Predictive tools are lacking for pain-related outcomes after endometriosis surgery. The objective of this study was to develop and validate a machine learning-based clinical model to predict poor pain-related quality of life after endometriosis surgery. Registry data from a prospective longitudinal cohort at a tertiary referral center (2013-2020) was used for model development and validation. Participants underwent an index endometriosis surgery, and completed the pain subscale of the Endometriosis Health Profile-30 (EHP-30) at baseline and 1-2-year follow-up. The outcome was poor pain-related quality of life defined as EHP-30 pain subscale above the 75th percentile for North America, at 1 to 2 years postsurgery. Thirty-two preoperative factors were evaluated, with final models retaining the top 10 most important predictors. Elastic net logistic regression, random forest (RF) and multilayer perceptron neural network models were developed. Internal validation was performed using 500 bootstrap samples, and a held-out test cohort. The study included 650 488 in the training cohort and 162 in a held-out test cohort. The RF model exhibited the most consistent discrimination, measured by the area under the receiver operating characteristic curve, between the training cohort (0.768; 95% CI: 0.690-0.837) and test cohort (0.766; 95% CI: 0.676-0.863, Δ = -0.002). The RF model also demonstrated the best integrated calibration index (0.029) and highest net benefit. Final preoperative predictors for the RF model included baseline EHP-30 score, surgery type (conservative fertility-sparing vs hysterectomy), anxiety scores, depression scores, pain catastrophizing scale scores, abdominal wall pain, pelvic floor myalgia, smoking status, back pain, and race/ethnicity. We present the RF model as the Endometriosis Pain Index to aid preoperative counselling for endometriosis surgery.
Balachandran S et al., 2026·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes.
This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth.
544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003).
Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Rojas HE et al., 2026·Journal of women's health (2002)
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis. Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada. Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity. N/A. Mid-cycle pain in the last month versus No mid-cycle pain in the last month. Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month. In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
Bouchard TP et al., 2026·Reproductive biomedicine online·Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Recurrent Pregnancy Loss · Immune and Thrombophilia Factors
Balachandran S et al., 2025·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC·Free to read
To investigate the impact of the COVID-19 pandemic on the care received by patients with recurrent pregnancy loss (RPL) in British Columbia, Canada. To explore the differential impact of socioeconomic status on health care utilization outcomes during the COVID-19 pandemic for patients with RPL.
This is a retrospective cohort study of patients from an RPL clinic located within a tertiary referral centre. Patients were divided into 2 groups based on the date of their initial visit to the clinic: (1) pre-pandemic group (March 1, 2018-February 28, 2020) and (2) pandemic group (March 1, 2020-February 28, 2022). Data were sourced from the RPL Clinic Database and Population Data BC. Outcomes assessed included visit trends, immediate pandemic impact, and socioeconomic effects.
Demographic and clinical characteristics were not significantly different between study groups, except for increased referral rates to fertility clinics by the RPL clinic during the COVID-19 pandemic (4.90% vs. 9.50%). The mean number of visits per patient was comparable between pre-pandemic (3.50 ± 2.00) and during the pandemic (3.40 ± 3.40). However, monthly initial visits were lower during the pandemic (12.50 ± 3.10) compared with pre-pandemic (14.40 ± 4.83). Telehealth was rare in the pre-pandemic period and increased dramatically during the pandemic, with virtual visits reaching up to 64% of total and 94% of initial visits. The pandemic's onset caused immediate drops in total (38.80%) and initial visits (51.70%). Health care utilization was higher among those with less material deprivation, whereas contrasting effects were observed in those with less social deprivation.
The COVID-19 pandemic impacted the care received by patients with RPL within a tertiary care centre. There was a shift in how services were provided to patients, uniquely impacting specific populations within the community.
Goodwin E et al., 2025·Journal of minimally invasive gynecology·Free to read
Endometriosis is a chronic and inflammatory condition that affects approximately 10% of the reproductive-age population. During the COVID-19 pandemic, there was a shift towards virtual care for endometriosis. Our aim was to evaluate the diagnostic and treatment outcomes of virtual-only care, compared to those who had both virtual and in-person visits.
Retrospective descriptive analysis of registry data.
This study was conducted in British Columbia, Canada, at a tertiary referral center for endometriosis and pelvic pain.
In this cohort (n = 389), we examined patients who received an initial virtual assessment followed by virtual care alone (Virtual Only group, n = 203) and those who had an initial virtual assessment followed by an in-person physical exam (Physical Exam group, n = 186).
Virtual care at the center during the COVID-19 pandemic.
The Physical Exam group was more likely to have surgery compared to the Virtual Only group (45.7% vs. 16%, p <.001). At the time of surgery, the groups did not differ based on type of surgery (e.g., excision of endometriosis and/or hysterectomy), endometriosis anatomic findings (e.g., stage and anatomic subtype), surgical complexity or surgical complications. At baseline, the two groups did not differ in their pain, mental health or quality of life scores. At 1-year follow-up, the two groups did not differ in these outcome measures.
There was a lower rate of surgery, but no differences in surgical findings or complications, nor in 1-year outcomes, after virtual only care for endometriosis compared to patients that had a virtual visit and then underwent a physical exam. These results support a hybrid model, where a virtual visit is the first contact and serves as a triage tool to determine whether a patient is appropriate for virtual only care or would benefit from a physical exam. Future research could incorporate population-based administrative data or qualitative approaches to understanding patient experiences and physician perspectives on virtual care for the treatment of endometriosis.
Fayek B et al., 2025·Reproductive sciences (Thousand Oaks, Calif.)
Endometriosis contributes to 5-21% of hospital admissions for pelvic pain. While hormonal therapies are pivotal in managing endometriosis-related pain, no single hormonal treatment suits all patients. We aimed to assess the effectiveness and tolerability of hormonal therapies and factors influencing response in endometriosis-associated pain treatment. Additionally, to investigate adjuvant neuromodulatory drug usage in patients who have used hormonal therapy. This cross-sectional study examined endometriosis patients undergoing hormonal therapy for pelvic pain at a tertiary referral centre for endometriosis and chronic pelvic pain (CPP). We assessed the proportion of patients reporting ineffectiveness of hormonal therapy and rates of discontinuation attributed to side effects. We evaluated factors related to treatment ineffectiveness and discontinuation due to side effects. Lastly, we determined the rates of adjuvant neuromodulatory drug use among patients who used hormonal therapy. 1011 patients were included in the study. Most hormonal therapies' ineffectiveness was related to worse CPP (P < .05). Cul-de-sac obliteration was correlated with better response to cyclic CHCs, DNG, and GnRH agonist (OR = 0.55, 95% CI [0.36 - 0.84]; OR = 0.53, 95% CI [0.29 - 0.98]; OR = 0.26, 95% CI [0.14 - 0.91], respectively). Adjuvant neuromodulatory drugs were more frequently utilized by patients who found hormone therapy ineffective except for those who used norethisterone acetate (NETA). Endometriosis pain is associated with a high chance of failed hormonal therapy. Cul-de-sac obliteration correlated with improved hormonal therapy response, highlighting the multifactorial influence on treatment outcomes. Patients who found hormone therapy ineffective tended to use adjuvant neuromodulatory drugs more frequently.
Eckler R et al., 2025·PloS one·Free full text on PubMed Central
To investigate the impact of the COVID-19 pandemic's onset on clinical and demographic characteristics, pregnancy complications, and monthly conception rates resulting in births through spontaneous conceptions and in-vitro fertilization (IVF) in British Columbia (BC), Canada.
This retrospective population-based cohort study examined individuals who gave birth (both live births and stillbirths) in BC between June 1, 2010, and March 31, 2021, with estimated conception dates from January 1, 2010 to June 30, 2020. Data were obtained from the BC Perinatal Data Registry. Two groups were identified based on the estimated conception date: the pre-pandemic conception group (conception from January-1-2010 to February-29-2020) and the pandemic conception group (conception from March-1-2020 to June-30-2020). A time series forecasting method (ARIMA) was employed to observe trends in conception rates during the study period.
304,244 individuals with pregnancies resulting in live births or stillbirths during the study period were evaluated. A total of 429,843 such conceptions were included in the study: 417,753 (97.2%) occurring before the onset of the pandemic and 12,090 (2.8%) in the pandemic period. In June 2020, conceptions resulting in births decreased by 26.6% compared with June 2019. Trends in conceptions resulting in live births were similar, with a conception rate of 235.2 per 100,000 women of reproductive age in June 2020, compared with the expected rate of 305.0 per 100,000. In March 2020, 0.5% of conceptions that resulted in births ended in stillbirths, compared to 1.7% in March 2019. IVF conceptions ending in births declined during the pandemic, dropping to 2.5 and 2.8 per 100,000 in March and April 2020, respectively, compared with the expected 13.1 per 100,000. However, by June 2020, these rates began to recover toward the expected levels. Rates of gestational diabetes mellites (GDM), gestational hypertension (GHTN), and postpartum intensive care unit (ICU) admissions were similar before and during the COVID-19 pandemic.
During the challenging period of the COVID-19 pandemic in BC, couples may have chosen to delay conception. Rates of conceptions resulting in stillbirths remained relatively unchanged. IVF conception rates were impacted by the suspension of elective procedures. Preterm birth rates slightly exceeded expected levels but remained within normal fluctuations, and small increases in GDM and GHTN prevalence were also observed.
Bedaiwy MA et al., 2025·Gynecologic and obstetric investigation
Accessory and cavitated uterine masses (ACUM) are rare Mullerian anomalies, defined as an isolated accessory cavitated mass lined with endometrial epithelium.
This article explores ACUM lesions from two aspects and integrates a case report of a successful laparoscopic-assisted intervention for ACUM in a 24-year-old woman with refractory dysmenorrhea with a review of current literature on laparoscopic surgical techniques. Unique to this case was the process of undergoing targeted genetic sequencing via the Find ITTM Panel Version 3.4 on the ACUM, looking for mutations in KRAS, PIK3CA, and FGFR2. A process that was inspired by recent reports that indicate that even normal endometrium can harbor cancer-associated mutations.
A comprehensive search of Ovid MEDLINE and Embase was performed. Studies were selected if they explored laparoscopic surgery's impact on ACUM patients' outcomes related to fertility, menorrhagia, or dysmenorrhea. Risk of bias assessment was performed using the JBI Critical Appraisal Checklist.
From 160 articles identified, 25 full-text articles were analyzed with a total of 75 unique patients discussed. Dysmenorrhea was present in 100% of cases (n = 75/75), and laparoscopic resection improved patient symptoms in 84% (n = 63/75) of cases. The mass excised in the case was positive for somatic missense mutations in RET (R813W) and HRAS (G12S) genes, identified at low variant allele frequencies.
These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.
Gentles AJ et al., 2025·The journal of pain·Free to read
There is increasing recognition that nociplastic pain and central sensitization may play a role in endometriosis-associated pain. The Pain Sensitivity Questionnaire Minor (PSQ-M) evaluates subjective widespread pain sensitivity, and is linked to pain outcomes in chronic pain populations. However, evidence connecting the PSQ-M to central sensitization in endometriosis is limited. Using the Central Sensitization Inventory (CSI) as a comparison, this study compared the PSQ-M as a clinical proxy for central sensitization in endometriosis individuals. Data collected from 983 endometriosis participants (mean age of 34 years), between January 2020 and December 2022, were analyzed from a prospective registry. A significant but weak positive correlation was observed between PSQ-M and CSI scores (r=0.099, p<0.001). A significant but weak correlation was found between the number of central sensitivity syndromes and pelvic pain-related comorbidities with the PSQ-M (r=0.093, p<0.001), compared to a stronger correlation with the CSI (r=0.687, p<0.05). PSQ-M scores were not significantly associated with baseline (r=0.013, p=0.797) or post-operative (r=-0.046, p=0.801) quality-of-life. There was no change in the PSQ-M and a small change in CSI after endometriosis surgery, suggesting that surgical treatment of endometriosis does not directly address central sensitization. In conclusion, the PSQ-M may not be the optimal clinical proxy for central sensitization in endometriosis. This study evaluates the Pain Sensitivity Questionnaire - Minor (PSQ-M) as a proxy for central sensitization in endometriosis. The PSQ-M showed weak correlations with central sensitivity syndromes and pain scores and was not associated with post-surgical quality-of-life, suggesting it may not be the optimal tool for assessing central sensitization in endometriosis.
Tucker DR et al., 2025·Human reproduction (Oxford, England)·Free full text on PubMed Central
Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?
Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.
Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.
STUDY DESIGN, SIZE, This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.
PARTICIPANTS/MATERIALS, SETTING, PTEN and ARID1A loss was assessed using established immunohistochemistry (IHC) methods as proxies for somatic loss by two independent raters. PTEN and ARID1A status for each participant was defined as loss (loss in at least one sample for a participant) or retained (no loss in all samples for a participant). Primary analyses examined associations between PTEN and ARID1A loss and disease burden based on anatomic subtype (superficial peritoneal endometriosis (SUP), deep endometriosis (DE), ovarian endometrioma (OMA)) and rASRM stage (I-IV). Secondary analyses explored associations of PTEN and ARID1A loss with demographics, surgical difficulty, and pain scores (baseline and follow-up). Additionally, using previously published data on KRAS codon 12 mutations for this cohort, we investigated associations between variables in the primary and secondary analyses and acquiring two or more somatic events (PTEN loss, ARID1A loss, or KRAS mutation) in this cohort. The risk of reoperation over the 5-9 years was also examined.
MAIN PTEN loss (68.3%; 86 participants) exceeded ARID1A loss (24.6%; 31 participants). Inter-rater reliability was substantial for PTEN (k = 0.69; 95% CI: 0.62-0.77) and ARID1A (k = 0.64; 95% CI: 0.51-0.77). PTEN loss was significantly associated with more severe anatomic subtypes (P < 0.001; participants with SUP only = 46.4%; participants with DE only or OMA only = 72.7%; participants with mixed subtypes = 85.1%), and higher stages (P = 0.024; Stage I = 47.8%; Stage II = 73.7%; Stage III = 80.8%; Stage IV = 81.0%). Results were similar for ARID1A loss, albeit with smaller sample size limiting power. PTEN loss was further associated with non-White ethnicities (P = 0.017) and greater surgical difficulty (more frequent need for ureterolysis) (P = 0.02). There were no differences in pain scores (baseline or follow-up) based on PTEN or ARID1A status. Reoperation was uncommon (13.5% of the cohort), and patterns in reoperation rates based on the presence of somatic alterations did not reach statistical significance.
LIMITATIONS, Sequencing was not performed to determine the type of PTEN and ARID1A somatic mutations resulting in loss of expression.
These results demonstrate a link between PTEN somatic loss and greater endometriosis disease burden. These findings underscore the potential relevance of PTEN loss and other somatic driver mutations in a future molecular classification of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Canadian Institutes of Health Research (CIHR) project grant (MOP-142273 and PJT-156084). P.J.Y. was supported by a Health Professional Investigator award from Michael Smith Health Research BC, Canada, and a Canada Research Chair (Tier 2) in Endometriosis and Pelvic Pain. M.S.A. was supported by a Michael Smith Health Research BC Scholar award, and CIHR project grants (369990, 462997, and 456767). The sponsors did not play any role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to [truncated]
Liu YD et al., 2024·The journal of pain·Free to read
To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.
Lee CE et al., 2024·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain.
A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery.
Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy.
At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients.
Ding A et al., 2024·The journal of sexual medicine·Free full text on PubMed Central
Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis.
To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization.
An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100).
Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no).
Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups.
Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis.
A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function.
Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.
Ibrahim M et al., 2024·J Obstet Gynaecol Can·Free to read
To evaluate the experiences of perimenopausal and postmenopausal women in British Columbia, their perceptions of expected reproductive aging, and potential concerns about endometrial cancer (EC). We interviewed 31 midlife community women of diverse backgrounds and hosted a workshop for more in-depth discussion. We summarized relayed experiences and beliefs through a thematic and descriptive analysis of participant stories and workshop feedback. Participants demonstrated a somewhat simplistic understanding of midlife changes, facing this phase of life with a "tough-it-out" attitude rather than seeking medical help for arising symptoms. Awareness of EC and EC-specific risk factors, such as obesity, was low. Confusion between cervical and EC was common. Although abnormal bleeding was seen as potentially of concern, many opted to wait before seeking medical help. Workshop participants stressed the need to include awareness about EC in a broader conversation about perimenopause and menopause and suggested strategies for disseminating EC awareness. Community women in British Columbia demonstrated low awareness of EC-associated symptoms and risk factors. There is little information to help distinguish when perimenopausal abnormal uterine bleeding is of concern and when to seek help. This highlights the need to enhance knowledge of EC and its risk factors in perimenopause among the public and among health care providers.
Orr NL et al., 2023·JAMA network open·Free full text on PubMed Central
A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization.
To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes.
DESIGN, SETTING, This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022.
The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score (measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 [never, rarely, sometimes, often, and always, respectively]).
A total of 239 patients (mean [SD] age, 34 [7] years; 189 [79.1%] White [11 (5.8%) identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; P = .02), deep dyspareunia (OR, 1.03; 95% CI, 1.01-1.04; P = .004), dyschezia (OR, 1.03; 95% CI, 1.01-1.04; P < .001), and back pain (OR, 1.02; 95% CI, 1.00-1.03; P = .02) at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up (mean [SD] score, 43.8 [18.2] vs 41.7 [18.9]; P = .05); however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up.
In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery.
Allaire C et al., 2023·CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne·Free full text on PubMed Central
[For a first-person account of endometriosis, see www.cmaj.ca/lookup/doi/10.1503/cmaj.230215][1] KEY POINTS Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside of the uterus, which can lead to estrogen-driven inflammation. The extent of disease can be
MacGregor B et al., 2023·International journal of women's health·Free full text on PubMed Central
Dysmenorrhea is the most common gynecologic condition among the female population and has a significant impact on life course potential. It has a widespread impact on a female's mental and physical well-being, with longstanding impairments on quality of life, personal relationships, and education and career attainment. Furthermore, untreated dysmenorrhea can lead to hyperalgesic priming, which predisposes to chronic pelvic pain. Primary dysmenorrhea is pain in the lower abdomen that occurs before or during menses and in the absence of pelvic pathology. One possible mechanism is endometrial inflammation and increased prostaglandin release, resulting in painful uterine contractions. Dysmenorrhea may also occur secondary to pelvic pathology, such as endometriosis, adenomyosis or due to cyclic exacerbation of non-gynecologic pain conditions. A thorough patient evaluation is essential to differentiate between potential causes and guide management. Treatment must be tailored to individual patient symptoms. Pharmacologic management with non-steroidal anti-inflammatory medications and/or combined hormonal contraceptives is most common. Heat therapy, exercise, vitamins and dietary supplements have limited evidence and can be offered for patients seeking non-pharmacologic adjunctive or alternative options. Greater awareness for both health-care providers and patients allows for early intervention to reduce impact on quality of life and life course potential.
Orr NL et al., 2023·The journal of pathology. Clinical research·Free full text on PubMed Central
The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p = 0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p = 0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR] = 1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR = 0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR = 1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis.
Eckler R et al., 2023·European journal of obstetrics, gynecology, and reproductive biology
To evaluate the odds of developing adverse maternal and perinatal outcomes in primiparous singleton pregnancies conceived with assisted reproductive technology (ART) compared with pregnancies conceived without ART.
A retrospective population-based cohort study using data from the British Columbia Perinatal Data Registry. The population included primiparous women with singleton live or stillbirths delivering at or after 20 weeks' gestation between April 1st 2008-March 31st, 2021. Women who conceived with ART were compared with those who conceived without ART. The main outcome measures were gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admission, stillbirth, and 5-minute Apgar score. Adjusted odds ratios were calculated.
The study population included 191,059 primiparous women: 183,819 conceived without ART, 7,240 conceived using ART. After controlling for age, body mass index, pre-gestational diabetes, and smoking status, singleton pregnancies conceived by ART had significantly higher odds of gestational diabetes (OR 1.18, 95 % confidence interval [CI] 1.10-1.26) and hypertensive disorders of pregnancy (OR 1.39, 95 % CI 1.29-1.51). There were also significantly increased odds of preterm birth (OR 1.35, 95 % CI 1.25-1.46), low birth weight (OR 1.35, 95 % CI 1.23-1.49), and neonatal intensive care unit admission (OR 1.21, 95 % CI 1.11-1.32). There was not a statistically significant difference in the odds of stillbirth (OR 1.06, 95 % CI 0.72-1.57) or 5-minute Apgar score < 7 (OR 1.10, 95 % CI 0.97-1.26).
There is an increased odds of developing several adverse maternal or neonatal outcomes in primiparous singleton pregnancies conceived by ART including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, and increased incidence of neonatal intensive care unit admissions.
Tucker DR et al., 2023·American journal of obstetrics and gynecology
After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life.
This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery.
This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank.
The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis.
Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.
A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.
Sivajohan B et al., 2022·NPJ digital medicine·Free full text on PubMed Central
Endometriosis is a chronic, debilitating, gynecologic condition with a non-specific clinical presentation. Globally, patients can experience diagnostic delays of ~6 to 12 years, which significantly hinders adequate management and places a significant financial burden on patients and the healthcare system. Through artificial intelligence (AI), it is possible to create models that can extract data patterns to act as inputs for developing interventions with predictive and diagnostic accuracies that are superior to conventional methods and current tools used in standards of care. This literature review explored the use of AI methods to address different clinical problems in endometriosis. Approximately 1309 unique records were found across four databases; among those, 36 studies met the inclusion criteria. Studies were eligible if they involved an AI approach or model to explore endometriosis pathology, diagnostics, prediction, or management and if they reported evaluation metrics (sensitivity and specificity) after validating their models. Only articles accessible in English were included in this review. Logistic regression was the most popular machine learning method, followed by decision tree algorithms, random forest, and support vector machines. Approximately 44.4% (n = 16) of the studies analyzed the predictive capabilities of AI approaches in patients with endometriosis, while 47.2% (n = 17) explored diagnostic capabilities, and 8.33% (n = 3) used AI to improve disease understanding. Models were built using different data types, including biomarkers, clinical variables, metabolite spectra, genetic variables, imaging data, mixed methods, and lesion characteristics. Regardless of the AI-based endometriosis application (either diagnostic or predictive), pooled sensitivities ranged from 81.7 to 96.7%, and pooled specificities ranged between 70.7 and 91.6%. Overall, AI models displayed good diagnostic and predictive capacity in detecting endometriosis using simple classification scenarios (i.e., differentiating between cases and controls), showing promising directions for AI in assessing endometriosis in the near future. This timely review highlighted an emerging area of interest in endometriosis and AI. It also provided recommendations for future research in this field to improve the reproducibility of results and comparability between models, and further test the capacity of these models to enhance diagnosis, prediction, and management in endometriosis patients.
Although racial and ethnic disparities in adverse birth outcomes have been well documented, it is unknown whether such disparities diminish in women who use medically assisted reproduction (MAR). We examined differences in the association between maternal race and ethnicity and adverse birth outcomes among women who conceived spontaneously and those who used MAR, including assisted reproduction technology (ART), eg, in-vitro fertilization, and also non-ART MAR, eg, fertility drugs.
We conducted a population-based retrospective cohort study using data on all singleton births (N = 7 545 805) in the United States from 2016 to 2017. The outcomes included neonatal and fetal death, preterm birth, and serious neonatal morbidity, among others. Modified Poisson regression was used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) and to assess the interactions between race and ethnicity and mode of conception.
Overall, 93 469 (1.3%) singletons were conceived by MAR. Neonatal mortality was twofold higher among infants of non-Hispanic Black versus non-Hispanic White women in the spontaneous-conception group (aRR = 1.9, 95% CI: 1.8-1.9), whereas in the ART-conception group, neonatal mortality was more than fourfold higher in infants of non-Hispanic Black women (aRR = 4.1, 95% CI: 2.9-5.9). Racial and ethnic disparities between Hispanic versus non-Hispanic White women were also significantly larger among women who conceived using MAR with regard to preterm birth (<34 weeks) and perinatal mortality.
Compared to women who conceived spontaneously, racial and ethnic disparities in adverse perinatal outcomes were larger in women who used MAR. More research is needed to identify preventive measures for reducing risks among vulnerable women who use medically assisted reproduction.
Alfaraj S et al., 2021·Journal of minimally invasive gynecology
Endometriosis fertility index (EFI) is a robust tool to predict the pregnancy rate in patients with endometriosis who are attempting non-in vitro fertilization conception. However, EFI calculation requires laparoscopy. Newly established imaging techniques such as sliding sign, which is used to diagnose pouch of Douglas obliteration, could provide a promising alternative. The objective of this study was to investigate the practicality of using ultrasound data to predict a low EFI (score ≤6).
Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017.
Tertiary referral center at British Columbia Women's Hospital.
We analyzed data for 2583 participants from the Endometriosis Pelvic Pain Interdisciplinary Cohort. In this cross-sectional study, we included 86 women aged <40 years.
Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery.
Logistic regression was used to obtain receiver operating characteristic area under the curve (AUC) for the prediction models. Significance was p <.05. Patients with a negative sliding sign were older and had severe endometriosis and longer duration of infertility. Patients with a negative sliding sign had significantly lower total EFI scores and lower surgical factors scores than patients with a positive sliding sign. Logistic regression showed that a negative sliding sign and EFI historic factors score can predict an EFI score ≤6 (sensitivity = 87.9%, specificity = 81.1%, AUC = 0.93 [95% confidence interval, 0.88-0.98]). Adding the diagnosis of endometrioma to the previous prediction model resulted in AUC = 0.95 (95% confidence interval, 0.90-0.995), sensitivity = 84.8%, and specificity = 92.5%.
The sliding sign could be a potential alternative to the EFI surgical factors, and it could be used in combination with EFI historic factors and the diagnosis of endometrioma to predict an EFI score ≤6 for patients who are not scheduled for immediate surgery.
Geoffrion R et al., 2021·Obstetrics and gynecology
To evaluate the prevalence and characteristics of recreational cannabis use in women with pelvic pain, and to examine the influence of cannabis legalization on these parameters.
We conducted a retrospective analysis of a prospective registry of women with self-reported moderate-to-severe pelvic pain referred to a tertiary care clinic in Vancouver, Canada, 2013-2019. We excluded patients aged 18 years or younger and those with unknown data on cannabis use. Demographic, clinical, and validated questionnaire data were extracted for two main analyses: 1) comparison of current cannabis users with current nonusers, and 2) comparison of current cannabis users who entered the registry before cannabis legalization (October 17, 2018) with those who entered the registry on or after legalization.
Overall, 14.9% (509/3,426) of patients were classified as current cannabis users. Compared with nonusers, cannabis users were younger (P<.001), had lower levels of education (P<.001) and lower household income (P<.001), were taking opioids (P<.001), antiinflammatories (P=.003), neuromodulators (P=.020), and herbal medications (P<.001) more frequently. They had worse questionnaire scores for depression, anxiety, pain catastrophizing, quality of life, and pelvic pain severity (P<.001 for all). After cannabis legalization, prevalence of current cannabis use increased from 13.3% (366/2,760) to 21.5% (143/666) (P<.001). Compared with prelegalization, postlegalization users were associated with higher levels of education (P<.001), worse anxiety (P=.036), and worse pain catastrophizing (P<.001) scores. They were taking fewer antiinflammatories (P<.001), neuroleptics (P=.027) and daily opioids or narcotics (P=.026), but more herbal medications (P=.010).
Recreational cannabis use increased among patients with pelvic pain after legalization in Canada. Cannabis users had worse pain-related morbidities. Postlegalization, cannabis users were less likely to require daily opioids compared with cannabis users before legalization. The role, perceived benefits, and possible risks of cannabis for pelvic pain require further investigation.
ClinicalTrials.gov, NCT02911090.
To evaluate the efficacy of surgical management for isthmoceles in patients presenting with secondary infertility. Data Sources: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2020. The search was limited to studies published in English. METHODS OF Study Selection: After the removal of duplicates, 3380 articles were screened for inclusion independently by 2 authors. These 2 authors assessed for studies which focused on women of reproductive age with a diagnosed isthmocele and secondary infertility who underwent any surgical intervention for defect repair with at least 1 of the goals being fertility restoration. TABULATION, INTEGRATION, A total of 13 studies, comprising of 1 randomized controlled trial, 6 prospective case series, and 6 retrospective case series describing 234 patients who underwent surgical management for an isthmocele and secondary infertility were included. The methodologic quality of the included studies was assessed independently by both reviewers. Next, the data extraction was performed independently and then compared to ensure no discrepancies. A total of 188 patients were treated by hysteroscopy, 36 by laparoscopy, 7 by laparotomy, and 3 through a vaginal approach. In total, 153 of the 234 patients (65.4%) achieved pregnancy across all studies within their respective study periods. Pregnancy rates in the randomized controlled trial were 21 of 28 (75%) for those treated by hysteroscopy compared with 9 of 28 (32%) for those untreated. Among the studies reporting pregnancy outcomes, 101 of 116 (87.1%) pregnancies resulted in a live birth. The incidence of adverse events was 2%, including the risk of reoperation. The results of this systematic review suggest that the surgical treatment of an isthmocele, particularly through hysteroscopy, in patients with residual myometrial thickness of at least 2.5 mm, may be effective in treating isthmocele-associated secondary infertility with a relatively low complication rate. Further high-quality studies are needed because of the small sample sizes and observational nature of most available data.
Arion K et al., 2020·Journal of women's health (2002)
Endometriosis is a complex condition that can negatively affect a woman's quality of life, including her sleep. This study aims to assess the multifactorial variables associated with poorer quality of sleep in women with endometriosis. Data from the Endometriosis Pelvic Pain Interdisciplinary Cohort (EPPIC) data registry were analyzed for women who underwent surgery at the BC Women's Center for Pelvic Pain and Endometriosis with histopathological confirmation of endometriosis (June 2015 to June 2017). The primary outcome was quality of sleep preoperatively, from the Chronic Pain Sleep Inventory (0-100 VAS). Bivariate analysis and multivariable linear regression were done to determine any significant associations between preoperative patient variables and overall quality of sleep, based on p-value of 0.05. Two hundred and seventy-five women met the study criteria. Poorer overall quality of sleep was independently associated with poorer functional quality of life (EHP-30) (b = -0.18, p = 0.0026), more depressive symptoms (PHQ-9) (b = -1.62, p < 0.001), and painful bladder syndrome (PBS) (b = -5.82, p = 0.035). This indicates that a 1 point increase in the EHP-30 (worsening quality of life), a 1 point increase in the PHQ-9 (worsening depression), and the presence of PBS increased the primary outcome (i.e., toward poorer quality of sleep) by 0.18, 1.62, and 5.82 points. Poorer quality of sleep in women with endometriosis is associated with poorer quality of life, more depressive symptoms, and bladder pain. Research into interventions that improve sleep is warranted as part of the management of some women with endometriosis.
Yong PJ et al., 2020·Human reproduction open·Free full text on PubMed Central
What are the use patterns and factors associated with combined hormonal contraception (CHC) ineffectiveness or discontinuation due to side-effects in patients with endometriosis and pelvic pain?
Worse chronic pelvic pain (CPP) severity and pelvic floor myalgia were associated with continuous CHC ineffectiveness, while poorer quality-of-life was associated with continuous CHC discontinuation due to side-effects.
CHC is a first line of therapy for endometriosis-associated pelvic pain in women. However, some patients state that CHC is ineffective for their pain, while others have to discontinue CHC due to side-effects.
Analysis of a prospective patient database from a tertiary care referral center for patients with endometriosis and pelvic pain between December 2013 and April 2015 was carried out.
PARTICIPANTS/MATERIALS A total of 373 patients of reproductive age with endometriosis from the database were included in the study. Data included patient self-reported questionnaires, physical examination findings and validated instruments. There were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). The primary outcome was CPP severity for the past 3 months (score of 0-10), and secondary outcomes were other pelvic pain scores, quality-of-life on the Endometriosis Health Profile 30 (EHP-30) and underlying conditions including irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia and depression, anxiety and pain catastrophizing.
MAIN Among the 373 cases in the dataset, prior cyclical CHC use was reported by 228 (61.1%) women, of which 103 (27.6%) stated it was ineffective for their pain and 94 (25.2%) stated they discontinued CHC due to side-effects. Previous continuous CHC use was reported by 175 (46.9%) women, of which 67 (18.0%) stated it was ineffective and 59 (15.8%) stated they discontinued due to side-effects. Worse CPP severity in the last 3 months was associated with a history of continuous CHC ineffectiveness (P < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects (P = 0.005). Among the underlying conditions, pelvic floor tenderness (as a marker of pelvic floor myalgia) was associated with CHC ineffectiveness.
LIMITATIONS This study involved patient recall and no longitudinal follow-up. Also, we do not have data on the type of side-effect that led to discontinuation. Medication ineffectiveness was reported subjectively by the patient rather than using standardized criteria. Finally, the diagnosis of endometriosis was based on previous surgery or a current nodule or endometrioma on examination/ultrasound; without prospective surgical data on all the patients, it was not possible to do a sub-analysis by current surgical features (e.g. stage).
In women with endometriosis, CHC ineffectiveness was associated with worse CPP and pelvic floor myalgia, which suggests myofascial or nervous system contributors to CPP that does not respond to hormonal suppression. A tender pelvic floor, as a sign of pelvic floor myalgia, may be a clinical marker of patients with endometriosis who are less likely to have an optimal response to hormonal suppression. For women who discontinue CHC due to side-effects, research is needed to help alleviate these side-effects as these patients report worse quality-of-life.
This work was supported by a Canadian Institutes of Health Research (CIHR) Transitional Open Operating Grant (MOP-142273) as well as BC Women's Hospital and the Women's Health Research Institute. PY is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB/CA has financial affiliations with Abbvie and Allergan; the other authors have no conflicts of interest.
Wahl KJ et al., 2020·Sexual medicine·Free full text on PubMed Central
Deep dyspareunia is a cardinal symptom of endometriosis, and as many as 40% of people with this condition experience comorbid superficial dyspareunia.
To evaluate the relationship between sexual pain and infertility concerns among women with endometriosis.
This is a cross-sectional study conducted at a university-based tertiary center for endometriosis. 300 reproductive-aged participants in the prospective Endometriosis Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov Identifier: NCT02911090) with histologically confirmed endometriosis were included (2013-2017).
The total score on the infertility concerns module of the Endometriosis Health Profile-30 categorized into 5 groups (0, 1-4, 5-8, 9-12, 13-16).
The odds of infertility concerns did not increase with severity of deep dyspareunia (odds ratio = 1.02, 95% CI: 0.95-1.09, P = .58). However, the odds of infertility concerns increased with severity of superficial dyspareunia (odds ratio = 1.09, 95% CI: 1.02-1.16, P = .011); this relationship persisted after adjusting for endometriosis-specific factors, infertility risk factors, reproductive history, and demographic characteristics (adjusted odds ratio [AOR] = 1.14, 95% CI: 1.06-1.24, P < .001). Other factors in the model independently associated with increased infertility concerns were previous difficulty conceiving (AOR = 2.09, 95% CI 1.04-4.19, P = .038), currently trying to conceive (AOR = 5.23, 95% CI 2.77-9.98, P < .001), nulliparity (AOR = 3.21, 95% CI 1.63-6.41, P < .001), and younger age (AOR = 0.94, 95% CI: 0.89-0.98, P = .005).
Severity of superficial dyspareunia, but not deep dyspareunia, was associated with increased odds of infertility concerns among women with endometriosis. Strengths of the study included the use of a validated measure of infertility concerns and disaggregation of sexual pain into deep and superficial dyspareunia. Limitations included the setting of a tertiary center for pelvic pain, which affects generalizability to fertility clinic and primary care settings. Women experiencing introital dyspareunia, who can have difficulties with achieving penetrative intercourse, may be concerned about their future fertility and should be counselled appropriately. Wahl KJ, Orr NL, Lisonek M, et al. Deep Dyspareunia, Superficial Dyspareunia, and Infertility Concerns Among Women With Endometriosis: A Cross-Sectional Study. Sex Med 2020;8:274-281.
Fertility and Outcomes · Conception After Excision
Yong PJ et al., 2020·Journal of minimally invasive gynecology
To systematically review and perform a meta-analysis of the risk of ectopic pregnancy in endometriosis.
MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO), and Cochrane Library to April 1, 2019. Inclusion criteria were cohort or case-control studies from 1990 onward. Exclusion criteria were cohort studies without controls, case reports or series, or no English full-text.
A total of 1361 titles/abstracts were screened after removal of duplicates, 39 full-texts were requested, and, after 24 studies were excluded, there were 15 studies in the meta-analysis.
TABULATION, INTEGRATION, Data were extracted using standardized spreadsheets with 2 independent reviewers, and conflicts were resolved by a third reviewer. We performed random effects calculation of weighted estimated average odds ratio (OR). Heterogeneity and publication bias were assessed with the I2 metric and funnel plots/Egger's test, respectively. The Ottawa-Newcastle Quality Assessment Scale was used with a cutoff of ≥7 for higher quality. There were 10 case-control studies (17 972 ectopic pregnancy cases and 485 266 nonectopic pregnancy controls) and 5 cohort studies (30 609 women with endometriosis and 107 321 women without endometriosis). For case-control studies, endometriosis was associated with increased risk of ectopic pregnancy with an OR of 2.66 (95% confidence interval [CI] = 1.14-6.21, p = .02). For cohort studies, the OR was 0.95 (95% CI = 0.29-3.11, p = .94), but after post hoc analysis of the studies with a Ottawa-Newcastle score ≥7, the OR was 2.16 (95% CI = 1.67-2.79, p <.001). For both case-control and cohort studies, there was high heterogeneity among studies (I2 = 93.9% and I2 = 96.6%, Q test p <.001) but no obvious evidence of systematic bias in the funnel plot, and Egger's test results were not significant (p = .35, p = .70), suggesting no strong publication bias. There were insufficient data to make any conclusions with respect to anatomic characteristics of endometriosis (e.g., stage) or mode of conception (e.g., assisted reproductive technology vs spontaneous).
Possible evidence of an association between endometriosis and ectopic pregnancy was observed (OR = 2.16-2.66). However, these results should be considered with caution, owing to high heterogeneity among studies. Continued research is needed to delineate the pregnancy implications of endometriosis.
Allaire C et al., 2020·Seminars in reproductive medicine
Endometriosis-associated chronic pelvic pain can at times be a complex problem that is resistant to standard medical and surgical therapies. Multiple comorbidities and central sensitization may be at play and must be recognized with the help of a thorough history and physical examination. If a complex pain problem is identified, most endometriosis expert reviews and guidelines recommend multidisciplinary care. However, there are no specific recommendations about what should be the components of this approach and how that type of team care should be delivered. There is evidence showing the effectiveness of specific interventions such as pain education, physical therapy, psychological therapies, and pharmacotherapies for the treatment of chronic pain. Interdisciplinary team models have been well studied and validated in other chronic pain conditions such as low back pain. The published evidence in support of interdisciplinary teams for endometriosis-associated chronic pain is more limited but appears promising. Based on the available evidence, a model for an interdisciplinary team approach for endometriosis care is outlined.
Elgendi M et al., 2020·Frontiers in digital health·Free full text on PubMed Central
Chronic pelvic pain affects one in seven women worldwide, and there is an urgent need to reduce its associated significant costs and to improve women's health. There are many correlated factors associated with chronic pelvic pain (CPP), and analyzing them simultaneously can be complex and involves many challenges. A newly developed interaction ensemble, referred to as INTENSE, was implemented to investigate this research gap. When applied, INTENSE aggregates three machine learning (ML) methods, which are unsupervised, as follows: interaction principal component analysis (IPCA), hierarchical cluster analysis (HCA), and centroid-based clustering (CBC). For our proposed research, we used INTENSE to uncover novel knowledge, which revealed new interactions in a sample of 656 patients among 25 factors: age, parity, ethnicity, body mass index, endometriosis, irritable bowel syndrome, painful bladder syndrome, pelvic floor tenderness, abdominal wall pain, depression score, anxiety score, Pain Catastrophizing Scale, family history of chronic pain, new or re-referral, age when first experienced pain, pain duration, surgery helpful for pain, infertility, smoking, alcohol use, trauma, dysmenorrhea, deep dyspareunia, CPP, and the Endometriosis Health Profile for functional quality of life. INTENSE indicates that CPP and the Endometriosis Health Profile are correlated with depression score, anxiety score, and the Pain Catastrophizing Scale. Other insights derived from these ML methods include the finding that higher body mass index was clustered with smoking and a history of life trauma. As well, sexual pain (deep dyspareunia) was found to be associated with musculoskeletal pain contributors (abdominal wall pain and pelvic floor tenderness). Therefore, INTENSE provided expert-like reasoning without training any model or prior knowledge of CPP. ML has the potential to identify novel relationships in the etiology of CPP, and thus can drive innovative future research.
Orr NL et al., 2020·The journal of sexual medicine
Deep dyspareunia, a common symptom in endometriosis, has previously been associated with bladder and/or pelvic floor tenderness (BPFT), which suggests a role for central nervous system sensitization. The Central Sensitization Inventory (CSI, 0-100) is a validated self-reported scale for patients with central sensitization.
The objective of this study was to phenotype deep dyspareunia using BPFT and the CSI.
The methods included cross-sectional analysis from a prospective registry from January 2018 to June 2018 at a tertiary center for endometriosis (ClinicalTrials.gov #NCT02911090). Included were women aged 18-50 years with endometriosis (previously surgically diagnosed, current visualized endometrioma on ultrasound, or current palpable or visualized nodule on ultrasound), who were newly or re-referred to the center. Severity of deep dyspareunia was self-reported using an 11-point numeric rating scale (0 = no pain; 10 = worst pain imaginable), categorized as no or low deep dyspareunia (0-4) and high deep dyspareunia (5-10). We identified the subgroup with high deep dyspareunia and presence of BPFT, where we hypothesized a central component of the sexual pain. This subgroup was compared with 2 other subgroups: no or low deep dyspareunia and high deep dyspareunia but no BPFT. The CSI was compared between the groups using analysis of variance, followed by post hoc testing (P < .05).
The main outcome measure was the CSI score ranging from 0 to 100.
Data from 163 women with endometriosis were analyzed. The mean age of this cohort was 36.4 ± 6.8 years, and the mean CSI score was 41.0 ± 18.6. 37 percent (61/163) had high deep dyspareunia and BPFT; 29% (47/163) had high deep dyspareunia and no BPFT; and 34% (55/163) had no or low deep dyspareunia. The CSI significantly differed between the 3 groups (analysis of variance: F = 22.4, P < .001). In post hoc testing, the CSI was higher in women with high deep dyspareunia and BPFT (51.3 ± 16.9), compared with women with no or low deep dyspareunia (30.9 ± 15.4, P < .001) and compared with women with high deep dyspareunia but no BPFT (39.4 ± 17.2, P = .001).
The CSI could be used to classify and phenotype patients with endometriosis-associated sexual pain.
Strengths include a prospective registry with integrated pain scores, validated questionnaires, and physical examination findings. Limitations include the lack of quantitative sensory testing for central sensitization.
In women with endometriosis, the subgroup with high deep dyspareunia and bladder and/or pelvic floor tenderness had a significantly higher score on the CSI than other subgroups, suggesting that this group may have a central component to their sexual pain. Orr NL, Wahl KJ,Noga H, et al. Phenotyping Sexual Pain in Endometriosis Using the Central Sensitization Inventory. J Sex Med 2020;17:761-770.
Rikhraj K et al., 2020·Journal of women's health (2002)
What is the impact of noncavity-distorting intramural fibroids on live birth rates in in vitro fertilization (IVF) cycles? We searched Embase, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to May 2018. We included studies with women undergoing IVF treatment who had at least one noncavity-distorting intramural fibroid. The studies had to report one or more of the following outcomes: live birth rate as our primary outcome, and implantation rate, clinical pregnancy rate, or miscarriage rate as our secondary outcomes. We excluded studies where women also had submucosal fibroids or had undergone myomectomy. Two authors independently selected studies and extracted data. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We included 15 studies with 5029 patients. Patients with noncavity-distorting intramural fibroids had 44% lower odds of live birth (estimated average odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.46-0.69) and 32% lower odds of clinical pregnancy (estimated average OR = 0.68, 95% CI = 0.56-0.83). Subgroup analysis of women with purely intramural fibroids showed significantly lower odds of live birth rates and clinic pregnancy rates. Analysis of prospective and retrospective studies shows that noncavity-distorting intramural fibroids have a significant adverse effect on live birth rates in women undergoing IVF. Further, well-designed prospective studies are needed to investigate whether removal of these fibroids improves IVF outcomes in this population.
Tan J et al., 2019·Current opinion in obstetrics & gynecology
The purpose of this review is to summarize and highlight recent critical advances in the diagnosis, classification, and management of adenomyosis.
Recent studies have clarified the specific mechanism through which adenomyotic lesions invade the underlying myometrium by epithelial-mesenchymal transition. Correlation studies using diagnostic MRI also strongly support the hypothesis of a different pathogenesis between the inner and outer myometrium forms of adenomyosis. Given advances in diagnostic imaging, several international organizations have also highlighted the importance of classification systems for adenomyosis. Finally, selective progesterone receptor modulators and gonadotropin-releasing hormone antagonists have demonstrated significant promise for treating pelvic pain and bleeding associated with adenomyosis, whereas novel fertility-preserving surgical techniques have been introduced to excise diffuse adenomyotic pathology while maintaining adequate uterine integrity.
Recent attempts at a uniform and reproducible classification system likely represent the first step for the development of a staging system for adenomyosis that can be correlated with the severity of clinical symptoms and promote an individualized therapeutic approach. Simultaneously, further insights into the etiology and pathogenesis as outlined in this review may also help in the development of targeted medical therapies.
Williams C et al., 2019·Journal of minimally invasive gynecology
To investigate ethnic differences for moderate-to-severe endometriosis.
Analysis of a prospective registry (Canadian Task Force classification II-2).
Tertiary referral center.
A total of 1594 women with pelvic pain and/or endometriosis.
None On logistic regression, adjusting for potential confounders, East/South East Asians were 8.3 times more likely than whites to have a previous diagnosis of stage III/IV endometriosis before referral (adjusted odds ratio [aOR], 8.33; 95% confidence interval [CI], 3.74-18.57), 2.7 times more likely to have a palpable nodule (aOR, 2.66; 95% CI, 1.57-4.52), 4.1 times more likely to have an endometrioma on ultrasound (aOR, 4.10; 95% CI, 2.68-6.26), and 10.9 times more likely to have stage III/IV endometriosis at the time of surgery at our center (aOR, 10.87; 95% CI, 4.34-27.21).
Moderate-to-severe endometriosis was more common in women with East or South East Asian ethnicity in our tertiary referral center. This could be explained by East/South East Asians with minimal to mild disease being less likely to seek care or genetic/environmental differences that increase the risk of more severe disease among East/South East Asians. (ClinicalTrials.gov, NCT02911090.).
Wu CQ et al., 2019·Journal of minimally invasive gynecology
Controversy exists regarding surgical management of endometriomas in infertile women before in vitro fertilization (IVF) because growing evidence indicates that surgery may impair the ovarian response. The objective of the present systematic review and meta-analysis was to compare surgical and expectant management of endometriomas regarding IVF outcomes. Prospective and retrospective controlled studies were found via the Cochrane Library, Embase, and MEDLINE databases. Thirteen studies (1 randomized controlled trial and 12 observational studies, N = 2878) were pooled, and similar live birth rates were observed in the surgically and expectantly managed groups (odds ratio = 0.83; 95% confidence interval [CI], 0.56-1.22; p = .98). The clinical pregnancy rates (odds ratio = 0.83; 95% CI, 0.66-1.05; p = .86), the number of mature oocytes retrieved, and the miscarriage rates were not statistically different between study groups. However, the total number of oocytes retrieved was lower in the surgery group (mean difference = -1.51; 95% CI, -2.60 to -0.43; p = .02). Findings suggest that surgical management of endometriomas before IVF therapy yields similar live birth rates as expectant management. However, future properly designed randomized controlled trials are warranted.
Arion K et al., 2019·Journal of minimally invasive gynecology
To evaluate the point-of-care preoperative transvaginal ultrasound (TVUS) sliding sign in comparison with palpation of a nodule on digital pelvic examination for the prediction of pouch of Douglas (POD) obliteration.
Analysis of data from a prospective data registry (Canadian Task Force classification II-2).
A tertiary referral center.
Women with suspected endometriosis who had preoperative pelvic examination and point-of-care TVUS followed by laparoscopic surgery between August 2015 and December 2016.
Women were preoperatively assessed for the prediction of POD obliteration with pelvic examination for a nodule and point-of-care TVUS uterine/cervix sliding sign.
The study included 269 women, 15.2% (41/269) of whom had POD obliteration at the time of surgery. A preoperative negative sliding sign had a sensitivity of 73.2% (95% confidence interval, 57.1%-85.8%) and a specificity of 93.9% (95% CI, 89.9%-96.6%) in the prediction of POD obliteration compared with preoperative palpation of a nodule on pelvic examination, which had a sensitivity of 24.4% (95% CI, 12.4%-40.3%) and a specificity of 93.4% (95% CI, 89.4%-96.3%). The difference in sensitivity was statistically significant (McNemar test, p <.001). A negative sliding sign was also associated with longer operating times and more difficult surgery including the need for ureterolysis.
The point-of-care TVUS sliding sign showed significantly improved sensitivity compared with palpation of a nodule on pelvic examination for the prediction of POD obliteration. Therefore, the point-of-care TVUS sliding sign improves the preoperative assessment of POD disease and thus may lead to more optimal surgical planning in women with suspected endometriosis.
Bao C et al., 2019·Sexual medicine·Free full text on PubMed Central
Pelvic pain and vulvar pain are common conditions in women. In this study, we sought to characterize the clinical picture of patients with concurrent pelvic pain and provoked vestibulodynia (PVD).
To analyze the association between sexual/clinical characteristics and a diagnosis of PVD among women with pelvic pain.
Cross-sectional analysis of a prospective registry at a tertiary referral center for pelvic pain and endometriosis, involving consecutive non-menopausal sexually active patients 18-49 years-old seen by a single gynecologist from January 2016-December 2017. The sample was divided into 2 groups: pelvic pain with PVD; and pelvic pain alone (without PVD).
Superficial dyspareunia and deep dyspareunia on a 11-point numeric rating scale, and the sexual quality-of-life subscale of the Endometriosis Health Profile-30 (0-100%).
There were 129 patients that met study criteria: one third with pelvic pain and PVD (n = 42) and two-thirds with pelvic pain alone (without PVD) (n = 87). Women with pelvic pain and PVD had significantly more severe superficial dyspareunia ≥7/10 (OR = 12.00 (4.48-32.16), P < .001), more severe deep dyspareunia ≥7/10 (OR = 4.08 (1.83-9.10), P = .001), and poorer sexual quality of life (Endometriosis Health Profile-30 ≥50%) (OR = 4.39 (1.67-11.57), P = .002), compared with the group with pelvic pain alone. Women with pelvic pain and PVD also had more anxiety, depression, and catastrophizing, more frequent tenderness of the bladder and pelvic floor, and more common diagnosis of painful bladder syndrome. On the other hand, there were no significant differences between the 2 groups in terms of dysmenorrhea, chronic pelvic pain, abdominal wall allodynia, positive Carnett test for abdominal wall pain, functional quality of life, endometriosis, and irritable bowel syndrome.
In the pelvic pain population, PVD may be associated with more negative impact on dyspareunia, sexual quality of life, and bladder/pelvic floor function, but it may not significantly impact abdominopelvic pain or day-to-day function in general. Bao C, Noga H, Allaire C, et al. Provoked Vestibulodynia in Women with Pelvic Pain. Sex Med 2019;7:227-234.
Lisonkova S et al., 2019·BMJ open·Free full text on PubMed Central
To examine temporal trend in maternal mortality/severe morbidity associated with hospitalisation due to ectopic pregnancy.
A population-based observational study.
All women hospitalised for ectopic pregnancy in Washington State, USA, 1987-2014 (n=20 418). The main composite outcome of severe morbidity/mortality included death, sepsis, need for transfusion, hysterectomy and systemic or organ failure, identified by diagnostic and procedure codes from hospitalisation files. Severe morbidity/mortality due to ectopic pregnancy were expressed as incidence ratios among women of reproductive age (15-64 years) and among women hospitalised for ectopic pregnancy. Comparisons were made between 1987-1991 (reference) and 2010-2014 using ratios of incidence ratios (RR) and ratio differences (RD). The Cochran-Armitage test for trend assessed statistical significance; logistic regression was used to obtain adjusted OR (AOR) and 95% CI, adjusted for demographic factors and comorbidity.
Hospitalisation for ectopic pregnancy declined from 0.89 to 0.16 per 1000 reproductive age women between 1987-1991 and 2010-2014 (p<0.001). Among reproductive age women, ectopic pregnancy mortality remained stable (0.03 per 100 000); and mortality/severe morbidity increased among women aged 25-34 years (p=0.022). Among women hospitalised for ectopic pregnancy, mortality increased from 0.29 to 1.65 per 1000 between 1987-1991 and 2010-2015 (p=0.06); severe morbidity/mortality increased from 3.85% to 19.63% (RR=5.10, 95% CI 4.36 to 5.98; RD=15.78 per 100 women, 95% CI 13.90 to 17.66; AOR for 1-year change was 1.08, 95% CI 1.07 to 1.08).
Hospitalisation for ectopic pregnancy declined in Washington State, USA, between 1987 and 2014; however, mortality/severe morbidity associated with ectopic pregnancy increased in female population aged 25-34 years.
Allaire C et al., 2018·American journal of obstetrics and gynecology
Chronic pelvic pain affects ∼15% of women, and presents a challenging problem for gynecologists due to its complex etiology involving multiple comorbidities. Thus, an interdisciplinary approach has been proposed for chronic pelvic pain, where these multifactorial comorbidities can be addressed by different interventions at a single integrated center. Moreover, while cross-sectional studies can provide some insight into the association between these comorbidities and chronic pelvic pain severity, prospective longitudinal cohorts can identify comorbidities associated with changes in chronic pelvic pain severity over time.
We sought to describe trends and factors associated with chronic pelvic pain severity over a 1-year prospective cohort at an interdisciplinary center, with a focus on the role of comorbidities and controlling for baseline pain, demographic factors, and treatment effects.
This was a prospective 1-year cohort study at an interdisciplinary tertiary referral center for pelvic pain and endometriosis, which provides minimally invasive surgery, medical management, pain education, physiotherapy, and psychological therapies. Exclusion criteria included menopause or age >50 years. Sample size was 296 (57% response rate at 1 year; 296/525). Primary outcome was chronic pelvic pain severity at 1 year on an 11-point numeric rating scale (0-10), which was categorized for ordinal regression (none-mild 0-3, moderate 4-6, severe 7-10). Secondary outcomes included functional quality of life and health utilization. Baseline comorbidities were endometriosis, irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia, and validated questionnaires for depression, anxiety, and catastrophizing. Multivariable ordinal regression was used to identify baseline comorbidities associated with the primary outcome at 1 year.
Chronic pelvic pain severity decreased by a median 2 points from baseline to 1 year (6/10-4/10, P < .001). There was also an improvement in functional quality of life (42-29% on the pain subscale of the Endometriosis Health Profile-30, P < .001), and a reduction in subjects requiring a physician visit (73-36%, P < .001) or emergency visit (24-11%, P < .001) in the last 3 months. On multivariable ordinal regression for the primary outcome, chronic pelvic pain severity at 1 year was independently associated with a higher score on the Pain Catastrophizing Scale at baseline (odds ratio, 1.10; 95% confidence interval, 1.00-1.21, P = .04), controlling for baseline pain, treatment effects (surgery), age, and referral status.
Improvements in chronic pelvic pain severity, quality of life, and health care utilization were observed in a 1-year cohort in an interdisciplinary setting. Higher pain catastrophizing at baseline was associated with greater chronic pelvic pain severity at 1 year. Consideration should be given to stratifying pelvic pain patients by catastrophizing level (rumination, magnification, helplessness) in research studies and in clinical practice.
Shum LK et al., 2018·Sexual medicine·Free full text on PubMed Central
Deep dyspareunia occurs in half of women with endometriosis, a condition present in 10% of reproductive-age women and associated with negative effects on sexual quality of life (SQoL). However, women with endometriosis can have other clinical factors (eg, superficial dyspareunia, other pelvic pains, and psychological or pain conditions) possibly affecting SQoL. To determine whether deep dyspareunia is associated with SQoL in women with endometriosis, independent of potential confounders. This study involved a prospective patient registry of women at a tertiary-level referral center for endometriosis and pelvic pain. Inclusion criteria were (i) referrals to the center recruited into the registry from January 2014 through December 2016 and (ii) subsequent surgery at the center with histologic confirmation of endometriosis. Exclusion criteria included menopausal status, age at least 50 years, never sexually active, or did not answer dyspareunia or SQoL questions. Bi-variable tests and multiple linear regression analysis were performed. SQoL measured by the 5-item sexual intercourse subscale of the Endometriosis Health Profile-30 (EHP-30) modular questionnaire (0-100%, with higher scores indicating worse SQoL). Consent rate for the prospective registry was 87%; 277 women met the study criteria (mean age = 34.2 ± 7.1 years). Most women had stage I to II endometriosis at time of surgery (64%), with the remaining having stage III to IV endometriosis. Through regression analysis, worse SQoL (higher EHP-30 sexual intercourse subscale score) was independently associated with: more severe deep dyspareunia (P < .0001), more severe superficial dyspareunia (P < .0001), increased depression (P < .001), higher pain catastrophizing (P = .04), bladder pain syndrome (P = .02), heterosexual orientation (P < .001), and new referral status (P = .02). In women with endometriosis at a tertiary referral center, more severe deep dyspareunia was associated with worse SQoL, independent of superficial dyspareunia, psychological comorbidities, and other potential confounders. Shum LK, Bedaiwy MA, Allaire C, et al. Deep Dyspareunia and Sexual Quality of Life in Women With Endometriosis. Sex Med 2018;6:224-233.
Orr NL et al., 2018·The journal of sexual medicine
The etiology of endometriosis-associated deep dyspareunia may include direct endometriosis-specific factors (eg, stage or invasiveness of disease) and/or indirect contributors such as bladder/pelvic floor dysfunction (eg, related to myofascial mechanisms or nervous system sensitization).
This study aimed to determine whether bladder/pelvic floor tenderness and painful bladder syndrome were associated with severity of deep dyspareunia in women with endometriosis, regardless of Stage (I/II vs III/IV) or other endometriosis-specific factors.
Observational study from a prospective patient registry (January 2014 to December 2016) at a tertiary centre for endometriosis. Included were women aged 18 to 49 years who had surgical removal and histopathologic confirmation of endometriosis at the centre. Cases with Stage I/II vs Stage III/IV endometriosis were analyzed separately. Bivariate associations with the primary outcome (severity of deep dyspareunia) were tested for bladder/pelvic floor tenderness, painful bladder syndrome, as well as endometriosis-specific factors identified at the time of laparoscopic surgery (eg, deep infiltrating endometriosis) and demographic factors (eg, age). Multivariable ordinal logistic regression was carried out to adjust for factors associated with the primary outcome.
Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale, categorized as none/mild (0-3), moderate (4-6), and severe (7-10), from a preoperative self-reported questionnaire.
Overall, 411 women had surgically confirmed endometriosis: 263 had Stage I/II and 148 had Stage III/IV endometriosis. Among women with Stage I/II endometriosis, severity of deep dyspareunia was associated with both bladder/pelvic floor tenderness and painful bladder syndrome (AOR = 1.94, 95% CI: 1.11-3.38, P = .019 and AOR = 1.99, 95% CI: 1.15-3.44, P = .013, respectively), independent of endometriosis-specific factors or other factors associated with deep dyspareunia severity. Similar associations were found in women with Stage III/IV endometriosis (bladder/pelvic floor tenderness AOR =2.51, 95% CI: 1.25-5.02, P = .01, painful bladder syndrome: AOR = 1.90, 95% CI: 1.01-3.57, P = .048).
Myofascial or nervous system mechanisms may be important for deep dyspareunia in women with endometriosis, even in those with moderate-to-severe disease (Stage III/IV).
Strengths include the prospective registry, and histological confirmation of endometriosis and staging by experienced endometriosis surgeons. Limitations include assessment of only one pelvic floor muscle (levator ani).
In women with Stage I/II or Stage III/IV endometriosis, severity of deep dyspareunia was strongly associated with bladder/pelvic floor tenderness and painful bladder syndrome, independent of endometriosis-specific factors, which suggests the role of myofascial or sensitization pain mechanisms in some women with deep dyspareunia. Orr NL, Noga H, Williams C, et al. Deep Dyspareunia in Endometriosis: Role of the Bladder and Pelvic Floor. J Sex Med 2018;15:1158-1166.
Yong PJ et al., 2018·The journal of sexual medicine
Deep dyspareunia is a common symptom in women, including in half of women with endometriosis, but little is known about its response to treatment and predictors of persistent deep dyspareunia over time.
To follow up deep dyspareunia severity over a 1-year prospective cohort at an interdisciplinary center, and to identify baseline predictors of more persistent deep dyspareunia at 1 year.
Prospective 1-year cohort study at a tertiary referral center for pelvic pain and endometriosis, where a range of interdisciplinary treatments are provided at a single center (surgical, hormonal, physical, and psychological therapies). Exclusion criteria were menopause, age >50 years, and never previously sexually active. Primary outcome (deep dyspareunia severity) and secondary outcome (sexual quality of life) were followed up over 1 year. Ordinal logistic regression was performed, controlling for baseline severity of deep dyspareunia, to identify baseline predictors of deep dyspareunia severity at 1 year.
Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale (0-10), categorized into absent-mild (0-3), moderate (4-6), and severe (7-10); secondary outcome was sexual quality of life measured by the Endometriosis Health Profile-30.
1-year follow-up was obtained for 278 subjects (56% response rate at 1 year; 278/497). Severity of deep dyspareunia improved over the 1 year (McNemar test, P < .0001): the proportion of patients in the severe category decreased from 55.0% to 30.4%, the moderate category remained similar from 17.7% to 25.0%, and the absent-mild category increased from 27.3% to 44.6%. Sexual quality of life also improved (56% to 43% on the sex subscale of the Endometriosis Health Profile-30) (Welch t test, P < .001). On ordinal regression, severity of deep dyspareunia at 1 year was independently associated with younger age (OR = 0.94, 95% CI = 0.91-0.97, P = .008), and with a higher baseline depression score on the Patient Health Questionnaire-9 (OR = 1.07, 95% CI = 1.03-1.11, P = .01).
Clinicians should consider employing an interdisciplinary approach for deep dyspareunia, and screening for and treating depression symptoms in these women.
Strengths of the study include its prospective nature, and assessment of deep dyspareunia specifically (as opposed to superficial dyspareunia). Limitations include non-randomized design, and the patients lost to follow-up over the 1 year.
Over 1 year in an interdisciplinary setting, improvements were observed in deep dyspareunia and sexual quality of life, but younger women and those with more severe depression at baseline had more persistent deep dyspareunia at 1 year. Yong PJ, Williams C, Bodmer-Roy S, et al. Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting. J Sex Med 2018;15:1765-1775.
Tan J et al., 2018·Journal of minimally invasive gynecology
Among the variety of treatment options to improve reproductive outcomes for infertile women with adenomyosis (AD), uterine-conserving surgery has shown varying success. Hence, we conducted a systematic review around the topic of fertility-sparing surgery across 18 studies and 1396 infertile women with focal and diffuse AD. Patients with focal AD showed mean pregnancy and miscarriage rates of 52.7% (range,14.3%-77.5%) and 21.1% (range, 0%-44.4%), respectively, whereas patients with diffuse AD had mean pregnancy and miscarriage rates of 34.1% (range, 9.4%-100%) and 21.7% (range, 12.5%-33.3%), respectively. Uterine rupture and preterm birth were observed in 6.8% (3/44) and 4.5% (2/44) of pregnant patients with diffuse AD versus 0% (0/35) and 10.9% (12/110) of patients with focal AD, respectively. No significant differences were observed between natural conception versus assisted reproductive technology (ART) with or without gonadotropin-releasing hormone agonist pretreatment. Overall, patients with focal AD appeared to have higher pregnancy rates after conservative surgery compared with diffuse AD, whereas a higher incidence of uterine rupture was reported after surgery for diffuse AD. However, significant heterogeneity precludes any direct comparison, and prospective controlled trials are required to further elucidate the benefits of fertility-preserving surgery over medical or expectant management for AD-related infertility. In view of the debatable benefits of conservative surgery and the possible increase in adverse pregnancy outcomes, particularly in cases of diffuse AD, clinicians should consider surgery on a case-by-case basis because it may be appropriate for women with concurrent AD-associated pelvic pain or menorrhagia, younger infertile women who have failed medical management or older women with infertility despite ART, and those with a history of recurrent pregnancy loss or implantation failure.
Yong PJ et al., 2017·Sexual medicine·Free full text on PubMed Central
Deep dyspareunia negatively affects women's sexual function. There is a known association between deep dyspareunia and endometriosis of the cul-de-sac or uterosacral ligaments in reproductive-age women; however, other factors are less clear in this population.
To identify anatomic sites and associated clinical factors for deep dyspareunia in reproductive-age women at a referral center.
This study involved the analysis of cross-sectional baseline data from a prospective database of 548 women (87% consent rate) recruited from December 2013 through April 2015 at a tertiary referral center for endometriosis and/or pelvic pain. Exclusion criteria included menopausal status, age at least 50 years, previous hysterectomy or oophorectomy, and not sexually active. We performed a standardized endovaginal ultrasound-assisted pelvic examination to palpate anatomic structures for tenderness and reproduce deep dyspareunia. Multivariable regression was used to determine which tender anatomic structures were independently associated with deep dyspareunia severity and to identify clinical factors independently associated with each tender anatomic site.
Severity of deep dyspareunia on a numeric pain rating scale of 0 to 10.
Severity of deep dyspareunia (scale = 0-10) was independently associated with tenderness of the bladder (b = 0.88, P = .018), pelvic floor (levator ani) (b = 0.66, P = .038), cervix and uterus (b = 0.88, P = .008), and cul-de-sac or uterosacral ligaments (b = 1.39, P < .001), but not with the adnexa (b = -0.16, P = 0.87). The number of tender anatomic sites was significantly correlated with more severe deep dyspareunia (Spearman r = 0.34, P < .001). For associated clinical factors, greater depression symptom severity was specifically associated with tenderness of the bladder (b = 1.05, P = .008) and pelvic floor (b = 1.07, P < .001). A history of miscarriage was specifically associated with tenderness of the cervix and uterus (b = 2.24, P = .001). Endometriosis was specifically associated with tenderness of the cul-de-sac or uterosacral ligaments (b = 3.54, P < .001).
In reproductive-age women at a tertiary referral center, deep dyspareunia was independently associated not only with tenderness of the cul-de-sac and uterosacral ligaments but also with tenderness of the bladder, pelvic floor, and cervix and uterus. Yong PJ, Williams C, Yosef A, et al. Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia. Sex Med 2017;5:e184-e195.
Franjoine SE et al., 2015·Minimally invasive surgery·Free full text on PubMed Central
Objective. To study the reproductive outcomes of modified laparoscopic fimbrioplasty (MLF), a surgical technique designed to increase the working surface area of the fimbriated end of the fallopian tube. We postulated that an improvement in fimbrial function through MLF will improve reproductive outcomes. Design. Retrospective cohort study. Setting. Academic tertiary-care medical center. Patients. Women with minimal endometriosis or unexplained infertility, who underwent MLF during diagnostic laparoscopy (n = 50) or diagnostic laparoscopy alone (n = 87). Intervention. MLF involved gentle, circumferential dilatation of the fimbria and lysis of fimbrial adhesions bridging the fimbrial folds. Main Outcome Measures. The primary outcome was pregnancy rate and the secondary outcome was time to pregnancy. Results. The pregnancy rate for the MLF group was 40.0%, compared to 28.7% for the control group. The average time to pregnancy for the MLF group was 13 weeks, compared to 18 weeks for the control group. The pregnancy rate in the MLF group was significantly higher for patients ≤35 ys (51.5% versus 28.8%), but not for those >35 ys (17.6% versus 28.6%). Conclusion. MLF was associated with a significant increase in pregnancy rate for patients ≤35 ys.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age. Its cardinal features are hyperandrogenism, chronic anovulation, and infertility. Some of the most important pathogenic associations of PCOS are insulin resistance and compensatory hyperinsulinemia (1, 2, 3). The hyperinsulinemia in turn stimulates ovarian androgen production. Several clinical studies have demonstrated that a reduction in the insulin level results in decreased ovarian androgen production (4, 5, 6).
Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic gluconeogenesis and increases peripheral insulin sensitivity and glucose uptake but does not cause hypoglycemia (6, 7, 8). The correction of the hyperinsulinemia by metformin in PCOS patients is accompanied by normalization of the elevated serum LH and ovarian androgen levels, leading to resumption of spontaneous ovulatory cycles, or responsiveness to ovulation induction by clomiphene citrate (CC) (1, 4, 5, 6, 8, 9). Clinical use of this agent for ovulation induction in CC-resistant PCOS patients has increased with little knowledge of the possible effect on early embryo development. We sought to assess whether metformin was embryotoxic using a mouse embryo model.
During controlled clinical trials, plasma metformin levels do not exceed 5 μg/mL, even at maximum doses (10). Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride; Sigma, St. Louis, MO) was dissolved in human tubal fluid (HTF) media (Irvine Scientific, Santa Ana, CA) to give working concentrations of 5, 25, and 100 μg. The culture dishes containing 1 mL of media at each concentration were incubated for overnight equilibration at 37°C and 5% CO2.
Thawed two-cell mouse embryos (Embryotech, Wilmington, MA) were pooled and randomly distributed into the culture dishes containing the various concentrations of metformin. The control consisted of HTF media alone (group 1). Groups 2, 3, and 4 were supplemented with metformin (5, 25, and 100 μg/mL). There were 40 embryos in each group. The embryos were incubated in an atmosphere of 5% CO2 at 37°C for 72 hours. The blastocyst development rate (BDR) was then calculated by dividing the number of embryos reaching the blastocyst stage by the total number of embryos cultured.
The relationship between BDR and concentration was assessed with repeated measures logistic regression using generalized estimated equation (GEE) methodology with a compound symmetry correlation structure. The sample size was sufficient to detect whether a specific concentration reduced the odds of development by a factor of 2.5. Statistical significance was assessed using two-tailed P<.05. Statistical computations were performed with SAS version 8.1 (SAS Institute Inc, Cary, NC). . .