Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen ß receptor polymorphisms with clinical outcomes.

PURPOSE: Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERß polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. METHODS: Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERß, respectively. RESULTS: All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. CONCLUSION: We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.

Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: A literature review.

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.

Risk of neural tube defects according to maternal body mass index: a systematic review and meta-analysis.

INTRODUCTION: The aim of our systematic review and meta-analysis was to evaluate the risk of neural tube defects (NTDs) according to the pre-pregnancy body mass index. MATERIALS AND METHODS: Electronic databases were searched (MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library). Selection criteria included prospective and retrospective cohort studies reporting the prevalence of fetal NTDs in obese, overweight, and underweight pregnant women. Odds ratios (ORs) comparing risk among these subsets of pregnancies with normal weight mothers were determined with 95% confidence intervals (CI). The evaluated outcome was the association between maternal underweight, overweight, and obesity and the risk of NTDs. RESULTS: We included ten studies published between 2000 and 2017, including underweight, overweight, and obese pregnant women with fetal NTD (cases) and pregnant women with recommended BMI with fetal NTD (controls). Compared with normal BMI women, obese mothers were at significantly higher risk of fetal NTDs (0.53 vs. 0.33%; OR 1.62 95% CI 1.32-1.99, p < .0001), while no difference for the risk of NTDs was found when comparing overweight (0.34 vs. 0.32%; OR 1.09 95% CI 0.92-1.3, p = .3) and underweight (0.65 vs. 0.24%; OR 1.34 95% CI 0.73-2.47, p = .34) with normal weight pregnant women. DISCUSSION: Obese pregnant women are at significantly higher risk NTDs, while no significant difference has been found in overweight and underweight pregnant women. Key message Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women.

Pregnancy and perinatal outcomes in pregnancy with diagnosis of chorionic bump on first-trimester sonography: a systematic review and meta-analysis.

OBJECTIVE: To assess the relationship between the presence of the sonographic finding of chorionic bump (CB) during first trimester and miscarriage rate or other perinatal outcomes. METHODS: PubMed, Medline, Embase, Cinahl and Clinicaltrials.gov databases, from inception to April 8, 2021 were explored utilizing combinations of the relevant medical subject heading (MeSH) terms, key words, and word variants for "CB" and "pregnancy." Prospective and retrospective case-control studies were eligible for inclusion. Odds ratios (ORs) comparing obstetrical outcomes among pregnancies with CB and normal pregnancies were determined with 95% confidence intervals (CI) using random-effects models. Primary outcome of interest was miscarriage rate. Secondary outcomes were: alive newborns (ANB) rate, adverse pregnancy outcomes (APO) and vaginal bleeding. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. RESULTS: Five studies including 173 pregnant women with CB (study group) and 1,263 pregnant women without CB (control group) were included. Pregnancies affected by CB resulted to be associated with a significantly higher miscarriage rate (43.3% vs 20.7%; OR 2.95 95% CI 2.02-4.31, p < .00001), and conversely with a significantly lower rate of ANB (60.3% vs 82%; OR 0.35 95% CI 0.20-0.63, p = .0004). In addition, the risk of APO was around three-fold higher in the study group (52.2% vs 4.12%; OR 2.98 95% CI 1.04-8.51, p = .04), while the rate of vaginal bleeding was higher in the study group, without reaching a statistical significance (48% vs 16.4%; OR 2.21 95% CI 0.64-7.65 p = .21). DISCUSSION: The presence of CB at first trimester ultrasound significantly increases the risk of miscarriage and APO, and intact the rate of ANB. This article is protected by copyright. All rights reserved. Key message: The presence of CB on early first trimester ultrasound increases three-fold the risk of miscarriage and adverse pregnancy outcomes and reduces the rate of alive newborns. It is important to consider CB as an ultrasound marker that requires a close surveillance throughout pregnancy to prevent long-term complications and provide adequate counseling to the patient.

Non-invasive treatment of vulvovaginal atrophy in menopause with CO2 laser.

Genitourinary syndrome of menopause (GSM) may affect up to 90% of menopausal women, including vulvovaginal atrophy (VVA), burning, pain, bleeding, irritation, dyspareunia, anorgasmia, and urinary symptoms. Vaginal symptoms from lack of estrogens can have a significant impact on the sexual health and quality of life (QoL) in as many as 50% of postmenopausal women. Several therapeutic alternatives, both hormonal and non- hormonal, have been proposed. Microablative CO2 laser is one of the three non-surgical energy-based therapies, with Erbium:YAG laser and temperature-controlled radiofrequency (RF). Microablative CO2 laser induces morphological changes in vaginal tissues and results of several clinical trials suggest that this type of laser improves symptoms of GSM. Moreover, this treatment seems to be safe. Given the increasingly widespread use of laser CO2 as a non-hormonal alternative treatment for GSM, the authors reviewed the current published literature evaluating this therapy, to compare efficacy and safety of different protocols.