Objective: To evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. Design: Observational prospective cohort study. Setting: University-affiliated obstetrics and fetal medicine Department in Italy. Population: Pregnant women with stage III-IV endometriosis according to revised American Fertility Society (r-AFS) classification, matched in a 1:2 ratio according with body mass index and parity with unaffected controls. Methods: UtA-PIs were assessed at 11–14, 19–22 and 26–34 weeks of gestation following major reference guidelines. A General Linear Model (GLM) was implemented to evaluate the association between endometriosis and UtA-PI Z-scores. Main Outcome Measure: UtA-PI Z-scores, calculated from published reference equations of previously validated normal range. Results: Significantly higher third trimester UtA-PI Z-scores were observed in patients with r-AFS stage III-IV endometriosis when compared to controls (p=0.024). In the GLM, endometriosis (p=0.026) and maternal age (p=0.007) were associated with increased third trimester UtA-PI Z-scores, whereas conception by in-vitro fertilization with frozen-thawed embryo transfer significantly decreased UtA-PI measures (p=0.011). No differences were observed in first or in second trimester UtA-PI Z-scores of cases vs. controls. Conclusions: Stage III-IV endometriosis according to r-AFS classification is associated with a clinically measurable impaired placental perfusion as shown by increased UtA-PI Z-scores in the third, but not in the first or second trimesters. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy/perinatal outcomes due to a defective late placental perfusion. Funding: N/A.

Background. Controversial evidence suggests a potential association between female genital mutilation (FGM/C) and adverse obstetric outcomes, with type III FGM/C (infibulation) carrying the greatest risk. Objectives: To assess current rate of adverse obstetric outcomes in women with type III female genital mutilation and cutting (FGM/C; infibulation) delivering across different settings worldwide. Search Strategy. Two authors searched relevant literature in the PubMed, Scopus, Embase, and ClinicalTrials.gov databases from inception to Jan 1, 2023, looking for articles reporting outcomes of women with type III FGM/C compared with women with no FGM/C. Selection criteria. Studies were selected if they included the main outcome of postpartum haemorrhage (PPH) or secondary outcomes, which included major conditions affecting maternal-neonatal health during labour and delivery. Data Collection and Analysis: DerSimonian-Laird random effects meta-analysis was performed and pooled effect estimates with corresponding 95% confidence intervals were computed. Heterogeneity was assessed using the I 2 statistic. Meta regression for relevant covariates was performed when data on relevant confounders were available. The Newcastle-Ottawa scale (NOS) was used to assess quality of observational studies. The level of evidence was assessed with the GRADE method. Main Results: 14 observational studies including 15,320 type III FGM/C women and 59,347 controls were eligible. The risk for postpartum haemorrhage was significantly increased in type III FGM/C, in the main analysis (OR 1.83, 95% CI 1.03 to 3.24, I 2=93%), in pooling of data adjusted for confounders (aOR 1.76, CI 1.42 to 2.17, I 2= 0%), and in sensitivity analysis of higher quality studies with NOS≥7 (OR 2.76, CI 1.38 to 5.51, I 2= 95%). Meta-regression showed that nulliparity was significantly and positively associated with postpartum haemorrhage. Similarly, analysis of data adjusted for confounders showed an increased risk of episiotomy in type III FGM/C (aOR 1.56, CI 1.03 to 2.35, I 2= 52%). Sensitivity analysis of studies with NOS≥7 revealed a significant increase for episiotomy (OR 7.53, CI 1.19 to 47.54, I 2= 96%), perineal tears (OR 4.24, CI 1.09 to 16.46, I 2= 66%), prolonged second stage of labour (OR 5.19, 95% CI 1.00 to 26.85, I 2= 66%), and Apgar score less than 7 (OR 4.19, CI 1.64 to 10.70, I 2= 0%). No difference was found regarding obstetric anal sphincter injuries and mode of delivery in these women. Deinfibulation achieved similar obstetric and neonatal outcomes to women who never had type III FGM. The overall quality of the studies was adequate (median NOS score: 7; IQR: 6-8), the level of evidence, according to the GRADE assessment, was low. Conclusions. These results consistently show an increased risk of adverse obstetric outcomes in women with FGM/C type III. Infibulation substantially increases the risk for PPH, particularly in nulliparae.

Objective: To evaluate the histological modifications of the vaginal mucosa after repeated microablative fractional CO2 lasers treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 lasers treatments using validated questionnaires. Design: Prospective intervention study. Setting: Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute Sample: 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. Methods: one cohort of patients submitted to at least two previous laser treatment cycles in the past years. Main outcome measures: Vaginal Health Index (VHI), Visual Analog Scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire – Urinary Incontinence (ICIQ-UI) and 5-point Likert scale. Moreover an histological examinations were carried out on all samples. Results: At 4 weeks after the last treatment VHI score and all FSFI items resulted significantly increased compared baseline. We observed a statistically significant decrease both in frequency and severity for all urinary symptoms after the follow up. We observed a statistically significant increase in the number of epithelial cell layer with a consequent increase in epithelial thickness, in the number of glycogen filled cells, and in the number of papillae, after the laser treatment. No signs of fibrosis were observed since neovascularization was observed in each single woman. Conclusions: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis.

Objective: To assess the correlations between clinical and hormonal parameters and comorbidity burden in Caucasian women presenting for fertility treatment. Design: Cross-sectional study. Setting: Single academic reproductive medicine center. Patient: Cohort of 3163 single-ethnicity women seeking medical help for fertility treatment, who underwent centralized lab testing for fertility-related hormonal assessment. Intervention: Complete clinical and laboratory data from the entire cohort of patients were retrospectively analysed. Main outcome measures: Assessment of i) the comorbidity burden scored via the Charlson Comorbidity Index (CCI; categorized as 0 vs. 1 vs. >2); and, ii) the potential associations between CCI and clinical and hormonal parameters. Results: Descriptive statistics and regression models tested the associations between clinical and laboratory parameters and CCI. Of 3163, CCI=0, CCI=1 and CCI>2 were found in 2977 (94.1%), 113 (3.6%) and 73 (2.3%) patients, respectively. Age, gravidity, Anti-Müllerian hormone (AMH) and thyroid stimulating hormone (TSH) values were found to be significantly different among CCI groups (all p≤ 0.01). At regression models, age at presentation and AMH emerged as independent predictors of CCI>1. Age at presentation <36 years (OR=1.742, 95% CI [1.284; 2.364]) and an AMH level <2.3 ng/ml (OR=1.864, 95% CI [1.29; 2.69]) were the most informative cutoff values for CCI >1. Conclusions: A younger age at presentation and lower AMH levels are significant predictors of decreased general health in women requiring clinical evaluation for fertility treatment. As observed for sperm parameters in men, AMH might serve as a proxy of women’s general health status. Key words: AMH, comorbidities, health, infertility