Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells.

STUDY QUESTION: Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)? SUMMARY ANSWER: Aneuploid embryo-derived EVs contain transcripts of PPM1J, LINC00561, ANKRD34C, and TMED10 with differential abundance from euploid embryo-derived EVs and induce upregulation of MUC1 transcript in dESCs. WHAT IS KNOWN ALREADY: We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown. STUDY DESIGN SIZE DURATION: Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 µl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy. PARTICIPANTS/MATERIALS SETTING METHODS: EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs. MAIN RESULTS AND THE ROLE OF CHANCE: Aneuploid cleavage stage embryos 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 of euploid embryos. Decidualization per se induced downregulation of MUC1 (log2fc = -0.54, P = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of MUC1 transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, P = 0.0201). LARGE SCALE DATA: Raw data have been uploaded to GEO (accession number GSE234338). LIMITATIONS REASONS FOR CAUTION: The findings of the study will require validation utilizing a second cohort of EV samples. WIDER IMPLICATIONS OF THE FINDINGS: The discovery that the transcriptomic profile of EVs secreted from aneuploid cleavage stage embryos differs from that of euploid embryos supports the possibility to develop a non-invasive methodology for PGT-A. The upregulation of MUC1 in dESCs following aneuploid embryo EV treatment proposes a new mechanism underlying implantation failure. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a Marie Sklodowska-Curie Actions fellowship awarded to SM by the European Commission (CERVINO grant agreement ID: 79620) and by a BIRTH research grant from Theramex HQ UK Ltd. The authors have no conflicts of interest to declare.

Reproductive outcomes after vaginal repair of isthmocele: A preliminary study and systematic review of the literature.

OBJECTIVE: Although vaginal repair of isthmocele is an effective and safe surgical option, data on reproductive and obstetrical outcomes are lacking. The aim of this study is to evaluate reproductive outcomes of women undergone vaginal repair of isthmocele. We also systematically reviewed the existent literature to offer a general view of available data. STUDY DESIGN: Retrospective analysis of a database prospectively collected between January 2018 and January 2022 at San Raffaele Hospital, Milan, Italy. We included secondary infertile women with ultrasound documented isthmocele who undergone vaginal repair. Post-surgical clinical, reproductive and obstetric outcomes were recorded. An advanced systematic search of the literature up to January 2023 was conducted. RESULTS: 17 women were included. The mean age of the included patients was 37.2 ± 2.7 years. The median of previous caesarian sections was 1 (1-2). One intra-operative complication (5.9 %) was reported (bladder injury, repaired at the time of surgery). At follow up, bleeding was successfully treated in 8 women (8/10; 80 %). Pregnancy was obtained in 7 women (7/17; 41.2 %): the conception was spontaneous in 4 women (4/7; 57.1 %) and trough assisted reproductive technology in 3 patients (3/7; 42.9 %). The mean time from surgery to pregnancy was 10.8 (±6.7) months. One spontaneous abortion was reported (1/7; 14.3 %), while live birth was achieved in 6 pregnancies (6/7; 85.7 %). All deliveries were by caesarian section at a median gestational age of 37.5 (36-38.25) weeks. No obstetrical complications were reported. At the time of caesarean section, no defects on the lower segment were retrieved. Regarding the systematic research, among the 21 studies screened, only 4 articles were included in the review. Pregnancy rate was around 60-70 % with very few obstetrical complications (0.01 %) such as abnormal placentation or preterm birth. CONCLUSIONS: Vaginal repair of isthmocele is a minimally invasive, safe and effective surgical approach in terms of postsurgical residual myometrium tichness. Systematic review to date has found low-quality evidences on the impact of vaginal surgery in the management of secondary infertility and obstetrics outcomes in women with isthmocele.

Minimally invasive surgery for ovarian endometriosis as a mean of improving fertility: Cystectomy vs. CO2 fiber laser ablation what do we know so far?

Minimally invasive surgery emerged in the 1980s as a safe and effective technique which requires smaller incisions and, usually, a shorter hospital stay compared to traditional surgery. Since then, minimally invasive surgery has expanded in many surgical specialties. One of its newest application in gynecology stands in the infertility management of young women with unexplained infertility or suspected endometriosis. In these cases, laparoscopy allows to diagnose and treat the disease aiming to increase at best the chances of spontaneous pregnancy or trough assisted reproductive technology. Nowadays, minimally invasive surgical approach of ovarian endometriosis consists of either laparoscopic cystectomy or ablative techniques such as laparoscopic CO2 fiber laser vaporization. Although cystectomy represents the gold standard according to the latest Cochrane review, some endometriosis experts are worried about its detrimental effect on healthy ovarian parenchyma and suggest preferring a less aggressive approach such as CO2 fiber laser vaporization. The aim of this review is to give an overview of the available evidences about the impact of the two surgical procedures on ovarian reserve markers and pregnancy outcome.

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

CO2 fiber laser vaporization for endometrioma treatment results in preserved ovarian responsiveness and improved embryo quality in infertile women undergoing ART.

BACKGROUND: Infertile women carrying ovarian endometriomas can be managed either with surgery or by in-vitro fertilization (IVF). The aim of this study was 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. METHODS: 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). RESULTS: 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=0.014), oocytes (P=0.042), MII oocytes (P=0.042) and formed embryos (P=0.004) 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. CONCLUSIONS: Our results demonstrate encouraging findings on IVF/ICSI outcomes after laser CO2 endometrioma ablation in terms of both quantity and quality of developed embryos.

Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma.

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.

A Systematic Review of Atypical Endometriosis-Associated Biomarkers.

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.

Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review.

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.

Natural Cycle Results in Lower Implantation Failure than Ovarian Stimulation in Advanced-Age Poor Responders Undergoing IVF: Fertility Outcomes from 585 Patients.

To compare pregnancy rate and implantation rate in poor responder women, aged over 40 years, who underwent natural cycle versus conventional ovarian stimulation. This is a retrospective single-center cohort study conducted at the GENERA IVF program, Rome, Italy, between September 2012 and December 2018, including only poor responder patients, according to Bologna criteria, of advanced age, who underwent IVF treatment through Natural Cycle or conventional ovarian stimulation. Between September 2012 and December 2018, 585 patients were included within the study. Two hundred thirty patients underwent natural cycle and 355 underwent conventional ovarian stimulation. In natural cycle group, both pregnancy rate per cycle (6.25 vs 12.89%, respectively, p = 0.0001) and pregnancy rate per patient101 with at least one embryo-transfer (18.85 vs 28.11% respectively, p = 0.025) resulted significant reduced. Pregnancy rate per patient managed with conventional ovarian stimulation resulted not significantly different compared with natural cycle (19.72 vs 15.65% respectively, p = 0.228), but embryo implantation rate was significantly higher in patients who underwent natural cycle rather than patient subjected to conventional ovarian stimulation (13 vs 8.28% respectively, p = 0.0468). No significant difference could be detected among the two groups in terms of abortion rate (p = 0.2915) or live birth pregnancy (p = 0.2281). Natural cycle seems to be a valid treatment in patients over 40 years and with a low ovarian reserve, as an alternative to conventional ovarian stimulation.

Fertility Outcome after CO2 Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study.

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.

Maternal Arsenic Exposure and Gestational Diabetes: A Systematic Review and Meta-Analysis.

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.

Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature.

The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III-IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III-IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00-0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.

Ovarian responsiveness in assisted reproductive technology after CO2 fiber laser vaporization for endometrioma treatment: preliminary data.

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 fibre 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 (95% CI: -1.27 to -0.116, P=0.027). CONCLUSIONS: CO2 laser-treated endometrioma is associated with favorable reproductive assisted reproductive technology outcomes.

Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis.

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.

Recurrence Rate after "One-Step" CO2 Fiber Laser Vaporization versus Cystectomy for Ovarian Endometrioma: A 3-Year Follow-up Study.

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.

Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review.

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-ß 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.

Does endometriosis influence the age of menopause?

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.

Obstetrical complications of endometriosis, particularly deep endometriosis.

Over the past few years, a new topic in the field of endometriosis has emerged: the potential impact of the disease on pregnancy outcomes. This review aims to summarize in detail the available evidence on the relationship between endometriosis, particularly deep endometriosis (DE), and obstetrical outcomes. Acute complications of DE, such as spontaneous hemoperitoneum, bowel perforation, and uterine rupture, may occur during pregnancy. Although these events represent life-threatening conditions, they are rare and unpredictable. Therefore, the current literature does not support any kind of prophylactic surgery before pregnancy to prevent such complications. Results on the impact of DE on obstetrical outcomes are debatable and characterized by several limitations, including small sample size, lack of adjustment for confounders, lack of adequate control subjects, and other methodologic flaws. For these reasons, it is not possible to draw conclusions on this topic. The strongest evidence shows that DE is associated with higher rates of placenta previa; for other obstetrical outcomes, such as miscarriage, intrauterine growth restriction, preterm birth and hypertensive disorders, results are controversial. Although it is unlikely that surgery of DE may modify the impact of the disease on the course of pregnancy, no study has yet investigated this issue.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms.

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

Complication and recurrence rate in laser CO2 versus traditional surgery in the treatment of Bartholin's gland cyst.

PURPOSE: The treatment of Bartholin's gland cysts by traditional surgery is characterized by some disadvantages and complications such as hemorrhage, postoperative dyspareunia, infections, necessity for a general anesthesia. Contrarily, CO2 laser surgery might be less invasive and more effective as it solves many problems of traditional surgery. The aim of our study is to describe CO2 laser technique evaluating its feasibility, complication rate and results vs traditional surgery. METHODS: Among patients treated for Bartholin's gland cyst, we enrolled 62 patients comparing traditional surgical excision vs CO2 laser surgery of whom 27 patients underwent traditional surgery, whereas 35 patients underwent CO2 laser surgery. Mean operative time, complication rate, recurrence rate and short- and long-term outcomes were assessed. RESULTS: The procedures required a mean operative time of 9 ± 5.3 min for CO2 laser surgery and 42.2 ± 13.8 for traditional surgery. Two patients (5.7 %) needed an hemostatic suture for intraoperative bleeding in the laser CO2 laser technique against 14.8 % for traditional surgery. Carbon dioxide allows a complete healing in a mean time of 22 days without scarring, hematomas or wound infections and a return to daily living in a mean time of 2 days. Instead, patients undergone traditional surgery required a mean time of 14 days to return to daily life with a healing mean time completed in 28 days. CONCLUSIONS: The minimum rate of intra- and post-operative complications, the ability to perform it under local anesthesia in an outpatient setting make CO2 laser surgery more cost-effective than traditional surgery.