bleeding, and functional-medicine considerations.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
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.
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.
Genetic and Immune Testing · Karyotype and Genetic Panels
Moustafa S et al., 2020·American journal of obstetrics and gynecology·
Open Access
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.
Farland LV et al., 2019·Obstetrics & Gynecology·
Open Access
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.
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·
Open Access
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.
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.
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.
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.
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.
Parasar P et al., 2017·Current obstetrics and gynecology reports
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.
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.
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·
Open Access
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
Yeung PP Jr et al., 2016·Front Public Health·
Open Access
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.
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.
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.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
Agostinis C et al., 2015·Mediators Inflamm·
Open Access
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.
Dun EC et al., 2015·JSLS : Journal of the Society of Laparoendoscopic Surgeons
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.
Franjoine SE et al., 2015·Minimally invasive surgery·
Open Access
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.
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 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.
Cancer and Fertility · Hormone Sensitive Cancer and Reproductive Care
Yang J et al., 2014·International journal of clinical and experimental medicine
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.
Porpora MG et al., 2013·Evid Based Complement Alternat Med·
Open Access
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·
Open Access
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.
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.
Buck Louis GM et al., 2011·Fertil Steril·
Open Access
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 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.
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.
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.
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.
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.
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%.
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.
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.
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 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
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.
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.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
Pittaway DE et al., 1984·The Journal of reproductive medicine
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.
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.
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.
Purpose Endometriosis is a benign estrogen-responsive disease which shares some characteristics with malignant tumors such as invasion and unrestrained growth. In this respect, the epidermal growth factor receptor family (EGFR or erbB-1 and erbB-2 to -4) is known to play an important role in tumor biology. The aims of the present study were: 1) to investigate the expression patterns of the four erbB receptors, 2) to ascertain if there was a correlation between the EGFR family expression and the expression of the estrogen receptor α (ERα). Methods Retrospective study: 48 peritoneal and 12 ovarian human endometriotic lesions were analyzed by immunohistochemistry. The confirmation of the immunohistochemical findings was made by Western blot analysis. Using the Mann-Whitney-U test, statistical analysis was performed. Results In peritoneal and ovarian endometriosis, all members of the EGFR family and ERα are detectable in stromal and epithelial cells, but the expression is different within the tissues. Only in ovarian endometriosis was a statistical association observed between EGF receptor and ERα expression (p<0.017). Conclusions The differential expression of the erbB receptors suggest that the erbB family might play an important role in the pathogenesis of endometriosis. A significant association between EGF receptor expression and the ERα expression was only found in ovarian endometriosis.