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Background: Endometriosis is an estrogen-dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants. Thus, necessity of identifying rare variants for the missing heritability is implicated in the literature. Therefore, our study aimed to identify novel rare genetic variants involved in the pathogenesis of endometriosis utilizing a family of multiple affected members., Methods: A family composed of four affected women along with their two unaffected mothers were recruited at a single gynecology and infertility clinic specialized in endometriosis. All patients presented with endometriomas, which was visualized by transvaginal ultrasonography. Two affected individuals had received laparoscopic endometrioma excision and therefore were diagnosed with recurrent disease. One mother had a history of endometrial serous adenocarcinoma (ESC) for which she underwent hysterectomy with bilateral oophorectomy. Three endometriosis cases were whole exome sequenced on Illumina NextSeq 550 platform with an average of 90% coverage. Candidate genes were confirmed by Sanger sequencing and followed-up with family segregation., Results: Novel rare variants were identified in TNFRSF1B (NM_001066.3: c.1072G>A, p.(Ala358Thr)) and GEN1 (NM_001130009.3: c.1574C>T, p.(Ser525Leu)) as possible genetic causes of endometriosis. A third novel rare variant was identified in CRABP1 (NM_004378.3:c.54G>C, p.(Glu18Asp)) only on the mother with ESC history and her daughters., Conclusion: Novel candidate genetic variants that might contribute to endometriosis were suggested that need replication through independent cohorts or validation by functional studies. The family has also received genetic counseling and that the affected daughters are on clinical follow-up, accordingly., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: This review aimed to compare isolated sciatic and sacral nerve root endometriosis in terms of anatomic distribution, patients' symptoms and history, diagnostics, treatments, and outcomes., Data Source: We searched PubMed, MEDLINE, Web of Science, and Embase from inception to October 2021 using a combination of keywords including "sciatic nerve endometriosis," "sacral nerve root endometriosis," and associated Medical Subject Headings. Relevant publications and references were also checked for further articles., Methods of Study Selection: Two independent researchers performed the study selection. We included all original research articles, case reports, and case series in English that reported on the isolated sciatic nerve and sacral nerve root endometriosis., Tabulation, Integration, and Results: The initial search identified 92 articles, and 40 articles, mostly case reports and case series, were included. The review included 362 patients: with 256 and 106 patients in the sacral and the sciatic groups, respectively. In both groups, most patients had right-sided endometriosis. In the sciatic group, most of the patients presented with foot drop, leg motor weakness, and sciatic dermatome hypoesthesia. The frequencies of all these symptoms were significantly higher in the sciatic group (all p <.001). By contrast, in the sacral group, most of patients presented with pudendal neuralgia (p <.001). Intraoperative, early, late, and 1-year postoperative complications did not differ significantly between the 2 groups., Conclusion: This study indicated that isolated sciatic and sacral nerve root endometrioses were more common on the right side. Laparoscopic surgery was more commonly performed over traditional open or transgluteal surgery techniques. Sacral nerve root endometriosis is often accompanied by deep infiltrating endometriosis. Magnetic resonance imaging and myelography may be useful diagnostic tools in the preoperative workup. There was usually no significant improvement after surgery in cases of isolated sciatic nerve endometriosis presenting with foot drop., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to analyze the available literature by conducting a systematic review to assess the possible effects of nerve-sparing segmental resection and conventional bowel resection on postoperative complications for the treatment of colorectal endometriosis., Material and Methods: Pubmed, Clinical Trials.gov, Cochrane Library, and Web of Science were comprehensively searched from 1997 to 2021 in order to perform a systematic review. Studies including patients undergoing segmental resection for colorectal endometriosis including adequate follow-up, data on postoperative complications and postoperative sequelae were enrolled in this review. Selected articles were evaluated and divided in two groups: Nerve-sparing resection (NSR), and conventional segmental resection not otherwise specified (SRNOS). Within the NSRs, studies mentioning preservation of the rectal artery supply (artery and nerve-sparing SR - ANSR) and not reporting preservation of the artery supply (NSR not otherwise specified - NSRNOS) were further analyzed., Prospero Id: CRD42021250974., Results: A total of 7549 patients from 63 studies were included in the data analysis. Forty-three of these publications did not mention the preservation or the removal of the hypogastric nerve plexus, or main rectal artery supply and were summarized as SRNOS. The remaining 22 studies were listed under the NSR group. The mean size of the resected deep endometriosis lesions and patients' body mass index were comparable between SRNOS and NSR. A mean of 3.6% (0-16.6) and 2.3% (0-10.5%) of rectovaginal fistula development was reported in patients who underwent SRNOS and NSR, respectively. Anastomotic leakage rates varied from 0% to 8.6% (mean 1.7 ± 2%) in SRNOS compared with 0% to 8% (mean 1.7 ± 2%) in patients undergoing NSR. Urinary retention (4.5% and 4.9%) and long-term bladder catheterization (4.9% and 5.6%) were frequently reported in SRNOS and NSR. There was insufficient information about pain or the recurrence rates for women undergoing SRNOS and NSR., Conclusions: Current data describe the outcomes of different segmental resection techniques. However, the data are inhomogeneous and not sufficient to reach a conclusion regarding a possible advantage of one technique over the other., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

As search for optimal therapy continues for endometriosis, aid of dietary supplements is gaining attention. Supplements can be used for their anti-inflammatory, anti-oxidant, anti-proliferative and immune modulatory charactheristics. We reviewed the literature, evaluated and synthesized effects of vitamin D, zinc, magnesium, omega 3, propolis, quercetin, curcumin, N-acetylcysteine, probiotics, resveratrol, alpha lipoic acid, vitamin C, vitamin E, selenium and epigallocatechin-3-gallate. Based on results of in vitro, animal and human studies, it might be safe to say that dietary supplements can be used as a complementary treatment for endometriosis.

Objective: This review aimed to categorize thoracic endometriosis syndrome (TES) according to whether the presenting symptoms were catamenial and to evaluate whether such a categorization enables a better management strategy., Data Sources: An electronic search was conducted using the PubMed/Medline database., Methods of Study Selection: The following keywords were used in combination with the Boolean operators AND OR: "thoracic endometriosis syndrome," "thoracic endometriosis," "diaphragm endometriosis," and "catamenial pneumothorax.", Tabulation, Integration, and Results: The initial search yielded 445 articles. Articles in non-English languages, those whose full texts were unavailable, and those that did not present the symptomatology clearly were further excluded. After these exclusions, the review included 240 articles and 480 patients: 61 patients in the noncatamenial group and 419 patients in the catamenial group. The groups differed significantly in presenting symptoms, surgical treatment techniques, and observed localization of endometriotic loci (p <.05)., Conclusion: This review points out the significant differences between patients with TES with catamenial and noncatamenial symptoms. Such categorization and awareness by clinicians of these differences among patients with TES can be helpful in designing a management strategy. When constructing management guidelines, these differences between patients with catamenial and noncatamenial symptoms should be taken into consideration., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To assess the reliability of YouTube® endometrioma cystectomy videos based on technical video analysis and considering the surgical steps., Material and Method: The present study yielded 756 videos after a search on YouTube® with the keywords "endometriosis cystectomy, endometrioma cystectomy, chocolate cyst cystectomy, and endometrioma surgery'' during the period from January 7, 2007 to January 7, 2019. The viewer interest parameters such as total number of subscribers, views, likes, dislikes, comments, source of the videos, and the date of upload were assessed. Besides, the surgical steps were also evaluated considering committee suggestions., Results: There were 140 (78.7 %) videos in Group 1 (not useful and slightly useful) and 38 (21.3 %) videos in Group 2 (useful and very useful). The mean numbers of subscribers, views, and likes were 5737.843 ± 15741.302, 10614.257 ± 32702.339, and 17.7 ± 43.57, respectively, in Group 1, and 851.052 ± 1613.599, 8192.55 ± 15989.955, and 11.92 ± 27.52, respectively, in Group 2. The type of surgery was significantly different between the study groups. The videos of cases with robotic surgeries presented more useful descriptive information (p =  0.003). There was a significant difference between the study groups regarding the type of hemostasis. The presence of didactic steps was higher in Group 2 (47.4 %) compared to Group 1 (28.6 %) (p =  0.02) CONCLUSIONS: Overall, only around 21 % of YouTube videos presenting endometrioma surgery were defined as useful or very useful. The interest rates of the viewers may not compatible with the usefulness rate of the videos., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To apply rapid online surveying to determine the knowledge and perceptions of the COVID-19 pandemic on patients with endometriosis in Turkey., Methods: An online survey was conducted by the Turkish Endometriosis & Adenomyosis Society and administered to patients with endometriosis who agreed to participate in the study. The survey included 25 questions prepared by an expert committee of four professionals (two gynecologists and two endometriosis specialists)., Results: Of the 290 questionnaires sent out, 261 (90%) were returned. A total of 213 (83.86%) patients reported that they were afraid of having endometriosis-related problems during the pandemic period. In addition, 133 (53.63%) patients thought the management of their endometriosis was affected because of the pandemic., Conclusion: Clinical studies clearly indicate that endometriosis is a condition associated with high levels of chronic stress. The COVID-19 pandemic has led the public to experience psychological problems such as post-traumatic stress disorder, psychological distress, depression, and anxiety. The majority of patients with endometriosis were afraid of having endometriosis-related problems during the pandemic period. The majority of elective endometriosis surgeries have not been postponed. Patients were highly aware of the pandemic and practiced social distancing and hygiene. Only 4 (1.59%) patients with endometriosis required hospitalization., (© 2020 International Federation of Gynecology and Obstetrics.)

Objective: Endometriosis is an estrogen-dependent chronic disease, which is regarded as a disease of reproductive-aged women. Endometriosis is most frequently diagnosed during reproductive period. We aimed to determine the frequency of endometrioma in women over 40 years of age who were operated for adnexial mass., Materials and Methods: A total of 1100 women over 40 years of age underwent surgery for adnexal mass were included in this cohort study between 2006 and 2016. Women who met the criteria were compared regarding the type of adnexial mass, age groups, menopausal status and malignant transformation., Results: A total of 299 women (27.2 %) with benign ovarian mass were determined to have endometrioma. Women with endometrioma were younger and nulliparous more frequently comparing women without endometrioma. Although 20 % of the patients in the endometrioma group were postmenopausal, 70 % of the patients in the control group were postmenopausal. Endometrioma-associated ovarian tumors were developed in nearly 11 % of women with endometrioma., Conclusions: Even though endometriosis is accepted as a disease of reproductive-aged women, it can occur over 40 years of age. Detailed anamnesis and careful gynecological examination provide key information for differential diagnosis. Accurate information about the risk of malignant transformation should be informed., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Peri/postmenopausal endometriosis is not as rare as once we thought. Accumulated data revealed that around 1/3-1/4 of women with surgically-diagnosed endometriosis after the age of 40. The uneasiness of the issue of malignant transformation or malignancy in such women created a challenge for us. Here the management strategy for women with endometriosis after the age of 40 is discussed in the light of scientific evidence.

Endometriosis is an estrogen-dependent disease that affects 5 to 15% of women of reproductive age. Data from large-cohort and case-control studies indicate an increased risk for ovarian cancers in women with endometrioma. Recently, as an ovarian cancer biomarker, human epididymal secretory protein E4 (HE4) has been increasingly investigated in the differentiating of endometrioma from ovary malignancy and in confirming the benign structure of the endometrioma. This case series study describes women who underwent surgery due to increased serum HE4 levels and higher Risk of Ovarian Malignancy Algorithm (ROMA) index, in whom the final pathology was reported as benign, although, ultrasonography and magnetic resonance imaging (MRI) findings showed features of "typical" endometrioma.

Endometriosis is a condition in which the endometrium, the layer of tissue that usually covers the inside of the uterus, grows outside the uterus. One of its severe effects is sub-fertility. The exact reason for endometriosis is still unknown and under investigation. Tracking the symptoms is not sufficient for diagnosing the disease. A successful diagnosis can only be made using laparoscopy. During the disease, the amount of some molecules (i.e., proteins, antigens) changes in the blood. Raman spectroscopy provides information about biochemicals without using dyes or external labels. In this study, Raman spectroscopy is used as a non-invasive diagnostic method for endometriosis. The Raman spectra of 94 serum samples acquired from 49 patients and 45 healthy individuals were compared for this study. Principal Component Analysis (PCA), k- Nearest Neighbors (kNN), and Support Vector Machines (SVM) were used in the analysis. According to the results (using 80 measurements for training and 14 measurements for the test set), it was found that kNN-weighted gave the best classification model with sensitivity and specificity values of 80.5% and 89.7%, respectively. Testing the model with unseen data yielded a sensitivity value of 100% and a specificity value of 100%. To the best of our knowledge, this is the first study in which Raman spectroscopy was used in combination with PCA and classification algorithms as a non-invasive method applied on blood sera for the diagnosis of endometriosis.

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline ovarian tumours and the endometriosis-associated malignant ovarian tumours were mostly early stage. What are the implications of these findings for clinical practice and/or further research? Additional studies need to be conducted to develop screening approaches for malignant transformation or an association in women with endometriosis. Till that time, a change of current clinical practices cannot be justified. However, counselling and treating women with endometriosis who are at high risk for cancer coexistence or conversion is encouraged.

Background/aims: To identify the role of serum caspase 3, Annexin A2 (ANXA2), and Soluble Fas Ligand (sFasL) levels in the prediction of endometriosis severity., Methods: The study was performed on 90 women who were candidates for laparoscopic surgery due to endometrioma or any other benign ovarian cysts detected by ultrasound examination, pelvic pain, or infertility. The control group comprised 29  patients. The second group comprised 29 patients with stage I-II endometriosis and the third group comprised 30 patients with stage III-IV endometriosis., Results: Significant differences were detected between the control and stage III-IV endometriosis groups and between stage I-II and stage III-IV endometriosis groups in terms of caspase-3 levels (both, p < 0.001), ANXA2 levels (p = 0.007 and p = 0.002), and sFasL levels (p = 0.022 and p = 0.044). After receiver operating characteristic analysis, the area under curve was 93% (95% CI 57-82) at 10.7 ng/mL cut-off level for caspase-3 with 90% sensitivity and 87% specificity., Conclusion: Serum caspase-3 level may be a reliable predictor of endometriosis severity., (© 2018 S. Karger AG, Basel.)

Objective: This study aimed to investigate the role of telomerase activity in the development of endometriosis-related infertility by evaluation of the serum telomerase in eutopic and ectopic endometrial tissue., Study Design: Eutopic endometrium, cystic wall/ovarian cortex, and venous blood were assessed in forty-seven patients. The following groups of patients were identified: females with endometriosis requiring surgical intervention and healthy control females. Patients with histopathologically confirmed endometriosis were further subdivided in the infertile (n=14) and fertile (n=17) groups. Patients who underwent hysterectomy and oophorectomy for benign gynecological conditions were enrolled in the healthy control group (n=16). Telomerase activity was evaluated with three-group, endometriosis-based and fertility-based designs. Analyses were performed regardless the menstrual cycle phase (Phase G), in proliferative (Phase P) (n=22) and secretory phases (Phase S) (n=25). Telomeric Repeat Amplification Protocol PCR was applied for telomerase activity assessment. All statistical analyses were performed with STATA 14.2, GraphPad Prisma 7.01., Results: In analyses of the eutopic endometrium, with three-group design, a significant difference was not found in Phase G and P (p=0.58 and p=0.33, respectively). However, a statistical difference was shown in Phase S (p=0.008). A significant difference was not established in Phase G, P and S of endometriosis-based design (p=0.35, p=1.0, p=0.13, respectively). No difference was detected in Phase G and P of fertility-based design (p=0.66 and p=0.14, respectively), whereas in secretory phase difference was approved (p=0,049). Telomerase activity was not established in ectopic endometrium and in serum assessment., Conclusions: Telomerase activity is useless as a biomarker in peripheric blood analysis. The absence of activity in cystic wall approves the high differentiation of endometriosis tissue, what is the possible reason of low malignancy risk. The high rate of telomerase activity in the eutopic endometrium of the infertile group may be considered as a cause of endometriosis-related infertility., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Endometriosis is characterized by development of the endometrial tissue outside the uterus like ovary, pelvic peritoneum, pelvic organs, and affects 6-10% of reproductive-aged women. The prevalence of endometrioma is 17-44% of women with endometriosis. Since endometriosis is mainly a disease for the women at their reproductive ages, it is important to consider ovarian reserve when managing the cases with ovarian endometriosis. There has been a long debate whether the endometrioma per se decreases the ovarian reserve and/or surgery for endometrioma - either by laparoscopy or by laparotomy - decreases it. Although the dispute for these questions is not totally settled down, in this article, we would like to give some clues for the answers in view of the literature.

Progestins are synthetic compounds that mimic the effects of progesteron. For over 50 years, oral progestins have been demonstrated to be effective in the treatment of endometriosis. They were reported to reduce or eliminate pain symptoms in approximately 90% of the patients. Progestins are available in many forms, including oral preparations, injections, subdermal implants and intrauterine systems. Continuous progestin use is an effective therapy for the treatment of painful symptoms associated with endometriosis but there had been no evidence of progestin use being superior to other types of treatment in endometriosis-related pain symptoms.

Endometriosis is traditionally defined as the presence of endometrial glands and stroma in ectopic locations, especially the pelvic peritoneum, ovaries and rectovaginal septum. YKL-40, a new biomarker of inflammation, is secreted by activated macrophages and neutrophils in different tissues with inflammation. Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation. We aimed to investigate the possible association between serum YKL-40 levels and endometriosis. A total number of 88 women were recruited for this case-control study. About 53 patients with surgically proven endometriosis were included, while 35 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with the severity. Two new groups were formed by combining patients with minimal and mild disease (Stage 1-2) and with moderate and severe disease (Stage 3-4). Serum YKL-40 levels were statistically higher in the endometriotic group compared to control group (p:0.001). YKL-40 levels were significantly higher in Stage 3-4 group compared to Stage 1-2 group (p values 0.001) as well. Correlation analysis revealed a positive correlation between serum YKL-40 levels and the stage of the disease. YKL-40 may be utilized as a marker for determining the severity of endometriosis.

Objective: To determine the prevalence of ovarian endometriosis in malignant epithelial ovarian tumours., Study Design: A retrospective analysis of 160 malignant and 23 borderline ovarian tumours during the period 1995-2001., Results: Fourteen (7.7%) of the tumours contained endometriosis. This affected 22% of the endometrioid and 10.8% of the mixed adenocarcinomas. The mean age of the ovarian endometriosis patients was 43+/-13 range 26-70 years. The incidence in borderline tumours 13% (3/23) was higher than that in ovarian cancer 6.9% (11/160) (P>0.05). Eight (57%) of cases were classified as atypical and six (43%) as typical endometriosis. Nine cases were FIGO (International Federation of Gynaecology and Obstetrics) stage I and 5 stage III., Conclusions: Both malignant and borderline ovarian tumours are associated with ovarian endometriosis. In addition, atypical endometriosis was found associated with endometrioid and mixed epithelial ovarian tumours.

The peritoneal environment in endometriosis is known to have growth-promoting effects on endometrial cells. To investigate whether follicular fluid, a contributor to the peritoneal fluid, stimulates endometrial cell proliferation, we incubated endometrial stromal cells in culture with various dilutions of follicular fluid obtained from women with or without endometriosis undergoing oocyte retrieval for in-vitro fertilization. Cell proliferation assays were performed using follicular fluid from 28 women (without endometriosis, n = 13; with endometriosis, n = 15) in eight different endometrial stromal cell culture set-ups. Cell proliferation was assessed by a colorimetric method. Maximum cell proliferation was detected when endometrial cells were incubated with 50% dilution of follicular fluid for 48 h. Follicular fluid from women with endometriosis induced significantly higher cell proliferation than follicular fluid from women without endometriosis (P < 0.05). Our findings indicate that follicular fluid contents may contribute to the growth-promoting factors in the peritoneal fluid of women with endometriosis.

Objective: To investigate monocyte chemotactic protein-1 concentrations in the peritoneal fluid (PF) of women with or without endometriosis, then assess peritoneal mesothelial cells as a potential source of monocyte chemotactic protein-1., Design: Prospective study., Setting: University medical center., Patient(s): Women with (n = 60) or without (n = 18) endometriosis., Intervention(s): First monocyte chemotactic protein-1 levels in PF were measured, then mesothelial cells in culture were treated with cytokines., Main Outcome Measure(s): In PF and culture supernatants, monocyte chemotactic protein-1 was measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA expression was evaluated by Northern analysis., Result(s): The median concentration of monocyte chemotactic protein-1 in PF of control women was 137 pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL). Within the moderate to severe endometriosis group, monocyte chemotactic protein-1 levels were higher in women with untreated endometriosis (354 pg/mL range 0 to 6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216 pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher in the proliferative phase than in the secretory phase. Mesothelial cells produced constitutively monocyte chemotactic protein-1; moreover, both interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of monocyte chemotactic protein-1., Conclusion(s): Levels of monocyte chemotactic protein-1 in PF were higher during the proliferative phase than secretory phase of control women and increased in moderate to severe endometriosis. The regulated expression of monocyte chemotactic protein-1 may recruit macrophages into PF and contribute to the pathogenesis of endometriosis.

This article reviews the pathogenesis of endometriosis, which involves retrograde dissemination of endometrium and/or development in situ by metaplasia, and there is evidence suggesting that genetic and hormonal factors may play a role. There is also substantial evidence that immunologic factors, namely peritoneal macrophages, T cells, natural killer cells, and soluble products secreted by these cells, are involved in the pathogenesis of endometriosis.

Objective: To investigate the presence and modulation of growth-regulated alpha, a member of the chemokine family with neutrophil chemotactic activity, in the peritoneal fluid of women with or without endometriosis., Methods: Peritoneal fluid samples were obtained at laparoscopy from 63 women with endometriosis and 19 fertile women without endometriosis. Endometrial tissue was obtained from uteri after hysterectomy for reasons other than endometrial disease or from endometrial biopsies of reproductive-age women. Cellular RNA was extracted and northern blots were hybridized with an oligonucleotide probe complementary to a specific sequence of growth-regulated alpha messenger RNA. Growth-regulated alpha in peritoneal fluid and culture supernatant was quantified using enzyme-linked immunosorbent assay. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney tests., Results: The median (range) concentration of growth-regulated alpha in peritoneal fluid samples from 19 normal fertile women was 27 pg/mL (0-108), from 24 women with moderate endometriosis 34 pg/mL (8-150), and from seven with severe endometriosis was 73 pg/mL (10-221) (P = .04, P = .01, respectively). In the moderate and severe endometriosis groups, the levels of growth-regulated alpha were significantly higher in the peritoneal fluid of women with untreated endometriosis (73 pg/mL [10-221]) than in women with medically treated endometriosis (25 pg/mL [8-47]). In mesothelial and endometrial stromal cells in culture, growth-regulated alpha messenger RNA and protein were detectable constitutively; however, both interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of growth-regulated alpha messenger RNA and protein in a dose- and time-dependent manner., Conclusions: Growth-regulated alpha levels are elevated in the peritoneal fluid of women with moderate and severe endometriosis. This chemotactic factor, which acts via the interleukin-8 receptor, may play a role in the pathogenesis of endometriosis.

Objective: To examine the mechanism of sperm motility inhibition by peritoneal fluid (PF) from women with endometriosis., Design: Prospective, randomized study., Setting: University-based andrology laboratory., Patients: Women with and without endometriosis., Interventions: Fresh semen or Percoll-purified sperm fractions were combined with PF from women with endometriosis (n = 20), from fertile women without endometriosis (n = 10), or with physiological saline., Main Outcome Measure: Sperm motility parameters were determined with computer assisted semen analysis. Data were evaluated by the analysis of variance and the Student's t-test., Results: Peritoneal fluid from women with minimal or mild endometriosis did not inhibit sperm motility in semen. Peritoneal fluid from women with moderate or severe endometriosis caused approximately 40%, 50%, and 80% declines in sperm motility and in percent progressive motile sperm after 4,7, and 24 hours, respectively. Sperm velocity was inhibited by approximately 30% and 60% after 7 and 24 hours, respectively. However, in the Percoll-purified sperm fractions the same PF did not inhibit sperm motility within the 4- to 7-hour time frame, and only a 17% to 42% inhibition occurred after the overnight incubation. Sperm velocity was not affected., Conclusion: Cellular components of seminal fluid appear to mediate the inhibitory action of PF. Assuming that the leukocyte components of semen and PF are common, the cell-mediated inhibition of sperm motility is a likely contributor to endometriosis related infertility.

The local environment of peritoneal fluid (PF) surrounding the endometriotic implant is immunologically dynamic and links the reproductive and immune systems. Peritoneal fluid contains a variety of free floating cells, including macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells. Macrophages are attracted to the peritoneal environment more abundantly than any other cell type. These scavengers promote cellular growth and viability through secretion of growth factors and cytokines. It is now becoming evident that cytokines play an important role in reproduction at various levels, including gamete function, fertilization and embryo development, implantation and postimplantation survival of the conceptus. Peritoneal fluid has been shown to affect negatively ovum capture by the fimbria, sperm survival, spermatozoon-oocyte interaction and embryonic development. We have recently identified the presence of two pro-inflammatory chemoattractant cytokines for monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women with endometriosis compared to those without endometriosis, but they are related to the severity of the disease. Over the past 70 years, at least a dozen theories have been proposed to explain the histogenesis and aetiology of endometriosis. It appears that the aetiology is multifactorial, and today a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation for peritoneal endometriosis.

Objective: To investigate the effect of endometriosis on implantation., Design: Case-control study from Yale University IVF-ET program., Patients: Two hundred eighty-four consecutive IVF cycles were analyzed retrospectively. Patients with endometriosis only (n = 35; 89 cycles) were compared with an age-matched control group with tubal infertility (n = 70; 147 cycles) and also to a group with unexplained infertility (n = 15; 48 cycles). Data from the endometriosis group was analyzed further in subgroups of minimal-mild (43 cycles) and moderate-severe (46 cycles)., Results: No difference was found in the number and the quality of oocytes retrieved and fertilization rates between the endometriosis, the tubal infertility, and the unexplained infertility groups. The quality and the number of embryos transferred in each group were comparable. A trend toward reduced pregnancy rate per transfer (14.8%) in the endometriosis versus tubal or unexplained infertility groups (25.7% and 23.3%, respectively) was observed. Implantation rate (gestational sac per transferred embryo) was significantly lower in the endometriosis versus the tubal infertility group (3.9% versus 8.1%; unexplained infertility group, 7.2%). Analysis of first cycles only across all groups revealed that the implantation rate also was significantly lower in the endometriosis versus the tubal infertility group (3.1% versus 9%; unexplained infertility group, 6.7%). Within the endometriosis group, although the pregnancy rate per cycle and per transfer were similar in subgroups, patients with minimal-mild endometriosis had the lowest implantation rate., Conclusion: We conclude that, in patients with endometriosis, implantation rate is low. Abnormal implantation, which may be secondary to endometrial dysfunction or embryotoxic environment, is a factor in endometriosis-associated subfertility.