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Infertile women carrying ovarian endometriomas can be managed either with surgery or by in vitro fertilization (IVF). The objective of this study is to compare ovarian responsiveness to controlled ovarian stimulation (COS) in assisted reproduction techniques (ART) in infertile women carrying small intact endometriomas and those managed by endometrioma cystectomy or CO2 fiber laser ablation.Retrospective case-control study of prospectively collected data including women underwent ART for endometriosis-related infertility. The study group consisted of infertile women undergoing endometriomas CO2 fiber laser vaporization before ART ('ART after laser CO2' group). Controls were infertile women with endometrioma managed by cystectomy before ART ('ART after cystectomy' group) and infertile women with small endometriomas undergoing ART as first approach ('ART only' group).Of the 86 included patients, 27 (31.4%) belonged to 'ART after laser CO2' group, 37 (43%) to 'ART after cystectomy' group and 22 (25.6%) to 'ART only' group. Surgical groups had larger endometriomas than patients referred to 'ART only' group. No between-groups differences were observed in terms of COS protocol, gonadotropins starting and total doses and length of COS. While women belonged to 'ART after cystectomy' group had fewer recruited follicles (p = .014), oocytes (p = .042), MII oocytes (p = .042) and formed embryos (p = .004) compared to women of 'ART only' group, no significant differences were found between patients of 'ART only' group 'ART after laser CO2' group. A greater number of good-quality embryos were observed in surgical groups. No between-groups differences were found in clinical pregnancy rates.Our results demonstrate encouraging findings on IVF/ICSI outcomes after laser CO2 endometrioma ablation in terms of both quantity and quality of developed embryos.

The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated with a potential reduction in the ovarian reserve due to the inadvertent removal and thermal damage of healthy ovarian tissue. New ablative techniques with reduced tissue penetration depth and less thermal spread to the surrounding parenchyma may represent a viable alternative to cystectomy. For these reasons, the aim of this manuscript is to demonstrate the ablation of the endometrioma capsule using a CO2 fiber laser technique and discuss the clinical outcomes. Once the cyst has been drained and washed, a biopsy is taken. After cyst eversion, vaporization of the inner surface of the cyst is performed using a CO2 fiber laser. The technique is simple and reproducible as even young surgeons without any surgical experience were more confident in performing laser CO2 vaporization instead of cystectomy. The positive effects of CO2 technology are reported in a randomized controlled trial, where the postoperative changes in the antral follicular count (AFC) and antimullerian hormone (AMH) levels were compared between patients who had their endometrioma excised (cystectomy) and those who had undergone endometrioma vaporization with CO2 laser. The patients treated with CO2 laser showed significantly increased AFC without a reduction in serum AMH levels as compared to the cystectomy group, in which both parameters were significantly reduced. The postoperative pregnancy rate was also assessed, and comparable pregnancy rates were found after both treatments. On the contrary, patients treated with the CO2 fiber laser technique had more favorable in-vitro fertilization (IVF) outcomes compared to cystectomy. In conclusion, the CO2 fiber laser technique may represent a viable alternative to cystectomy in the surgical treatment of endometrioma in terms of ovarian preservation, pregnancy rates, and IVF outcomes. Moreover, it has the advantage of being independent of the surgeon's skills and personal experience.

Study Objective To assess the postoperative likelihood of conception in patients with endometriomas managed by either CO2 laser vaporization or cystectomy. Design A retrospective study with prospective recording of data. Setting University hospital. Patients One hundred and forty-two patients with symptomatic endometriomas. Interventions Patients underwent a standardized laparoscopic stripping technique (Group 1) or cyst vaporization with CO2 fiber laser (Group 2). Patients wishing to become pregnant were allowed to attempt a spontaneous conception after surgery. If spontaneous conception failed, patients were referred for in vitro fertilization (IVF). Measurements and Main Results The primary objective was to compare pregnancy rates between the 2 groups. The secondary objective was the identification of independent predictors of pregnancy. Thirty-nine women in Group 1 (53.4%) and 39 women in Group 2 (56.5%) desired to conceive after surgery. Three patients (7.7%) in Group 1 became pregnant following donor-IVF and were excluded. Pregnancies were recorded in 72.2% of patients treated with cystectomy and in 74.3% of those managed with CO2 fiber laser (p = .83). Twenty patients (55.6%) in Group 1 and 14 patients (35.9%) in Group 2 conceived spontaneously (p = .08). Among patients who failed spontaneous conception, 21 patients (28%) achieved pregnancy through IVF (Group 1: n = 6, 16.7%; Group 2: n = 15, 38.5%; p = .08). Twenty patients (26.7%) never became pregnant. Age at the time of surgery (odds ratio (OR) = 0.86; 95% Confidence intervals (CI): 0.78–0.96, p = .002) and duration of infertility (OR=0.80; 95% CI: 0.69–0.92, p = .006) were identified as independent indicators for pregnancy. Conclusion CO2 laser-treated endometrioma is associated with pregnancy rates equal to those observed after cystectomy and favorable IVF outcomes. The one step CO2 fiber laser technique may represent a viable alternative to cystectomy.

This meta-analysis aimed to offer a general picture of the available data on the effects of early-life factors on the risk of developing endometriosis in adult life. An advanced, systematic search of the online medical databases PubMed, EMBASE and CINAHL was limited to full-length manuscripts published in English in peer-reviewed journals up to February 2019. Log of relative risk (RR) was employed to calculate the pooled effect sizes using both fixed and random effects modelling and I-squared tests to assess heterogeneity. Funnel plots were used to investigation publication bias. The meta-analysis was registered in PROSPERO (ID CRD42019138668). Six studies that included a total of 2360 women affected by endometriosis were analysed. The pooled results showed that the risk of developing endometriosis in adult life was significantly increased by being born prematurely (logRR 0.21, 95% CI -0.03 to 0.40), having a low birthweight (logRR 0.35, 95% CI -0.15 to 0.54), being formula-fed (logRR 0.65, 95% CI -0.35 to 0.95) and having been exposed to diethylstilbestrol (DES) in utero (logRR 0.65, 95% CI 0.26 to 1.04. Among intrauterine and early neonatal exposures, prematurity, birthweight, formula feeding and DES were risk factors for the development of endometriosis in adult life.

Study Objective To assess postoperative recurrence rates in patients with endometriomas managed by either “one-step” CO2 fiber laser vaporization or cystectomy. Design Retrospective study with prospective recording of data. Setting University hospital. Patients One hundred twenty-five patients with symptomatic endometriomas. Interventions Patients underwent a standardized laparoscopic stripping technique (group 1) or cyst vaporization with CO2 fiber laser (group 2). After surgery, patients were incorporated in a prolonged surveillance program with periodic clinical follow-up to check for recurrence of the cyst and/or recurrence of symptoms. Endometrioma recurrence was defined as an ovarian cyst (>10 mm) with a typical aspect arising on the operated ovary identified by transvaginal ultrasound. Measurements and Main Results The primary endpoint was the comparison of recurrence rates between the 2 groups. The secondary endpoint was the evaluation of endometriosis-related pain recurrence in the 2 groups. Other endpoints selected for analysis included the identification of risk factors for the recurrence of endometrioma and of endometriosis-related symptoms. The mean follow-up was 29 ± 13 months (range, 13–49). Recurrence of ovarian endometriosis was recorded in 6.3% of patients (n = 4) treated with cystectomy and in 4.9% of patients (n = 3) managed with CO2 fiber laser (p = .74). Recurrence of endometriosis-related pain was observed in 5 patients (7.8%) in group 1 and in 6 patients (9.8%) in group 2 (p = .67). Mean endometrioma diameter > 5 cm at the time of surgery was identified as the only independent poor prognostic indicator for cyst recurrence (p = .008; odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19–3.32). Moreover, the presence of deep endometriosis at surgery (p = .032; OR, 4.60; 95% CI, 1.14–18.57) and discontinuation of hormonal treatment (p = .015; OR, 3.18; 95% CI, 1.25–8.06) were independent poor prognostic indicators for pain recurrence. Conclusion This study suggests that one-step CO2 fiber laser vaporization may be effective for endometrioma treatment because it is associated with recurrence rates comparable with those occurring after cystectomy, with the advantage of being an ovarian tissue-sparing technique.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Study question Could EVs secreted by aneuploid embryos a) serve for development of RNA biomarkers for PGT-A and b) elicit a relevant transcriptomic response in decidualised ESCs? Summary answer Aneuploid embryo EVs a) contain PPM1J, LINC00561, ANKRD34C and TMED10 in differential abundance from euploid EVs and b) induce up-regulation of MUC1 in decidualised ESCs. What is known already Embryo aneuploidy accounts for approximately 50% of all recurrent implantation failures in women >35 years old. PGT-A identifies euploid embryos to increase implantation probability but the technology is controversial as it requires an invasive embryo biopsy with an elusive long-term biosafety. The development of non-invasive methods to screen out aneuploid embryos is paramount. It is also critical to decode the embryo-endometrial dialog underlying implantation failure. We have previously reported that IVF embryos secrete EVs that can be internalised by ESCs, conceptualising that successful implantation to the endometrium is facilitated by EVs, which may additionally serve as biomarkers of ploidy status. Study design, size, duration Embryos destined for biopsy on days 5-7 for PGT-A were grown under standard conditions. Spent media (30μl) were collected from euploid (n = 175) and aneuploid embryos (n = 145) at both cleavage (days 1-3) and blastocyst (days 3-5) stage. Media samples from n = 35 cleavage embryos were pooled in order to obtain five euploid and four aneuploidy pools. Blastocyst media were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy. Participants/materials, setting, methods The study was realised at a research hospital. EVs were isolated from euploid and aneuploid Day3 pools with differential ultracentrifugation and EV-RNA sequencing was performed following the SMARTer Stranded Total RNA-Seq approach. ESCs were decidualised (E2:10nM, P4:1uM, cAMP:0.5 mM twice every 48 hours) and treated for 24 hours with 50 ng/ml euploid or aneuploid EVs extracted from blastocyst media. RNA sequencing was performed on ESCs following the Truseq RNAseq protocol. Main results and the role of chance Aneuploid cleavage stage embryos (n = 4) secreted EVs that were less abundant in RNA fragments originating from the genes PPM1J (log2fc=-5.13, p = 0.011), LINC00561 (log2fc=-7.87, p = 0.010) and ANKRD34C (log2fc=-7.30, p = 0.017) and more abundant in TMED10 (log2fc=1.63 p = 0.025) compared to EVs (n = 5) from euploid embryos. Decidualisation per se induced downregulation of MUC1 (log2FC=-0.54, p = 0.0028) in ESCs as prerequisite for the establishment of receptive endometrium. The expression of MUC1 transcript in decidualised ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2FC=0.85, p = 0.0201). Limitations, reasons for caution The findings of the study may require validation utilising a second cohort of EVs samples. Wider implications of the findings This discovery that the RNA cargo of EVs secreted from aneuploid cleavage stage embryos is diverse from that of euploid embryos potentiates the development of non-invasive methodology for PGT-A. The upregulation of MUC1 in decidualised ESCs following aneuploid embryo EV treatment proposes a new mechanism underlying implantation failure. Trial registration number NA

Background Data about endometrioma ablation using energies with little thermal spread reported good results in terms of ovarian reserve and postoperative pregnancy rates. The aim of the present study was to assess the impact of 'one step' CO2 fiber laser vaporization for endometrioma on subsequent controlled ovarian stimulation. Methods This prospective observational cohort study included a consecutive series of infertile patients who have undergone CO2 fiber laser vaporization for endometrioma treatment. The primary endpoint was to assess the number of follicles per ovary growing during controlled ovarian stimulation. The secondary endpoints included the number of oocytes retrieved, the total number of embryos obtained and the cumulative clinical pregnancy rate per patient treated. Results Twenty-six patients underwent assisted reproductive technology after surgery for endometriosis-related infertility. In unilateral operated ovaries at the end of controlled ovarian stimulation no significant differences emerged from comparison of total recruited follicles in the operated ovary and in the contralateral ovary (p=0.55). If considering only bilateral endometriomas, the number of recruited follicles at the end of controlled ovarian stimulation was similar in both operated ovaries (p=0.79). The number of cumulative clinical pregnancies was 15 (57.7%; 95% CI: 38.5-76.9 %). When comparing women aged ≤ 35 years to those aged > 35 years, controlled ovarian stimulation outcomes were significantly higher in the younger patients. Age at the time of assisted reproductive technology was the only independent predictor for follicular growth during ovarian hyperstimulation (CI: -1.27 to -0.116, p=0.027). Conclusions CO2 laser-treated endometrioma is associated with favorable reproductive assisted reproductive technology outcomes.

Gestational diabetes mellitus (GDM) is a metabolic complication associated with adverse outcomes for mother and fetus. Arsenic (As) exposure has been suggested as a possible risk factor for its development. The aim of this meta-analysis was to provide a comprehensive overview of published evidence on the association between As and GDM. The systematic search from PubMed, MEDLINE, and Scopus was limited to full-length manuscripts published in peer-reviewed journals up to April 2020, identifying fifty articles. Ten studies met the inclusion criteria, nine for quantitative synthesis with a total of n = 1984 GDM cases. The overall pooled risk was 1.56 (95% Confidence Interval - CI = 1.23, 1.99) with moderate heterogeneity (χ2 = 21.95; I2% = 64). Several differences among the included studies that may account for heterogeneity were investigated. Stratification for exposure indicator confirmed a positive association for studies assessing urine As. A slightly higher risk was detected pooling studies based in Asia rather than in North America. Stratification for GDM diagnostic criteria showed higher risks when diagnosis was made according to the Canadian Diabetes Association (CDA-SOGC) or World Health Organization (WHO) criteria, whereas a lower risk was observed when adopting the American Diabetes Association (ADA) criteria. These results provide additional evidence for a possible association between As exposure and GDM, although the data need to be interpreted with caution due to heterogeneity.

Background In recent years, excisional surgery has been questioned as an ideal surgical approach for endometriomas because it is associated with potential removal of healthy ovarian tissue and loss of ovarian follicles with subsequent reduction of ovarian reserve. The aim of our study was to evaluate the benefits of CO2 laser vaporization through a clinical trial assessing the postoperative changes in ovarian reserve as indicated by antral follicle count (AFC) and anti-Müllerian hormone (AMH). Materials and Methods Fifteen patients undergoing surgery for primary unilateral or bilateral symptomatic endometriomas were enrolled in the study. During surgery, the cystic lining was completely vaporized with CO2 laser fiber (AcuPulse Duo system, Lumenis); before surgery and at 1 and 3 months after surgery, ovarian reserve was evaluated by pelvic ultrasound to determine the AFC, and blood sample to determine AMH levels. Results The AFC of the operated ovary was significantly increased after treatment at 1 and 3 months' follow-up (p = 0.0021; p = 0.005, respectively); the increase is particularly significant in women younger than 35 years (p = 0.012). No statistically significant changes were reported in serum AMH concentrations at 1 or 3 months' follow-up. No recurrences of symptoms and no recurrences of endometrioma were reported. Conclusions These data support the hypothesis that endometrioma vaporization with CO2 laser fiber may be a valid method to preserve ovarian function; however, further studies are required before advocating the routine use of CO2 laser vaporization for the management of ovarian endometriosis.

Deep pelvic endometriosis is a specific entity defined by endometriotic lesions extending more than 5 mm under the peritoneum, including the infiltrative forms involving vital structures, such as the bowel, ureters, bladder, and rectovaginal lesions. Intestinal endometriosis is the most common extra-pelvic site and involves more frequently the rectovaginal septum, the recto-sigmoid followed by the rectum, ileum, appendix, and cecum. Several theories have been proposed for the pathogenesis of deep pelvic endometriosis: the retrograde menstruation theory, the theory of coelomic remnants metaplasia and the stem cells theory. In addition, genetic factors seem to play a role on individual’s susceptibility to endometriosis. In the last years, advances in knowledge regarding the histological definition of endometriosis occurred, introducing the profibrotic nature of the disease inside its “new” definition. In general, the natural history of endometriosis toward fibrosis resembles that characteristic of other fibrotic disease, involving myofibroblast and smooth muscle cell action, as well as the production of high levels of Transforming Growth Factor (TGF)-β, epithelial-to-mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation and finally collagen deposition. In line with these concepts, histologic analyses show that in deep lesions, endometrial-like tissue represents a minor component.

Endometriosis-related fibrosis represents a complex phenomenon with underlying mechanisms yet to be clarified. Fibrosis is consistently present in all disease forms and contributes to classic endometriosis-related symptoms of pain and infertility. The purpose of this literature review was to examine the role of various cellular populations and biologic mechanisms and signaling pathways in inducing fibrogenesis of endometriotic lesions. A search was performed through PubMed and MEDLINE for animal and human studies published in English in the last 23 years that examined fibrosis in superficial, ovarian, and deep infiltrating endometriosis. The main cell types found to be involved in the development of fibrosis were platelets, macrophages, ectopic endometrial cells, and sensory nerve fibers. Interactions among each of the cell types contribute to the production of fibrosis through the production of soluble factors, mostly transforming growth factor-β but also other cytokines and neuropeptides. Cell types known to be critical to the pathophysiology of endometriosis also contribute to fibrogenesis, thus supporting the theory that fibrosis is an inherent part of endometriosis.

To assess postoperative recurrence rates in patients with endometriomas managed by either "one-step" CORetrospective study with prospective recording of data.University hospital.One hundred twenty-five patients with symptomatic endometriomas.Patients underwent a standardized laparoscopic stripping technique (group 1) or cyst vaporization with COThe primary endpoint was the comparison of recurrence rates between the 2 groups. The secondary endpoint was the evaluation of endometriosis-related pain recurrence in the 2 groups. Other endpoints selected for analysis included the identification of risk factors for the recurrence of endometrioma and of endometriosis-related symptoms. The mean follow-up was 29 ± 13 months (range, 13-49). Recurrence of ovarian endometriosis was recorded in 6.3% of patients (n = 4) treated with cystectomy and in 4.9% of patients (n = 3) managed with COThis study suggests that one-step CO

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Endometriosis is an inflammatory disease affecting 7-10% of women throughout their reproductive life. Few data are available regarding the age at menopause of women affected by this disease. Most of the available evidence, although scanty, would indicate that both ovarian surgery for endometriomas and endometriosis per se appear to influence age at menopause. Other factors might interfere with the age at menopause of women affected by endometriosis. The purpose of this review was to examine the age at menopause in women with a history of endometriosis and to identify factors that might affect the timing of menopause.