Most previous studies have focused on the obstetric and perinatal outcomes of different endometrial preparation protocols for frozen embryo transfer (FET) and have shown that hormone replacement therapy (HRT) is associated with a higher risk of large for gestational age (LGA) and macrosomia. However, the associations between endometrial preparation protocols and cognitive function in children are poorly understood. This study aimed to evaluate whether the cognitive function of children born after HRT-FET differs from that of children born after natural cycle-frozen embryo transfer (NC-FET). This retrospective cohort study enrolled singletons born to women with a regular menstrual cycle by FET from 2004 to 2017 who completed the follow-up assessment at a university-affiliated reproductive center between 2010 and 2022 when they were 3- to 6-year-old. The participants were categorized into two groups: children born after HRT-FET and children born after NC-FET. The groups were compared in terms of the verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), full-scale intelligence quotient (FIQ) and incidence of intellectual disability (FIQ < 80). Subgroup analysis was performed by stratifying offspring based on sex or fertilization method. A total of 790 children were included in the study. After adjusting for potential confounders, no statistically significant differences were found between the endometrial preparation protocols in children’s VIQ (coefficient − 1.91, 95
Obesity is associated with reduced female fertility and poorer in vitro fertilization (IVF) outcomes. Although pre-IVF lifestyle-based weight loss is commonly recommended for women with overweight or obesity, whether specific strategies improve reproductive outcomes remains uncertain. We compared two pre-IVF lifestyle interventions with usual care in women undergoing IVF. In this single-center, parallel-group randomized clinical trial conducted at Shengjing Hospital of China Medical University, Shenyang, China, women aged 20–38 years with a body mass index (BMI) of 24–40 kg/m² planning IVF were randomly assigned in a 1:1:1 ratio to 12-hour time-restricted feeding plus moderate physical activity (TRF + PA), a calorie-restricted diet (CRD), or usual care. Recruitment took place from March 14, 2023, to August 20, 2024, and follow-up was completed on February 20, 2026. The primary outcome was cumulative live birth. Secondary outcomes included cumulative clinical pregnancy, miscarriage, obstetric complications, embryological outcomes, anthropometric changes, and metabolic measures. A total of 273 women underwent randomization. Cumulative live birth did not differ between groups, occurring in 46.6
While reproductive history is recognized as a determinant of women’s long-term health, its impact on mortality risk remains poorly characterized. This study aimed to elucidate the association between key reproductive factors and subsequent all-cause and cause-specific mortality within the Tehran Lipid and Glucose Study (TLGS) population. We analyzed data from a prospective cohort of 5,165 women (aged ≥ 20 years) with a history of at least one pregnancy. Associations between reproductive factors and mortality were estimated using Cox proportional hazards regression models, adjusting for age, body mass index (BMI), smoking status, education, physical activity levels, diabetes history, hypertension history, and dyslipidemia. Over the follow-up period, 497 deaths were recorded, representing 9.6
Nonclassic congenital adrenal hyperplasia (NCCAH) is a common autosomal recessive endocrinopathy, primarily caused by partial 21-hydroxylase (CYP21A2) deficiency, and represents a significant but often underrecognized cause of female infertility. Clinically, affected women frequently present with hyperandrogenism, menstrual irregularities, and ovulatory dysfunction, which can lead to misdiagnosis as polycystic ovary syndrome (PCOS). Traditionally, reproductive failure in NCCAH has been attributed solely to androgen excess disrupting folliculogenesis. However, recent evidence reveals a multifactorial pathophysiology. Beyond hyperandrogenism, premature follicular-phase progesterone elevation, disruption of the hypothalamic–pituitary–ovarian (HPO) axis, impaired endometrial receptivity, and increased risk of early pregnancy loss collectively contribute to infertility. Accurate diagnosis requires a structured approach, including basal and adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP) measurement, comprehensive endocrine profiling, and genetic testing. Therefore, fertility optimization should extend beyond isolated androgen suppression. This review critically summarizes current knowledge of NCCAH-related infertility mechanisms and proposes an integrated, multidisciplinary management strategy—encompassing targeted targeted glucocorticoid (GC) therapy, ovulation induction, assisted reproductive technology (ART), careful obstetric monitoring, and genetic counseling—to improve fertility and pregnancy outcomes in this patient population.
This systematic review and meta-analysis was conducted to clarify the effects of abstinence duration on semen quality in human studies. This review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. PubMed (MEDLINE), Scopus, and Web of Science were searched from inception to the most recent update. Human studies evaluating ejaculatory abstinence duration in relation to semen parameters were included. For methodological clarity, studies were classified into (1) single-ejaculate abstinence-comparison studies (paired or independent-group designs) and (2) repeated or frequent ejaculation studies involving consecutive ejaculations. Only single-ejaculate abstinence-comparison studies contributed to the primary meta-analyses. Random-effects meta-analyses were performed for semen volume, sperm concentration, total sperm count, total sperm motility, progressive sperm motility, and sperm morphology. Subgroup and sensitivity analyses were conducted, and risk of bias was assessed using ROBINS-I. Eighty-two studies were included in the qualitative synthesis, of which 59 contributed to the quantitative meta-analyses. Comparisons involving longer abstinence intervals (e.g., ≥ 4–5 days compared with 2–3 days) were associated with significantly higher semen volume (MD − 1.07 mL, indicating higher volume with longer abstinence) and total sperm count (MD − 80.61 × 10⁶ sperm per ejaculate). In contrast, very short abstinence intervals were associated with significantly higher total sperm motility (MD 4.37
Infertile patients with low basal luteinizing hormone (LH) levels have low oocyte retrieval rate, but whether progestin-primed ovarian stimulation (PPOS) protocol with clomiphene citrate (CC) could enhance oocyte retrieval rate in these patients remains unclear. This prospective randomized controlled trial was performed between January 2018 and February 2021, included 230 infertile patients with low basal LH levels (LH < 2.27 mIU/mL). In study group, 115 patients received human menopausal gonadotropin (hMG) 150 or 225 IU/d + CC 50 mg/d + medroxyprogesterone acetate (MPA) 10 mg/d from the third day of menstruation. In control group, 115 patients received hMG 150 or 225 IU/d + MPA 10 mg/d from the third day of menstruation. Viable embryos were cryopreserved for later transfer. The primary outcome measure was the oocyte retrieval rate. CC contributed to LH secretion. The hMG+MPA+CC group showed a decreased oocyte retrieval rate (0.71 ± 0.22 vs. 0.76 ± 0.18, mean difference (MD) -0.06 (-0.11 to -0.01); P = 0.043) and a decreased number of cryopreserved embryos (2.89 ± 2.43 vs. 3.90 ± 2.39, MD -0.89 (-1.50 to -0.28); FDR-P = 0.035). Two groups had similar number of retrieved oocytes (8.83 ± 5.41 vs. 10.69 ± 5.85, MD -0.99 (-2.27 to 0.29); FDR-P = 0.213) and oocyte utilization rate (0.40 ± 0.25 vs. 0.46 ± 0.24, MD -0.07 (-0.14 to -0.01); FDR-P = 0.084). Two groups had comparable cumulative clinical pregnancy rates (61.05
Despite advancements in imaging techniques, the non-invasive diagnosis of adenomyosis remains particularly challenging due to the overlap of imaging features with other uterine diseases, and the lack of consistent correlation with clinical presentation, with histological confirmation after hysterectomy still necessary. In this context, circulating miRNAs emerge as promising candidates for accurate non-invasive diagnosis. To determine whether women with adenomyosis exhibit a distinct circulating plasma miRNA profile that can serve as a diagnostic marker, miRNA sequencing was performed to compare the plasma miRNA profile of women with adenomyosis with infertile and healthy fertile controls (n = 10/group). Adenomyosis was diagnosed by transvaginal ultrasound using Morphological Uterus Sonographic Assessment (MUSA) criteria. Plasma and endometrial biopsies were collected during the secretory phase from women undergoing hormone replacement therapy. Total RNA was extracted from plasma, libraries were prepared using NEXTFLEX® Small RNA-Seq v4 kits, and miRNAseq was performed on the NextSeq 550 NGS platform. Differentially expressed (DE) miRNAs were identified using the edgeR method (false discovery rate < 0.05). The discriminatory potential of DEmiRNAs was evaluated by receiver operating characteristic (ROC) curve analysis using the area under the curve (AUC). Validation was performed by quantitative PCR on plasma and endometrium (n = 15/group). The target genes of DEmiRNAs were retrieved from miRTarBase and subjected to functional enrichment analysis. A total of 11 disease-specific DEmiRNAs were identified in adenomyosis compared to infertile controls (5 up- and 6 downregulated), and 23 healthy control-referenced DEmiRNAs compared to fertile controls (19 up- and 4 downregulated). Among disease-specific DEmiRNAs, miR-4433 and miR-652-5p demonstrated strong diagnostic performance for adenomyosis compared to infertile controls (AUC = 0.92 and 0.91, respectively; p < 0.001). For healthy control-referenced DEmiRNAs, 11 miRNAs showed statistically significant diagnostic value (p < 0.01), with the highest AUCs observed for miR-3200-5p, miR-193b-5p, and miR-4732-5p (AUC = 0.88, 0.88 and 0.87, respectively). Validation experiments corroborated the upregulation of miR-4433 and miR-92a-3p upregulation in plasma and endometrium. This study supports the potential of circulating miRNAs as non-invasive biomarkers for adenomyosis and contributes to understanding its molecular basis. The concordance between circulating and endometrial miRNA expression suggests a possible link between systemic molecular alterations and endometrial pathology.
Oocyte developmental competence depends not only on nuclear maturation but also on cytoplasmic functions required for fertilization and early embryogenesis. The endoplasmic reticulum (ER) is the major intracellular calcium store in mammalian oocytes and acts as a spatial organizer of cytoplasmic maturation. ER-associated features are increasingly discussed in relation to in vitro maturation, aging, cryopreservation, fertilization failure, and visible smooth endoplasmic reticulum aggregates, but their biological and clinical meanings are not always clearly understood. This review integrates evidence on ER remodeling during oocyte maturation and its relevance to oocyte quality in assisted reproduction. During meiotic maturation, the ER undergoes stage- and species-specific reorganization that supports calcium-store positioning, inositol 1,4,5-trisphosphate receptor-dependent calcium release, and activation competence. ER remodeling during maturation is also linked to cytoskeletal organization, mitochondrial function, lipid handling, plasma-membrane Ca2+ influx, and degradative quality-control systems. These interfaces place ER remodeling within a broader multi-organelle network rather than a single calcium-signaling pathway. ER homeostasis and unfolded protein response (UPR) signaling contribute to cytoplasmic quality, whereas excessive ER stress can impair maturation through calcium imbalance, mitochondrial dysfunction, and defective stress adaptation. In clinical and laboratory settings, altered ER or smooth endoplasmic reticulum (SER)-related features may reveal cytoplasmic vulnerability after in vitro maturation, cryopreservation, aging, or fertilization failure, but they should not be interpreted as isolated or deterministic markers of oocyte competence. ER remodeling links oocyte maturation biology with several clinically relevant features of oocyte quality in assisted reproduction. Its translational value will depend on integrating structural observations, calcium-signaling competence, maturation history, and developmental endpoints while maintaining clear boundaries between mechanistic evidence and clinical decision-making.
Autoimmune abnormalities are increasingly recognized as contributing factors to unexplained infertility. Among these, antinuclear antibodies (ANAs) are the most frequently detected autoantibodies and have been associated with adverse embryologic outcomes. However, the mechanisms by which isolated ANA positivity (defined as ANA positivity in the absence of anti–extractable nuclear antigen [anti-ENA] antibodies) may influence oocyte developmental competence and early embryonic development remain poorly understood. This study aimed to characterize follicular fluid (FF) molecular alterations associated with isolated ANA positivity using an integrative multi-omics approach. In this prospective cohort study, 70 infertile women undergoing their first assisted reproductive technology (ART) cycle were enrolled, including 32 women with isolated ANA positivity (serum ANA ≥ 1:80 and anti-ENA negative) and 38 ANA-negative controls. FF samples collected on the day of oocyte retrieval were subjected to integrated metabolomic and proteomic analyses. Differential expression and functional enrichment analyses were performed, followed by correlation and network analyses to explore associations between FF molecular profiles and oocyte as well as embryo developmental competence. Key metabolites were further evaluated using receiver operating characteristic (ROC) analyses to characterize their exploratory discriminatory performance. Women with isolated ANA positivity showed significantly poorer embryo developmental outcomes than ANA-negative controls, including lower IVF/ICSI fertilization rates and reduced numbers of high-quality embryos and blastocysts (all P < 0.05). After adjustment for potential confounders, multivariate linear regression analysis suggested that isolated serum ANA positivity was independently associated with impaired early embryonic development (P < 0.05). Integrated multi-omics analyses revealed significant dysregulation of pathways related to steroid hormone biosynthesis, immune-related pathways including complement and coagulation cascades, amino acid metabolism, and glycerophospholipid metabolism. Among the identified molecular features, three metabolites—L-phenylalanine, SM(d18:1/16:0), and hydrocortisone—were consistently associated with embryo developmental potential and showed stable correlations independent of ANA titers. A combined preliminary metabolite panel was identified that discriminates ANA-positive from ANA-negative women with excellent discriminatory performance (AUC = 0.968). In exploratory analyses of dichotomized oocyte- and early embryo–related outcomes, the panel showed moderate discriminatory performance (AUCs = 0.719–0.771). Isolated ANA positivity is associated with metabolic reprogramming in the follicular microenvironment and impaired early embryonic development. The identified exploratory metabolite signatures provide insight into immune–metabolic alterations that may underlie ANA-associated infertility and may inform future prognostic model development. Their associations appeared consistent across the ANA-titer subgroups examined. However, the panel remains preliminary and at the discovery stage and requires validation in independent cohorts before its clinical relevance or utility can be determined.
Abstract Background Emerging evidence suggests microbial dysbiosis may contribute to gynaecological pathologies, including endometriosis and recurrent implantation failure (RIF). The vaginal microbiome is well-characterised, with Lactobacillus -dominance as a hallmark of health, yet interactions between vaginal, cervical, and endometrial microbiomes remain inconclusive. The adjacent sites to the vagina, rectal and urinary environments in infertile women are scarcely studied. Methods This cross-sectional study included 136 reproductive-aged women, enrolled at the Reproductive Unit of the University Hospital Virgen de las Nieves (Granada, Spain) between March 2019 and March 2024. Each participant provided five samples during the mid-secretory phase: vaginal and cervical swabs, endometrial brushing, urine, and rectal swabs. The microbiome was analysed using 16S rRNA gene sequencing (V4 region) with functional profiles inferred using PICRUSt2. Diversity and bacterial abundance were compared between endometriosis, RIF, and controls, adjusting for age, body mass index, and antimicrobial use. Results In total, 520 samples from 104 women were analysed and revealed shared microbial profiles across the vagina, cervix, endometrium, and urine. The rectal microbiome differed significantly from urogenital sites (Global PERMANOVA, adj p -value = 0.001, R 2 = 0.259). A Lactobacillus gradient in the reproductive tract was observed, with dominance > 98% in the lower tract, 69.72% in urine, and 46.25% in the endometrium. Moreover, Lactobacillus negatively correlated with all other genera within the reproductive tract. Significant differential abundance was detected between body sites: 15 bacteria between vagina-cervix, 166 vagina-uterus and 172 cervix-uterus (all adj p -values < 0.05). Diversity comparisons between the condition groups (endometriosis and RIF) and controls at each anatomical sites revealed no significant differences in microbial communities and functional pathways. However, four bacterial genera showed a significantly different abundance between the endometriosis and controls in the vagina. Conclusions Our study results provide knowledge about the microbial composition throughout the female urogenital tract and rectum, highlighting the interindividual variability rather than the site-specificity. The vaginal bacteria that associated with endometriosis should be investigated further for clarifying their potential as non-invasive biomarkers of the disease. Microbiomes of other urogenital sites do not seem to associate with endometriosis, and microbiomes of the urogenital-rectal axis do not seem to correlate with RIF. Trial registration N/A.
Ovarian aging is characterized by the progressive depletion of the follicular reserve and deterioration of reproductive endocrine function, yet its cellular basis has been disproportionately attributed to oocyte and granulosa cell decline. Theca cells — the principal androgen-producing cell type of the ovarian follicle — have remained critically underappreciated in this context. Operating through the classical two-cell, two-gonadotropin model, theca cells supply androgen precursors that granulosa cells aromatize into estradiol, and their dysfunction therefore impairs estrogen biosynthesis irrespective of granulosa cell competence. During ovarian aging, theca cells undergo quantitative decline, transcriptional reprogramming, and progressive steroidogenic impairment. Single-cell transcriptomic analyses reveal age-dependent upregulation of senescence pathways — including CDKN1A, NF-κB, and SASP-associated factors — alongside downregulation of FOXP1, a transcription factor that normally suppresses cellular senescence through direct repression of CDKN1A. Senescent theca-interstitial cells elaborate pro-inflammatory mediators, most notably CCL5, TNF-α, IL-1β, and IL-6, which suppress steroidogenic gene expression, induce granulosa cell apoptosis, and promote ovarian fibrosis, collectively accelerating follicular atresia. At the molecular level, mitochondrial dysfunction driven by aberrant GSK3β activation impairs oxidative phosphorylation and steroidogenic capacity, while dysregulation of the PTEN/PI3K/Akt/FOXO1 axis uncouples theca cells from LH-dependent gonadotropin signaling. Theca cell dysfunction further underlies distinct clinical entities, including premature ovarian insufficiency, diminished ovarian reserve, and polycystic ovary syndrome. Emerging therapeutic strategies — encompassing mesenchymal stem cell-derived exosomes, senolytics, mitochondria-targeted interventions, and Wnt/β-catenin pathway modulation — have demonstrated efficacy in restoring theca cell function in preclinical models. This review repositions theca cells as active, bidirectionally regulated participants in ovarian aging—integral to, rather than upstream of, the oocyte–granulosa–theca unit—and proposes theca-specific biomarkers and targeted interventions as priorities for future translational research.
Cryptorchidism is one of the most common congenital disorders of the pediatric urogenital system. In addition to regulating the passage of substances into and out of the seminiferous epithelium, the blood-testis barrier (BTB) plays a critical role in maintaining a stable microenvironment for spermatogenesis. BTB alterations in cryptorchidism remain poorly characterized. This study aimed to establish a surgical unilateral cryptorchidism model in rats (SUCMR) and to investigate the injury and recovery patterns of both the BTB and spermatogenic function within this model. The SUCMR was performed on 6-week-old male Sprague-Dawley rats, and testicular changes were observed after maintaining the modeling state for multiple time points. Simultaneously, another batch of rats underwent testicular descent surgery after maintaining the modeling for different durations to observe testicular recovery. The testis mass and volume, epididymal mass, epididymal sperm count and sperm malformation rate were quantified. After HE staining of testicular tissue, the seminiferous tubule structure was observed, and the seminiferous tubule diameter and seminiferous epithelium thickness were statistically analyzed. Biotin tracing experiments and transmission electron microscopy were performed to detect the BTB integrity. The expression of key BTB proteins ZO-1, OCCLUDIN, and CLAUDIN-11 was detected by WB. According to the normality of data distribution, a paired t-test or the Wilcoxon signed-rank test, an unpaired t-test or the Mann-Whitney U test, a one-way analysis of variance (ANOVA) or the Kruskal-Wallis test were used. A p-value of less than 0.05 was considered statistically significant. In SUCMR, sloughing of the seminiferous epithelium was observed, resulting in testicular atrophy and spermatogenic abnormalities. The SUCMR impaired the integrity of the BTB and leaded to a progressive decrease in the expression of the key barrier proteins. Testicular atrophy and spermatogenic function injury induced by short-term SUCMR were reversible. But the disruption to the BTB was irreversible when the SUCMR was maintained for 4 weeks or longer. In this model, spermatogenic dysfunction and BTB injury progressed with increasing duration of abdominal retention, and abnormalities induced by 4 or 6 weeks of SUCMR did not recover within the post-orchiopexy observation period.
Elevated sperm DNA fragmentation (SDF) is associated with male factor infertility, recurrent pregnancy loss, and poor reproductive outcomes. An option for management includes the utilization of testicular sperm; however, the comparative reproductive efficacy of fresh versus cryopreserved testicular sperm men with elevated SDF remains unclear. Therefore, the objective of this study was to identify differences in reproductive outcomes between fresh and cryopreserved testicular sperm in patients with elevated SDF who are undergoing intracytoplasmic sperm injection (ICSI) after testicular sperm extraction (TESE). This was a retrospective cohort study of a multi-site fertility network of patients with elevated SDF who underwent TESE and subsequent ICSI using either fresh or cryopreserved testicular sperm. A total of 60 men with elevated SDF underwent TESE and subsequent IVF with ICSI. 66.7
Untrustworthy randomised controlled trials (RCTs) and other study types are an increasingly recognised problem in health and medical research. Assessing and responding to this problem is essential for ensuring the reliability of scientific evidence informing clinical practice. We consider theory, methods and tools for assessing research integrity and the trustworthiness of both aggregate and individual-level data from peer-reviewed, published RCTs. We review approaches to the assessment of trustworthiness based on published checklists, the statistical analysis of aggregate and individual participant data, and the use of AI tools. We found checklists that examine the trustworthiness of data considering questions about the timeframe, authors, governance, and plausibility of a published, peer-reviewed paper. These checks of authenticity are complemented by statistical techniques that identify unusual patterns in aggregate or individual data, including new procedures for simulating data to determine if any of the possible distributions are realistic. The unique character of RCTs provides additional opportunities for checks, specifically for the baseline data. The approaches presented offer a series of novel, quantitative tools for assessing research integrity and data trustworthiness across published RCTs. These techniques can detect instances of data duplication, questionable research practices, and check if any aspects of the study or results are unrealistic. They work best when employed beyond isolated, single-trial analyses and, when embedded in AI platforms, should scale to meet the volume of corrupted papers already published and the stream of fake research from paper mills.
Diminished ovarian reserve (DOR) is defined as the decline in both quantity and quality of oocytes in the ovarian cortex. In recent years, DOR has shown an increasing trend among young women. However, the specific etiology and detailed pathogenesis in this population remain unclear. Granulosa cells (GCs) play crucial roles in oocyte growth, development, energy absorption, and transcriptional regulation. This study aimed to investigate the differential expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) in GCs from young women with DOR, and to explore the potential molecular mechanisms through competing endogenous RNA (ceRNA) network analysis. A total of 80 young women (≤ 35 years) undergoing in vitro fertilization-embryo transfer (IVF-ET) were prospectively enrolled between April 2024 and December 2024, including 40 with normal ovarian reserve (NOR) and 40 with DOR. Granulosa cells were collected during oocyte retrieval. High-throughput sequencing was performed to identify differentially expressed miRNAs, lncRNAs, and mRNAs. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was conducted. The ceRNA regulatory network was constructed using Cytoscape. Quantitative real-time PCR (qRT-PCR) was used to validate the sequencing results. Compared with the NOR group, young women with DOR showed significantly higher basal follicle-stimulating hormone (FSH) levels, and significantly lower anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) (all P < 0.05). The DOR group also had significantly lower numbers of retrieved oocytes, metaphase II oocytes, two-pronuclear zygotes, and day 3 available embryos (all P < 0.05). A total of 36 differentially expressed miRNAs (5 upregulated, 31 downregulated), 102 differentially expressed lncRNAs (55 upregulated, 47 downregulated), and 234 differentially expressed mRNAs (69 upregulated, 165 downregulated) were identified. Functional enrichment analysis revealed that these differentially expressed RNAs were mainly involved in fatty acid metabolism, AKT-mTOR signaling pathway, apoptosis, DNA damage and repair, and steroidogenesis. Bioinformatics analysis predicted a ceRNA network containing 20 lncRNA-mRNA pairs, 108 lncRNA-miRNA pairs, and 89 miRNA-mRNA pairs. Two potential ceRNA axes were identified by qRT-PCR-based expression validation: lncRNA MSTRG.39605.16/miR-143-5p/FADS1 and lncRNA NONHSAT208904.1/miR-199b-3p/ACP3, both associated with fatty acid metabolism regulation. However, direct molecular interactions within these axes remain to be functionally validated.” Transcriptional alterations in granulosa cells from young women with DOR are primarily enriched in fatty acid metabolism, AKT-mTOR signaling, and apoptosis pathways. The predicted ceRNA networks represent hypothetical regulatory mechanisms that may potentially be involved in DOR pathogenesis through modulation of fatty acid metabolic processes, pending functional validation. These findings provide candidate molecular markers and potential targets for future mechanistic studies of this condition.
Donated eggs are essential for a range of Medically Assisted Reproduction (MAR) procedures, but relatively little has been written about how donors are recruited. This study examined egg donor recruitment processes at a commercial egg-bank in Florida (USA). It documents what proportion of applicants were ultimately accepted and, if rejected, at what step, whether this was by choice or selection, whether their initial ID-release choice was important, and how this compares to the recruitment of sperm donors. Anonymised records of all egg donor applicants in 2018 and 2019 (n = 2,443) were examined to determine the number passing through (or lost) at each stage of the recruitment process and ultimately how many had successful egg retrieval and cryopreservation. Statistical analysis was carried out to examine differences between the initial ID-release choice made by egg donor applicants (ID-release vs. non-ID release). Few applicants (2.5
Elevated maternal body mass index (BMI) increases miscarriage risk in assisted reproductive technology, but it is unclear whether this risk differs between singleton and twin pregnancies. Twin gestations impose greater metabolic and hemodynamic demands, which may amplify the adverse effects of elevated BMI. This study aimed to determine whether pregnancy plurality modifies the association between maternal BMI and miscarriage risk following frozen-thawed embryo transfer (FET). In this retrospective cohort study, 13,911 FET cycles performed at a tertiary reproductive medicine center between January 2019 and June 2024 were included. Maternal BMI was categorized as underweight (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary outcome was total miscarriage (pregnancy loss before 28 weeks), with secondary outcomes including early miscarriage (< 12 weeks), late miscarriage (12–28 weeks), clinical pregnancy and live birth. Generalized estimating equation (GEE) models were used to estimate adjusted odds ratios (aORs) with 95
Anti-Müllerian hormone (AMH) actions during ovarian follicular development appear to be stage-dependent. AMH expression increases during preantral follicle growth, which regulates granulosa cell proliferation. Preantral follicles are located in the ovarian cortex, an avascular region with limited oxygen supply. Therefore, experiments were performed to determine the mechanism of AMH in promoting cell cycle progression and cellular energy production of granulosa cells under hypoxia in preantral follicles. Ovaries were collected from macaques. Paraffin sections were obtained for immunohistochemistry to detect carbonic anhydrase IX. Preantral follicles were isolated for culture at 5
Physical activity is a potentially modifiable lifestyle factor relevant to male reproductive health, yet evidence among men with confirmed impaired semen quality remains limited. This study examined the association between self-reported physical activity intensity and changes in semen parameters in men with abnormal baseline semen quality. This prospective observational cohort study included men undergoing fertility evaluation at a single reproductive center between June 2024 and January 2026. Eligible participants had at least one semen parameter below the WHO sixth-edition reference limits. All participants received standardized lifestyle counseling, but no specific exercise modality, supervised training program, or physical activity group was assigned by the investigators. Physical activity during follow-up was assessed using a study-specific structured questionnaire that recorded self-reported weekly activity duration and intensity using the Borg scale with a practical Talk Test description. Participants were classified at follow-up as inactive, low-activity, or moderate-activity. Associations with 3-month semen parameters were evaluated. A total of 1,316 men were included: 434 in the inactive group, 430 in the low-activity group, and 452 in the moderate-activity group. Compared with inactivity, moderate-intensity physical activity was associated with favorable adjusted differences in sperm concentration, motility, normal morphology, total progressively motile sperm count, and DNA fragmentation index. The largest relative difference was observed for total progressively motile sperm count, which was 51.01
This study aimed to develop a predictive model for diminished ovarian reserve (DOR) in reproductive-aged women with Hashimoto’s thyroiditis (HT) by integrating transvaginal three-dimensional ultrasound and clinical multimodal data, to enable early identification and accurate risk assessment of DOR, and provide a visualized decision-support tool for personalized reproductive health management. A prospective cross-sectional study enrolled 300 eligible reproductive-aged women with HT, who underwent transvaginal three-dimensional ultrasound to measure bilateral ovarian volume, blood flow parameters, and antral follicle count (AFC). Participants were randomized at a 7:3 ratio into training (n = 210) and validation (n = 90) sets. LASSO regression was used to identify independent DOR risk factors for nomogram construction, with performance assessed using ROC curves, calibration curves, and decision curve analysis (DCA). Four independent risk factors were identified: pelvic inflammation history, ovarian vascularization index (VI), bilateral AFC, and positive thyroid globulin antibody (TGAb). The nomogram exhibited a significantly higher AUC than each individual factor (Delong’s test, all p < 0.05), with AUC values of 0.989 (training set) and 0.985 (validation set), corresponding sensitivities of 0.964 and 0.882, and specificities of 0.930 and 0.974. Calibration curves indicated strong concordance between predicted and actual DOR probabilities, and DCA showed greater net benefit across threshold probabilities. The nomogram integrating transvaginal three-dimensional ultrasound parameters and clinical indicators demonstrates excellent predictive accuracy for assessing DOR risk in reproductive-aged women with HT, providing a practical, visualized tool for personalized risk evaluation and reproductive health management.
