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Objective: To assess the association between increased maternal prepregnancy body mass index (BMI) and the risk of congenital heart defect (CHD) in offspring. Methods: This systematic review and meta‐analysis searched PubMed/MEDLINE, Web of Science and Scopus from inception to 20 April 2023. Risk estimates were abstracted or calculated for increased BMI categories (overweight, obesity, moderate obesity and severe obesity) compared with normal weight (reference). Fixed‐effects or random‐effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes before and during pregnancy. Subgroup analyses for specific CHD subtypes were conducted if there were at least two studies with available data. Findings were presented for groups of defects, categorized using severity and topographic–functional criteria, and for individual defects. The certainty of the evidence for each effect estimate was evaluated according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Results: Overall, 31 studies comprising 4 861 693 patients and 86 136 CHD cases were included. The risk of CHD increased progressively from moderate to severe obesity (pooled odds ratio (OR), 1.15 (95% CI, 1.11–1.20) and 1.39 (95% CI, 1.27–1.53), respectively). Sensitivity analysis indicated that this effect persisted independently of maternal diabetes status before or during pregnancy. In the subgroup analysis, obesity was associated with up to a 1.5‐fold increase in the risk of severe CHD (pooled OR, 1.48 (95% CI, 1.03–2.13)). Severe obesity was associated with an even higher risk, with 1.8‐times higher odds compared with the reference group for specific CHD subtypes, including tetralogy of Fallot (pooled OR, 1.72 (95% CI, 1.38–2.16)), pulmonary valve stenosis (pooled OR, 1.79 (95% CI, 1.39–2.30)) and atrial septal defect (pooled OR, 1.71 (95% CI, 1.48–1.97)). Conclusions: Maternal weight is a crucial modifiable risk factor for CHD, particularly for severe forms of defect. Further research is needed to investigate whether weight management before pregnancy might serve as a preventive measure against CHD. In pregnant women with obesity, fetal echocardiography should be a routine diagnostic procedure. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To provide gestational‐age (GA)‐specific reference ranges for mean uterine artery (UtA) pulsatility index (PI) based on longitudinal data assessment throughout pregnancy. Methods: This was a prospective longitudinal cohort study of singleton low‐risk pregnancies with adequate health and nutritional status at the time of enrolment and without fetal anomaly, receiving prenatal care between January 2018 and July 2021 at the Maternal Fetal Medicine Unit of IRCCS San Raffaele Scientific Institute, Milan, Italy. Women were recruited at ≤ 12 + 6 weeks' gestation and underwent serial standardized ultrasound monitoring, including UtA‐PI measurement, by experienced certified operators until delivery. Association of UtA‐PI with GA was modeled with fractional polynomial regression. Equations for mean ± SD of the estimated curves were calculated, as well as GA‐specific reference charts of centiles for UtA‐PI from 10 + 0 to 39 + 0 gestational weeks. Results: We included 476 healthy, low‐risk pregnant women and a total of 2045 ultrasound scans (median, 4 (range, 3–9) per patient) were available for analysis. Mean UtA‐PI was 1.84 ± 0.55, 1.07 ± 0.38 and 0.78 ± 0.23 in the first, second and third trimesters of pregnancy, respectively. Goodness‐of‐fit assessment revealed that second‐degree smoothing was the most accurate fractional polynomial for describing the course of UtA‐PI throughout gestation; therefore, it was modeled in a multilevel framework for the construction of UtA‐PI curves. We observed a rapid and substantial decrease in mean UtA‐PI before 16 weeks, with subsequent smoother decrement of the slope and more stable values from 20 until 39 weeks. The 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97th centiles according to GA for UtA‐PI are provided, as well as equations to allow calculation of any value as a centile. Conclusions: UtA‐PI shows a progressive non‐linear decrease throughout pregnancy. The new reference ranges for GA‐specific mean UtA‐PI constructed using rigorous methodology may have a better performance compared with previous models for screening for placenta‐associated diseases in the early stages of pregnancy and for evaluating the potential risk for pregnancy‐induced hypertension and/or small‐for‐gestational age later in pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Abstract Pathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p

Study Objective: Although cystectomy remains the gold standard for the surgical treatments of endometriomas, concerns about the negative effect on ovarian reserve are rising. Laser-CO 2 vaporization of endometriomas has shown encouraging data on ovarian reserve preservation, postoperative pregnancy rates, and recurrence. The aim of this study was to assess postoperative recurrence rate and pregnancy rate in patients with endometriomas managed by CO 2 fiber laser vaporization after at least 5 years following surgery., Design: Retrospective study., Setting: Italian tertiary center from October 2023 to February 2024., Patients: We included women aged >18 years who underwent laparoscopic CO 2 fiber laser vaporization for endometriomas. Age ≥40 years, previous ovarian surgery, previous salpingectomy or hysterectomy, negative histologic finding for endometriosis, or any findings of malignancy at histology were exclusion criteria., Intervention: Ovarian endometriomas were vaporized through laparoscopic CO 2 fiber laser. After surgery, patients were included in a surveillance program with periodic clinical follow-ups., Measurements and Main Results: Seventy-eight patients were included. The mean age was 33.2 ± 4.6 years, the basal anti-Müllerian hormone was 2.7 ± 1.9 ng/mL, and the median diameter of the endometriomas was 4 (3-5) cm. The median duration of follow-up was 72.5 months (67-84.5). After surgery, 65.5% (n = 36) of women with reproductive desire achieved a pregnancy, 55.6% spontaneously, and 44.4% through Assisted Reproduction Techniques, with a mean time to pregnancy of 17.7 ± 18.1 months. A Kaplan-Meier curve for the 7 patients who experienced an ipsilateral recurrence showed that the median time to recurrence was 26 months and the estimated rate of disease-free patients was 91.03% at 100 months (95% confidence interval 82.10%-95.62%)., Conclusion: CO 2 fiber laser vaporization is an effective and safe surgical treatment of ovarian endometriomas, combining the advantage of being an ovarian tissue-sparing technique with long-term postoperative recurrence rate comparable with that described in literature for the cystectomy., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a female-specific chronic condition that affects 1 in 10 women and other individuals with a uterus worldwide with common symptoms that include pelvic pain and infertility. Reliable and effective non-invasive biomarkers for endometriosis do not exist, and therefore currently a diagnosis of endometriosis requires direct visualization of lesions at surgery. Similarly, few safe and effective management strategies exist for endometriosis, with hormonal interventions and surgery only providing temporary symptom control. The development of endometriosis involves the implantation and proliferation of ectopic endometrial cells which triggers local and systemic inflammation and fibrosis. While multiple genetic, environmental, and lifestyle factors appear to influence the natural history of endometriosis, chronic inflammation is a hallmark feature associated with development and progression of the disease. Data further shows that endometriosis commonly co-occurs with autoimmune diseases, adding evidence that immune dysfunction likely contributes to the pathogenesis of this disorder. Specific innate and adaptive immune system drivers of endometriosis remain to be identified and additional research is needed to elucidate the mechanistic underpinnings of this debilitating disease. In this narrative review, we discuss the shared biological mechanisms and plausible immune-related connections between endometriosis and autoimmunity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pamela Stratton, MD reports financial support was provided by Office of Research on Women's Health, National Institutes of Health. Pamela Stratton, MD reports a relationship with Massachusetts Institute of Technology that includes: travel reimbursement. PS has received royalties from UpToDate for a section about acute pelvic pain, from Frontiers in Reproductive Health as Specialty Chief Editor, Gynecology, and reviewed a book proposal on endometriosis for Elsevier. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Importance: Evidence suggests that aberrant uterine contractility in nonpregnant women with endometriosis and adenomyosis contributes to symptoms and potentially heralds their pathogenesis. However, uterine peristalsis remains understudied, inconsistently measured, and poorly understood., Objective: To summarize evidence on uterine contractility across the menstrual cycle phases in women with endometriosis and adenomyosis., Data Sources: PubMed/MEDLINE, Embase, and Scopus databases searched up to May 2, 2024., Study Selection and Synthesis: Observational studies compared quantitative measures of uterine contractility using magnetic resonance imaging, ultrasound, electrophysiology, or direct intrauterine pressure recording across different menstrual cycle phases between women with endometriosis/adenomyosis and controls on the basis of predefined problem/population, intervention, comparison, and outcome criteria. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled estimates for primary (risk ratios with 95% confidence intervals [CIs]) and secondary (mean difference [MD] with 95% CIs) outcomes were calculated using random-effects models., Main Outcomes: Pooled risk of retrograde menstruation uterine contraction pattern in cases vs. controls; pooled MD in continuous measures of uterine contractility (frequency, amplitude, and velocity of contractions) across all the menstrual cycle phases in cases vs. controls., Results: Nine studies met the inclusion criteria; most were studies that evaluated women with endometriosis. An increased risk of retrograde uterine contractions during menstruation was observed in women with endometriosis compared with that in controls (risk ratio, 8.63; 95% CI, 3.24-22.95; I 2 , 0). The pooled MDs in contraction frequency between cases and controls were 0.82 (95% CI, 0.13-1.52; I 2 , 18.61%) in the menstrual phase and 0.52 (95% CI, 0.22-0.83; I 2 , 27.18%) in the luteal phase. Results for the follicular and periovulatory phases were more heterogeneous. Higher contraction amplitudes in women with endometriosis or adenomyosis were reported across all menstrual cycle phases. Because of the paucity of data, especially for adenomyosis, evidence certainty was graded as low for most comparisons., Conclusion and Relevance: The approximately ninefold increased risk of retrograde pattern during menstruation in endometriosis supports the potential role of retrograde menstruation in its etiopathogenesis. Abnormal uterine contractility, likely not limited to the menstrual phase, may be a mechanical factor contributing to development of endometriosis and related symptoms, including menstrual pain and infertility, with limited, mostly concordant evidence for adenomyosis., Registration Number: PROSPERO ID CRD42024512273-accepted on February 23, 2024., Competing Interests: Declaration of Interests N.S. has nothing to disclose. G.D.S. has nothing to disclose. P. Viganò has received honoraria as Co-Editor in Chief of the Journal of Endometriosis and Uterine Disorders, outside the submitted work. P.S. reports royalties from UpToDate for a section about acute pelvic pain; from Frontiers in Reproductive Health as Specialty Chief Editor, Gynecology; and from AbbVie for participating in a Chronic Pelvic Pain Advisory Board, outside the submitted work. E.S. reports funding from Ferring, Gedeon-Richter, Theramex, and IBSA; and honoraria from IBSA, Gedeon-Richter, and Sandoz, outside the submitted work. P. Vercellini is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and of the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; and reports royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate, outside the submitted work., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The rate of preterm birth of singletons conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is increased, being as high as 15% to 16% across Europe and the United States. However, the underlying etiology, phenotype, and mechanisms initiating preterm birth (PTB) are poorly understood., Objective: To quantify the PTB risk and examine supposed etiology in IVF/ICSI singleton pregnancies compared to naturally conceived., Study Design: Overview of reviews including all available systematic reviews with meta-analysis comparing PTB risk in IVF/ICSI and naturally conceived singletons. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was performed up to December 31, 2023. Information available on etiology, phenotype, initiation of PTB, and relevant moderators was retrieved and employed for subgroup analyses. Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The extent of overlap in the original studies was measured using the corrected covered area assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to rate evidence certainty. The protocol was registered on PROspective Register of Systematic Reviews (CRD42023411418)., Results: Twelve meta-analyses (16,522,917 pregnancies; ˃433,330 IVF/ICSI) were included. IVF/ICSI singletons showed a significantly higher PTB risk compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89; PTB<32 weeks: OR: 2.19, 95% CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR: 1.79, 95% CI: 1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95% CI: 1.72-3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh only (OR: 1.79, 95% CI: 1.55-2.07) vs frozen-thawed embryo transfers (OR: 1.39, 95% CI: 1.34-1.43). There was minimal study overlap (13%). The certainty of the evidence was graded as low to very low., Conclusion: Singletons conceived through IVF/ICSI have a 2-fold increased risk of PTB compared to natural conception, despite the low certainty of the evidence. There is paucity of available data on PTB etiology, phenotype, or initiation. The greater risk increase is observed in fresh embryo transfers and involves iatrogenic PTB and PTB ˂32 weeks, likely attributable to placental etiology. Future studies should collect data on PTB etiology, phenotype, and initiation. IVF/ICSI pregnancies should undertake specialistic care with early screening for placental disorders, cervical length, and growth abnormalities, allowing appropriate timely follow-up, preventive measures, and therapeutic interventions strategies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Although gastric peroral endoscopic myotomy (G-POEM) has shown substantial efficacy in patients with medically refractory gastroparesis (GP), comprehensive long-term data on its effectiveness are lacking., Methods: We conducted a systematic review and meta-analysis including observational studies assessing long-term efficacy after G-POEM in patients with refractory GP. Our primary outcome was the pooled rate of clinical success 1-year after G-POEM. Secondary outcomes included clinical success at 2 and 3 years and the rate of adverse events according to the American Society for Gastrointestinal Endoscopy classification., Results: Thirteen studies, involving 952 patients with refractory GP undergoing G-POEM, were eligible. The pooled 1 year-clinical success was 0.72 (95% confidence interval [CI]: 0.56, 0.85, I 2 = 94.9%). The clinical success was 0.67 (95% CI: 0.47, 0.97, I 2 = 95.8%) when considering only studies defining success as 1 point decrease in Gastroparesis Cardinal Symptoms Index score and at least 25% decrease in two subscales. For patients who had 1-year success, the pooled clinical success at 2 and 3 years were 0.71 (95% CI: 0.45, 0.92, I 2 = 94.9%) and 0.58 (95% CI: 0.19, 0.92, I 2 = 97.1%), respectively. The pooled rate of adverse events was 0.08 (95% CI: 0.06, 0.10, I 2 = 0%)., Conclusion: G-POEM is associated with successful outcomes in about 70% of treated cases after 1 year, with durable long-term effects lasting up to 3 years. In the future, new uniform outcome definitions and strict patient selection criteria are warranted to delineate G-POEM outcomes more accurately., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth., Objective: The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia., Study Design: This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios., Results: The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001)., Conclusion: In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore the utility of the total fibroids-to-uterine volume (FTUV) ratio as a simple, preoperative tool to assist in counseling patients seeking pregnancy who are undergoing myomectomy for intramural (IM) fibroids., Study Design: This is an historical cohort study on reproductive-aged patients seeking pregnancy who underwent laparotomic myomectomy for intramural fibroids from January 2017 to December 2021. Only G3 to G5 fibroids, according to the 2011 International Federation of Gynecology and Obstetrics (FIGO) classification, were included. Pre-operative transvaginal ultrasound (TVUS) was performed to measure the volume of intramural myomas (diameter 1 *diameter 2 *diameter 3 *0.52) and to calculate their total volume. The total fibroids-to-uterine volume (FTUV) ratio was calculated as the proportion of the uterine volume occupied by the sum of IM fibroids volumes., Results: A total of 166 women with pre-surgical TVUS evaluation of IM fibroids were included, with a mean age of 36.22 ± 5.15 years. The FTUV ratio was identified as a positive predictor of clinical pregnancy after surgery (adjOR, 1.04; 95 % CI, 1.02-1.06; p = 0.0001), whereas age showed a negative association (adjOR, 0.90; 95 % CI, 0.83-0.98; p = 0.012). Endometrial cavity distortion prior to surgery was also positively associated with pregnancy post-surgery (adjOR, 3.50; 95 % CI, 1.51-8.08; p = 0.003). Consistent results were found for live births, with the FTUV ratio being a significant positive predictor of live birth after surgery (adjOR, 1.03; 95 % CI, 1.01-1.05; p = 0.001) and age showing a negative association (adjOR, 0.88; 95 % CI, 0.80-0.96; p = 0.004). Parity prior to surgery also positively impacted live birth post-surgery (adjOR, 2.65; 95 % CI, 1.30-5.40; p = 0.007). An FTUV ratio threshold of 53.39 % accurately predicted clinical pregnancy in 68.46 % of cases (sensitivity of 71.70 % and specificity of 66.67 %). For live births, a higher FTUV ratio threshold of 59.21 % predicted outcomes accurately in 69.13 % of cases (sensitivity of 65.85 % and specificity of 70.37 %)., Conclusion: The use of the FTUV ratio in pre-operative ultrasound evaluation of IM fibroids may improve counseling for patients desiring to conceive after myomectomy. By providing a personalized assessment of the amount of myometrial volume occupied by fibroids, the FTUV ratio can help predict fertility outcomes after surgery, enabling better-informed decisions and treatment planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Patients with pathogenic variants in the GATA Binding Protein 2 ( GATA2 ), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males., Methods: A 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student's t -test and Mann-Whitney U test or Fisher's exact test were used to compare differences in continuous or categorical variables, respectively. Spearman's rho coefficient was employed for correlations., Results: Of 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require >2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males., Conclusion: Females with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease., Competing Interests: PS, also add participated in an Endometriosis Research Day at the Open Endoscopy Forum Cambridge, Massachusetts, and reviewed a book proposal on endometriosis for Elsevier. Outside of this work, PS has received royalties from UpToDate for a section about acute pelvic pain, from Frontiers in Reproductive Health as Specialty Chief Editor, Gynecology, and participated in an AbbVie advisory board. PS also participated in an Endometriosis Research Day at the Open Endoscopy Forum Cambridge, Massachusetts, and reviewed a book proposal on endometriosis for Elsevier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dancy, Stratton, Pichard, Marciano, Cowen, McBride, Van Doorslaer, Merideth, Salmeri, Hughes, Heller, Parta, Hickstein, Kong, Holland and Zerbe.)

Background: Despite the rising rates of opportunistic salpingectomy at the time of surgery for non-malignant conditions, salpingectomy is not widely adopted during vaginal hysterectomy (VH) and has not been extensively investigated., Objectives: The aim of the primary study was to determine the feasibility of bilateral opportunistic salpingectomy at the time of VH. Secondary aims included surgical outcomes, factors associated with patient selection, and the prevalence of incidental tubal malignancies., Search Strategy: In this systematic review and meta-analysis we searched Pubmed, Embase and ClinicalTrials.gov databases from inception to September 1, 2023, using relevant keywords., Selection Criteria: Original articles with no language restriction reporting outcomes of women undergoing planned VH with opportunistic salpingectomy, were considered eligible. Studies including patients undergoing VH with and without opportunistic salpingectomy were also included., Data Collection and Analysis: The Newcastle-Ottawa scale was used to assess quality of observational studies. DerSimonian-Laird random effects meta-analysis was performed and pooled effect estimates and proportions with corresponding 95% confidence intervals were computed. Heterogeneity was assessed using the I 2 statistic., Results: Seven observational cohort studies including 4808 women undergoing opportunistic salpingectomy at the time of VH and 10 295 patients undergoing VH alone were selected. The pooled proportion of success was 81.83 per 100 observations (95% CI: 75.35-87.54). Opportunistic salpingectomy at the time of VH, when feasible, was associated with a significant reduction in intraoperative complications (OR 0.06, 95% CI: 0.01, -0.37, P = 0.03) and total operative time (95% CI: -17.80, -1.07, P = 0.03) compared to those where it failed. Successful salpingectomy was significantly hindered by nulliparity (OR 0.12, 95% CI: -17.69, -1.21, P < 0.001) and favored by pelvic organ prolapse (OR 3.20, 95% CI: 1.35, 7.55, P = 0.008). Immunohistochemical tubal abnormalities were found in 13/579 (2.1%) patients. The overall quality of the evidence, according to the GRADE assessment, was low., Conclusion: Opportunistic salpingectomy is safe, effective, and feasible at the time of VH. Nulliparity and pelvic organ prolapse are factors potentially influencing surgical outcomes., (© 2024 International Federation of Gynecology and Obstetrics.)

The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022326433 )., (© 2024. The Author(s).)

Background and Aims: Nonanesthesiologist-administered propofol (NAAP) is increasingly accepted, but data are limited on drug administration using target-controlled infusion (TCI) in clinical practice. TCI adjusts the drug infusion based on patient-specific parameters, maintaining a constant drug dose to reduce the risk of adverse events (AEs) because of drug overdosing and to enhance patient comfort. The aims of this study were to assess the rate of AEs and to evaluate patient satisfaction with NAAP using TCI in a retrospective cohort of 18,302 procedures., Methods: Low-risk patients (American Society of Anesthesiologists score I and II) undergoing outpatient GI endoscopic procedures, including EGDs and colonoscopies, were sequentially enrolled at IRCCS San Raffaele Hospital (Milan, Italy) between May 2019 and November 2021., Results: Data from 7162 EGDs and 11,140 colonoscopies were analyzed. Mean patient age was 59.1 ± 14.8 years, and mean body mass index was 24.9 ± 3.7 kg/m 2 . The male-to-female ratio was equal at 8798 (48.1%):9486 (51.9%). AEs occurred in 240 procedures (1.3%) out of the total cohort, with no differences between EGDs and colonoscopies (100 [1.4%] and 140 [1.2%], respectively; P = .418). Most patients (15,875 [98.9%]) indicated they would likely repeat the procedure with the same sedation protocol. Age (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .008) was the only independent factor associated with overall AEs., Conclusions: NAAP using TCI is an effective and safe sedation method for routine endoscopy. The proper propofol dosage based on individual patients and the presence of trained operators are crucial for NAAP sedation management., Competing Interests: Disclosure The following author disclosed financial relationships: S. Danese: Speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Study Question: Does endometriosis prevalence differ in patients with obstructive Müllerian anomalies (OMA) versus those with nonobstructive Müllerian anomalies (NOMA), and in patients with NOMA versus those without Müllerian anomalies?, Summary Answer: The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without Müllerian anomalies., What Is Known Already: The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without Müllerian anomalies would support the embryonic remnants/celomic metaplasia hypothesis., Study Design, Size, Duration: This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword 'endometriosis' in combination with 'Müllerian anomalies', 'obstructive Müllerian anomalies', 'female genital malformations', 'retrograde menstruation', 'infertility', 'pelvic pain', and 'classification'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used., Participants/materials, Setting, Methods: Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without Müllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with Müllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete Müllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines., Main Results and the Role of Chance: Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36-58%) in patients with OMA, and 19% (95% CI, 15-24%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54-8.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20-27%), and that in patients without Müllerian anomalies was 21% (95% CI, 20-22%), with a common OR of 0.95 (95% CI, 0.57-1.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons., Limitations, Reason for Caution: Some NOMA subtypes may create a partial obstacle to menstrual efflux and/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without Müllerian anomalies., Wider Implications of the Findings: The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors., Study Funding/competing Interest(s): No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest., Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Backgrounds: The rapid advancement of generative artificial intelligence (AI) systems, such as Midjourney, has paved the way for their use in medical training, producing computer-generated images. However, despite clear disclosures stating that these images are not intended for medical consultations, their accuracy and realism are yet to be thoroughly examined., Methods: A series of requests were addressed to the Midjourney AI tool, a renowned generative artificial intelligence application, with a focus on depicting appropriate systemic anatomy and representing aesthetic surgery operations. Subsequently, a blinded panel of four experts, with years of experience in anatomy and aesthetic surgery, assessed the images based on three parameters: accuracy, anatomical correctness, and visual impact. Each parameter was scored on a scale of 1-5., Results: All of images produced by Midjourney exhibited significant inaccuracies and lacked correct anatomical representation. While they displayed high visual impact, their unsuitability for medical training and scientific publications became evident., Conclusions: The implications of these findings are multifaceted. Primarily, the images' inaccuracies render them ineffective for training, leading to potential misconceptions. Additionally, their lack of anatomical correctness limits their applicability in scientific articles. Although the study focuses on a single AI tool, it underscores the need for collaboration between AI developers and medical professionals. The potential integration of accurate medical databases could refine the precision of such AI tools in the future., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

A female proband and her affected niece are homozygous for a novel frameshift variant of CLPP. The proband was diagnosed with severe Perrault syndrome encompassing hearing loss, primary ovarian insufficiency, abnormal brain white matter and developmental delay., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with a significant impact on the health and quality of life of women affected. A novel hypothesis by evolutionary biologists suggested that these two diseases are inversely related to one another, representing a pair of diametrical diseases in terms of opposite alterations in reproductive physiological processes but also contrasting phenotypic traits. However, to fully explain the phenotypic features observed in women with these conditions, we need to establish a potential nexus system between the reproductive system and general biological functions. The recent discovery of kisspeptin as pivotal mediator of internal and external inputs on the hypothalamic-pituitary-gonadal axis has led to a new understanding of the neuroendocrine upstream regulation of the human reproductive system. In this review, we summarize the current knowledge on the physiological roles of kisspeptin in human reproduction, as well as its involvement in complex biological functions such as metabolism, inflammation and pain sensitivity. Importantly, these functions are known to be dysregulated in both PCOS and endometriosis. Within the evolving scientific field of "kisspeptinology", we critically discuss the clinical relevance of these discoveries and their potential translational applications in endometriosis and PCOS. By exploring the possibilities of manipulating this complex signaling system, we aim to pave the way for novel targeted therapies in these reproductive diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spotlighting a 500-year-old detail in Michelangelo's "David," this paper delves into the intricate connection between technique and art in the medical field, especially in esthetic surgery. With rapid technological advancement, medical specialties are becoming increasingly segmented, leading to potential oversights in holistic human examination. Drawing from ancient Greek concepts, "Techne," "Ars," and "Episteme" are explored as symbolic representations of the convergence of skill and knowledge. Art, defined as a reflection of human creativity and emotion, was historically intertwined with science, as symbolized by the nine Muses. The Renaissance period, exemplified by works like "David," underlines the profound relationship between art and anatomy. Dr. Gelfman's observations on the "David sign" serve as a testament to the continuous dance between medical science and artistic representation. This paper underscores the timeless value of a comprehensive approach in medical practice, urging professionals to amalgamate technical precision with an artistic understanding of the human form. LEVEL OF EVIDENCE: Level V, opinion expert., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Advanced endometriosis is associated with a reduction of IVF success. Surgical damage to the ovarian reserve following the excision of endometriomas has been claimed as a critical factor in the explanation of this detrimental effect. However, it is generally inferred that other mechanisms might also hamper IVF success in affected women. They include diminished responsiveness to ovarian stimulation, altered steroidogenesis, a decline in oocyte quality, reduced fertilization and embryo development, and impaired implantation. To navigate these limitations, we scrutinized available literature for studies specifically designed to address distinct phases of the IVF process. Utmost consideration was given to intra-patient ovarian response comparisons in women with unilateral endometriomas and to studies applying a meticulous matching to control confounders. The following observations have been drawn: 1) endometriosis has a negligible impact on ovarian response. A slight reduction in stimulation response can only be observed for endometriomas larger than 4 cm. Follicular steroidogenesis is unaffected; 2) oocyte quality is not hampered. Fertilization rates are similar, and intracytoplasmic sperm injection (ICSI) is not justified. Embryonic development is uncompromised, with no increase in aneuploidy rate; 3) endometrial receptivity is either unaffected or only slightly impacted. In conclusion, our study suggests that, aside from the well-known negative effect on ovarian reserve from excisional endometrioma surgeries, endometriosis does not significantly affect IVF outcomes., (© 2023. The Author(s).)

Background: Management of anastomotic leaks after Ivor-Lewis esophagectomy remains a challenge. Although intracavitary endoscopic vacuum therapy (EVT) has shown great efficacy for large dehiscences, the optimal management of smaller leaks has not been standardized. This study aims to compare EVT versus self-expandable metal stent (SEMS) in the treatment of leaks < 30 mm in size, due to the lack of current data on this topic., Methods: Patients undergoing EVT (cases) or SEMS (controls) between May 2017 and July 2022 for anastomotic leaks < 3 cm following oncologic Ivor-Lewis esophagectomy were enrolled. Controls were matched in a 1:1 ratio based on age (± 3 years), BMI (± 3 kg/m 2 ) and leak size (± 4 mm)., Results: Cases (n = 22) and controls (n = 22) showed no difference in baseline characteristics and leak size, as per matching at enrollment. No differences were detected between the two groups in terms of time from surgery to endoscopic treatment (p = 0.11) or total number of procedures per patient (p = 0.05). Remarkably, the two groups showed comparable results in terms of leaks resolution (90.9% vs. 72.7%, p = 0.11). The number of procedures per patient was not significant between the two cohorts (p = 0.05). The most frequent complication in the SEMS group was migration (15.3% of procedures)., Conclusion: EVT and SEMS seem to have similar efficacy outcomes in the treatment of anastomotic defects < 30 mm after Ivor-Lewis esophagectomy. However, larger studies are needed to corroborate these findings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.

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.

To review the current evidence on the risk of gestational diabetes mellitus (GDM) in women with endometriosis, taking into account relevant confounders such as the higher frequency of Assisted Reproductive Technologies (ART) conceptions. Database searches on PubMed, Medline, Embase and Scopus through June 2022, using combinations of relevant keywords. A total of 18 studies, involving N = 4,600,885 women, were included. The overall risk of GDM in endometriosis patients was significantly higher than in controls (OR, 1.23; 95% CI 1.07-1.51). This significant association persisted in natural pregnancies (OR, 1.08; 95% CI 1.04-1.12) but not in pregnancies conceived through ART (OR, 0.93;95% CI 0.70-1.24). Based on the limited number of studies that examined this association in relation to endometriosis phenotype, an increased risk was found in more severe stages (OR, 3.20; 95% CI 1.20-8.54) but independently from localization of the lesions. Endometriosis increases the risk of GDM, with a possible progressive effect in more advanced stages of the disease. Although the effect magnitude may be limited in some subgroups, this finding has a clinically relevant impact due to both the strong biological plausibility and to the relatively high incidence of both endometriosis and GDM., (© 2023. The Author(s).)

Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo-endometrium crosstalk. Inflammatory and immune deregulatory mechanisms have been shown to impair both endometrial receptivity and embryo competence at the implantation site. The aim of this study was to investigate the potential additional impact of co-existing autoimmunity in women affected by endometriosis on the early stages of reproduction. This was a retrospective, multicenter case-control study enrolling N = 600 women with endometriosis who underwent in vitro fertilization-embryo transfer cycles between 2007 and 2021. Cases were women with endometriosis and concomitant autoimmunity matched based on age and body mass index to controls with endometriosis only in a 1:3 ratio. The primary outcome was the cumulative clinical pregnancy rate (cCPR). The study found significantly lower cleavage ( p = 0.042) and implantation ( p = 0.029) rates among cases. Autoimmunity ( p = 0.018), age ( p = 0.007), and expected poor response ( p = 0.014) were significant negative predictors of cCPR, with an adjusted odds ratio of 0.54 (95% CI, 0.33-0.90) for autoimmunity. These results suggest that the presence of concomitant autoimmunity in endometriosis has a significant additive negative impact on embryo implantation. This effect might be due to several immunological and inflammatory mechanisms that interfere with both endometrial receptivity and embryo development and deserves further consideration.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Candiani, Ottolina, Salmeri, D'Alessandro, Tandoi, Bartiromo, Schimberni, Ferrari and Villanacci.)

Purpose: Uterine arteriovenous malformations (UAVM) are rare vascular lesions characterized by an abnormal arteriovenous communication between the branches of uterine artery and the myometrial venous plexus. UAVM can be a serious cause of massive post-partum hemorrhage (PPH) leading to potentially life-threatening anemic shock. This review aims to summarize main experiences on clinical presentation and management of UAVM in the setting of unexplained PPH., Methods: A systematic review of the literature in Scopus, PubMed and MEDLINE was conducted. A case report of a PPH UAVM-related in a patient managed at the authors' center is also provided., Results: Eleven studies met the inclusion criteria. The mean age of cases was 30. In 3/11 cases, previous uterine surgeries were reported and 72.7% cases gave birth by cesarean section. Nine cases had a secondary PPH (24 h up to 12 week post-partum), whereas only one case had a primary PPH. Our case report had both a primary and a secondary PPH. Reported vaginal bleedings were profuse and blood loss entity ranged from 1000 to 2000 ml. In all cases a color Doppler ultrasound was performed first to suspect UAVM and in 10/11 cases a subsequent pelvic angiography confirmed the diagnosis of UAVM as leading cause of the unexplained PPH. In 81.8% cases a conservative management by uterine artery embolization (UAE) was adopted: bilateral UAE was always successful; in 1 out of 2 cases treated by unilateral UEA, emergency total hysterectomy was performed for a sudden hemodynamic instability., Conclusion: Maternal mortality pregnancy-correlated is a major health concern worldwide, mostly due by PPH. UAVM should be considered in clinical practice among possible causes of unexplained PPH., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fetal growth restriction is a pathological condition occurring when the fetus does not reach the genetically determined growth potential. The etiology of fetal growth restriction is expected to be multifactorial and include fetal, maternal, and placental factors, the latter being the most frequent cause of isolated fetal growth restriction. Severe fetal growth restriction has been related to both an increased risk of perinatal morbidity and mortality, and also a greater susceptibility to developing diseases (especially cardio-metabolic and neurological disorders) later in life. In the last decade, emerging evidence has supported the hypothesis of the Developmental Origin of Health and Disease, which states that individual developmental 'programming' takes place via a delicate fine tuning of fetal genetic and epigenetic marks in response to a large variety of 'stressor' exposures during pregnancy. As the placenta is the maternal-fetal interface, it has a crucial role in fetal programming, such that any perturbation altering placental function interferes with both in-utero fetal growth and also with the adult life phenotype. Several epigenetic mechanisms have been highlighted in modulating the dynamic placental epigenome, including alterations in DNA methylation status, post-translational modification of histones, and non-coding RNAs. This review aims to provide a comprehensive and critical overview of the available literature on the epigenetic background of fetal growth restriction. A targeted research strategy was performed using PubMed, MEDLINE, Embase, and The Cochrane Library up to January 2022. A detailed and fully referenced synthesis of available literature following the Scale for the Assessment of Narrative Review Articles guidelines is provided. A variety of epigenetic marks predominantly interfering with placental development, function, and metabolism were found to be potentially associated with fetal growth restriction. Available evidence on the role of environmental exposures in shaping the placental epigenome and the fetal phenotype were also critically discussed. Because of the highly dynamic crosstalk between epigenetic mechanisms and the extra level of complexity in interpreting the final placental transcriptome, a full comprehension of these phenomenon is still lacking and advances in multi-omics approaches are urgently needed. Elucidating the role of epigenetics in the developmental origins of health and disease represents a new challenge for the coming years, with the goal of providing early interventions and prevention strategies and, hopefully, new treatment opportunities., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of this study was to evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. In this prospective cohort study, pregnant women with stage III-IV endometriosis according to the revised American Fertility Society (r-AFS) classification were matched for body mass index and parity in a 1:2 ratio with unaffected controls. 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. 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). According to these results, r-AFS stage III-IV endometriosis is associated with a clinically measurable impaired late placental perfusion. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy and perinatal outcomes due to a defective late placental perfusion.

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.

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.

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.