Endometriosis-related Infertility Research Articles

Optimizing IVF Success: A Case Study of Melatonin-Assisted Frozen Embryo Transfer for Poor Oocyte Quality and Endometriosis

ABSTRACT The case study investigates the journey of a couple facing infertility. It intensifies the challenges, including poor oocyte quality and endometriosis. In spite of two failed in vitro fertilization cycles, the decision for ovum pickup (OPU) was made, followed by intra-cytoplasmic sperm injection (ICSI), embryo treatment with melatonin, and frozen embryo transfer (FET) to optimize the chances of a successful pregnancy. The couple opted for this approach. OPU yielded four poor-quality oocytes, prompting ICSI and melatonin treatment to enhance embryo quality. The embryos were exposed to culture supplementation with melatonin for 72 hours before being transferred to conventional media. After 5 days or 120 hours, the embryos developed into 3BB quality blastocysts, indicative of developmental stage and morphology. The blastocysts were then cryopreserved, and after 2 months, FET was conducted, resulting in the transfer of two embryos, which subsequently led to a positive pregnancy indication, as indicated by a β-hCG level of 233 mUI/ml measured 14 days post transfer. This approach highlights the effectiveness of melatonin supplementation in improving embryo quality and ultimately facilitating successful pregnancy in complex scenarios like endometriosis-related infertility.

Postoperative reproductive outcomes in patients with endometriosis-associated infertility: A single-centre retrospective study.

Endometriosis is a chronic inflammatory disease known to contribute to infertility. Laparoscopic excision of endometriotic lesions represents a standard treatment modality for symptomatic women. Our study aims to assess the potential benefits of laparoscopic excision of endometriosis in patients experiencing infertility associated with the condition, as well as to define the clinical factors that may impact the cumulative pregnancy rate. In this retrospective analysis, a total of 102 patients with endometriosis-related infertility were enrolled. All participants underwent reproductive surgery and were then categorized into two groups: those who conceived were assigned to Group A, while those who did not were assigned to Group B. The correlation between clinical factors and pregnancy rate was assessed using the log rank test, and both univariate and multivariate analyses were conducted utilizing the Cox regression model. Results The median age of the patients was 33.5 years, with a median follow-up duration of 70 months. Throughout the study period, 71 patients (69.6%) conceived (Group A), while the remaining 31 patients (30.4%) did not conceive (Group B), irrespective of the use of Assisted-Reproduction Technologies. The Cox regression model revealed that factors such as the duration of infertility, presence of deep infiltrating endometriosis, bowel endometriosis, rASRM stages, pelvic adhesions, and recurrent disease negatively impacted postoperative conception rates. Conversely, complete excision and coagulation of endometriotic lesions, as well as ablation of ovarian endometriomas, emerged as independent positive predictive factors for postoperative clinical pregnancy. The retrospective design of the study, as well as a small number of patients. Complete excision of endometriosis during reproductive surgery may yield a positive effect and optimize the likelihood of pregnancy in patients with endometriosis-related infertility.

Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature

Role of Molecular Biomarkers in Endometriosis-Related Infertility: A Narrative Review of the Literature

Analysis of factors affecting pregnancy rate after laparoscopic surgery for infertility associated with endometriosis

ObjectiveTo analyze the factors that might influence the pregnancy rate in patients with infertility related to endometriosis (EMs) after undergoing laparoscopic surgery, providing guidance for our clinical diagnostic and therapeutic decision-making. MethodsA retrospective analysis was conducted on clinical records and 1-year postoperative pregnancy outcomes of 335 patients diagnosed with endometriosis-related infertility via laparoscopic surgery, admitted to our department from January 2018 to December 2020. ResultsThe overall pregnancy rate for patients with endometriosis (EMs) related infertility 1-year post-surgery was 57.3 %, with the highest pregnancy rate observed between 3 to 6 months after surgery. Factors such as Body Mass Index (BMI) (P = 0.515), presence of dysmenorrhea (P = 0.515), previous pelvic surgery (P = 0.247), type of EMs pathology (P = 0.893), and preoperative result of serum carbohydrate antigen 125 (CA125)（P = 0.615）had no statistically significant effect on postoperative pregnancy rates. The duration of infertility (P = 0.029), coexistence of adenomyosis (P = 0.042), surgery duration (P = 0.015), intraoperative blood loss (P = 0.050), preoperative result of serum anti-Müllerian hormone (AMH) (P = 0.002) and age greater than 35 (P = 0.000) significantly impacted postoperative pregnancy rates. The post-surgery pregnancy rate in patients with mild (Stage I-II) EMs was notably higher than those with moderate to severe (Stage III-IV) EMs (P = 0.009). Age (P = 0.002), EMs stage (P = 0.018), intraoperative blood loss (P = 0.010) and adenomyosis (P = 0.022) were the factors that affected the postoperative live birth rate. ConclusionFor patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors.

Management of patients with endometriosis and infertility: laparoscopic treatment and spontaneous pregnancy rate.

To evaluate factors involved in spontaneous pregnancy rate after surgery for endometriosis in patients with endometriosis and infertility. This retrospective study spanned from 2014 to 2020 and included a follow-up period of two years of patients with endometriosis-related infertility who underwent laparoscopic surgery. Women aged 25 to 43 years with patent tubes, no/mild male factor and no other infertility factors were selected and grouped according to fertility management as follows: patients immediately prescribed ART (16.5%, ART-p); patients who chose not to undergo ART (83.5%) and achieved spontaneous pregnancy (71.8% SP-p); and patients who first chose not to undergo ART but had it subsequently (28.2%, NSP-p). A total of 200 patients were analyzed. Of the 167 patients who waited for spontaneous pregnancy, 71.8% achieved it. We observed a tendency of higher endometriosis ASRM scores in the ART-p group compared with patients who waited for spontaneous pregnancy, and lower scores in individuals that achieved spontaneous pregnancy. When we looked at how long it took to achieve pregnancy, we found that individuals in the SP-p group achieved pregnancy in 5.7 months, while subjects in the NSP-p group took 1.8 times longer than their peers in the SP-p group (p<0.001). However, once prescribed ART, the individuals in the NSP-p group achieved pregnancy within a similar time when compared with subjects in the SP-p group. In order to identify individuals that might benefit from ART early on, we performed a multivariable analysis and developed a decision tree (81.3% accuracy and 53.3% sensitivity). The present results indicated that, after surgery, the majority of patients achieved spontaneous pregnancy. The decision tree proposed in this study allows the early identification of patients who might require ART, thus decreasing the time between surgery and pregnancy and improving overall outcomes.

Soluble Factors CD14, CD163, and Migration Inhibitory Factor Are Associated with Endometriosis-Related Infertility

Objectives: Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serve as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. Design: Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. Participants: Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. Methods: The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. Results: Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the rASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the rASRM endometriosis score. In receiver operating characteristic analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. Limitations: Some limitations of the current study deserve to be underlined. First, the sensitive ELISA method was the sole-validated tool for detecting the markers in patient samples. Second, healthy or fertile women were not involved as the control group. Conclusions: The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.

Role of TNF superfamily members lymphotoxin-α, sCD40L, and TNF-α in endometriosis-related infertility

Introduction: TNF-α, LT-α, and sCD40L belong to the TNF superfamily and play a pivotal role in chronic inflammatory disease. Yet, these soluble molecules are largely unexplored in endometriosis cases with infertility. The present study aimed to evaluate serum and peritoneal fluid levels of these molecules and correlate its level to the endometriosis severity. Methods: Peripheral blood and peritoneal fluid samples were obtained from 87 infertility cases who underwent laparoscopy, consisting of 44 endometriotic women and 43 non-endometriotic women. The levels of TNF-α, LT-α, and sCD40L were determined using ELISA. Results: Serum and peritoneal TNF-α levels were significantly elevated in the endometriosis group compared to the control group ( p = 0.028; p = 0.027), but not the sCD40L and LT-α level. Serum and peritoneal TNF-α levels were significantly different between late-endometriosis (stage III or IV) compared to the control group ( p = 0.026, p = 0.041, respectively). Moreover, the serum LT-α level was significantly higher in late-endometriosis cases compared to the early-endometriosis (stage I or II) cases ( p = 0.03) and showed a positive correlation with endometriosis rASRM score ( p = 0.001). ROC curve analysis showed a significant diagnostic value of serum LT-α in differentiating the late cases to the early endometriosis patients (AUC = 0.751, p = 0.007). A negative correlation between LT-α and total Endometriosis Fertility Index (EFI) score was also observed ( p = 0.012). Conclusion: Severe endometriosis and lower EFI score are associated with higher serum LT-α level. Serum LT-α is a potential staging biomarker among endometriosis cases. Serum and peritoneal TNF-α levels were elevated in women with severe endometriosis among infertility cases. Further study should address the role and predictive value of LT-α in endometriosis-related infertility.

Impact of oil-based contrast agents in hysterosalpingography on fertility outcomes in endometriosis: a retrospective cohort study

BackgroundPrevious studies have suggested that oil-based contrast agents used during hysterosalpingography (HSG) in infertile patients can enhance fertility. However, limited research has investigated the effect of oil-based contrast medium specifically in individuals with endometriosis-related infertility.ObjectiveThis study aims to explore the impact of oil-based contrast medium on fertility outcomes in women with endometriosis-related infertility.MethodsConducted at the First Affiliated Hospital of Guangxi Medical University (January 2020 to June 2022), the study included 512 patients undergoing HSG. Patients were categorized into oil-based and non-oil-based groups, and after propensity score matching, demographic characteristics were compared. Main outcomes included clinical pregnancy rates, live birth rates, early miscarriage rates, and ectopic pregnancy rates.ResultsIn our analysis, the Oil-based group showed significantly better outcomes compared to the Non-oil-based group. Specifically, the Oil-based group had higher clinical pregnancy rates (51.39% vs. 27.36%) and increased live birth rates (31.48% vs. 19.93%). This trend held true for expectant treatment, IUI, and IVF/ICSI, except for surgical treatment where no significant difference was observed. After adjusting for various factors using propensity score matching, the Non-oil-based group consistently exhibited lower clinical pregnancy rates compared to the Oil-based group. The Odds Ratio (OR) was 0.38 (95%CI: 0.27–0.55) without adjustment, 0.34 (0.22–0.51) in multivariable analysis, 0.39 (0.27–0.57) using inverse probability of treatment weighting (IPTW), and 0.22 (0.14–0.35) in propensity score matching.ConclusionOil-based contrast medium used in HSG for women with endometriosis-related infertility is associated with higher clinical pregnancy rates and live birth rates compared to Non-oil-based contrast medium.

Ultrasound-guided Lipiodol® hysterosalpingography: A prospective study on pregnancy and complication rates.

Fluoroscopic hysterosalpingography (HSG) with Lipiodol® is safe and has a therapeutic effect on fertility: transient in endometriosis-related infertility and sustained in unexplained infertility. Ultrasound is replacing fluoroscopy as the preferred imaging modality for HSG due to comfort and radiation safety (no ionising radiation). The safety of ultrasound-guided Lipiodol® HSG is uncertain. Prospectively observe pregnancy and complication rates after ultrasound-guided Lipiodol® HSG. A single-centre prospective study of women with unexplained infertility undergoing ultrasound-guided Lipiodol® uterine bathing and tubal flushing after tubal patency confirmed with ExEm® Foam HyFoSy (hysterosalpingo-foam-sonography). Pregnancy outcomes at six months and serum and urinary thyroid function at one, three and eight weeks were recorded. Pain scores were recorded during and immediately after HSG. Descriptive statistics are reported. Fifty-two participants were enrolled between July 2019 and April 2021, median age 33 years (range 21-45). Only 45 (87%, 45/52) completed the Lipiodol® HSG; 5/7 experienced intravasation during initial HyFoSy. Of 30 women at follow-up, 57% had biochemical (17/30, 95% CI 37%-75%), 53% clinical (16/30 95% CI 34%-72%) and 35% ongoing pregnancies (11/30, 95% CI 20%-56%). The rate of subclinical hypothyroidism (SCH) at two months was 41% (7/17). One intravasation event occurred during Lipiodol® HSG (2%, 1/45). Median pain score was 5/10 (range 0-9, interquartile range 2.5-7). No anaphylaxis, infection or oil embolism was observed. Outpatient ultrasound-guided Lipiodol® HSG was safe, with pregnancy rates comparable to previous studies of fluoroscopic guidance. Rates of intravasation and SCH were also similar, confirming the need to monitor thyroid function.

Advances in approaches to diagnose endometriosis

Endometriosis is a common, underdiagnosed, systemic inflammatory, and endocrine pain disorder that impacts the quality of life of millions of persons with a uterus globally. It is associated with chronic pelvic pain and an increased risk of subfertility. It has also been associated with cardiovascular disease, depression, thyroid and autoimmune disorders, ovarian and breast cancers, and poor pregnancy outcomes. Treatment of endometriosis-related pain and infertility can be medical and/or surgical, although misdiagnosis due to symptoms that overlap with other conditions and reliance on definitive diagnosis by histologic confirmation of endometriosis at surgery have contributed to a prolonged diagnosis-to-treatment timeline. A paradigm shift in endometriosis diagnosis is underway, with greater reliance on clinical and family history, physical examination, and imaging, without surgical confirmation, and then proceeding with medical and/or surgical therapies, although any one diagnostic approach alone is insufficient. Although there are no validated, specific molecular biomarkers for endometriosis, recent candidates have promise for diagnosing the disease and facilitating symptom management. This review presents current and evolving approaches to diagnose endometriosis with the goal of expediting the diagnosis-to-treatment timeframe, so patients can have confidence in a diagnosis for their symptoms, expectations set about disease management across the lifespan, and a patient-centered treatment plan promptly initiated. To provide context, the review begins with a summary of disease characteristics, followed by genetic and environmental risks for developing endometriosis, the central role of estrogen and inflammation in the pathophysiology of pain and infertility relevant to the disease and biomarker discovery, and nonsurgical approaches that are increasingly being acknowledged by professional organizations across the globe to be of value in the diagnosis of this enigmatic disease with diverse manifestations.

METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility

BackgroundEndometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation.MethodsWe examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A.ResultsThe expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein.ConclusionsMETTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.

Xiaoyi Yusi decoction improves fertilization and embryo transfer outcomes in patients with endometriosis.

To investigate the effect of - Xiaoyi Yusi decoction (XYYSD, ), a Traditional Chinese Medicine (TCM), on fertilization and embryo transfer (IVF-ET) in patients with endometriosis, and to study the mechanism underpinning the action. Women who underwent IVF-ET were divided into three groups by simple randomization: the treatment ( 32; with TCM treatment), patient (28; with endometriosis alone), and control (33; with male factor alone) groups. The luteal phase short-acting gonadotropin-releasing hormone agonist prolonged protocol was used in all three groups. To compare the changes in TCM scores and reproductive outcomes before and after TCM intervention in patients with endometriosis, partial least-squares discriminant analysis was used to analyze the follicular fluid samples of each group and screen and compare metabolites using the MetaboAnalyst software. The clinical data indicated that following TCM intervention, kidney deficiency and blood stasis symptom patterns improved dramatically in patients with endometriosis and that their clinical pregnancy rate increased significantly (71.9% 57.1%, 0.05). Metabolomics showed that the two groups of samples were separated before and after TCM intervention. After TCM intervention, the intervention group was close to the control group, indicating that the TCM had a certain effect. Pathway analysis revealed that after TCM intervention, the metabolism of glycerin phospholipid, pyruvate, and citric acid was regulated. Through the pyruvate and glycerophospholipid metabolism pathways and tricarboxylic acid cycle, the TCM XYYSD successfully improved kidney deficiency and blood stasis symptom pattern, as well as the clinical reproductive outcomes of patients with endometriosis-related infertility.

Probiotics and NLRP3 mRNA inflammasome levels in women with endometriosis-related infertility undergoing assisted reproductive technologies.

This research was conducted at Bukovinian State Medical University and the Centre of Reproductive Medicine and included a total of 30 infertile women. The control group consisted of 10 women with tubal infertility resulting from a prior history of inflammation, who, following a comprehensive clinical and laboratory assessment, exhibited no other underlying health conditions and could be regarded as essentially healthy individuals. Participants in the control group ranged from 21 to 42 years, with an average age of 29.75 years. The control group did not receive the probiotic Femina Probiz. The main group, on the other hand, included 20 women diagnosed with external genital endometriosis who were undergoing assisted reproductive technologies. These patients were administered the probiotic Femina Probiz manufactured by Unic Biotech Ltd in India. They were instructed to take one tablet containing 10×10^9 Lactobacillus organisms twice daily for one month as part of their preparatory treatment before proceeding with assisted reproductive technologies. The levels of NLRP3 inflammasome were measured before and after this preparatory phase. The incidence of primary infertility was significantly higher in patients belonging to the main group.

Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment

Endometriosis is a pervasive gynecological ailment which usually results in unease and infertility and is signified by an accumulation of endometrial-like tissue outside the uterus. Current endometriosis medications, which often entail surgical intervention and hormone therapy, are geared around easing discomfort as well as improving fertility. However, alternative approaches targeting angiogenesis have shown promise in managing endometriosis-associated infertility. This case report highlights the implications of combining antiangiogenic therapy (bevacizumab) with dichloroacetate (DCA) therapy in a patient with endometriosis seeking infertility treatment. A 34-year-old woman presented with a five-year history of severe pelvic pain and primary infertility due to stage IV endometriosis. The patient sought other possibilities after repeated unsuccessful attempts using assisted reproductive technology. A revolutionary therapy strategy combining bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and DCA, a metabolic modulator, has been proposed considering the potential significance of angiogenesis in endometriosis-related infertility. The patient underwent a six-month treatment regimen consisting of intravenous bevacizumab infusions combined with oral DCA administration. The theory behind this combination was to target the metabolic reprogramming typically associated with the disease in addition to altering the abnormal angiogenic signaling pathways that contribute to the pathogenesis of endometriosis. Given the scores on the visual analogue scale, the patient's pelvic pain substantially decreased during the time frame of treatment. Additionally, a notable improvement in ovarian reserve markers was observed, including an increase in anti-Müllerian hormone levels and the number of antral follicles. This case report suggests that the combination of bevacizumab and DCA may have a synergistic effect in managing endometriosis-associated infertility. This form of therapy may provide patients who have failed typical infertility treatment options with an innovative therapeutic approach since it targets both angiogenesis and metabolic changes.

Spatiotemporal Trends and Age-Period-Cohort Analysis for the Burden of Endometriosis-Related Infertility: An Analysis of the Global Burden of Disease Study 2019.

Endometriosis is a common nonfatal gynecological disease, and infertility is one of its main dangers. Endometriosis-related infertility causes serious damage to women's health and places a burden on women of reproductive age. The aim of this study was to describe the current burden of endometriosis-associated infertility and to analyze its spatiotemporal trends. Age-standardized prevalence rate (ASPR) data from 1990 to 2019 for Endometriosis-related primary infertility (ERPI) and secondary infertility (ERSI) were obtained from the Global Burden of Disease Study (GBD) 2019. These data spanning three decades cover the global, sociodemographic index (SDI) regions, GBD regions, and 204 countries and territories. Spatiotemporal trends were analyzed by calculating the estimated annual percentage change (EAPC) and using a time-period-cohort model. Globally, the ASPR of ERPI and ERSI showed a weak downward trend from 1990 to 2019, with EAPCs of -1.25 (95% CI: -1.39 to -1.11) and -0.6 (95% CI: -0.67 to -0.53), respectively. The spatiotemporal trends in ERPI and ERSI varied substantially between regions and age groups. When endometriosis-related infertility burden was linked to SDI values, a strong negative correlation was observed between the ASPR of ERSI and its EAPC and SDI values. When modeling with age-period-cohort, ERPI burden was found to be highest at ages 20-25 years, while ERSI burden was persistently higher at ages 20-45 years. Using 2000-2004 as the reference period, both ERPI and ERSI burden decreased with each year among women. Significant variability in burden between regions was found for the birth cohort factor. The global burden of endometriosis-related infertility declined minimally from 1990 to 2019. However, this burden varied considerably across regions, age groups, periods, and birth cohorts. The results of this study reflect spatiotemporal trends in the burden of endometriosis-related infertility over the study period and may be used to help improve health management, develop timely and effective prevention and control strategies, and provide epidemiologic theoretical evidence for reducing the burden for endometriosis-related infertility.

The Role of Peritoneal Immunity in Peritoneal Endometriosis and Related Infertility.

Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms.

Reproductive outcome and gynecologic comorbidities in women with endometriosis in a non-IVF setting: a retrospective study

BackgroundEndometriosis-related infertility is a disease associated with significant morbidity and distress to the couple and requires timely, multidisciplinary, and often high-cost care involving assisted reproductive technologies (ART). Many health care systems in the Middle East do not provide coverage for ART. This study aims to describe the reproductive outcome in a form of a clinical pregnancy rate in women with endometriosis-related infertility in a health care system that does not provide coverage for ART.ResultsThis is a retrospective observational cohort study on women who attended the gynecology clinic in a tertiary center in Oman with the diagnosis of endometriosis from January 2011 to December 2019. Women of reproductive age seeking pregnancy were included in the analysis. Out of total women with endometriosis, (144/262) 55.0% were included in the analysis with a mean age of 31.10 ± 5.73 years. The mean duration of follow-up was 30.18 months and 43/144 (29.9%) of our patients had a follow-up > 60 months. Based on surgical staging, 11.8% had mild disease, 70.1% had moderate to severe disease and 18.1% were not operated. After a thorough assessment, (30.2%) were advised to seek in vitro fertilization (IVF) as a primary treatment for infertility but 23.08% declined the advice. Of the 144, 24.3% achieved a clinical pregnancy. (16/144), 11% conceived spontaneously. 11/144) 7.6% conceived with ovulation induction ± intrauterine insemination (OI ± IUI) and the rest conceived with a self-sponsored IVF. The overall clinical pregnancy rate was not statistically different between those who had surgery and those did not have surgery (P value 0.474). The pregnancy rate based on the management plan were; surgery + IVF (7/25, 28.0%), surgery + OI/IUI (10/47, 21.3%), surgery alone (9/33, 27.3%). The pregnancy rate was not statistically different between the groups (P value 0.782).In addition to endometriosis, a significant proportion (63/144, 43.8%) of these women have a coexisting gynecologic morbidity including 2.1% non-endometrioma ovarian cyst, 13.9% myomas, 4.2% adenomyosis, 8.3% Mullerian anomalies, 2.1% polycystic ovary syndrome, 6.3% pelvic inflammatory disease or tubo-ovarian abscess and 1.4% biopsy-proven endometritis.ConclusionThe reproductive outcome of patients with endometriosis in this study population was generally poorer than what is reported in the literature with an overall pregnancy rate of 24.3% and a spontaneous pregnancy rate of 11%. Several causes can be noted for such an outcome, including advanced disease stage, coexisting gynecologic morbidities, and poor access to advance fertility management.

Fertility Preservation in Women with Endometriosis.

Several mechanisms have been implicated in the pathogenesis of endometriosis-related infertility. For patients considering surgery, the risk of iatrogenic injury is among the most important factors in the context of fertility preservation, along with age and individual reproductive goals. In the case of endometrioma excision, evidence overwhelmingly demonstrates the negative impact of surgery on ovarian reserve, with significant reductions in antimullerian hormone (up to 30% in unilateral versus up to 44% in bilateral endometriomas). The surgical endometriosis patient should be thoroughly counseled regarding fertility preservation and discussion should include tissue, embryo, and oocyte cryopreservation options. For the latter, data support cryopreservation of 10-15 oocytes in women ≤35 years and over 20 for those >35 years for a realistic chance to achieve one or more live births. When performing surgical interventions for endometriosis, reproductive surgeons should employ fertility-conserving surgical methods to reduce the likelihood of postoperative iatrogenic diminished ovarian reserve.

P-329 Oocyte donation outcomes in endometriosis patients with multiple IVF failures

Abstract Study question What are the reproductive outcomes and the prognostic factors of live birth rates in endometriosis patients referred to oocyte donation after multiple in vitro fertilization(IVF)-failures? Summary answer In this specific population, oocyte donation appears to be a viable option to optimize the reproductive outcomes, as the cumulative live birth rate reaches 63.2%. What is known already Assisted Reproductive Technology(ART) is currently recognized as one of the main therapeutic options to manage endometriosis-related infertility, often resulting in satisfactory outcome. A burning issue in this field remains how to deal with patients undergoing recurrent ART failures. As there appear to be two main factors contributing to the failures, i.e., a deleterious effect of endometriosis on embryo implantation and altered oocyte and embryo quality, two competing therapeutic strategies can be considered:(i) endometriosis surgery and (ii) oocyte donation. However, no data has been published to date in the specific population of endometriosis patients with previous IVF failures, undergoing oocyte donation. Study design, size, duration Observational cohort study including fifty-seven women with endometriosis-related infertility and multiple IVF failures (≥ 2 failed IVF cycles) referred to oocyte donation who consulted at our institution between January 2013 and June 2022. Participants/materials, setting, methods Endometriosis was diagnosed based on published imaging criteria using transvaginal sonography and magnetic resonance imaging and confirmed histologically in women who had a history of surgery for endometriosis. The main outcomes measured were the clinical pregnancy rate (CPR) and the cumulative live birth rate (CLBR). We compared the characteristics of women who had a live birth versus those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. Main results and the role of chance Fifty-seven patients underwent 90 oocyte donation cycles, after 244 failed autologous IVF cycles. The mean age of the population was 36.8 ± 3.3 years, with a mean infertility duration of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial endometriosis, 2 patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, the CPR and the CLBR per patient were 49/57 (85.9%) and 36/57 (63.2%), respectively. After multivariate analysis, only being nulligravida (p = 0.002) remained an independent negative predictive factor of the live birth rate. Limitations, reasons for caution In 35.1% of patients there was no surgical/histological proof of endometriosis. However, for all the study participants, endometriosis was diagnosed and staged using patient interviews, clinical examination, and imaging techniques to assess for endometriosis phenotypes, which is in line with the structured diagnostic process acknowledged as being appropriate for endometriosis. Wider implications of the findings In this specific population, poor embryo quality may be the main limiting factor of ART success rates, rather than impaired endometrial receptivity. These data are reason for clinicians not to systematically refer infertile endometriosis patients with recurrent IVF failures to surgery. Trial registration number not applicable

Transcriptomic analysis of granulosa cells in patients with endometriosis-related infertility: identification of potential molecular mechanisms

Transcriptomic analysis of granulosa cells in patients with endometriosis-related infertility: identification of potential molecular mechanisms