Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

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Background. Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease. Objective. (1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment. Materials and Methods. A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors’ judgments were categorized as “low risk,” “high risk,” or “unclear risk” of bias. Results. Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be “low.” 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice. Conclusions. The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.

Introduction: In the last years, spinal anesthesia (SA) has emerging as alternative to general anesthesia (GA) for the laparoscopic treatment of gynecological diseases, for better control of postoperative pain. The aim of the review is to compare the advantages of SA compared to GA. Methods: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until March 2021. Randomized controlled trials (RCTs) and non-randomized studies (NRSs) about women who underwent SA and GA for gynecological laparoscopic surgery. Relevant data were extracted and tabulated. Results: The primary outcomes included the evaluation of postoperative pain (described as shoulder pain), postoperative nausea and vomiting, and operative times. One hundred and eight patients were included in RCTs, 58 in NRSs. The qualitative analysis had conflicting results and for the most of parameters (hemodynamic variables, nausea and postoperative analgesic administration) no statistically significant differences were observed: in the NRSs studies, contradictory results regarding the postoperative pain in SA and GA groups were reported. Regarding the quantitative analysis, in the RCT studies, women who received SA had not significantly lower operative times (RR -4.40, 95% CI -9.32 to 0.53) and a lower incidence of vomiting (RR 0.51, 95% CI 0.17 to 1.55); on the other hand, in the NRS studies, women who received SA had longer operative times (RR 5.05, 95% CI -0.03 to 10.14) and more episodes of vomiting (RR 0.56, 95% CI 0.10 to 2.97) compared to those with GA: anyway, the outcomes proved to be insignificant. Conclusions: Current evidence suggests no significant advantages to using SA over GA for laparoscopic treatment of gynecological diseases.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy. The Rotterdam criteria indicate four distinct phenotypes. In phenotypes with the typical ovarian morphology (ovarian volume ≥10 ml) the sensibility to clomiphene citrate (CC) ovulation therapy was demonstrated inversely proportional to the ovarian volume. In this retrospective study we evaluated the influence of ovarian volume on the success rate of CC ovulation induction in women with anovulatory phenotype 2 characterized only by the presence of hyperandrogenism and anovulation (ANOV + HA). Statistical analysis was conducted by stratifying patients both on the basis of CC dose (Group 1: n = 37, 50 mg; Group 2: n = 9, 100 mg; and Group 3: n = 12, 150 mg) and on the basis of response to therapy. Eighty women were evaluated but overall only 58 women (72.5%) reached ovulation. In the phenotype studied, we didn't find any correlations between ovarian volume and the chance of ovulation with the gradient increase in CC; furthermore, ovarian volume was comparable in CC responders and non-responders. Our study has shown that in the phenotype 2 examined, ovarian volume did not have any predictive value of the dosage required to induce ovulation. The significance of this result is discussed.

Aim of our study was to assess the ovulation rate, with mid-luteal progesterone level and ultrasound follicles monitoring, in PCOS CC-resistant patients undergone transvaginal hydrolaparoscopy ovarian drilling. A prospective observational study was carried out in 123 PCOS, infertile, CC-resistant patients who undergone THL ovarian drilling. Each woman was evaluated by hormonal measurement, and ultrasound evaluation during 6 months follow-up. Progesterone serum levels were assessed on days 20-24 of the cycle after surgical treatment. Pg levels >3 ng/mL were considered as ovulation. Ovulation frequency and the highest mean follicular diameters during the monitoring were recorded. 117 patients complete the study, since six patients were lost to follow-up. Mean follicular diameter during ovulation monitoring was 16.37 mm. Ovulation rate at the follow up was 64.1% one month after treatment, 79.5% after three months and 82.9% after six months. 28 patients conceived during follow-up period. Pregnancy rate was 70.1%. Our study has shown that THL ovarian drilling improves ovulation and pregnancy rate in women with CC-resistant PCOS. We believe that this approach should be offered as second-line therapy at all PCOS CC-resistant women who fail the medical methods of ovulation induction.

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