Publications by authors named "Mohamed A Bedaiwy"

144 Publications

Reproductive outcomes following surgical management for isthmoceles: A systematic review.

J Minim Invasive Gynecol 2021 Apr 8. Epub 2021 Apr 8.

Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Objective: 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 two authors for studies. These two authors assessed for studies which focussed on reproductive aged women with a diagnosed isthmocele and secondary infertility who underwent any surgical intervention for defect repair with at least one of the goals being fertility restoration.

Tabulation, Integration, And Results: 13 studies, comprised of 1 randomized controlled trial (RCT), 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 methodological 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. 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 RCT were 21/28 (75%) for those treated via hysteroscopy compared to 9/28 (32%) for those untreated. Among studies reporting pregnancy outcomes, 101/116 (87.1%) pregnancies resulted in a live birth. The incidence of adverse events was 2%, including risk of reoperation.

Conclusion: The results of this systematic review suggest that surgical treatment of isthmocele, particularly via hysteroscopy in patients with residual myometrial thickness (RMT) of at least 2.5mm, may be effective in treating isthmocele-associated secondary infertility with a relatively low complication rate. Further high-quality studies are needed due to the small sample sizes and observational nature of most available data.
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http://dx.doi.org/10.1016/j.jmig.2021.03.012DOI Listing
April 2021

Corrigendum to 'Comparing 36.5°C with 37°C for human embryoculture: a prospective randomized controlled trial' [Reproductive BioMedicine Online 36 (2018) 620-626].

Reprod Biomed Online 2021 Mar 10. Epub 2021 Mar 10.

Department of Obstetrics and Gynecology, Assiut University, Egypt; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, University of British Columbia, Canada.

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http://dx.doi.org/10.1016/j.rbmo.2021.03.001DOI Listing
March 2021

Recreational Cannabis Use Before and After Legalization in Women With Pelvic Pain.

Obstet Gynecol 2021 01;137(1):91-99

University of British Columbia, and the Centre for Health Evaluation & Outcome Sciences, Vancouver, British Columbia, Canada.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Clinical Trial Registration: ClinicalTrials.gov, NCT02911090.
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http://dx.doi.org/10.1097/AOG.0000000000004207DOI Listing
January 2021

Interdisciplinary Teams in Endometriosis Care.

Semin Reprod Med 2020 May 20;38(2-03):227-234. Epub 2020 Oct 20.

Department of Obstetrics and Gynecology, The University of British Columbia, Vancouver, Canada.

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.
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http://dx.doi.org/10.1055/s-0040-1718943DOI Listing
May 2020

Chronic Intervillositis of Unknown Etiology (CIUE): Prevalence, patterns and reproductive outcomes at a tertiary referral institution.

Placenta 2020 10 12;100:60-65. Epub 2020 Aug 12.

University of British Columbia, Department of Obstetrics and Gynaecology, Vancouver, BC, V6Z 2K8, Canada. Electronic address:

Introduction: the objective of this study was to evaluate the incidence of Chronic Intervillositis of Unknown Etiology (CIUE) at our institution and to report on the pregnancy outcomes based on severity of lesions.

Methods: retrospective cohort study including 29 889 perinatal specimens from 27 968 patients. The pathology database at our institution was queried for the keywords "intervillositis" and "CIUE" between February 2006 and April 2019. Histology was re-examined using a standardized diagnostic criterion to confirm diagnosis. Cases in which diagnosis was confirmed were categorized as low grade (5-49% intervillous space involvement) or high grade (≥50% involvement). Interventions and pregnancy outcomes were recorded.

Results: The overall prevalence of CIUE is 0.17% (47 of 27 968 patients), with significantly higher prevalence in 1st trimester products of conception compared with 2nd and 3rd trimester specimens (0.38% vs 0.09%; p < 0.0001). A total of 97 specimens were initially diagnosed with chronic intervillositis. 56 out of 97 (57.7%) specimens met our diagnostic criteria for CIUE on review. Pregnancies with confirmed CIUE had significantly higher rates of pregnancy loss compared with pregnancies with chronic intervillositis not meeting our study criteria for CIUE (94% vs 71%; p = 0.003). Pregnancy loss between low grade (42.9%; 24 out of 56 cases of CIUE) and high grade (57.1%; 32 out of 56 cases) CIUE were not significantly different.

Discussion: CIUE prevalence is low at 0.17%, but it is associated with pregnancy loss, particularly in the first trimester. High grade disease may be associated with worse pregnancy outcomes than low grade disease.
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http://dx.doi.org/10.1016/j.placenta.2020.07.032DOI Listing
October 2020

Quality of ultrasonography reporting and factors associated with selection of imaging modality for uterine fibroids in Canada: results from a prospective cohort registry.

CMAJ Open 2020 Jul-Sep;8(3):E506-E513. Epub 2020 Aug 12.

Department of Obstetrics and Gynaecology (Bougie), Queen's University, Kingston, Ont.; Department of Obstetrics and Gynecology (Bedaiwy), The University of British Columbia, Vancouver, BC; Department of Obstetrics and Gynecology (Laberge), CHU de Québec, Laval University, Quebec, Que.; Applied Health Research Centre (Lebovic), LKSKI, St. Michael's Hospital, Toronto, Ont.; Department of Obstetrics and Gynecology (Leyland), McMaster University, Hamilton, Ont.; Department of Medical Imaging (Atri), University of Toronto; Department of Obstetrics and Gynecology (Murji), Mount Sinai Hospital, University of Toronto, Toronto, Ont.

Background: Uterine fibroids are common in women and their management is heavily influenced by information gathered through imaging. We aimed to evaluate the type and quality of imaging performed for assessment of uterine fibroids in Canada.

Methods: Starting in July 2015, premenopausal women with symptomatic fibroids were enrolled in a prospective, noninterventional, observational registry (Canadian Women With Uterine Fibroids Registry [CAPTURE]) that included 19 Canadian sites. Clinical characteristics were extracted from the baseline visit. We evaluated the association between demographic and clinical variables of interest with regard to imaging type using unadjusted and adjusted logistic regression models.

Results: Of 1493 women, 1148 had ultrasonography, 135 had magnetic resonance imaging (MRI), 80 had other types of imaging and 130 did not have imaging reported within 12 months of the baseline visit. After adjusting for demographic and clinical characteristics, patients who underwent MRI had larger fibroids (odds ratio [OR] per 1-cm increase 1.11, 95% confidence interval [CI] 1.05-1.17) and more numerous fibroids (1 v. > 1; OR 1.74, 95% CI 1.14-2.64) compared with those who underwent ultrasonography only. For ultrasonography reporting, quality criteria were met for 268 of 1148 patients (23.3%). There was a difference in the quality of reporting among the 19 sites ( < 0.001). Logistic regression model accounting for within-site variability showed that reporting results from ultrasonography in the province of Quebec were less likely to meet all quality criteria (OR 0.20, 95% CI 0.06-0.66) and those from sites in more populated cities (≥ 400 000 inhabitants) were more likely to do so (OR 6.15, 95% CI 2.20-17.18).

Interpretation: We determined that imaging modality for fibroids is associated with patient characteristics. The quality of reporting results for ultrasonography of fibroids in Canada falls short of internationally endorsed guidelines and needs improvement.

Study Registration: ClinicalTrials.gov, no. NCT02580578.
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http://dx.doi.org/10.9778/cmajo.20200004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850143PMC
August 2020

Epidermal growth factor promotes stromal cells migration and invasion via up-regulation of hyaluronate synthase 2 and hyaluronan in endometriosis.

Fertil Steril 2020 Oct 3;114(4):888-898. Epub 2020 Aug 3.

Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. Electronic address:

Objective: To investigate the role(s) of hyaluronan synthase 2 (HAS2) and hyaluronan in disease progression of endometriosis and epidermal growth factor (EGF)-induced motility changes of endometriotic cells.

Design: A case-control experimental study and in vitro primary cell culture study.

Setting: University hospital-affiliated research centers.

Patients: A total of 21 women with stage I/II endometriosis, 33 women with stage III/IV endometriosis with endometrioma, and 32 women without endometriosis were included in our study.

Interventions: Serum, eutopic endometrial tissues, and/or ectopic endometriotic tissues were collected. Primary eutopic endometrial stromal cells (EuESCs) and ectopic ovarian endometriotic stromal cells (OvESCs) were isolated and cultured from women with ovarian endometrioma, and then treated with or without EGF.

Main Outcome Measures: The concentrations of EGF and hyaluronan in serum were analyzed by enzyme-linked immunosorbent assay. The expressions and localizations of EGF receptor (EGFR), phosphorylated-(p)EGFR, HAS2, and hyaluronan receptor CD44 in tissues were examined by immunohistochemistry. The mRNA and protein levels of HAS2 in EuESCs and OvESCs were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively, and the concentrations of hyaluronan in conditioned medium were examined by enzyme-linked immunosorbent assay (ELISA). Cell motility was evaluated by transwell migration/invasion assays.

Results: Serum EGF and hyaluronan concentrations were higher in women with stage III/IV endometriosis than in women with stage I/II or without endometriosis. EGFR, pEGFR, HAS2, and CD44 were immunolocalized in eutopic endometrium and ectopic endometriotic lesions, and the expressions of pEGFR and HAS2 were elevated in ectopic endometriotic lesions compared to eutopic endometrium. Treatment with EGF upregulated HAS2 and hyaluronan expression as well as cell migration and invasion in both EuESCs and OvESCs, and pharmaceutical blocking of EGFR abolished these effects. In addition, knockdown of HAS2 by small interfering RNA attenuated both basal and EGF-induced hyaluronan expression and cell motility changes. Notably, ERK1/2 and AKT signaling pathways were shown to be downstream of EGF in regulating HAS2 and hyaluronan expression as well as cell migration and invasion.

Conclusion: EGF increased the expression of endometriosis-associated hyaluronan and its synthase HAS2, both of which mediated EGF-induced stromal cell migration and invasion in women with endometriosis.
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http://dx.doi.org/10.1016/j.fertnstert.2020.05.005DOI Listing
October 2020

Pathogenesis of bowel endometriosis.

Best Pract Res Clin Obstet Gynaecol 2021 Mar 6;71:2-13. Epub 2020 Jun 6.

Department of Obstetrics and Gynecology, University of British Columbia, 275 - 2660 Oak Street, Vancouver, British Columbia, V6H 3Z6, Canada. Electronic address:

The pathogenesis of bowel endometriosis is multifactorial. There is a predilection for disease of the rectum/sigmoid colon because refluxed endometrium is more likely to settle in the pouch of Douglas and its movement is delimited by the sigmoid colon, in addition to the close proximity of the rectum/sigmoid to posterior extrinsic uterine adenomyosis and to ovarian endometriomas. Once situated, deep bowel endometriosis has features of invasion, angiogenesis, and fibrosis (repeated tissue injury and repair), with emerging research on oxidative stress and the microbiome. Furthermore, deep bowel endometriosis is associated with neurogenesis and/or the recruitment of local nerve fibers and is capable of invading existing nerves, which in turn may also promote fibrosis. Recently, somatic cancer driver mutations (e.g., in KRAS) were identified in deep bowel endometriosis, which may play a role in the genetic/epigenetic theory of endometriosis. In the future, it is possible that bowel endometriosis could be classified based on molecular features.
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http://dx.doi.org/10.1016/j.bpobgyn.2020.05.009DOI Listing
March 2021

Negative Sliding Sign during Dynamic Ultrasonography Predicts Low Endometriosis Fertility Index at Laparoscopy.

J Minim Invasive Gynecol 2021 02 13;28(2):249-258.e2. Epub 2020 May 13.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, University of British Columbia, Vancouver, Canada (all authors).. Electronic address:

Study Objective: 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).

Design: Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017.

Setting: Tertiary referral center at British Columbia Women's Hospital.

Patients: 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.

Interventions: Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery.

Measurements And Main Results: 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%.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jmig.2020.05.003DOI Listing
February 2021

Spontaneous Rupture of Leiomyoma Diagnosed Preoperatively with Noncontrast Computed Tomography.

Case Rep Obstet Gynecol 2020 24;2020:5364165. Epub 2020 Mar 24.

Department of Obstetrics and Gynecology, Women's Hospital of British Columbia, University of British Columbia, Vancouver, Canada.

Background: Spontaneous rupture of benign uterine fibroids is extremely rare and has been associated with fibroid degeneration. It can cause acute intraperitoneal bleeding requiring immediate surgical intervention.

Case: A previously healthy 50-year-old, Caucasian, nullipara presented with syncope, hemodynamic instability, and an acute abdomen. Noncontrast computed tomography images showed a positive sentinel clot sign in the pelvis as well as a large uterine fibroid with internal hyperdense clot suggesting acute rupture. Urgent laparotomy and hysterectomy confirmed a ruptured, actively bleeding, uterine fibroid with final pathological diagnosis of a benign leiomyoma.

Conclusion: Prompt diagnosis and emergency surgical intervention were necessary to control acute hemorrhage from a ruptured uterine fibroid. Noncontrast computed tomography is an important adjunct to contrast-enhanced computed tomography and was vital for diagnosis in this case.
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http://dx.doi.org/10.1155/2020/5364165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128062PMC
March 2020

Role of interleukin-1β in nerve growth factor expression, neurogenesis and deep dyspareunia in endometriosis.

Hum Reprod 2020 04;35(4):901-912

Department of Obstetrics and Gynaecology, University of British Columbia, BC Children's Hospital Research Institute and Women's Health Research Institute, Vancouver, British Columbia, Canada, V6H3N1.

Study Question: Does interleukin-1β (IL-1β) play a role in promoting nerve growth factor expression, neurogenesis and deep dyspareunia in endometriosis?

Summary Answer: IL-1β directly stimulates nerve growth factor (NGF) expression in endometriosis and is associated with local neurogenesis around endometriosis and more severe deep dyspareunia.

What Is Known Already: Local nerve density around endometriosis (using the pan-neuronal marker PGP9.5) is associated with deep dyspareunia in endometriosis, mediated in part by NGF expression.

Study Design, Size, Duration: This in vitro study included endometriotic tissue samples from 45 patients.

Participants/materials, Setting, Methods: This study was conducted in a university hospital affiliated research institute and included 45 women with surgically excised deep uterosacral/rectovaginal endometriosis (DIE, n = 12), ovarian endometriomas (OMA, n = 14) or superficial peritoneal uterosacral/cul-de-sac endometriosis (SUP, n = 19). Immunolocalisation of IL-1β, IL-1 receptor type 1 (IL-1R1), NGF and PGP9.5 in endometriotic tissues was examined by immunohistochemistry (IHC), and the intensity of IHC staining in the endometriotic epithelium and stroma was semi-quantitatively evaluated using the Histoscore method (H-score). For each case, deep dyspareunia was pre-operatively rated by the patient on an 11-point numeric rating scale (0-10). In addition, primary endometriosis stromal cells were isolated and cultured from surgically excised endometriosis. These cells were treated with IL-1β alone or in combination of Anakinra (an inhibitor of IL-1R1), small inference RNA (siRNA) against IL-1R1, siRNA against c-FOS or NGF neutralising antibody. The mRNA and protein levels of target genes (NGF and c-FOS) were assessed by reverse-transcription qPCR and western blot/ELISA, respectively. Furthermore, immunofluorescent microscopy was used to examine the neurite growth of rat pheochromocytoma PC-12 cells, as an in vitro model of neurogenesis.

Main Results And The Role Of Chance: For IHC, IL-1β expression in the endometriosis epithelium was significantly associated with more severe deep dyspareunia (r = 0.37, P = 0.02), higher nerve fibre bundle density around endometriosis (r = 0.42, P = 0.01) and greater NGF expression by the endometriosis epithelium (r = 0.42, P = 0.01) and stroma (r = 0.45, P = 0.01). In primary endometriosis stromal cells, treatment with exogenous IL-1β significantly increased the mRNA and protein levels of NGF and c-FOS. Pre-treatment with Anakinra, siRNA against IL-1R1, or siRNA against c-FOS, each attenuated IL-1 β-induced increases of NGF expression. In addition, supernatants from IL-1β treated endometriosis stromal cells significantly stimulated PC-12 neurite growth compared to controls, and these effects could be attenuated by pre-treatment with NGF neutralising antibody or Anakinra.

Large-scale Data: N/A.

Limitations, Reasons For Caution: We did not have data from cultures of endometriosis glandular epithelium, due to the known difficulties with primary cultures of this cell type.

Wider Implications Of The Findings: Our study revealed a mechanism for deep dyspareunia in endometriosis, whereby IL-1β stimulates NGF expression, promoting local neurogenesis around endometriosis, which in turn leads to tender pelvic anatomic sites and thus deep-hitting dyspareunia. There may also be potential for drug targeting of IL-1β and/or NGF in the management of endometriosis-associated pain.

Study Funding/competing Interest(s): This study was funded by grants from the Canadian Institutes of Health Research (MOP-142273 and PJT-156084). P.Y. is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB has financial affiliations with Abbvie and Allergan. Otherwise, there are no conflicts of interest to declare.
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http://dx.doi.org/10.1093/humrep/deaa017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192531PMC
April 2020

A Quantitative Analysis of Sleep Quality in Women with Endometriosis.

J Womens Health (Larchmt) 2020 09 13;29(9):1209-1215. Epub 2020 Mar 13.

Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.

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 -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,  = 0.0026), more depressive symptoms (PHQ-9) (b = -1.62,  < 0.001), and painful bladder syndrome (PBS) (b = -5.82,  = 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 (., 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.
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http://dx.doi.org/10.1089/jwh.2019.8008DOI Listing
September 2020

Prevalence of thyroid autoimmunity and effect of levothyroxine treatment in a cohort of 1064 patients with recurrent pregnancy loss.

Reprod Biomed Online 2020 Apr 30;40(4):582-592. Epub 2019 Nov 30.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynaecology, University of British Columbia, BC Women and Children's Hospital, Vancouver BC, Canada. Electronic address:

Research Question: Does initiating levothyroxine treatment based on thyroid-stimulating hormone (TSH) >2.5 mIU/l or thyroid autoimmunity improve pregnancy continuation rates in recurrent pregnancy loss (RPL) patients?

Design: A retrospective cohort study of 1064 RPL patients, in which subjects were classified as either euthyroid (TSH 0.1 to ≤2.5 mIU/l), borderline-subclinical hypothyroid (borderline-SCH, TSH 2.5 to ≤4 mIU/l) or subclinical hypothyroid (SCH, TSH 4 to ≤10 mIU/l). For subjects with ≥2 pregnancy losses and a subsequent pregnancy with known outcome, a comparison was done of the pregnancy continuation rate past 10 weeks of treated and untreated borderline-SCH (n = 98) and untreated euthyroid (n = 279) subjects, and between subjects with positive (n = 18) and negative (n = 206) thyroid peroxidase (TPOAb tests) within the borderline-SCH and euthyroid groups.

Results: 72.7% were euthyroid (721/992), 19.4% (192/992) were borderline-SCH, and 5.4% (54/992) were subclinically hypothyroid (SCH). Of 401 women with a subsequent pregnancy of known outcome at 10 gestational weeks, 21% received treatment with levothyroxine. 57.7% of subjects had a TPOAb test, which was positive in 9.25% (37/400) in euthyroid, 16.5% (22/133) in borderline-SCH subjects and 35.3% (12/34) in SCH subjects. Treatment did not improve pregnancy continuation rates in borderline-SCH subjects (P = 0.392). There was no difference in pregnancy outcomes based on TPOAb status and treatment for borderline-SCH subjects (P = 0.4214), or based on TPOAb status for euthyroid subjects (P = 0.2668).

Conclusions: Treatment of hypothyroidism in pregnancy should be initiated based on a TSH >4 mIU/l. Treatment initiation based on thyroid autoimmunity or a TSH >2.5 mIU/l may result in overtreatment.
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http://dx.doi.org/10.1016/j.rbmo.2019.11.014DOI Listing
April 2020

CHC for pelvic pain in women with endometriosis: ineffectiveness or discontinuation due to side-effects.

Hum Reprod Open 2020 28;2020(2):hoz040. Epub 2020 Feb 28.

Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver V6H3N1, Canada.

Study Question: 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?

Summary Answer: 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.

What Is Known Already: 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.

Study Design Size Duration: 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 Setting And Methods: 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 Results And The Role Of Chance: 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 ( < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects ( = 0.005). Among the underlying conditions, pelvic floor tenderness (as a marker of pelvic floor myalgia) was associated with CHC ineffectiveness.

Limitations And Reasons For Caution: 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).

Wider Implications Of The Findings: 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.

Study Funding/competing Interests: 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.
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http://dx.doi.org/10.1093/hropen/hoz040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048681PMC
February 2020

Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis.

Reprod Sci 2020 09 18;27(9):1731-1741. Epub 2020 Feb 18.

Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Endometriosis is characterized by the presence of ectopic endometrial tissues. Mechanisms of tissue dissemination in endometriosis may be similar to those involved in tumor metastasis. We hypothesize that dysregulation of kisspeptin (KISS1), a metastasis suppressor in endometrial carcinoma, may contribute to the pathogenesis of endometriosis. In this study, we characterized the immunoreactivity of kisspeptin and its receptor, KISS1R, in eutopic and ectopic endometrial tissue of women with and without endometriosis, in proliferative and secretory menstrual cycle phases. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on samples from women with (n = 35) and without (n = 14) endometriosis. Samples from women with endometriosis included eutopic endometrium (n = 20) samples, superficial endometriotic implants (SUP, n = 10) deep infiltrating endometriotic implants (DIE, n = 15), and ovarian endometriomas (OMA, n = 15). Immunoreactivity was quantified using histoscores. KISS1 and KISS1R immunoreactivity was significantly lower in eutopic endometrial stroma of women with versus without endometriosis, regardless of the menstrual cycle phase (P = 0.001 and P = 0.015 respectively). In endometriotic implants, KISS1 levels were significantly lower in both glandular and stromal components of DIE (P < 0.01) and OMA (P < 0.01) compared to SUP. KISS1R immunoreactivity was lower in the glandular component of OMA (P = 0.035) compared to SUP. KISS1 and KISS1R levels are lower in eutopic endometrial stroma from women with versus without endometriosis, consistent with a role for decreased KISS1 expression in the pathogenesis of endometriosis. As deeply invasive lesions showed lower KISS1 levels than superficial lesions, downregulation of KISS1 levels may contribute to implant invasiveness.
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http://dx.doi.org/10.1007/s43032-020-00167-wDOI Listing
September 2020

Deep Dyspareunia, Superficial Dyspareunia, and Infertility Concerns Among Women With Endometriosis: A Cross-Sectional Study.

Sex Med 2020 Jun 13;8(2):274-281. Epub 2020 Feb 13.

Center for Pelvic Pain and Endometriosis, BC Women's Hospital, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; Women's Health Research Institute, Vancouver, BC, Canada; BC Center for Vulvar Health, Gordon and Leslie Diamond Health Care Center, Vancouver, BC, Canada. Electronic address:

Introduction: Deep dyspareunia is a cardinal symptom of endometriosis, and as many as 40% of people with this condition experience comorbid superficial dyspareunia.

Aim: To evaluate the relationship between sexual pain and infertility concerns among women with endometriosis.

Methods: 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).

Main Outcome Measure: 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).

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.esxm.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261667PMC
June 2020

Phenotyping Sexual Pain in Endometriosis Using the Central Sensitization Inventory.

J Sex Med 2020 04 24;17(4):761-770. Epub 2020 Jan 24.

BC Women's Centre for Pelvic Pain and Endometriosis, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; Women's Health Research Institute, Vancouver, BC, Canada; BC Centre for Vulvar Health, Gordon and Leslie Diamond Health Care Centre, Vancouver, BC, Canada. Electronic address:

Introduction: 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.

Aim: The objective of this study was to phenotype deep dyspareunia using BPFT and the CSI.

Methods: 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).

Main Outcome Measure: The main outcome measure was the CSI score ranging from 0 to 100.

Results: 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).

Clinical Implications: The CSI could be used to classify and phenotype patients with endometriosis-associated sexual pain.

Strength & Limitations: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jsxm.2019.12.019DOI Listing
April 2020

Endometriosis and Negative Perception of the Medical Profession.

J Obstet Gynaecol Can 2020 03 18;42(3):248-255. Epub 2019 Dec 18.

British Columbia Women's Health Research Institute, Vancouver, BC; Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, BC; British Columbia Women's Centre for Pelvic Pain and Endometriosis, Vancouver, BC. Electronic address:

Objective: This study sought to identify factors independently associated with a negative impression of the medical profession in patients with endometriosis who were presenting to a tertiary referral centre.

Methods: A cross-sectional analysis was conducted on a prospective data registry between December 2013 and June 2017 at a tertiary referral centre for pelvic pain and endometriosis. The main outcome variable, negative impression about the medical profession, was measured with the four-item subscale of the Endometriosis Health Profile-30 and divided into three groups: no (0), some (1-8), and many (9-16) negative impressions. Patients with a surgical and histological diagnosis of endometriosis were included. Postmenopausal women were excluded. Bivariate analyses determined significant associations (P < 0.05) between variables from the registry and the main outcome. Variables with a significant association were put into ordinal logistic regression with sequential backwards elimination.

Results: Negative impression of the medical profession was independently associated with previous surgery that did not help symptoms (adjusted odds ratio [aOR] 1.77; 95% confidence interval [CI] 1.09-2.87; P = 0.021), presentation to an emergency room in the past 3 months (aOR 1.90; 95% CI 1.17-3.07; P = 0.009), and previous visits to a complementary health care provider (aOR 2.16; 95% CI 1.42-3.29; P < 0.0005), while controlling for an endometriosis pain-related morbidity composite variable.

Conclusion: Negative perception of the medical profession in women with endometriosis was associated with surgical treatment failure, emergency room use, and accessing complementary health care. Each identified factor offers an opportunity for intervention to improve the perception of the medical profession among women with endometriosis.
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http://dx.doi.org/10.1016/j.jogc.2019.08.034DOI Listing
March 2020

Endometrial macrophages, endometriosis, and microbiota: time to unravel the complexity of the relationship.

Fertil Steril 2019 12;112(6):1049-1050

Division of Reproductive Endocrinology & Infertility, Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.fertnstert.2019.09.021DOI Listing
December 2019

The Impact of Noncavity-Distorting Intramural Fibroids on Live Birth Rate in Fertilization Cycles: A Systematic Review and Meta-Analysis.

J Womens Health (Larchmt) 2020 02 10;29(2):210-219. Epub 2019 Dec 10.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of British Columbia, BC Women's Hospital, Vancouver, BC, Canada.

What is the impact of noncavity-distorting intramural fibroids on live birth rates in 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.
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http://dx.doi.org/10.1089/jwh.2019.7813DOI Listing
February 2020

Atherosclerotic cardiovascular disease in women with endometriosis: a systematic review of risk factors and prospects for early surveillance.

Reprod Biomed Online 2019 Dec 8;39(6):1007-1016. Epub 2019 Jun 8.

Department of Obstetrics & Gynaecology, The University of British Columbia, Vancouver British Columbia, Canada. Electronic address:

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) share similar pathogenic mechanisms. Hence, this systematic review evaluates the association between endometriosis and lifetime ASCVD risk including co-prevalence with dyslipidaemia, atherosclerosis and non-invasive markers of endothelial dysfunction. The electronic databases Embase, PubMed, MEDLINE, Cochrane Register of Trials and ClinicalTrials.gov were systematically searched for relevant articles. Two prospective cohort studies demonstrated an increased lifetime ASCVD risk after controlling for demographic and lifestyle confounders in women with endometriosis, as measured by higher incidence of myocardial infarction (relative risk [RR] 1.52), angiography-confirmed angina (RR 1.91), or requiring coronary artery bypass graft surgery (RR 1.35). Among 10 studies that included 407 patients with surgically proven endometriosis and 557 controls, RR of developing hypercholesterolemia and hypertension were 1.25 and 1.14, respectively, while higher serum lipoprotein a and lower paraoxonase 1 levels were found in women with endometriosis that was negatively correlated with stage of disease (r = -0.74, P < 0.0001). Hence, currently available evidence suggests that women with endometriosis are at higher lifetime risk of developing ASCVD than women without endometriosis. However, robust causal evidence is still lacking and future studies are needed to determine whether women with endometriosis represent a high-risk population for lifelong ASCVD risk.
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http://dx.doi.org/10.1016/j.rbmo.2019.05.021DOI Listing
December 2019

Authors' Reply.

J Minim Invasive Gynecol 2020 01 11;27(1):238-239. Epub 2019 Oct 11.

Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.jmig.2019.09.786DOI Listing
January 2020

Endometriosis and Ectopic Pregnancy: A Meta-analysis.

J Minim Invasive Gynecol 2020 02 20;27(2):352-361.e2. Epub 2019 Sep 20.

BC Women's Centre for Pelvic Pain and Endometriosis (Drs. Yong, Matwani, Brace, Bedaiwy, and Allaire) Vancouver, BC, Canada; Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada (Dr. Matwani); Department of Obstetrics and Gynecology, University of Calgary, Calgary, Alberta, Canada (Dr. Brace); Department of Obstetrics and Gynecology, University of British Columbia (Drs. Yong, Bedaiwy, Albert, and Allaire), Vancouver, BC, Canada; Women's Health Research Institute (Drs. Yong, Bedaiwy, Albert, and Allaire), Vancouver, British Columbia; Schulich Library of Physical Sciences, Life Sciences, and Engineering, McGill University (Dr. Quaiattini), Montreal, Quebec, Canada.

Objective: To systematically review and perform a meta-analysis of the risk of ectopic pregnancy in endometriosis.

Data Sources: 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.

Methods Of Study Selection: 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, And Results: 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 I 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 (I = 93.9% and I = 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jmig.2019.09.778DOI Listing
February 2020

Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

PLoS One 2019 17;14(7):e0219064. Epub 2019 Jul 17.

Department of Obstetrics & Gynaecology, BC Children's Hospital Research Institute, The University of British Columbia, Vancouver, Canada.

Purpose: Deep infiltrating endometriosis (DIE) is defined as an endometriotic lesion penetrating to a depth of >5 mm and is associated with pelvic pain, but the underlying mechanisms are unclear. Our objective is to investigate whether plasminogen activator inhibitor-1 expression (PAI-1) in endometriotic tissues is increased in women with DIE.

Methods: In this blinded in vitro study, immunohistochemistry and Histoscore were used to examine the expression of PAI-1 in glandular epithelium (GECs) and stroma (SCs) in a total of 62 women: deep infiltrating uterosacral/rectovaginal endometriosis (DIE; n = 13), ovarian endometrioma (OMA; n = 14), superficial peritoneal uterosacral/cul-de-sac endometriosis (SUP; n = 23), uterine (eutopic) endometrium from women with endometriosis (UE; n = 6), and non-endometriosis eutopic endometrium (UC; n = 6). The following patient characteristics were also collected: age, American Fertility Society stage, hormonal suppression, phase of menstrual cycle, dysmenorrhea score and deep dyspareunia score.

Results: PAI-1 expression in GECs and SCs of the DIE group was significantly higher than that of SUP group (p = 0.01, p = 0.01, respectively) and UE group (p = 0.03, p = 0.04, respectively). Interestingly, increased PAI-1 expression in GECs and SCs was also significantly correlated with increased dysmenorrhea (r = 0.38, p = 0.01; r = 0.34, p = 0.02, respectively).

Conclusions: We found higher expression of PAI-1 in DIE, and an association between PAI-1 and worse dysmenorrhea.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219064PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637014PMC
March 2020

A critical review of recent advances in the diagnosis, classification, and management of uterine adenomyosis.

Curr Opin Obstet Gynecol 2019 08;31(4):212-221

Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, The University of British Columbia.

Purpose Of Review: The purpose of this review is to summarize and highlight recent critical advances in the diagnosis, classification, and management of adenomyosis.

Recent Findings: 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.

Summary: 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.
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http://dx.doi.org/10.1097/GCO.0000000000000555DOI Listing
August 2019

Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife.

J Minim Invasive Gynecol 2019 Jul - Aug;26(5):781-784. Epub 2019 Apr 25.

Department of Obstetrics and Gynecology (Drs. Taskin, Tan, Rowe, and Bedaiwy and Ms. Rikhraj). Electronic address:

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) are both essentially diseases of inflammation. It is well established that inflammation is the leading mechanism in the initiation and maintenance of vascular injury and in the development and progression of atherosclerosis. Thus, if women with endometriosis do indeed have increased general inflammation, they are at increased risk of developing microvascular dysfunction and atherosclerosis. Currently available evidence suggests that young female patients with proven endometriosis may be at a higher lifetime risk of developing cardiovascular disease; this may be unrecognized due to the relatively young age of women found to have endometriosis. Other mechanisms proposed to explain the link between endometriosis and ASCVD include similarities in the genetic underpinnings of each condition, including microRNA dysfunction and the association between endometriosis and early menopause, a risk for developing ASCVD. Although physicians today primarily focus on traditional risk factors when evaluating an individual female patient's risk of developing ASCVD, we believe that a history of endometriosis should be included as a possible risk factor and needs further exploration. A better understanding of the mechanisms linking endometriosis with ASCVD will hopefully guide the implementation of new therapies to mitigate the increased cardiovascular disease burden that patients with endometriosis might face.
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http://dx.doi.org/10.1016/j.jmig.2019.02.022DOI Listing
January 2020

Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis.

Reprod Biomed Online 2019 Jun 22;38(6):951-960. Epub 2018 Dec 22.

Department of Obstetrics and Gynaecology, University of British Columbia and the Children's and Women's Hospital and Health Centre of British Columbia, Vancouver, BC, Canada. Electronic address:

Sperm DNA fragmentation (sDF) has emerged as a valuable tool for evaluating male fertility, yet the relationship between DNA fragmentation in the male gamete and idiopathic recurrent pregnancy loss (RPL) remains a topic of ongoing debate. Hence, a meta-analysis was conducted of 12 prospective and 2 retrospective studies involving 530 men with a history of RPL who underwent sDF testing compared with 639 fertile control participants. The main outcome measures were sDF measured by comet assay, TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL), sperm chromatin dispersion (SCD) or sperm chromatin structure assay. Overall, couples with a history of idiopathic RPL demonstrated higher levels of sDF than fertile couples (average mean difference 11.98, P < 0.001). Subgroup analysis demonstrated a similar average mean difference between the RPL and control groups using SCD compared with TUNEL, while mean paternal age and mean sperm motility in the RPL groups tested by meta-regression demonstrated no significant effect on the mean differences in sDF (P > 0.10). These results support the diagnostic value of sDF over standard semen analysis, as well as a possible paternally derived genetic origin of unexplained RPL. Further prospective studies are required to further assess the predictive utility of sDF for assessing couples with unexplained RPL.
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http://dx.doi.org/10.1016/j.rbmo.2018.12.029DOI Listing
June 2019

Provoked Vestibulodynia in Women with Pelvic Pain.

Sex Med 2019 Jun 4;7(2):227-234. Epub 2019 Apr 4.

BC Women's Center for Pelvic Pain and Endometriosis, Vancouver, British Columbia, Canada; Women's Health Research Institute, Vancouver, British Columbia, Canada; Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada; BC Centre for Vulvar Health, Vancouver, British Columbia, Canada. Electronic address:

Introduction: 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).

Aim: To analyze the association between sexual/clinical characteristics and a diagnosis of PVD among women with pelvic pain.

Methods: 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).

Main Outcome Measures: 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%).

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.esxm.2019.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523038PMC
June 2019

Uterine artery occlusion at myomectomy? Toward a better definition of the indications.

Fertil Steril 2019 04 8;111(4):685-686. Epub 2019 Mar 8.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1016/j.fertnstert.2019.01.024DOI Listing
April 2019

Temporal trends in severe morbidity and mortality associated with ectopic pregnancy requiring hospitalisation in Washington State, USA: a population-based study.

BMJ Open 2019 02 19;9(2):e024353. Epub 2019 Feb 19.

Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To examine temporal trend in maternal mortality/severe morbidity associated with hospitalisation due to ectopic pregnancy.

Design: A population-based observational study.

Setting And Participants: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1136/bmjopen-2018-024353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367962PMC
February 2019