Increased ApoE Expression in Follicular Fluid and the ApoE Genotype Are Associated With Endometriosis in Chinese Women.

More than 10% of women suffer from endometriosis (EMT) during their reproductive years. EMT can cause pain and infertility and requires further study from multiple perspectives. Previous reports have indicated that an increase inapolipoprotein E (ApoE) may be associated with a lower number of retrieved mature oocytes in older women, and an association between ApoE and spontaneous pregnancy loss may exist in patients with EMT. The purpose of this study was to investigate the existence of an increase in ApoE in follicular fluid (FF) and the possible relationship between ApoE and EMT in Chinese women. In the current study, 217 Chinese women (111 control subjects and 106 EMT patients) were included. The ApoE genotypes were identified by Sanger sequencing. We found that ApoE expression in FF was higher in patients with EMT than in the control group. In addition, a significant difference in ApoE4 carriers (ϵ3/ϵ4, ϵ4/ϵ4) was found between the control subjects and the patients with EMT. Furthermore, a nonparametric test revealed significant differences in the numbers of blastocysts and high-quality blastocysts, but not the hormone levels of FSH, LH, and E2, between the two groups. We also established a multifactor (BMI, high-quality blastocysts, and ϵ4) prediction model with good sensitivity for identifying patients who may suffer from EMT. Our results demonstrate that ApoE expression in FF is increased in EMT, the ApoE-ϵ4 allele is significantly linked to EMT, and a combined analysis of three factors (BMI, high-quality blastocysts, and ϵ4) could be used as a predictor of EMT.

Decreased occurrence of endometriosis in women with Chlamydia trachomatis infection.

PROBLEM: Despite abundant reports on the risk role of uterine outflow tract obstruction in endometriosis, information on the occurrence of endometriosis in women with Chlamydia trachomatis infection causing fallopian tube obstruction is unknown. We investigated the role of Chlamydia trachomatis infection with or without fallopian tubal patency in the occurrence of endometriosis. METHODS: This is a retrospective case-controlled cohort study with 539 women who had laparoscopic surgery for several indications during the period between January, 2003 and June, 2010. Women with ectopic pregnancy, uterine anomaly, chromosomal abnormality, primary amenorrhea, and perimenopausal women were excluded. Endometriosis was diagnosed by laparoscopic inspection and confirmed by histopathology. Tubal patency was diagnosed by HSG or laparoscopic chromopertubation test. Presence of chlamydia infection was examined by RT-PCR and serological test. RESULTS: Two-hundred and seven women were enrolled. Eighty-six (41.5%) women had chlamydia infection. Tubal patency and occurrence of endometriosis were significantly decreased among women with chlamydia infection comparing to women without it (P = .005 and P = .0008, respectively). Even among women with patent tube, laparoscopic detection of endometriosis was significantly decreased in chlamydia infected comparing to non-infected women (P = .02). Multiple logistic regression model revealed that previous history of chlamydia infection significantly decreased the occurrence of endometriosis, and was independent of age, menstrual status, parity and tubal patency (odds ratio .44; 95% confidence interval .24-.80; P = .007). CONCLUSION: A decreased occurrence of peritoneal endometriosis was observed in women with Chlamydia trachomatis infection. The possible impairment of retrograde menstrual flow by chlamydia-infected tubal damage may decrease the risk of endometriosis.

A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome.

Background and Aim: Anogenital distance (AGD) can serve as a life-long indicator of androgen action in gestational weeks 8-14. AGD has been used as an important tool to investigate the exposure to endocrine-disrupting compounds in newborns and in individuals with male reproductive disorder. Endometriosis and polycystic ovary syndrome (PCOS) are two common gynecological disorders and both are related to prenatal androgen levels. Therefore, we performed a systematic review to evaluate the relationships of AGD with these gynecological disorders. Methods: PubMed, Web of Science, and Embase were searched for published studies up to January 25, 2021. No language restriction was implemented. Results: Ten studies were included in this review. Five focused on women with endometriosis, and six investigated women with PCOS. According to these studies, PCOS patients had longer AGD than controls, while endometriosis patients had shorter AGD than controls. In conclusion, this study provides a detailed and accurate review of the associations of AGD with endometriosis and PCOS. Conclusion: The current findings indicate the longer AGD was related to PCOS and shorter AGD was related to endometriosis. However, further well-designed studies are needed to corroborate the current findings.

The effect of endometriosis on sexual function as assessed with the Female Sexual Function Index: systematic review and meta-analysis.

AIM: To systematically compare sexual function between non-treated women with and without endometriosis. METHODS: A systematic review was performed on PubMed/Medline, Scopus, EMBASE, Web of Science and Cochrane Library databases searching studies that analyzed sexual function (assessed with the 19-item Female Sexual Function Index [FSFI]), and dyspareunia, chronic pelvic pain and dysmenorrhea (assessed with a visual analogue scale [VAS]) in women with and with endometriosis. RESULTS: In 4 studies, non-treated women with endometriosis presented a higher risk of female sexual dysfunction (mean total FSFI score ≤ 26.55; OR = 2.38; 95% confidence interval [CI] = 1.12, 5.04). Although mean total FSFI scores were not significantly different between women with and without endometriosis (mean difference [MD] = -2.15; 95% CI -4.96, 0.67); all FSFI domain scores were significantly lower in women with endometriosis (n = 4 studies): desire (MD = -0.43; 95% CI -0.57, -0.19); arousal (MD = -0.66; 95% CI -1.15, -0.17); lubrication (MD = -0.41; 95% CI -0.79, -0.02); orgasm (MD = -0.40; 95% CI -0.73, -0.06); satisfaction (MD = -0.45; 95% CI -0.72, -0.18); and pain (MD = -1.03; 95% CI -1.34, -0.72). Women with endometriosis displayed differences (more severity) in terms of VAS scores (2 studies) for dyspareunia (MD = 1.88; 95% CI 0.38, 3.37) and chronic pelvic pain (MD = 2.92; 95% CI 1.26, 4.58); but not for dysmenorrhea. CONCLUSION: Non-treated women with endometriosis displayed altered sexual function as evidenced by lower scores in all FSFI domains, and severity of dyspareunia and chronic pelvic pain.

Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure.

BACKGROUND: Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis. OBJECTIVE AND RATIONALE: We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments. SEARCH METHODS: We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment. OUTCOMES: Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response. WIDER IMPLICATIONS: Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.

Pain and Quality of Life after Laparoscopic Excision of Endometriosis.

STUDY OBJECTIVE: To evaluate the long-term impact of laparoscopic excision of endometriosis on quality of life through pain reduction as measured by the Endometriosis Health Profile-30 (EHP-30) in uterine-sparing (preservation of the uterus and at least 1 ovary) and nonuterine-sparing (removal of the uterus) surgery. DESIGN: Cohort study. SETTING: Academic medical center. PATIENTS: Sixty-one women who had undergone laparoscopic excision of endometriosis for pelvic pain were enrolled in a tissue-procurement study. INTERVENTIONS: Patients who had previously completed an EHP-30 preoperatively and at 4 weeks postoperatively were mailed a copy of the EHP-30 2.6 to 6.8 years after their index surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome was quality of life as measured by changes in the EHP-30 scores before their index surgery and those measured weeks and years later. The secondary outcome was a comparison of the EHP-30 scores between patients who underwent excision of endometriosis alone and those who underwent excision of endometriosis with hysterectomy +/- oophorectomy. From 2011 to 2015, 61 women underwent laparoscopic excision of endometriosis for pelvic pain. Forty-six of the 61 patients completed the EHP-30 for a response rate of 75%. The patients demonstrated significant improvement in all 5 scales of the EHP-30 (pain, control and powerlessness, emotional well-being, social support, and self-image) at 4 weeks postoperatively (p <.001), which persisted for up to 6.8 years in follow-up (p <.001) when compared with their baseline scores. The improvement in EHP-30 scores did not differ by American Society for Reproductive Medicine staging or index surgery. Definitive surgery (total laparoscopic hysterectomy/bilateral salpingo-oophorectomy) was not associated with improved outcomes when compared with uterine-sparing surgery. CONCLUSION: Laparoscopic excision of endometriosis offers improvement in all quality-of-life domains as measured by the EHP-30, including a reduction in pain, an effect that may persist for up to 6.8 years. These findings suggest that laparoscopic excision of endometriosis with uterine preservation can be considered as an option for discussion during counseling for treatment of endometriosis.

Prevalence of negative sliding sign representing pouch of Douglas obliteration during pelvic transvaginal ultrasound for any indication.

OBJECTIVES: Pouch of Douglas (POD) obliteration can be predicted with a high degree of certainty and reproducibility using the dynamic transvaginal ultrasound (TVS) sliding-sign technique. So far, studies on POD obliteration prediction have focused on tertiary-care populations with high prevalence of endometriosis; however, POD obliteration may exist in individuals with asymptomatic endometriosis or other conditions. Our primary aim was to determine the prevalence of a negative sliding sign, representing POD obliteration, in a cohort of patients undergoing TVS for any gynecological indication. METHODS: This was a prospective observational study of consecutive women with an indication for gynecological TVS, conducted at a high-volume ultrasound practice between July and August 2018. Clinical and surgical history, indication for TVS and TVS findings were documented. The prevalence of TVS-confirmed POD obliteration, determined by interpretation of the sliding sign, was calculated for the entire cohort and for the subgroups of women with and without risk factors for endometriosis. High risk for endometriosis was defined as having (1) a TVS referral for endometriosis-like pelvic pain or endometriosis specifically and/or (2) clinical symptoms or signs suggestive of endometriosis. Low risk was defined as the absence of these characteristics. RESULTS: During the study period, 1043 consecutive women underwent TVS. After excluding those who underwent transabdominal ultrasound, had a history of hysterectomy or with missing data, 909 women were analyzed. The prevalence of a negative sliding sign in the entire cohort was 47/909 (5.2%). A negative sliding sign was observed in 22/639 (3.4%) women with a low risk for endometriosis and 25/243 (10.3%) of those with a high risk for endometriosis (difference in proportions, 6.9% (95% CI 2.8-10.9%); P < 0.001). CONCLUSIONS: We have demonstrated an overall prevalence of a negative sliding sign, suggesting POD obliteration, of 5.2% (or 1/20) in women seeking TVS for a gynecological indication. The prevalence of negative sliding sign in low-risk women is not negligible (3.4% or 1/29 women). These women are most likely to have asymptomatic endometriosis or another important etiology of POD obliteration. The prevalence of a negative sliding sign is approximately three-times higher in women with signs and/or symptoms of endometriosis (10.3% vs 3.4%). Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVOS: La obliteración del fondo de saco de Douglas (FSD) puede predecirse con un alto grado de certeza y reproducibilidad usando la técnica del signo deslizante en una ecografía transvaginal dinámica (TVS, por sus siglas en inglés). Hasta ahora, los estudios sobre la predicción de la obliteración del FSD se han centrado en las poblaciones de atención terciaria con alta prevalencia de endometriosis; sin embargo, la obliteración del FSD puede ocurrir en personas con endometriosis asintomática u otras afecciones. El objetivo principal fue determinar la prevalencia de un signo deslizante negativo, como indicador de la obliteración del FSD, en una cohorte de pacientes que se sometieron a TVS por cualquier indicación ginecológica. MÉTODOS: Se trató de un estudio observacional prospectivo de mujeres en una lista consecutiva a quienes se les indicó una TVS ginecológica, realizada en una consulta de ecografía de gran volumen de pacientes entre julio y agosto de 2018. Se documentaron los antecedentes clínicos y quirúrgicos, las indicaciones para la TVS y los hallazgos de la TVS. La prevalencia de la obliteración del FSD confirmada por la TVS, determinada por la interpretación del signo deslizante, se calculó para toda la cohorte y para subgrupos de mujeres con y sin factores de riesgo de endometriosis. El riesgo elevado de endometriosis se definió como el hecho de tener (1) una remisión para TVS debido a dolor pélvico similar a la endometriosis o endometriosis específicamente y/o (2) síntomas o indicios clínicos que sugerían endometriosis. El riesgo bajo se definió como la ausencia de estas características. RESULTADOS: Durante el período de estudio, 1043 mujeres se sometieron a TVS de forma consecutiva. Se analizaron 909 mujeres, tras excluir a las que se sometieron a una ecografía abdominal, las que tenían antecedentes de histerectomía o aquellas para las que faltaban datos. La prevalencia de un signo deslizante negativo en toda la cohorte fue de 47/909 (5,2%). Se observó un signo deslizante negativo en 22/639 (3,4%) de las mujeres con bajo riesgo de endometriosis y en 25/243 (10,3%) de aquellas con alto riesgo de endometriosis (diferencia de proporciones, 6,9% (IC 95%: 2,8-10,9%); P<0,001). CONCLUSIONES: Se demuestra una prevalencia general de un signo deslizante negativo, que sugiere la obliteración del FSD en el 5,2% (o 1/20) de mujeres que se someten a TVS para una indicación ginecológica. La prevalencia del signo deslizante negativo en las mujeres de bajo riesgo no es desdeñable (3,4% o 1/29 mujeres). Estas mujeres son las más propensas a tener endometriosis asintomática u otra etiología importante de obliteración del FSD. La prevalencia de un signo deslizante negativo es aproximadamente tres veces mayor en mujeres con signos y/o síntomas de endometriosis (10,3% vs 3,4%). Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (n = 419), with the aim to evaluate the prevalence of concomitant uterine disorders. The US coexistence of endometriosis with uterine fibroids and/or adenomyosis was investigated according to three age intervals (<35years; 35 ≥ years <45; ≥45 years) and to endometriosis phenotypes: ovarian endometriosis (OMA), deep infiltrating endometriosis (DIE), or both. The US diagnosis of fibroids was made in 3.1% of cases, adenomyosis was found in 21.2%, and the co-existence of both uterine disorders with endometriosis was reported in 14.6% of patients. When analyzed according to age, patients aged >35 years were more likely to be affected by uterine fibroids (p = .003), adenomyosis (p = .030) and both adenomyosis and fibroids (p < .0001). No statistically significant association was found between endometriosis phenotypes and myometrial pathologies. Uterine disorders coexistence should be considered in the assessment of women with endometriosis, in order to better define a treatment strategy for infertility, especially in women older than 35 years.

Hypothetical roadmap towards endometriosis: prenatal endocrine-disrupting chemical pollutant exposure, anogenital distance, gut-genital microbiota and subclinical infections.

BACKGROUND: Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. OBJECTIVE AND RATIONALE: In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. SEARCH METHODS: We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota-immune system interactions. OUTCOMES: On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis. WIDER IMPLICATIONS: Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.

Adiposity and Endometriosis Severity and Typology.

STUDY OBJECTIVE: Prior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology. DESIGN: Cross-sectional study among women with no prior diagnosis of endometriosis. SETTING: Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA. PATIENTS: A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. INTERVENTIONS: Gynecologic laparoscopy/laparotomy regardless of clinical indication. MEASUREMENTS AND MAIN RESULTS: Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators. CONCLUSION: Our research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.

Relationship between Patient Age and Disease Features in a Prospective Cohort of 1560 Women Affected by Endometriosis.

OBJECTIVE: To assess the relationship between age, location of the disease, and surgical procedures performed in patients undergoing surgical management of endometriosis. DESIGN: Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database. SETTING: University tertiary referral center. PATIENTS: Women who underwent surgical management of symptomatic endometriosis between April 2009 and April 2014. INTERVENTIONS: Patients were allocated to 6 groups according to their age at the time of surgery: ≤20, 21 to 25, 26 to 30, 31 to 35, 36 to 40 and >40 years. Patient characteristics, prior history, location of endometriotic lesions, stage of disease, intraoperative findings, and surgical procedures were retrieved from a prospectively recorded database. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, symptoms, location of endometriosis, and type of surgery performed were compared between groups. In total, 1560 procedures were performed. Of these, more than one-half were carried out in women between the age of 26 to 35 years and the majority were performed in women aged between 26 and 30 years. Only 2% of procedures were performed in women under the age of 20 years. The mean stage of the disease at the time of surgical diagnosis was stage II for women younger than 20 years, stage III for those in the age group of 21 to 25 years, and stage IV for those older than 26 years. The rate of diagnosis of deep colorectal nodules increased progressively from 20 to 26 years and remained stable thereafter. CONCLUSION: Our data confirm that endometriosis is a disease that probably progresses from adolescence until the adult period when symptoms (pain or infertility) become debilitating and require surgery. Our data suggest that policies relating to the prevention and early diagnosis of endometriosis should focus on women younger than 25 years.

The Role of Fertility Preservation in Women with Endometriosis: A Systematic Review.

OBJECTIVE: To summarize the available evidence concerning fertility preservation techniques in the context of women with endometriosis. DATA SOURCES: We searched for studies published between 1984 and 2019 on endometriosis and Assisted Reproductive Technology outcomes. We searched MEDLINE and PubMed and performed a manual search of reference lists within identified studies. METHODS OF STUDY SELECTION: A total of 426 articles were identified, and 7 studies were eligible to be included for the systematic review. We included all published studies, excluding reviews, case reports, and animal studies. TABULATION, INTEGRATION, AND RESULTS: Despite a significant increase in the number of studies addressing fertility preservation over the study period, we found a relative lack of evidence addressing the use of fertility preservation techniques in women with endometriosis. The studies identified included 2 case reports, 1 histological science study, and 4 retrospective cohort studies. CONCLUSION: Women with endometriosis may benefit from fertility preservation techniques. However, there currently is a paucity of data in this population, especially when compared with other indications for fertility preservation. Although much knowledge can be translated from the oncofertility discipline, we have identified and discussed endometriosis-related changes to ovarian reserve and oocyte health that justify further well-designed research to confirm that fertility preservation outcomes are similar for women with endometriosis.

Hospital-Associated Cost of Endometriosis in Canada: A Population-Based Study.

STUDY OBJECTIVE: To describe the hospital-associated cost of endometriosis in Canada from April 2008 to March 2013. DESIGN: Population-based descriptive study. SETTING: Canada, with the exception of the province of Quebec. PATIENTS: All women aged 15 to 59 years discharged with endometriosis between April 2008 and March 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over 5 years, 47 021 women were admitted for endometriosis, resulting in a total hospital cost of Canadian dollars (CaD) $152.21 million (US dollars [US $] 147.79 million) and per-case cost of CaD $3237 (US $3143). Uterine endometriosis accounted for 28.29% of cases, ovarian endometriosis 27.44%, and other endometriosis 44.27%. Cost for uterine endometriosis was the highest at CaD $4137 (US $4017) per case, followed by ovarian endometriosis (CaD $3506; US $3404) and other endometriosis (CaD $2495; US $2422). The highest number of cases were in the groups aged 35 to 39 years (20.77%) and 40 to 44 years (20.44%). Hysterectomy accounted for 29.57% of surgical procedures. Encounters with hysterectomy were the costliest at CaD $5062 (US $4915) per case, followed by the ones with other surgical procedures at CaD $2477 (US $2405) per case, and admissions with no surgical procedure at CaD $2164 (US $2101) per case. CONCLUSION: The hospital cost associated with endometriosis was approximately CaD $30 million (US $29.56 million) per year, whereas uterine endometriosis, hysterectomy, and older age were found to have a higher average cost per case. Although this study focuses specifically on hospital admission and does not account for outpatient costs or indirect costs, it nonetheless highlights the economic burden of this debilitating disease on Canadian society during the study period.

High prevalence of autoimmune diseases in women with endometriosis: a case-control study.

The immune system seems to be involved in the pathogenesis of endometriosis. Peritoneal chronic inflammation is present and natural killer cells and macrophages abnormalities have been reported in women with the disease. Moreover, a higher production of serum autoantibodies has been found, which could be related to various factors; some still need to be clarified. The correlation between endometriosis and autoimmune diseases is still unclear with few and conflicting available data. The aim of this study was to evaluate the prevalence of autoimmune diseases, as conditions with a possible common pathogenetic factor, in women affected by endometriosis, in order to address future research on its pathogenesis. This retrospective case-control study includes one hundred and forty-eight women with endometriosis and 150 controls. All women were aged between 18 and 45. Informed consent was obtained from all participants of the study. Considered autoimmune diseases include systemic lupus erythematosus (SLE), celiac disease (CD), inflammatory bowel disease (IBD), and autoimmune thyroiditis. Statistical comparison of patients and control group was performed by means of chi-square test or Fisher's exact test as appropriate. Statistical comparison of parametric variable (age) among the groups was performed by t-test for unpaired data. Age was expressed as mean. A value of .05 or less was considered as significant. In the case group, five patients were affected by IBD, while the disease was not observed in the control group (p = .07). SLE was found in eight patients in the case group, while only one was found in the control group (p = .01). Fifteen women in the case group were affected by CD, while the disease was present only in one woman in the control group (p<.0001). A significant correlation was also found between endometriosis and autoimmune thyroiditis: 80 patients with endometriosis had thyroid diseases versus 14 patients in the control group (p<.0001). Our study reports an association between endometriosis and autoimmune disorders, showing a higher prevalence of autoimmune diseases in women affected by endometriosis. These results support a possible autoimmune pathogenesis of endometriosis.

Possible Role of the Posterior Compartment Peritonectomy, as a Part of the Complex Surgery, Regarding Recurrence Rate, Improvement of Symptoms and Fertility Rate in Patients with Endometriosis, Long-Term Follow-Up.

STUDY OBJECTIVE: Beside the pain, there are 2 further problems in the management of endometriosis: the high recurrence rate (10% per year) and the high rate of impaired fertility. The objective of this study was to investigate the pathogenesis of these 2 factors. DESIGN: This is a retrospective cohort study, and the aim is to evaluate the complete excision of endometriotic lesions, including the posterior compartment of the peritoneum, with regard to postoperative outcome, focusing on relieving pain, increasing fertility rate, and decreasing recurrence rate. SETTING: Charité-University Clinic, Department of Gynaecology, Endometriosis research Centre. PATIENTS: Fifty-four patients were enrolled in this study, with severe deep infiltrating endometriosis (scored by ENZIAN) and superficial endometriosis, as well as endometriomas (revised American Society for Reproductive Medicine [rASRM] I = 3; II = 15; III = 10; and IV = 26). INTERVENTIONS: Posterior compartment peritonectomy (visible endometriotic lesions and inflamed altered peritoneum) was performed in all patients as part of a complex surgery: complete excision of endometriosis. MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes were evaluated, based on the postoperative follow-up (up to 5 years) of 54 investigated patients. In 36 women (66%) preoperative complaints were eliminated. Furthermore, of 28 women seeking improved fertility, pregnancy was reported in 13 cases (46%). In 7 (54%) cases pregnancy occurred spontaneously, and in the remainder with assisted fertilization. In addition, long-term follow-up demonstrated a recurrence rate in 1.8% of patients. CONCLUSION: Overall, the number of complaints was significantly reduced. Only in the case of reproductive-aged women with ongoing postoperative complaints was it important to preserve the uterus. Although this pilot study on systematic posterior peritonectomy showed improvement in recurrence and fertility rate, the main question remains: will this surgical technique achieve better results and outcomes in the future? This has to be addressed in a prospective randomized study.

Identification of Predictive Factors in Endometriosis for Improvement in Patient Quality of Life.

STUDY OBJECTIVE: To investigate predictive factors for change in quality of life (QOL) between pre- and postoperative periods in patients with endometriosis. DESIGN: A prospective and multicenter cohort study. SETTING: Five districts including a tertiary referral center and private and general public hospitals. PATIENTS: Nine hundred eighty-one patients aged 15 to 50 years underwent laparoscopic treatment (preferred approach) for endometriosis between January 2004 and December 2012. INTERVENTIONS: Laparoscopic treatment for endometriosis. All revised American Fertility Society stages were included. MEASUREMENTS AND MAIN RESULTS: QOL was evaluated using the 36-Item Short Form Survey questionnaire. Factors influencing changes for each 36-Item Shorty Form Survey domain score between t0 (before surgery) and 1 year after surgery were predicted on the basis of univariate and multivariable analyses. The effect size (ES) method was used to measure changes in QOL. Univariate analysis revealed that 47% of stage IV endometriosis patients presented an improvement in the postoperative Physical Component Summary (PCS) score (ES ≥ 0.8) versus 26%, 31.3%, and 27.5% of patients with stage I, II, and III, respectively (p <.001). Forty-four percent and 38% of patients with chronic pelvic pain (CPP) presented an improvement in postoperative PCS and Mental Component Summary scores (ES>0.8) versus 23% and 24% of patients without CPP, respectively (p <.001). Multivariable analysis (ES > 0.8 vs ES < 0) revealed that women with CPP were more likely to experience greater improvement in postoperative PCS and Mental Component Summary scores than women without CPP (relative risk [RR] = 2.7; 95% confidence interval [CI], 1.7-4.4; p <.001 and RR = 1.8; 95% CI, 1.2-2.8; p <.01, respectively). Accordingly, fertile patients were more likely to show higher rates of improvement in the postoperative PCS score than infertile patients (RR = 1.8; 95% CI, 1.1-3.1; p <.05). CONCLUSION: Patients presenting with severe endometriosis and who experience higher levels of pain are more likely to show improvement in QOL after surgery. CPP is the most significant independent predictive factor for changes in QOL scores.

Comparison of Laparoscopic Hysterectomy in Patients with Endometriosis with and without an Obliterated Cul-de-sac.

STUDY OBJECTIVE: To determine if intraoperative outcomes for patients undergoing laparoscopic hysterectomy with endometriosis and an obliterated cul-de-sac are different than patients with endometriosis and no obliteration of the cul-de-sac. DESIGN: A retrospective cohort study. SETTING: An academic tertiary care hospital. PATIENTS: Patients undergoing total laparoscopic hysterectomy with endometriosis between 2012 and 2016. INTERVENTIONS: Total laparoscopic hysterectomy, laparoscopic modified radical hysterectomy, and other procedures as indicated. MEASUREMENTS AND MAIN RESULTS: A total of 333 patients undergoing hysterectomy were found to have endometriosis at the time of surgery. Ninety-six (29%) patients were found to have stage IV endometriosis as defined by the American Society for Reproductive Medicine staging criteria. Of those, 55 (57%) had an obliterated cul-de-sac, and 41 (43%) did not. The remaining 237 (71%) patients had stage I, II, or III endometriosis. Fifty-one (93%) patients with an obliterated cul-de-sac required laparoscopic modified radical hysterectomy compared with 12 (29%) patients with stage IV endometriosis without obliteration and 60 (25%) patients with stages I through III endometriosis (p < .0001). The median total surgical time in minutes differed among the 3 groups as follows: obliterated cul-de-sac = 159 minutes, stage IV endometriosis without obliteration = 108 minutes, and stages I through III endometriosis = 116 minutes (p <.0001). Additional procedures at the time of hysterectomy were more frequently performed for patients with an obliterated cul-de-sac and included salpingectomy (p = .02), ureterolysis (p <.0001), enterolysis (p <.0001), cystoscopy (p = .0006), ureteral stenting (p <.0001), proctoscopy (p <.0001), oversewing of the bowel (p <.0001), and anterior resection and anastomosis (p = .006). CONCLUSION: Patients with stage IV endometriosis and an obliterated cul-de-sac required laparoscopic modified radical hysterectomy and various other intraoperative procedures more than patients with stage IV endometriosis without obliteration and stages I through III. Patients with obliterated cul-de-sacs who are identified intraoperatively should be referred to minimally invasive gynecologic specialists because of the difficult nature of these procedures and extra training required to perform them safely with limited morbidity.

When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted. METHODS OF STUDY SELECTION: Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible. TABULATION, INTEGRATION, AND RESULTS: In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p <.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified. CONCLUSION: Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).

Identifying Preoperative Factors Associated with Nonresponders in Women Undergoing Comprehensive Surgical Treatment for Endometriosis.

STUDY OBJECTIVE: To examine whether existing quality of health outcome measures can be used to predict or have an association with nonresponse surgery for endometriosis. DESIGN: Retrospective cohort study. SETTINGS: Single endometriosis referral center. PATIENTS: Women (n = 198) undergoing surgery for endometriosis. INTERVENTIONS: Validated health questionnaires and visual analogue scales. MEASUREMENTS AND MAIN RESULTS: Patients were given validated health questionnaires, including Endometriosis Health Profile 30, Gastrointestinal Quality of Life Index, EuroQol-5, Hospital Anxiety and Depression Scale, preoperatively and at 12 months after full surgical excision of endometriosis. Visual analogue scales were also used that measured dyschezia, dysmenorrhea, dyspareunia, and chronic pelvic pain. Surgical management was dependent on severity of disease. Superficial disease was treated by laparoscopic peritoneal excision or laser ablation. Deep infiltrating disease involving the bowel was excised completely together with laparoscopic bowel surgery (shave, disc, or segmental resection) with/without concomitant total hysterectomy and bilateral salpingo-oophorectomy. Nonresponders were defined as women who failed to demonstrate an improvement in pain scores 12 months postoperatively. We examined preoperative and postoperative questionnaires, visual analogue scores, and other variables such as age at onset of symptoms, type of surgery, and the presence of postoperative complications comparing responder and nonresponder women to identify the factors associated with nonresponse. Of 102 women treated for superficial endometriosis, 25 (24.51%) were nonresponders. No factors were associated with nonresponse at 12 months. Of 96 women treated for severe endometriosis involving the bowel, 10 (10.41%) were nonresponders. Nonresponders had significantly less preoperative pain (p = .031) and feeling of control (p = .015) than responders. There was no association between nonresponders and women who underwent a hysterectomy with bilateral salpingo-oophorectomy or those with complications. Radical bowel surgery (resection) was associated with nonresponders. CONCLUSION: Minimal preoperative factors are associated with nonresponse for women having surgery for endometriosis. The severity of pain experienced by women with endometriosis may be used to predict their response to surgery.

Is Endometriosis More Common and More Severe Than It Was 30 Years Ago?

OBJECTIVE: Current estimates of endometriosis prevalence and incidence are highly variable, leading to uncertainty regarding true endometriosis frequency or validity of quantified changes over time. We present a comprehensive review of the prevalence, incidence, and stage of endometriosis worldwide as reported over the past 30 years. DATA SOURCES: We conducted a systematic search of observational studies using the PubMed, Web of Science, EMBASE, and CINAHL databases to identify research papers published in English between January 1989 and June 2019. Search terminologies were limited to titles containing endometriosis and prevalence or incidence, or epidemiology, or frequency, or occurrence, or statistics. METHODS OF STUDY SELECTION: Two independent reviewers screened abstracts for study eligibility, and data from included studies were abstracted. TABULATION, INTEGRATION, AND RESULTS: Overall, 69 studies describing the prevalence and/or incidence of endometriosis met the inclusion criteria. Among these, 26 studies involved general population samples, 17 of which were from regional/national hospitals or insurance claims systems. The other 43 studies were conducted in single clinic or hospital settings. Prevalence estimates for endometriosis widely varied from 0.2% to 71.4% depending on the population sampled. The prevalence reported in general population studies ranged from 0.7% to 8.6%, whereas that reported in single clinic- or hospital-based studies ranged from 0.2% to 71.4%. When defined by indications for diagnosis, endometriosis prevalence ranged from 15.4% to 71.4% among women with chronic pelvic pain, 9.0% to 68.0% among women presenting with infertility, and 3.7% to 43.3% among women undergoing tubal sterilization. A meta-regression was conducted with year as the predictor of prevalence. No trend across time was observed among "general population in country/region" studies (ß = 0.04, p = .12) or among "single hospital or clinic" studies (ß = -0.02, p = .34); however, a decrease over time was observed among general population studies abstracted from health systems or insurance systems (ß = -0.10, p = .005). CONCLUSION: As with all human studies, population sampling and study design matter. Heterogeneity of inclusion and diagnostic criteria and selection bias overwhelmingly account for variability in endometriosis prevalence estimated across the literature. Thus, it is difficult to conclude if the lack of observed change in frequency and distribution of endometriosis over the past 30 years is valid.