Gynecological Endocrinology最新文献

Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through homocysteine pathway alterations. To investigate the associations between MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms and GDM risk, including gene‒gene interactions, in Chinese Han pregnant women, this retrospective cohort study analyzed 1312 Chinese Han pregnant women. The MTHFR C677T, A1298C, and MTRR A66G polymorphisms were genotyped using allele-specific PCR. Polymorphism-GDM associations were assessed using logistic regression, adjusting for maternal age, prepregnancy BMI, and folate intake. Gene‒gene interactions were evaluated using multiplicative interaction models. After confounder adjustment, the MTHFR 677TT genotype was associated with GDM (OR 1.89, 95% CI 1.24-2.93) compared to wild-type. The MTRR 66AG and 66GG genotypes were associated with GDM, with ORs of 2.73 (95% CI: 1.93-3.89) and 3.10 (95% CI: 1.72-5.41), respectively. Significant gene‒gene interactions were observed between MTHFR C677T & A1298C (OR 2.22, 95% CI 1.25-4.23 for TT/AA combination) and MTHFR C677T & MTRR A66G (OR 6.06, 95% CI 3.48-14.10 for TT/AG combination), indicating synergistic effects that surpass the expected multiplicative combination of individual polymorphism effects. MTHFR C677T and MTRR A66G polymorphisms independently and interactively increase GDM odds in Chinese Han women, enabling personalized risk prediction and targeted prevention.

Objective: We aimed to identify independent predictors of ongoing pregnancy in patients undergoing mild-OS FET cycles, focusing on follicular phase characteristics and luteal support regimens.

Methods: In this multicenter, retrospective cohort study conducted between January 2021 and August 2024 across Bahceci in vitro fertilization (IVF) centers in Türkiye, 489 FET cycles with mild-OS using letrozole were analyzed. Biochemical and ongoing pregnancy outcomes were assessed in relation to demographic characteristics, ovarian stimulation parameters, ovulation triggering strategies, and LPS approaches. Multivariate logistic regression was used to determine independent predictors.

Results: The overall biochemical and ongoing pregnancy rates were 58.5% and 43.4%, respectively. Subcutaneous progesterone (with or without vaginal route) improved biochemical pregnancy rates compared to vaginal-only LPS (67.1% vs. 52.7%, p = 0.008), although this did not translate into significantly higher ongoing pregnancy rates. In adjusted models, only younger female age (OR = 0.94, 95% CI: 0.90 to 0.99, p = 0.01) and a higher number of embryos transferred (OR = 2.00, 95% CI: 1.16 to 3.45, p = 0.01) were independently associated with ongoing pregnancy. Follicular diameter, number of follicles >10 mm, estradiol and LH levels, or triggering with hCG did not significantly impact outcomes.

Conclusion: In mild-OS FET cycles, while subcutaneous progesterone support may improve early implantation outcomes, ongoing pregnancy is primarily influenced by female age and embryo number. These findings support a flexible approach to LPS and triggering in mild-OS protocols without compromising clinical success.

Background: Women during hormonal transitional phases present an increase in mood disturbances. Recently, purified and specific cytoplasmic pollen extract (PureCyTonin®), a natural non-hormonal alternative, has proven to be effective to treat symptoms during perimenopause, and menopause especially vasomotor ones. However, its effects on mood disturbances still need further study.

Objective: To investigate the potential in vitro effects of the pollen extract on dopaminergic and GABAergic systems in order to be proposed as an alternative to treat symptomatic midlife women and other brain-related symptoms.

Method: In vitro experiments were performed to evaluate the effects of pollen extract on dopamine and GABA uptake, as well as GABA_A and dopamine D_2S receptor binding.

Results: Pollen extract inhibited both dopamine and GABA uptake in a concentration-dependent manner (mean IC₅₀ = 79.5 µg/mL and 137 µg/mL, respectively). It also displaced [³H]-muscimol from GABA_A receptors, suggesting potential allosteric modulation. Contrary to this, pollen extract showed moderate affinity for D_2S receptors (≥1000 µg/mL). These mechanisms might enhance neurotransmitter tone in hormone-sensitive brain regions.

Conclusion: Purified and specific pollen extract modulates dopaminergic and GABAergic systems in vitro and help restore neurochemical balance across hormonal transitions, supporting its non-hormonal beneficial role in managing mood, sleep, and somatic symptoms with a safety profile. There is a need for further research in this regard in the clinical setting.

Objective: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in more than 50 genes. We aimed to conduct an etiological analysis of a CHH Chinese family and summarize the clinical presentations and genetic changes of reported similar cases.

Methods: Whole-exome sequencing (WES) was performed to identify the molecular cause in the proband. In silico tools were employed to analyze the pathogenicity of the variants. Reported cases with similar clinical features and associated genes were summarized by searching through PubMed/MEDLINE using keywords 'FGFR1,' 'CHH,' and 'Kallmann syndrome (KS).'

Results: Genetic analysis revealed a novel likely pathogenic deletion mutation in the FGFR1 gene (NM_023110.3: c.263_264del (Val88Alafs*22)) in a Chinese family exhibiting micropenis and underdeveloped testes. A total of 38 cases with CHH or KS have been previously reported.

Conclusion: This study identified a novel FGFR1 deletion variant responsible for CHH, expanding the known mutational spectrum of FGFR1. Typical manifestations include delayed puberty and diverse presentations. The genotype-phenotype correlation in CHH remains unclear and may involve oligogenic effects and epigenetic regulation.

Recent publications have suggested that a novel prolonged-release formulation of ethinylestradiol (EE) 20 µg and dienogest (DNG) 2 mg offers improved bleeding profiles and minimal impact on coagulation. These conclusions, however, are based on incomplete safety assessments and potentially misleading pharmacokinetic assumptions. This critical appraisal highlights several concerns: (1) discrepancies between published and regulatory data on bleeding/spotting rates compared to established EE/DRSP combinations; (2) inappropriate reliance on clotting-time-based activated protein C resistance (APCr) assays that fail to detect contraceptive-induced hypercoagulability; and (3) a strikingly high incidence of venous thromboembolism (VTE) reported in clinical trials of prolonged-release EE/DNG, significantly exceeding rates associated with both traditional EE-based and newer body-identical estrogen-containing contraceptives. Furthermore, these VTE cases are not transparently discussed in the peer-reviewed literature, raising ethical concerns about selective reporting. The pharmacokinetic profile of this formulation does not appear to mitigate estrogenic hepatic effects in a clinically meaningful way. Robust evaluation using validated thrombin generation assays such as the endogenous thrombin potential (ETP)-based APCr test, alongside independent post-marketing studies, is essential before asserting a neutral or favorable safety profile. Until then, claims regarding improved safety remain unsubstantiated.

Objective: To assess the effects of a 12-week combined treatment with myo-inositol (2 g) and Banaba extract (48 mg) standardized to 1% corosolic acid (MBN) on insulin resistance (HOMA-IR) and hepatic insulin extraction index (HIEI) in overweight and obese postmenopausal women.

Methods: We conducted a retrospective observational study including 31 postmenopausal women (mean age 51 ± 1.2 years) attending the Gynecological Endocrinology Center of Modena, Italy. All patients received daily supplementation with MBN for 12 weeks. Hormonal and metabolic parameters-including fasting glucose, insulin, C-peptide, and HOMA-IR-were assessed before and after treatment. In addition, an oral glucose tolerance test (OGTT) was performed at both time points, with glucose, insulin, and C-peptide curves measured and corresponding area under the curve (AUC) values at 240 minutes calculated. HIEI was calculated as the insulin/C-peptide ratio. Data were analyzed globally and then stratified by family history of diabetes.

Results: After treatment, fasting insulin, HOMA-IR, and HIEI were significantly reduced. The OGTT showed a 23.5% decrease in glucose AUC, with greater reductions in insulin AUC (-42%) compared to C-peptide AUC (-16.8%), suggesting enhanced hepatic insulin clearance. Patients with a family history of diabetes showed reductions in insulin and C-peptide, while those without showed only a decrease in insulin and HIE, with no changes in C-peptide.

Conclusions: Combined MBN supplementation improved insulin sensitivity and hepatic insulin clearance in overweight and obese postmenopausal women, with particularly pronounced effects in those with a family history of diabetes. These findings underscore the potential of targeted integrative strategies to mitigate insulin resistance in this population.

Background: Approximately one in eight women aged 15-49 years seek medical care for infertility. Oxidative stress is a critical factor in female infertility. The Composite Dietary Antioxidant Index (CDAI) is a novel metric for assessing overall dietary antioxidant capacity. This study aimed to investigate the association between CDAI, its individual components, and infertility risk.

Methods: A cross-sectional analysis was conducted using 2013-2020 National Health and Nutrition Examination Survey (NHANES) data. The CDAI was calculated based on dietary intake of vitamins A, C, E, zinc, selenium, and carotenoids. Weighted logistic regression models were used to assess associations between CDAI (and its components) and infertility. Restricted cubic spline (RCS) analysis was applied to evaluate potential non-linear relationships. Subgroup and sensitivity analyses were performed to test the robustness of the findings.

Results: A negative association between CDAI and infertility was observed (OR = 0.95; 95%CI [0.91-0.99], P = 0.014). Stratification by CDAI quartiles showed a consistent decreasing trend in infertility risk (Q4 vs. Q1: OR = 0.52; 95%CI [0.33-0.84], P for trend = 0.003). RCS analysis indicated a linear negative relationship between CDAI and infertility (P for non-linear = 0.278). Higher carotenoid intake was inversely associated with infertility risk, whereas intakes of vitamin A and C showed V-shaped, non-linear associations with infertility (P for non-linear < 0.05). These findings remained stable across subgroup and sensitivity analyses.

Conclusion: CDAI is linearly and inversely associated with the prevalence of female infertility, highlighting the potential importance of antioxidant-rich diets in promoting women's reproductive health.