Revised American Fertility Society Classification Research Articles

P-743 Laparoscopic radical excision of deep endometriosis: A positive impact of fertility outcome

Abstract Study question Does laparoscopic radical excision of deep endometriosis (DE) and endometrioma enucleation impact fertility outcomes and recurrence rates when compared to partial excision group? Summary answer In stage IV endometriosis, laparoscopic radical surgery significantly reduced the recurrence rates.The laparoscopic radical excision group tended to have a higher rate of natural conception. What is known already Endometriosis-related symptoms can be significantly improved through surgery, leading to better pregnancy rates. However, the optimal surgical approach can vary due to the complexity of DE. As a result, the recurrence of postoperative symptoms and pregnancy rates can differ due to the lack of randomized trials comparing primary surgery with first-line IVF studies. Thus, the ESHRE stated that there was no evidence supporting surgical management of DE prior to ART to improve pregnancy rates. However, the higher probability of postoperative spontaneous conception in patients undergoing radical resection versus conservative treatment of DE has been reported. Study design, size, duration study design: Retrospective cohort study in a tertiary referral center. size: 77 patients diagnosed with moderate or severe endometriosis and DE. duration: between 2018 and 2020 Participants/materials, setting, methods 77 patients underwent laparoscopic surgery for dysmenorrhea or infertility. Group 1 (n = 22) underwent conservative treatment through partial excision of endometriosis, indicating incomplete resection. Group 2 (n = 55) underwent radical excision of endometriosis and restoration of pelvic anatomy, indicating complete resection. We compared the baseline characteristics, peri-operative data, and follow-up outcomes, aiming to investigate whether radical excision yields superior results in terms of recurrence rate, re-intervention, and pregnancy rate. Main results and the role of chance Main results: Group 2 showed significantly higher surgical complexity with higher revised American Fertility Society classification scores, a greater proportion of severe endometriosis, multiple sites with endometriotic lesions, and longer operation times. Both groups had comparable pregnancy, recurrence, and re-intervention outcomes during the follow-up period of 28.2±16.4 months. While Group 2 tended to have a higher pregnancy rate (84% versus 67%, p = 0.56) and higher live birth rates (80% versus 67%, p = 0.59) when compared with group 1. In the population with stage IV endometriosis, group 2 significantly reduced the recurrence rates (9% versus 50%, p = 0.04) when compared to group 1. Conclusions: The group that underwent laparoscopic endometrioma enucleation with radical excision of extra-ovarian endometriosis exhibited significantly higher surgical complexity. In the population with stage IV endometriosis, radical surgery significantly reduced the recurrence rates. Surgical excision of ovarian endometriosis and extra-ovarian disease is advisable to limit disease progression and ensure complete symptom resolution. Additionally, the laparoscopic radical excision group tended to have a higher rate of natural conception, indicating potential benefits for fertility in patients who have moderate and severe endometriosis with DE. Limitations, reasons for caution The main limitations were the small sample size and recall bias. But, additionally, the limited cases in the research group might have influenced the results and restricted the extrapolation of related conclusions. Further studies with larger sample sizes are needed in the future. Wider implications of the findings We believe that a standardized surgical technique outlining a step-by-step method to delineate all important structures and address altered planes as in endometriosis, with the aim of restoring normal pelvic anatomy, ensures the avoidance of high complication rates, leads to lower recurrence rates and positive impact on fertility outcomes. Trial registration number not applicable

P-321 increased expression of TGF-β1 contributes to the downregulation of progesterone receptor expression in the eutopic endometrium of infertile women with minimal/mild endometriosis

Abstract Study question Do immune cells regulate progesterone resistance and endometrial receptivity of eutopic endometrial stromal cells (ESCs) by transforming growth factor-β1 (TGF-β1)? Summary answer By activating TGF-β/Smad signaling in eutopic ESCs, elevated TGF-β1 from CD45+ immune cells could attenuate expression of progesterone receptor (PR), and further decrease endometrial receptivity. What is known already Endometriosis is a hormone-dependent disease related to impaired immunoregulation. We characterized the trascriptomic transformation of eutopic endometrium from patients with minimal/mild endometriosis and controls across the menstrual cycle. However, the regulatory mechanism of altered immune microenvironment on eutopic ESCs remains unclear. Study design, size, duration Single-cell RNA transcriptomes were profiled using 10x Genomics platform. Primary culture of eutopic ESCs was performed to explore the effects of TGF-β1 on the expression of Smad / PR, and the in vitro decidualization. Additionally, co-immunoprecipitation (Co-IP) was used to explore the direct interaction between Smad and PR. Participants/materials, setting, methods Endometrial tissue samples were obtained from twenty-four women who were laparoscopically confirmed minimal/mild endometriosis according to the revised American Fertility Society classification. Additionally, four patients who were laparoscopically endometriosis-free were enrolled as controls. All samples were collected in DMEM/F12 medium and processed in one of two ways, either for single-cell sequencing (n = 10) or primary cell culture (n = 14). Main results and the role of chance The results of single-cell RNA sequencing revealed that the percentage of CD45+ cells in eutopic endometrium was increase in both proliferative (26% vs 24.1%) and secretory (19.3% vs 8.3%) stages. Overexpression of TGF-β1 of CD45+ cells was observed in eutopic endometrium of endometriosis in both proliferative and secretory stages. We found attenuate expression of PRB (p = 0.026) and PRA (p = 0.678) after using TGF-β1 in eutopic ESCs by western blot. Similarly, qRT-PCR results showed that the mRNA level of PR (p＜0.001), PRB (p = 0.003) and HOXA10 (p＜0.001) decreased significantly after TGF-β1 treatment, but that increased (p＜0.01) after SB431542 treatment in the eutopic ESCs. Moreover, TGF-β1 has a negative effect on the in vitro decidualization of eutopic ESCs (p = 0.003). And the group with treatment of both TGF-β1 and SB435142 in eutopic ESCs showed significant decidual-like changes with increased prolactin level (p = 0.01). Co-IP showed no physical interaction between the PR and p-Smad3/Smad3 proteins. Limitations, reasons for caution This study focused on CD45+ immune cells and the cytokine, TGF-β1. Further in vivo and in vitro studies are needed to elucidate the specific types of immune cell and the mechanisms that behind endometrial receptivity decrease in endometriosis. Wider implications of the findings Our results demonstrate abnormal activation of CD45+ cells in eutopic endometrium with minimal/mild endometriosis. And overexpression of TGF-β1 was found by CD45+ cells. We found that TGF-β1 suppresses PR expression and decidualization in eutpoic ESCs. These results provide a novel insight into the mechanisms behind progesterone resistance in endometriosis. Trial registration number not applicable

Live surgery of colorectal endometriosis broadcasted from a surgeon's routine operating theater is not associated with higher complications rate.

Although live surgeries are routinely included in surgical congress programs, they are the subject of an ongoing debate in terms of patient safety and teaching value. The goal of our study was to assess the risk of postoperative complications related to live surgery broadcast from the surgeon's routine theater, in patients managed for deep endometriosis infiltrating the digestive tract. We report a retrospective comparative study, enrolling women managed for colorectal endometriosis by a gynecologic surgeon, from September 2013 to March 2020 in two referral centers. We compared the rate of postoperative bowel fistula in women managed during live surgery in the routine operating theater, with that observed in women for whom surgery was not broadcast. Among 813 women, 33 (4.1% of cases) underwent surgical procedures transmitted live to various conference rooms located outside the hospital and were compared with 780 patients who underwent non-broadcast surgery. Women's age, body mass index, past surgical and obstetrical history, and major preoperative complaints were comparable. Cases presented with impaired constipation score, more frequent sciatic pain, and infiltration of the vagina, whereas overall revised American Fertility Society classification scores were more severe in controls. The rate of rectal nodules over 3cm in size was comparable between the two groups (72.7% in cases vs. 72.1% in controls). Operative time was also comparable (153±52 minutes vs. 148±79minutes). Cases were more frequently managed by disk excision of rectal nodules (63.7% vs. 30.3%), and more frequently involved the sacral plexus (18.2% vs. 7.3%). Postoperative complications were comparable between the two groups, in terms of bowel fistula (3% in the live surgery group vs. 4.1% in controls), pelvic abscess requiring secondary laparoscopy (3% vs. 4.9%), or bladder dysfunction requiring self-catheterization after discharge (6.1% vs. 5.3%). Performing laparoscopic management of colorectal endometriosis with live transmission of surgery from a surgeon's routine operating theater, is not related to a higher risk of major postoperative complications.

Feasibility of Laparoscopic Hysterectomy in Stage IV Pelvic Endometriosis: Our Technique and Outcomes.

Context:The definitive surgical treatment of severe endometriosis remains to be hysterectomy whether done by laparoscopy or laparotomy.Aim:The aim of this study was to assess the feasibility and outcome of laparoscopic hysterectomy in severe pelvic endometriosis.Settings and Design:This retrospective study was carried out in a tertiary center over a period of 5 years (January 2013–December 2017).Subjects and Methods:A total of 70 patients who underwent laparoscopic hysterectomy for severe pelvic endometriosis with a score of more than 40, which was defined by the revised American Fertility Society classification, were included in the study. Feasibility of laparoscopic hysterectomy and other clinical parameters such as operative time, blood loss, recurrence of the disease, and need for postoperative medical treatment was analyzed.Results:The mean age of the patients was 43.2 ± 4.56. Majority of the women (62.8%) had dysmenorrhea as the primary complaint, followed by menorrhagia (21.4%). Intraoperatively rectovaginal septum was involved in 95% of the cases with complete obliteration of the pouch of Douglas in 80% of the cases. The ureter was involved in 34% of the cases. The bladder was densely adherent in 71.4% of the patients. There was no conversion to laparotomy in any of these patients and no visceral injuries. The mean duration of surgery was 3 h. The estimated blood loss ranged from 100 to 500 ml. The duration of hospital stay was 2–5 days. There was no recurrence during follow-up in any of these patients.Conclusions:Laparoscopy in experienced hands is feasible and safe even in difficult cases of Stage IV pelvic endometriosis apart from offering superior results.

Bladder and Urinary Deep Pelvic Endometriosis: A Step-by-Step Standard Approach

To demonstrate how to treat bladder and ureteral deep pelvic endometriosis using a laparoscopic approach with partial cystectomy and resection and end-to-end anastomosis of the ureter. Step-by-step explanation of the surgery using a video approved by the local institutional review board. University Hospital of Strasbourg, France. A 27-year-old nulliparous woman with severe endometriosis stage IV (revised American Fertility Society classification score >40) of the bladder and left ureter. On pelvic magnetic resonance imaging, we found dilatation of the left ureter and left hydronephrosis induced by a 17-mm endometriosis nodule. A JJ probe was placed on the left ureter before the surgery because of dilatation of the ureter and decreased renal function. During the exploration, we found an abdominal cavity free of adhesion. There was an endometriosis implant in the bladder in front of the uterus and a large nodule of the left uterosacral ligament that was compressing the ureter. In the first step, we made a section of the round ligament to perform anterior ureterolysis and progressive dissection of the nodule surrounding the ureter. Once the nodule was resected, tight stenosis was observed approximately 1 cm from the bladder. The vesicouterine and vesicovaginal spaces were then dissected to pass under the nodule to the vagina. We opened the dome of the bladder using the thunderbeat (Olympus) and dissected the bladder to remove the transfixing nodule while staying away from the ureters. The closure of the bladder was performed by 2 lateral sutures and a running suture using a braided suture (V-Loc) 2-0, with good tightness as checked by a blue test. Ureteral resection was performed around the JJ probe in place to remove the stenotic zone; thereafter, we performed an end-to-end anastomosis of the ureter using 4 sutures of monofilament (Monocryl) 4-0 with a good anatomic result. Finally, an omentoplasty was fixed around the ureter using a 2-0 monofilament suture (Monocryl). The postoperative course was uneventful. A Foley catheter was left in place for 10 days, and the JJ probe was removed 6 weeks later. The operative time was 140 minutes. The step-by-step explanation technique was simple with minimal operative difficulty and a low rate of morbidity. This video shows how deep urinary endometriosis can be treated laparoscopically. Mastering suturing is essential to avoid complications.

The levels of matrix metalloproteinase-9 and neutrophil gelatinase-associated lipocalin in different stages of endometriosis

This study was designed to explore matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) levels and MMP-9/NGAL ratio in women with and without endometriosis diagnosed surgically and/or histopathologically. The correlation between biomarkers and the severity of the disease is analysed. The revised American Fertility Society classification system was used to determine the severity of endometriosis. Serum MMP-9 and Ca125, urine NGAL levels were measured in all participants. Serum MMP-9 levels were significantly higher in the study group (n = 60) compared to controls (n = 31) (15.0 pg/mL (6.0–143.0) vs. 12.0 (4.0–18.0), respectively; p=.002). MMP-9 levels were significantly higher in severe endometriosis compared to mild endometriosis subgroups (p<.001). No significant difference was found between NGAL levels in study and control groups (p>.05). The diagnostic value of MMP-9 and NGAL is not superior than CA-125 for endometriosis. Nevertheless, MMP-9 might be a potential predictive marker for advanced stage of the disease.Impact StatementWhat is already known on this subject? The gold standard diagnostic test for diagnosis of endometriosis is laparoscopy combined with histopathological confirmation of eutopic endometrial glands and/or stroma. Both invasiveness and possible accompanying complications limit the preference regarding the surgical approach. Among non-invasive markers none has been accepted as gold standard neither for diagnosis nor for determining the severity of the disease. MMPs are extracellular endopeptidases, which have a significant role in degradation and remodelling of extracellular matrix for cellular migration and invasion. Among these, MMP-9 has been shown to be higher in eutopic/ectopic endometrial tissue in women with endometriosis and has been suggested to have a role in pathogenesis of endometriosis by promoting invasion of the endometriotic lesions. NGAL is an acute phase protein, which is involved in a variety of physiological and pathophysiological processes. The molecule has also been revealed to correlate with endometriosis pathophysiology through the epithelial–mesenchymal transition process which is the basis for the onset of endometriosis. But also, NGAL which composes a complex with MMP-9 (MMP-9 and NGAL complex), has been shown to protect MMP-9 from autodegradation in vitro which might be a contributing factor for endometriosis pathophysiology.What the results of this study add? MMP-9 cut-off level for prediction of severe endometriosis is a novel finding obtained from this study with acceptable sensitivity and specificity. On the other hand, NGAL seems to have no significant value either for diagnosis of for determining severity of the disease. After all, MMP-9 might be an easy use acceptable biomarker for endometriosis but further studies on larger populations are needed.What the implications are of these findings for clinical practice and/or further research? MMP might be a potential non-invasive predictive marker for advanced stage disease.

Laparoscopic surgery with urinary tract reconstruction and bowel endometriosis resection for deep infiltrating endometriosis.

Deep infiltrating endometriosis (DIE) is the most severe form of endometriosis. It causes chronic pelvic pain, severe dysmenorrhea, deep dyspareunia, dyschezia, and dysuria, markedly impairing the quality of life of women of reproductive age. A number of randomized controlled trials on surgical and medical treatments to reduce the pain associated with endometriosis have been reported, but few have focused on this in DIE. DIE causes not only pain but also functional invasion to the urinary organs and bowel, such as hydronephrosis and bowel stenosis. In addition to DIE resection, surgical treatment involves adhesion separation as well as resection and reconstruction of the urinary organs and bowel; high-level skills are required. The severity of DIE should be evaluated preoperatively as accurately as possible. Using ENZIAN in conjunction with the AFS (The revised American Fertility Society classification of endometriosis) classification makes a more detailed assessment of DIE possible. The operative procedures used for laparoscopic resection of urinary DIE and reconstruction of the urinary organs are chosen based on the type of lesion (intrinsic/extrinsic) and length of stenosis. In addition to ureteroneocystostomy, the psoas bladder hitch and Boari bladder flap procedures are applied when necessary to extend the urinary tract. Bowel resection for bowel endometriosis is classified into classic segmental resection and conservative approaches (shaving/discoid). When these procedures are employed, it is advisable to work in consultation with urologists and gastroenterologists and to inform the patients of the associated risks and outcomes. Furthermore, postoperative medication is essential because it is difficult to conduct repeated surgeries.

Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis.

Endometriosis, characterized by the presence of endometrial-like tissue at extrauterine sites, is a common, chronic, estrogen-dependent, inflammatory condition associated with pelvic pain, subfertility, dysmenorrhea, and dyspareunia, affecting about 10% of reproductive-age women in any population. The diagnosis of endometriosis is usually delayed on an average by 8 to 11 years leading to significant consequences in terms of disease progression. The current study was aimed to validate enzyme-linked immunosorbent assay based on the epitopes of stomatin-like protein 2, tropomodulin 3 (TMOD3), and tropomyosin 3 (TPM3) for diagnosis of minimal-mild endometriosis (revised American Fertility Society Classification (rAFS) stage I-II) and to compare the performance with the reported markers: cancer antigen (CA) 125, CA19-9, α-enolase, Serine/threonine-protein kinase (PDIK1L), and syntaxin 5. This was a cross-sectional, multicenter study conducted during the year 2012 to 2015. Women with minimal-mild endometriosis (rAFS stage I-II [n = 133]) and healthy controls (n = 104) were screened for 11 novel autoimmune markers and reported markers α-enolase, PDIK1L, syntaxin 5, CA-125, and CA19-9. The sensitivity and diagnostic accuracy of serum antibodies against all the 11 epitopes were higher than that of CA-125, CA19-9, α-enolase, PDIK1L, and syntaxin 5 for diagnosis of rAFS stage I to II endometriosis. The sensitivity of 6 biomarkers (anti-TMOD3b-autoAb, anti-TMOD3c-autoAb, anti-TMOD3d-autoAb, anti-TPM3a-autoAb, anti-TPM3c-autoAb, and anti-TPM3d-autoAb) was higher at the specificity of ≥80% for diagnosis of rAFS stage I to II endometriosis as well as ultrasound-negative endometriosis. Further, logistic regression models of this panel of biomarkers showed increase in sensitivity, specificity, and diagnostic accuracy than individual biomarkers. The panel of 6 autoimmune biomarkers could be useful in setting up of noninvasive diagnostic test for detection of minimal-mild endometriosis.

Fertility outcome of laparoscopic treatment in patients with severe endometriosis and repeated in vitro fertilization failures

To evaluate fertility outcomes in infertile women with severe endometriosis (The revised American Fertility Society classification [AFS] 3-4) and repeated IVF failures, who underwent surgery due to exacerbation of endometriosis-related symptoms. Retrospective cohort study. University hospital. All women who failed IVF treatment before surgery and who underwent laparoscopic surgery for severe endometriosis betweenJanuary 2006 and December2014. All patients were operated by highly skilled surgeons specializing in laparoscopic surgery for advanced endometriosis. Only patients with evidence of endometriosis in the pathology specimens were included in this study. Delivery rate after surgery. Seventy-eight women were included in the present study. All women were diagnosed with severe endometriosis during surgery (AFS 3-4) and all women had experienced failed IVF treatments before surgery. All women were symptomatic before their surgery. After surgical treatment 33 women (42.3%) delivered. Three women (9%) conceived spontaneously and all other women conceived after IVF treatment. Women who delivered were younger (32.5 [±4.1] years vs. 35.5 [±3.8] years), were less often diagnosed with diminished ovarian reserve before surgery (6% vs. 28.8%), and were more often diagnosed with normal uterine anatomy (by preoperative transvaginal ultrasound and during operation). In addition, performing salpingectomy during surgery was associated with a trend of improvement in delivery rates after surgery (70% in women who delivered vs. 51% in women who failed to deliver). Symptomatic women with severe endometriosis and repeated IVF implantation failures may benefit from extensive laparoscopic surgery when performed by an experienced multidisciplinary surgical team to improve IVF outcome.

Endometriosis Fertility Index ou classification de l’American Society of Reproductive Medicine pour les patientes infertiles endométriosiques opérées. Lequel est le plus pertinent ?

The revised American Fertility Society classification system has been most used after surgery by all consensus on endometriosis fertility. However, it does not predict pregnancy. The EFI score has been recently developed to aim at predicting clinical pregnancy after surgery. Several study performed its external validation. It may be a useful new tool to counsel couples for personalized postoperative management.

Quality of life outcomes in women with endometriosis are highly influenced by recruitment strategies.

To what extent are outcome measures in endometriosis-related quality of life studies influenced by the setting in which patient recruitment is performed? Quality of life outcomes in women with endometriosis are highly influenced by recruitment strategies. Most studies on quality of life in women with endometriosis are conducted in tertiary care centres or patient associations. It is conceivable that the setting in which patient recruitment is performed influences the quality of life results. This has not been investigated before. Retrospective questionnaire based cohort study (part of the World Endometriosis Research Foundation (WERF) EndoCost study). The investigated women were recruited in three settings: a tertiary care centre for endometriosis (n = 135); five secondary care centres (n = 63); an endometriosis patient association (n = 291). The secondary and tertiary care population included women with a laparoscopic and/or histological diagnosis of endometriosis. The patient association population consisted of women with a self-reported diagnosis of surgically confirmed endometriosis. The populations did not differ in terms of age, co-morbidities and education level. Delay of diagnosis was the longest in the patient association (median 7 years) (tertiary care 2 years; secondary care 1.5 years) (P < 0.001). The tertiary care population reported more laparotomies (64%) than the other populations (secondary care 43%; patient association 47%) (P = 0.002). Affected job was least prevalent in the secondary care setting (35%) (patient association 64%; tertiary care 56%) (P < 0.001). Affected relationships were most prevalent in the patient association setting (52%) (tertiary care 38%; secondary care 22%) (P < 0.001). Chronic pain was least prevalent in patients in secondary care (44%) (tertiary care 65%; patient association 61%) (P = 0.009). Substantial differences in quality of life were detected between secondary care (median physical component 50.4, mental component 49.6); tertiary care (physical component 46.2, mental component 46.2) and the patient association (physical component 45.0, mental component 44.6) (P < 0.001, P = 0.018). The response rate was relatively low (35%). Analysis of the hospital populations revealed that non-responders and responders did not differ with respect to age or revised American Fertility Society classification, indicating that the non-responder bias is limited. However, other factors, such as social and marital status or symptomatology, might be different for non-responders. Missing values were analysed as if the symptom was not present. Missing values never exceeded 10%, except for one value. Therefore, it can be expected that the effect of missing data on the outcome is negligible. Twenty-five patients belonged to more than one category. A sensitivity analysis showed that the influence of assigning patients to another category was limited. Outcomes regarding quality of life are highly influenced by recruitment strategy. None of the groups appeared to be a representative selection of the total population of women with endometriosis. An alternative strategy for creating a representative population for cost and quality of life studies is probably to recruit women who live in a specific geographic area rather than women that visit a specific hospital or are a member of a patient association. The WERF EndoCost study was funded by the World Endometriosis Research Foundation. The sponsors did not have a role in the design and conduct of this study: collection, management, analysis, interpretation of the data; preparation, review, approval of the manuscript. L.H. is the chief executive and T.M.D. was a board member of WERF at the time of funding. T.M.D holds the Merck-Serono Chair and the Ferring Chair in Reproductive Medicine in Leuven, Belgium and has served as consultant for Merck-Serono, Schering-Plough, Astellas, and Arresto. Not applicable.

Advanced Stage Endometriosis in Adolescents and Young Women

Study ObjectiveTo describe the prevalence and characteristics of advanced stage endometriosis in adolescents and young women treated in a tertiary referral center. DesignRetrospective cohort. SettingTertiary referral center. Patients and Interventions86 adolescents and young women (≤22 y) who underwent surgery for endometriosis. The operative reports were reviewed for endometriosis stage, surgical findings, surgical procedures, and pathology. Main Outcome MeasuresEndometriosis stage reported according to the revised American Fertility Society classification. ResultsEarly stage endometriosis (stage I or II) was found in 66 (76%) and advanced stage endometriosis (stage III or IV) in 20 (23%). The surgical findings in the 20 patients with advanced stage endometriosis included ovarian endometriomas in 14 cases, rectovaginal nodule in 1 case, and diaphragmatic and pulmonary endometriosis in 1 case. Women with advanced stage endometriosis were found to be slightly older at time of diagnosis than those with early stage disease (mean age 20.4 ± 1.4 y vs 18.7 ± 2.2 y respectively, P < .001). ConclusionIn adolescents and young women with endometriosis, advanced stage disease is not uncommon. The main presentation of advanced stage endometriosis in this age group is ovarian endometriomas rather than extensive peritoneal or adhesive disease.

Reproductive Performance after Surgery for Endometriosis: Predictive Value of the Revised American Fertility Society Classification and the Endometriosis Fertility Index

Background/Aims: To determine whether the revised American Fertility Society (rAFS) classification and endometriosis fertility index (EFI) predict pregnancy rates (PRs) in patients with surgically confirmed endometriosis attempting natural conception. Methods: We retrospectively assessed 194 women with endometriosis who underwent laparoscopic surgery; 161 women completed the follow-up. Pregnancy outcomes, rAFS stages and EFI scores were documented. Cumulative PRs were compared using Kaplan-Meier survival analysis. Results: The cumulative PR 36 months after surgery was 46.6% (stage I, 53.6%; stage II, 36.0%; stage III, 51.7%, and stage IV, 41.7%; log-rank test, χ² = 4.143, p = 0.246). In the 1st year, PRs significantly differed between patients with rAFS stage IV and those with stages I-III (Pearson's χ² test, χ² = 6.024, p = 0.014). Significant differences in cumulative PRs were observed among EFI scores (group 1, EFI score 0-3, 8.3%; group 2, EFI score 4-7 41.2%, and group 3, EFI score 8-10 60.9%; log-rank test, χ² = 16.254, p < 0.001). Conclusions: EFI scores, but not rAFS stage, predict PRs in patients with endometriosis-associated infertility. EFI scores may be used to guide postoperative treatment.

Determination of cathepsins B, D and G concentration in eutopic proliferative endometrium of women with endometriosis by the surface plasmon resonance imaging (SPRI) technique

ObjectiveTo determine the concentrations of cathepsins B, D and G in proliferative eutopic endometrium of patients with and without endometriosis, by use of the surface plasmon resonance imaging (SPRI) technique. Study designA total of 55 patients were recruited in the study: 31 patients with endometriosis (stages I–IV) and 24 controls. Endometrial samples were obtained in the first phase of the menstrual cycle from regularly menstruating premenopausal women, prior to laparoscopy, by the use of aspiration biopsy. Endometriosis was appropriately classified according to the Revised American Fertility Society classification and confirmed by histopathology in every case. The SPRI technique was used to determine the concentration of cathepsins B, D and G. To compare the two groups for quantitative data, Mann–Whitney–Wilcoxon's test was used due to the non-normal distribution of the tested variables and normality of distribution was assessed using Shapiro–Wilk W test. ResultsThe concentration of the three examined cathepsins was higher in the proliferative eutopic endometrium of patients with endometriosis, especially in advanced stages, e.g. III and IV, when compared to healthy individuals. Corresponding median values were, for cathepsin B: [7.93pmol/mg (min–max 2.82–15.71) vs 1.2pmol/mg (min–max 0.7–15.49) p=0.0014], for cathepsin D: [1.86pmol/mg (min–max 0.51–5.4) vs 1.03pmol/mg (min–max 0.4–2.72) p=0.00041] and for cathepsin G: [0.6pmol/mg (min–max 0.33–2.51) vs 0.3pmol/mg (min–max 0.16–1.29) p=0.00051]. ConclusionsIncreased concentrations of cathepsins B, D and G in the proliferative eutopic endometrium may play a role in the implantation of endometrial tissue outside the uterine cavity.

Endometriosis fertility index score maybe more accurate for predicting the outcomes of in vitro fertilisation than r-AFS classification in women with endometriosis.

BackgroundEndometriosis is a common disease. The most widely used staging system of endometriosis is the revised American Fertility Society classification (r-AFS classification) which has limited predictive ability for pregnancy after surgery. The endometriosis fertility index (EFI) is used to predict fecundity after endometriosis surgery. This diagnostic accuracy study was designed to compare the predictive value of the EFI with that of the r-AFS classification for IVF outcomes in patients with endometriosis.Methods199 women with endometriosis receiving IVF treatment after surgery were analysis. The EFI score and r-AFS classification in their ability to predict these IVF outcomes were compared in the same population. ROC curves were used to analyse the predictive values of the EFI and r-AFS indices for clinical pregnancy, and their accuracies were evaluated by sensitivity, specificity, and the Youden’s index.ResultsThe Area Under the Curve (AUC) of the EFI score (AUC = 0.641, Standard Error(SE) = 0.039, P = 0.001, 95% CI = 0.564-0.717, cut-off score = 6) was significantly larger than that of the r-AFS classification (AUC = 0.445, SE = 0.041, P = 0.184, and 95% CI = 0.364-0.526). The antral follicle count, oestradiol level on day of hCG, number of oocytes retrieved, number of oocytes fertilised, and number of cleaved embryos in the greater than or equal to 6 EFI score group was greater than that of the lower than or equal to 5 EFI score group, and the dose of gonadotropin of the greater than or equal to 6 EFI score group were less than that in the lower than or equal to 5 EFI score group. Implantation rate, clinical pregnancy rate, and cumulative pregnancy rate in the greater than or equal to 6 EFI score group were higher than in the lower than or equal to 5 EFI score group.ConclusionsIt suggests that the EFI has more predictive power for IVF outcomes in endometriosis patients than the r-AFS classification. The clinical pregnancy rate was higher in patients with EFI greater than or equal to 6 score than with EFI lower than or equal to 5 score.

Association of an oestrogen receptor gene polymorphism in Chinese Han women with endometriosis and endometriosis-related infertility

Endometriosis is a steroid-dependent complex disease. The oestrogen receptor plays an important role by mediating oestrogen action and eutopic or ectopic endometrium development. This study investigated whether single-nucleotide polymorphisms in the genes for oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) are associated with endometriosis and endometriosis-related infertility. The participants included 157 infertile and 155 fertile endometriosis women as well as 92 women with primary infertility and 265 fertile women as controls. The iPLEX Gold system (MassARRAY system, Sequenom) was used for genotyping of ESR1 and ESR2. Statistical analysis showed that ESR1 (rs3798573 A/G) was significantly associated with endometriosis and endometriosis-related infertility (P=0.011, P=0.009). No association was found with ESR1 (rs1159327 A/G, rs3020348 A/C) and ESR2 (rs17179740 A/G) either for endometriosis or endometriosis-related infertility. According to the revised American Fertility Society classification, all of the detected single-nucleotide polymorphisms had no association with endometriosis in stage I–II or in stage III–IV. The results suggest that the ESR1 polymorphism rs3798573 A/G is associated with increased risk of endometriosis and endometriosis-related infertility in Han women from central China.Endometriosis is an oestrogen-dependent complex disease, which is one of the most common causes of infertility. Oestrogen receptors (ESR), which mediate oestrogen actions, are considered to play an essential role in the pathogenesis of endometriosis. Therefore, ESR may also play an important role in endometriosis-related infertility. To investigate the association between ESR and endometriosis or endometriosis-related infertility, detection of ESR polymorphisms have been carried out in several populations by other researchers; however, the results remain controversial. In a previous study of ours, through a pooling-based genome-wide scan of endometriosis and controls, we obtained two highly ranked single-nucleotide polymorphisms (SNP) that were individually located in introns of the genes ESR1 and ESR2. To find more evidence of a relationship between ESR and endometriosis or endometriosis-related infertility, the current study selected for genotyping another two ESR1 SNP from a Japanese genome-wide association study in endometriosis. According to the genotypes and the patients’ histories, we found that the ESR1 polymorphism rs3798573 A/G was associated with risk of endometriosis and infertile endometriosis in Han women from central China.

Prognostic value of the revised American Fertility Society classification system and preoperative serum CA-125 level for the first recurrence of advanced endometriosis after conservative laparoscopy

To evaluate the prognostic value of the revised American Fertility Society (rAFS) classification system and preoperative serum CA-125 levels for the first recurrence of endometriosis after laparoscopy.

Effect of aromatase inhibitor (letrozole) with long agonist protocol on the results of ICSI/ET in females with minimal and mild endometriosis

BackgroundICSI/ET in endometriosis patients has poor outcome by traditional protocols. The key enzyme in the biosynthesis of estradiol, aromatase, has been demonstrated within endometriosis. Combined administration of aromatase inhibitor and GnRH-agonist may efficiently suppress estrogen biosynthesis through a combined pituitary, ovarian and local factors in the implants. ObjectiveEvaluate the effect of using letrozole in improvement of the results of ICSI/ET in endometriosis women with long agonist protocol. PatientsSixty infertile women with minimal and mild endometriosis according to the revised American Fertility Society classification were scheduled for ICSI/ET. MethodsWomen were randomized into two groups. Group 1: using the traditional luteal long agonist protocol using triptorelin 0.1 and Group 2: using letrozole 5mg/day started 5days after the start of GnRH agonist for 5days. All patients were monitored with day 6 serum estradiol level and estradiol at day of HCG. The number of days of stimulation, number of retrieved oocytes, number of MII oocytes, cleavage rate, and pregnancy rate were studied in both groups. ResultsDays of stimulation were significantly higher in the treated group (p=0.019). Oocytes number was not affected (10.57±6.14) and (11.21±6.41) (p=0.516) in groups 1 and 2 respectively also, the number of embryos was not affected (p=0.955). Nine (32.1%) pregnant cases of 28 were in the first group while 8 from 27 in the second group (29.6%). ConclusionLetrozole significantly affected days of stimulation of ICSI cycle in endometriosis patients without affecting pregnancy rate.

Right endometrioma is related with more extensive obliteration of the Douglas pouch

To investigate that endometrioma is an asymmetric disease with left lateral predisposition as compared to other benign ovarian cyst and also, whether endometrioma side is related with endometriosis severity. Operative and histopathologic findings of 340 women who underwent cystectomy for treatment of endometriotic (n = 239) and nonendometriotic ovarian cysts (n = 101) by laparoscopy (n = 268) or laparotomy (n = 72) between January 2005 and August 2009 were evaluated retrospectively. We compared left and right sided distribution of endometriotic and nonendometriotic ovarian cysts, and we also investigated the extent of endometriotic foci, obliteration of pouch of Douglas and endometriosis stage according to the revised American Fertility Society classification of endometriosis to assess whether endometrioma side is related with the severity of endometriosis. Of 239 women with endometriosis, endometrioma was found in the left ovary (n = 109), right ovary (n = 58) and bilaterally (n = 72). Of 101 control group women functional and dermoid cysts were found in the left ovary (n = 48), right ovary (n = 43) and bilaterally (n = 10). Among women with unilateral ovarian endometrioma (n = 167) a left cyst (63.3%) was found more frequently than a right cyst (34.7%) (P < 0.0001). In women with a left ovarian endometrioma pouch of Douglas was open in 99 (90.8%) cases. However, it was partially obliterated in 3 (2.8%) and completely obliterated in 7 (6.4%) cases. On the other hand, in women with a right endometrioma it was open in 44 (75.9%) cases and partially obliterated in 2 (3.4%) and completely obliterated in 12 (20.7%) cases. In women with a right endometrioma, the possibility of the pouch of Douglas obliteration is significantly higher than the women with a left endometrioma (P = 0.006). Moreover, we also showed that in women with a right endometrioma, incidence of the pouch of Douglas obliteration is higher and the endometriosis tends to be more severe compared to women with a left endometrioma. Our most relevant observation is obliteration of Douglas pouch which was found to be more extensive in women with right ovarian endometrioma. Our results showing left lateral predisposition of endometriomas are in agreement with the previous reports and highlight the retrograde menstruation theory for the pathogenesis of this enigmatic disorder.

Association between endometriosis and polymorphisms in insulin-like growth factor binding protein genes in korean women

Genetic factors are known to be associated with the development and progression of endometriosis, however the genes related with endometriosis have not been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed to be involved in proliferation and apoptosis of cells which play an important role in pathophysiologic mechanism of endometriosis. This study aimed to determine the association between endometriosis and polymorphisms of IGFBP genes in Korean women. Case-control study The rs1995051, rs1065780 and Met253Ile single nucleotide polymorphism (SNP)s in the IGFBP1 gene and A(-672)G, A(-202)C and c.95C>G SNPs in the IGFBP3 gene were analyzed in 128 women with endometriosis and 108 normal control women by Taqman assay, PCR-RFLP and direct sequencing. Clinical stage was classified according to the revised American Fertility Society Classification The haplotype genotype composed by combination of three IGFBP1 gene polymorphisms was not related with endometriosis, while the haplotype genotype of IGFBP3 gene has a significant association with endometriosis. Women not carrying AAG (-672A/-202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have 3.19-times higher risk of endometriosis compared with those with the AAG homozygotes, and this trend was found not in early endometriosis but in advanced endometriosis. The AAG haplotype allele of A(-672)G, A(-202)C and c.95C>G polymorphisms in IGFBP3 gene may be associated with advanced endometriosis in Korean women.