Reproductive Biology and Endocrinology最新文献

Background: This retrospective cohort study aimed to evaluate the impact of insulin resistance (IR) on clinical outcomes in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.

Methods: A total of 1,768 PCOS patients undergoing IVF/ICSI cycles at Shenzhen Zhongshan Obstetrics & Gynecology Hospital between October 2010 and November 2024 were stratified into two cohorts: non-IR group (HOMA index < 2.69, n = 867) and IR group (HOMA index ≥ 2.69, n = 901). Baseline characteristics and clinical outcomes were compared between the groups. Linear logistic regression and multivariate logistic regression analysis were conducted to assess the independent impact of IR on fertilization efficiency and pregnancy outcomes.

Results: Patients with IR exhibited significantly higher BMI (25.44 ± 3.55 vs. 21.59 ± 3.20, p < 0.001), longer infertility duration (3.74 ± 2.75 vs. 3.25 ± 2.43, p < 0.001), increased antral follicle counts (26.74 ± 10.74 vs. 25.05 ± 9.79, p < 0.001) and lower basal follicle-stimulating hormone (FSH) level (9.78 ± 3.25 vs. 10.64 ± 3.83, p < 0.001) compared to those without IR. Additionally, the fertilization rate (82.02% vs. 83.86%, p = 0.005) and 2PN rate (81.07% vs. 83.96%, p < 0.001) were significantly lower in PCOS patients with IR. Linear regression indicated that IR had a more pronounced inverse effect on 2PN rate (B: -2.540, p = 0.009) than on fertilization rate (B: -0.664, p = 0.490). Subgroup analysis and interaction analysis demonstrated that IR functioned as an independent risk factor for impaired oocyte fertilization in normal-weight PCOS patients (B: -22.694, p = 0.011). No statistically significant associations between IR status and clinical or live birth pregnancy outcomes were observed in the regression models.

Conclusions: IR adversely affects oocyte fertilization competence and early embryonic development in normal-weight PCOS patients undergoing assisted reproductive technology (ART). These effects may be attributable to IR-induced metabolic dysregulation, which compromises folliculogenic and cytoplasmic maturation processes critical to gamete competence. These findings underscore the importance of addressing metabolic dysfunction in IR-affected PCOS populations to optimize ART outcomes.

Trial registration: This is a retrospective study.

Emerging evidence highlights the decline of testosterone levels among young males, linked to modern lifestyle shifts rather than aging alone. This exploratory cross-sectional study investigates the interplay between modifiable lifestyle factors and testosterone levels in 50 males aged 18-22 years, focusing on underrepresented variables such as exercise type, carbonated beverage intake, and sunlight exposure. Serum testosterone levels were measured via chemiluminescent immunoassay, and lifestyle data were collected through previously validated questionnaires. Multiple regression analyses revealed hypertrophy training (β = 20.3, p < 0.001), sunlight exposure > 60 min (β = 10.3, p = 0.03), and supplement use (β = 20.5, p < 0.001) as positive predictors of testosterone. Conversely, daily carbonated beverage consumption (β=-10.2, p = 0.01), tobacco use (β=-15.6, p < 0.001), and sleep deprivation (β=-18.2, p < 0.001) were significant negative correlates. Diet type influenced outcomes, with non-vegetarians showing higher testosterone (β = 8.7, p = 0.03) compared to vegetarians. Notably, BMI and chronic diseases were nonsignificant in this young cohort. These findings underscore the multifactorial nature of testosterone regulation, emphasizing holistic lifestyle interventions-such as resistance training, reduced ultra-processed food intake, and sleep optimization-as critical for endocrine health in urbanized youth. The study challenges traditional obesity-centric frameworks, advocating for holistic approaches to mitigate endocrine disruption in emerging adulthood.

Obese or overweight patients considering IVF are generally counselled to reduce weight closer to target BMI (i.e., < 30 kg/m²) by interventions entailing dietary change with a structured exercise program. There is little disagreement that supervised weight loss can improve reproductive outcome when successful, although there are refractory cases where weight goals are unmet. Because low-grade chronic inflammation and altered immune function are characteristic of obesity and antagonize implantation, any pre-IVF weight loss facilitated by semaglutide (SG) would be helpful. However, no preclinical data have considered the ovarian implications of SG. Several formulations of SG are now available to assist in chronic weight management, treatment of type-2 diabetes, or both. SG is 31-amino acid lipopeptide with action at the glucagon-like peptide-1 (GLP-1) receptor, which augments insulin secretion while lowering hepatic glucagon output. SG thus enters a multiorgan network where insulin, AMP-activated protein kinase (AMPK), insulin-like growth factor-1 (IGF-1), mammalian target of rapamycin (mTOR), and sirtuin pathways manage ambient nutritional conditions. As GLP-1 directly influences insulin release and curtails satiety, SG adjusts many biochemical cascades where potential interference with oocyte development or embryo/endometrial crosstalk require clarification. Particularly if used outside manufacturer's guidance (i.e., for aesthetic or personal reasons), SG could bring unwelcome challenges to fertility clinics where obesity and dyslipidemia are merely exchanged for the new problems of starvation and sarcopenia. Here we examine known GLP-1 actions where energy balance, ovarian aging, and oocyte competence converge; off label SG use should be avoided until its signaling effects throughout the reproductive axis are more carefully studied.

Background: Age is known to affect the success of assisted reproductive technology (ART) treatment. While significant research efforts have been directed at investigating the effects of aging on oocytes, few studies have examined the effect of aging on the endometrium. We sought to assess whether age negatively impacts peak endometrial thickness achieved in frozen embryo transfer (FET) cycles.

Methods: This was a retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) database between 2016 and 2020. Young (< 35) and older (≥35yo) non-identified oocyte donor (NOD) recipients were included to assess the impact of age on endometrial thickness; young and older gestational carriers (GCs) served as the respective controls for these two groups. The primary outcome was peak endometrial thickness achieved in an FET cycle; additional outcomes included cycle cancellation rate, clinical pregnancy rate and live birth rate.

Results: We observed a weak association between age and endometrial thickness in both NOD recipient and GC cycles. Though pregnancy rates were slightly lower at endometrial thicknesses < 8 mm, we observed no difference in clinical pregnancy rate with endometrial thicknesses between 8 and 18 mm. We found a significantly higher clinical pregnancy rate in GCs compared to NOD recipients in both the young and older age groups, and noted a decreasing clinical pregnancy rate with age in all groups.

Conclusion: Our data suggest an age-related decline in pregnancy rates in donor oocyte recipients and gestational carrier cycles, in which an endometrial factor would not necessarily be anticipated; this endometrial factor does not appear to be related to endometrial thickness. Therefore, our data support the existence of an endometrial factor that cannot be assessed by measurements of thickness, but nevertheless plays a crucial role in the success of an embryo implantation.

Clinical trial number: Not applicable.

Obstructive sleep apnea (OSA) has long been recognized as a significant risk factor for hypertension, and in recent years, its association with hypertensive disorders of pregnancy (HDP) has gained increasing attention, especially in the unique population of pregnant women. However, this relationship remains underappreciated in clinical practice. While early studies have suggested a link between OSA and adverse pregnancy outcomes, the mechanisms connecting OSA to HDP are not fully understood. This literature review explores potential pathways, including intermittent hypoxia, oxidative stress, systemic inflammation, dysregulation of the sympathetic nervous system, endothelial dysfunction, and atherosclerosis. It also examines current treatments, especially CPAP therapy, and its variable effectiveness in managing HDP symptoms, as well as potential alternatives such as throat strengthening exercises and external hypoglossal stimulation. Future research should focus on improving OSA screening during pregnancy, developing better diagnostic tools, and integrating routine OSA evaluations in prenatal care for early intervention. Clarifying the mechanisms linking OSA and HDP will help refine treatment strategies. Large-scale, randomized controlled trials are needed to assess the efficacy of combination therapies and develop evidence-based clinical guidelines.

The growing influence of private equity (PE) in reproductive medicine makes it increasingly important to examine its impact from the perspectives of physicians, patients, and investors. As PE firms increasingly acquire fertility clinics and related healthcare services, they bring promises of operational efficiency, expanded access, and innovation. At the same time, these developments have come under growing scrutiny, raising critical concerns about the commercialization of care, equity of access, and the long-term impact on clinical outcomes. From the physician's viewpoint, PE involvement presents both opportunities and challenges-shaping medical autonomy, clinical decision-making, and the ability to prioritize patient-centered care. The article critically assesses these dynamics, weighing the potential benefits of investment against concerns over profit-driven models, regulatory scrutiny, and the shifting role of healthcare professionals in an increasingly corporatized landscape.

Background: AMH is a dependable indicator of ovarian reserve function and assessment of ovarian responsiveness. The relationship between reduced ovarian reserve and pregnancy loss remains poorly understood and requires further investigation. Currently, it has not been systematically evaluated in populations with PGT which could exclude the influence of embryonic chromosomal abnormalities on the outcomes.

Methods: This study enrolled 1982 non-PCOS patients who underwent PGT and had their first frozen-thawed embryo euploidy blastocyst transfer between January 2016 and August 2023. Primary outcomes included early pregnancy loss rates (defined as spontaneous miscarriage during the early first trimester) with secondary outcomes encompassing clinical pregnancy rates and live birth rates. The cohort was divided into three subgroups using quintile-based categorization of AMH levels: low (≤ 1.872 ng/mL, n = 260); medium (1.873-5.276 ng/mL, n = 779); high (≥ 5.277 ng/mL, n = 258). After propensity score matching, 143 patients in each group were ultimately included in the current research.

Results: The matched data revealed a higher rate of EPL in the low AMH level group and a lower rate of clinical pregnancy and live births (P < 0.05). Compared to the medium AMH level group, the low AMH group had a considerably higher risk of EPL, with an unadjusted OR of 1.76 (95% CI, 1.10-2.82) and an adjusted OR of 1.85 (95% CI, 1.13-3.04). A significant association between low AMH levels and EPL was also found in the < 35 subgroup. Moreover, there was no discernible non-linear relationship between AMH levels and EPL rates in the restricted cubic spline (P-non-linear = 0.356). Subgroup analyses demonstrated the effect of AMH levels on EPL was more significant in younger patients, those with primary infertility, AFC ≥ 10, and transferred with D6 blastocysts.

Conclusion: In non-PCOS women < 35 years undergoing euploid blastocyst transfer, low AMH (≤ 1.8 ng/mL) independently predicts EPL risk. AMH could as a biomarker of oocyte competence beyond chromosomal integrity. Future research should focus on mechanistic studies to elucidate non-chromosomal pathways linking AMH to pregnancy loss.

Clinical trial number: Not applicable.

Background: Aging affects gene expression in pathways essential for energy metabolism, DNA repair, cell cycle regulation, and antioxidant defenses, directly affecting oocyte quality and viability. Single-cell RNA deep sequencing studies of aged versus young human MII oocytes revealed many differentially expressed genes. In addition, single human oocyte transcriptome analysis at both germinal vesicle (GV) and MII stages revealed distinct stage-dependent pathways impacted by aging, with a decrease in mitochondrial-related transcripts from GV to MII oocytes, and a much greater reduction in MII oocytes with advanced age.

Objective: Our aim was to investigate the age-related differences in gene expression of germinal vesicle (GV) oocytes between young and advanced age patients.

Patients and methods: Immature GV oocytes were donated by 6 patients, divided into two age groups: The "Young" group (ages 16-29) had three participants (mean age: 23.3 ± 6.6 years), and the "Elderly" group (ages 38-40) included three participants (mean age: 39 ± 1 year). After retrieval, oocytes were denuded and donated GV oocytes were cryopreserved at -196⁰C until analysis. For library preparation, we used the NEBNext^® Single Cell/Low Input RNA Library Prep Kit for Illumina, Sect. 1 (cat no. E6420S, New England Biolabs (NEB), USA), strictly adhering to the manufacturer's instructions. Gene expression quantification was performed using feature Counts from the Subread package (v1.5.3), and comprehensive quality control reports were generated using MultiQC (v1.25.1). To further corroborate the differential expression of hub genes associated with oocyte aging identified in our preliminary analysis, quantitative real-time PCR (qPCR) was performed for four selected hub genes (MYL4, POMZP3, and LINC002087).

Results: Of top 10 significantly differently expressed genes 7 (LINC02087, POMZP3, LINC02749, MYL4, AGPAT2, GCA, and LIMK1) were downregulated and 3 (CLEC3A, ARPP21, and CITED2) showed significant upregulation in young versus old oocytes. These genes underscore the impact of aging on critical oocyte pathways, including chromosomal stability, epigenetic regulation, mitochondrial function, immune response, structural integrity, and calcium signaling. Moreover, among these genes, LINC02087 was the most downregulated (log2FC = -7.66), while CITED2 showed the strongest upregulation (log2FC = 3.43) in young versus old oocytes. Following the RNA extraction of pooled GV oocytes of 8 elderly and 9 young donors' GV oocytes. We observed significant differences in gene expression levels between the two age groups, in line with the single-cell RNASeq.

Conclusion: Understanding the effects of aging on the oocyte transcriptome could identify biomarkers that characterize good MII oocyte quality. The different genes expressions in aged oocytes highlight their poten