Objective:In vitro oocyte maturation (IVM) is widely used in assisted reproductive technologies; however, its potential effects on epigenetic regulation and embryonic development remain incompletely understood. In this study, we compared the developmental competence and epigenetic characteristics of transgenic mouse embryos derived from in vitro-matured and in vivo-matured oocytes. Methods:A human OCT4-enhanced green fluorescent protein (EGFP) construct was microinjected into fertilized oocytes, and embryo development was evaluated by assessing cleavage and blastocyst formation rates. The methylation status of the OCT4 promoter was assessed using methylation-specific polymerase chain reaction (PCR), and the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l) and endogenous Oct4 were analyzed using quantitative real-time PCR. Results:Embryos derived from IVM oocytes exhibited significantly reduced cleavage and blastocyst formation rates compared with those derived from in vivo-matured oocytes. In addition, differences in OCT4 promoter methylation patterns and altered expression of DNMTs were observed between the two groups. In particular, increased Dnmt3a expression and decreased Oct4 expression were associated with embryos derived from IVM oocytes. Conclusion:These findings suggest that IVM is associated with epigenetic alterations that may influence early embryonic development and the quality of transgenic embryos. Improved understanding of these effects may contribute to the optimization of IVM protocols and outcomes in assisted reproductive technologies.
Objective: Pregnant women with coronavirus disease 2019 (COVID-19) are more likely than nonpregnant women to require admission to an intensive care unit, and many may require antiviral therapy. Remdesivir, an antiviral drug used to treat COVID-19, may exert toxic effects on specific tissues and organs. Therefore, this study investigated the effects of remdesivir on endometrial tissue in pregnant female mice.Methods: Thirty female Naval Medical Research Institute (NMRI) mice were divided into five groups. The control group received no treatment, and the sham group received the remdesivir solvent, dimethyl sulfoxide. The 2-, 4-, and 8-mg groups received the corresponding doses of remdesivir. Treatment continued for 10 days. After injection and mating, the presence of a vaginal plug was considered to indicate gestational day 1. On gestational day 4.5, uterine tissue damage, pinopode status, serum estradiol levels, and tissue expression of interleukin-6 and interleukin-1β were examined.Results: Serum estradiol levels and interleukin-6 expression in endometrial tissue decreased in a dose-dependent manner after remdesivir treatment. Remdesivir treatment was also associated with fewer uterine pinopodes and histological evidence of endometrial tissue injury (p<0.05).Conclusion: In pregnant mice, remdesivir reduced serum estradiol levels, decreased the number of endometrial pinopodes, and suppressed interleukin-6 expression. These findings suggest that remdesivir may adversely affect the endometrium and potentially compromise implantation; however, direct functional validation is required.
A broad range of genetic and epigenetic factors contributes to female infertility, a substantial proportion of which is related to ovulatory disorders. Any factor that disrupts the normal function of key ovarian components, including the follicle, the enclosed oocyte, and surrounding somatic cells, may contribute to female infertility. Investigating the molecular factors involved in folliculogenesis and reproductive pathways may substantially improve the treatment of diseases affecting the female reproductive system. Long non-coding RNAs (lncRNAs), as key regulators of molecular and biological processes, play important roles in ovarian function and female fertility. These effects are mediated through interactions with DNA, RNA, and proteins, and lncRNAs are involved in processes such as granulosa cell differentiation, follicular growth, and ovarian hormonal regulation. Altered lncRNA expression may contribute to reproductive disorders such as polycystic ovary syndrome, endometriosis, and primary ovarian insufficiency. In addition, several lncRNAs have been proposed as potential biomarkers for the diagnosis of female reproductive disorders and as novel therapeutic targets. However, many functional mechanisms of these molecules remain unclear. This review summarizes recent scientific findings on the role of lncRNAs in the pathophysiology of female infertility and evaluates their potential for the development of novel diagnostic and therapeutic approaches. A better understanding of these molecular pathways may support more effective strategies for managing and treating female infertility.
OBJECTIVE:This study aimed to investigate whether chronic exposure to environmentally relevant concentrations of ibuprofen promotes follicular atresia in female rats and to explore potential underlying mechanisms affecting ovarian function. METHODS:Ten adult female Wistar rats were randomly assigned to two groups (n=5 per group): a control group and an ibuprofen-exposed group. The experiment was conducted over a 4-month period. The control group received standard drinking water, whereas the ibuprofen group received drinking water supplemented with ibuprofen. Body weight and ovarian index were recorded throughout the study. Ovarian tissues were examined histologically to quantify atretic follicles and to assess structural alterations. Immunohistochemical analysis was performed to evaluate B-cell lymphoma 2 (Bcl-2) expression. Biochemical analyses were conducted to measure oxidative stress markers, including malondialdehyde and catalase, and serum levels of estradiol and interleukin 6 (IL-6) were determined. RESULTS:Chronic ibuprofen exposure was associated with a significant increase in follicular atresia and induced marked histopathological alterations in ovarian tissue. Both body weight gain and the ovarian index were reduced in the ibuprofen group compared with controls. Biochemical analyses demonstrated elevated oxidative stress, along with disrupted serum estradiol and IL-6 levels. In addition, Bcl-2 expression was downregulated in ibuprofen-exposed rats. CONCLUSION:Even at environmentally relevant concentrations, ibuprofen exposure may compromise ovarian function by promoting follicular atresia through multiple interacting pathways, including oxidative stress, inflammatory responses, downregulation of Bcl-2, and impaired estradiol synthesis. These findings highlight the potential reproductive health risks associated with chronic low-dose environmental exposure to ibuprofen.
Objective:Endometriosis is a chronic inflammatory disorder that affects approximately 10% of reproductive-age women and is frequently associated with subfertility. This study evaluated the potential ameliorative effect of lactoferrin on endometriosis-associated subfertility in a rat model. Methods:Rats were allocated into four groups: Sham, Sham+Lacto, Endo, and Endo+Lacto. In these group labels, "Endo" denotes endometriosis and "Lacto" denotes lactoferrin. Endometriosis was surgically induced in the Endo and Endo+Lacto groups, whereas rats in the Sham and Sham+Lacto groups underwent abdominal incision without uterine manipulation. Lactoferrin (300 mg/kg/day) was orally administered for 30 days to the Sham+Lacto and Endo+Lacto groups. After treatment, five females from each group were mated with mature males to assess fertility index parameters. Results:Endo rats exhibited a significant increase in serum follicle-stimulating hormone (FSH) and a significant decrease in serum luteinizing hormone (LH) compared with Sham controls. In addition, marked histopathological alterations were observed in ovarian and eutopic uterine tissues. Maternal uterine and ovarian weights were significantly reduced in the Endo group, whereas fertility index parameters showed no significant differences among the experimental groups. Neonatal outcomes did not differ significantly between the Endo and Sham groups. In contrast, lactoferrin treatment significantly ameliorated gonadotropin imbalance, alleviated ovarian and eutopic endometrial histopathological alterations, and significantly increased neonatal weight and size in endometriotic rats, whereas neonatal length and pup number were not significantly changed. Conclusion:Lactoferrin treatment ameliorated gonadotropin imbalance by improving serum FSH and LH levels, restoring ovarian and uterine tissue architecture, and enhancing fertility index parameters and neonatal outcomes. These findings suggest that lactoferrin may represent a promising non-hormonal approach for mitigating endometriosis-associated subfertility.
Objective:Naproxen has received considerable attention due to its environmental persistence and incomplete removal during wastewater treatment. This study evaluated the ovarian toxicity of naproxen at an environmentally relevant dose to assess its potential reproductive risks. Methods:Female Wistar albino rats were exposed for 100 days to naproxen alone (98.39 μg/L) or to a mixture containing naproxen (98.39 μg/L), ibuprofen (117.14 μg/L), diclofenac (609.12 μg/L), and trifloxystrobin (0.04 mg/kg/day) at a 4:1:3:2 ratio. Ovarian tissues were analyzed for oxidative stress biomarkers, B-cell lymphoma 2 (Bcl-2) expression, and follicle counts. Serum was analyzed for interleukin 6 (IL-6) and progesterone concentrations. Results:Compared with controls, both treated groups had a significantly higher ovary index, lower catalase activity, and lower progesterone levels, whereas body weight, malondialdehyde levels, and serum IL-6 levels did not differ significantly. Morphometric and immunohistochemical analyses demonstrated reduced preantral follicle counts and Bcl-2 expression in the treated groups. Conclusion:Chronic exposure to naproxen, alone or in combination, at an environmentally relevant dose was associated with ovarian dysfunction, impaired progesterone production and antioxidant status, and disrupted ovarian follicle dynamics.
Objective:In mammals, a lower testicular temperature is required for normal spermatogenesis. Testicular temperature can increase due to multiple factors, including lifestyle-related exposures, ultimately leading to damage to germ cells and impaired sperm parameters. Nigella sativa (black seed) has been reported to improve sperm parameters and exhibits a wide range of therapeutic properties. This study investigated the effects of black seed on antioxidant and anti-inflammatory activity in testicular tissue of adult male mice following scrotal hyperthermia. Methods:Twenty-four male mice were randomly assigned to control, hyperthermia, and hyperthermia+black seed (Hyper+BS) groups. In the hyperthermia group, the animals' testes were exposed to water at 43 °C for 20 minutes, five times on alternate days. In the treatment group, following induction of hyperthermia, animals received black seed (300 mg/kg/day) orally for 35 days. At the end of the experiment, animals were euthanized for histological and molecular analyses. Results:Black seed treatment conferred significant protective effects. Total sperm count and motility were significantly improved in the Hyper+BS group compared with the hyperthermia group (p≤0.0001 and p=0.0266, respectively). Black seed administration also significantly reduced tumor necrosis factor-α and interleukin-1β levels (p=0.0012 and p=0.0003, respectively). In addition, B-cell lymphoma 2 (Bcl-2) gene expression and glutathione levels were significantly increased in the Hyper+BS group (p=0.0038 and p≤0.0001, respectively). Conclusion:These findings suggest that black seed may serve as a low-risk supportive natural supplement for preserving male fertility under conditions of scrotal hyperthermia. However, its routine clinical application requires validation through well-designed human studies.
Objective: This study investigated the impact of smoking and antioxidant supplementation on in vitro fertilization (IVF) outcomes among couples undergoing IVF treatment at a tertiary infertility center.Methods: This retrospective cohort study included 327 couples who underwent IVF between January 2018 and January 2019. Participants were categorized according to smoking status and antioxidant use before and during treatment. The primary outcome was clinical pregnancy, and secondary outcomes included embryo-related parameters and live birth. Multivariable logistic regression analyses were performed to identify independent predictors of treatment outcomes.Results: Among the study population, smoking was reported by the male partner only in 38.5% of couples, by the female partner only in 8.0%, and by both partners in 21.4% of couples. Pre-treatment antioxidant use was reported by the male partner only in 23.5% of couples, by the female partner only in 6.1%, and by both partners in 6.7% of couples. Smoking status was not significantly associated with clinical pregnancy or live birth in univariate analyses. Male pre-treatment antioxidant use was associated with higher clinical pregnancy and live birth rates in unadjusted analyses; however, this association did not persist after multivariable adjustment. Increasing female age and smoking by both partners were independently associated with reduced odds of live birth, whereas embryological parameters—particularly the total number of embryos formed—were the strongest predictors of treatment success.Conclusion: Smoking by both partners was independently associated with reduced live birth rates, whereas the apparent benefit of male antioxidant supplementation may be influenced by confounding factors. Embryological characteristics remain the primary determinants of IVF success.
Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide (NAD+), has recently emerged as a promising therapeutic candidate for age-related diseases. This review critically evaluates preclinical evidence regarding the effects of NMN on ovarian health, with particular emphasis on its potential to attenuate ovarian aging, improve follicular reserve, and restore endocrine function. Animal studies have demonstrated that NMN supplementation enhances mitochondrial function, reduces oxidative stress, and modulates sirtuin activity in ovarian tissue. These effects contributed to improved oocyte quality, delayed ovarian senescence, and prolonged reproductive lifespan. In models of chemotherapy-induced ovarian insufficiency and age-related ovarian decline, NMN administration was associated with increased folliculogenesis and normalization of hormonal profiles. Furthermore, the anti-inflammatory and anti-apoptotic properties of NMN suggest potential therapeutic applications in conditions such as premature ovarian insufficiency and polycystic ovary syndrome. Despite encouraging findings in rodent models, clinical translation remains limited. This review summarizes the key molecular pathways influenced by NMN, including the NAD+/sirtuin-1 (SIRT1) axis, and highlights important gaps in current knowledge. Collectively, the available evidence underscores the therapeutic potential of NMN while emphasizing the need for well-designed human studies to establish its efficacy and safety in reproductive medicine.
Objective:To establish a standardized and reproducible rat model of endometriosis by refining the classic Vivian technique, with the aim of minimizing methodological variability and replicating key features of human disease. Methods:Sixty female Sprague-Dawley rats (6 weeks old) were evaluated for estrous-cycle phase using vaginal cytology, and only animals in proestrus or estrus were selected. Under ketamine-xylazine anesthesia, a 1-cm segment of the uterine horn was excised, opened longitudinally, and sutured to the peritoneal wall with the endometrial surface facing the peritoneum. Protocol refinements included strict graft orientation, fixation with four interrupted sutures, and perioperative ceftriaxone prophylaxis. A second laparotomy was performed one month later to assess lesion development, followed by histological confirmation. Results:All animals (100%) developed macroscopically visible lesions. These lesions presented as cystic, fluid-filled masses with hyperemic surfaces and neovascularization; adhesions to the bowel or omentum were also observed. Lesion size was quantified using digital imaging software. Histological analysis confirmed the presence of endometrial-like tissue composed of cuboidal epithelium, glandular structures, and stromal elements. No perioperative mortality occurred. Conclusion:This standardized rat model reliably reproduces hallmark features of human endometriosis, including angiogenesis and adhesion formation. The protocol refinements address common sources of variability in rodent models and provide a stepwise, reproducible framework for mechanistic investigation and preclinical evaluation of novel therapies.
Objective:This study examined the potential protective role of date palm fruit extract (DPFE) and its underlying mechanisms against busulfan-induced sperm damage and infertility. Methods:Sixty male Wistar rats were allocated to control, busulfan alone (10 mg/kg), DPFE alone (4 mg/kg), and busulfan+DPFE co-treatment groups for a period of 56 days. Semen parameters were evaluated along with DNA fragmentation, assessed using the sperm chromatin dispersion test, and protamine deficiency, detected by chromomycin A3 staining. Testicular oxidative stress was assessed by measuring malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities. Results:Phytochemical analysis confirmed the high polyphenolic and flavonoid content of DPFE. Busulfan significantly induced testicular oxidative stress, as evidenced by increased MDA levels and reduced SOD and CAT activities. These alterations were accompanied by significant declines in sperm motility and viability, deterioration of sperm morphology, and marked increases in protamine deficiency and DNA fragmentation. Co-administration of DPFE significantly counteracted these adverse effects by normalizing testicular oxidative status, reflected by decreased MDA levels and restoration of SOD and CAT activities. Consequently, DPFE improved sperm motility and morphology and, importantly, reduced the proportion of sperm exhibiting high DNA fragmentation and protamine deficiency. Conclusion:Antioxidant-rich DPFE exerts a significant protective effect against busulfan-induced testicular toxicity, with its mechanism strongly linked to attenuation of testicular oxidative injury, thereby improving conventional sperm quality and, critically, preserving sperm chromatin structure and DNA integrity.
Objective:This study compared the traditional blastocyst grading system with quantitative measurements of blastocyst expansion in relation to total pregnancy rate, implantation rate, and clinical pregnancy rate. Methods:A retrospective analysis was performed using data collected from patients undergoing frozen single embryo transfer cycles between 2021 and 2024. Single vitrified-warmed blastocyst transfers in self-patients were included, whereas cleavage-stage transfers and donor programs were excluded. All blastocysts were morphologically graded using the Gardner grading system. The degree of expansion was assessed morphometrically by measuring the inner diameter of the blastocyst from images obtained at the equatorial plane during embryo transfer, using Hamilton Thorne laser software. Multiple statistical tests were applied to analyze both qualitative and quantitative assessments of blastocysts in relation to clinical outcomes. Results:When comparing morphological parameters such as the quality of inner cell mass (ICM), trophectoderm (TE), and blastocyst expansion level, ICM and TE quality were found to significantly influence clinical outcomes. In comparing qualitative and quantitative (mean diameter) assessments of blastocysts with clinical outcomes, TE grade and blastocyst expansion level assessed qualitatively showed significant effects, whereas ICM quality and quantitative expansion measurements did not demonstrate statistical significance. Conclusion:Qualitative assessments of TE grade and blastocyst expansion level appear to be stronger predictors of clinical outcomes than ICM grade and morphometric assessment of blastocyst expansion. Larger datasets, including morphometric evaluation of ICM and TE cells, are recommended to clarify the predictive value of morphometric parameters.
The digital transformation of reproductive health has been accelerated by rapid advances in Femtech, which offers new approaches to addressing infertility-related challenges. This review synthesizes the current evidence across three domains: consumer-facing technologies for fertility awareness and at-home diagnostics; the integration of digital health tools, including telehealth and mobile health (mHealth), into clinical management pathways; and the application of artificial intelligence (AI) in assisted reproductive technology (ART). Fertility tracking applications and home-based diagnostic tools may improve accessibility and support patient engagement in reproductive health management; however, evidence regarding their effects on clinically meaningful outcomes, including pregnancy and live birth rates, remains limited or inconsistent. Telehealth and mHealth platforms have been widely adopted and have demonstrated high patient satisfaction and feasibility, with clinical outcomes comparable to those of traditional in-person care in selected settings. In ART, AI-based approaches show promise for gamete and embryo assessment, selection, and outcome prediction, although the current evidence is derived largely from observational and validation studies and does not yet demonstrate consistent improvements in clinical outcomes. Despite these advances, important challenges remain, including variability in evidence quality, data privacy concerns, regulatory uncertainty, and disparities in digital access. Overall, although Femtech technologies have substantial potential to enhance reproductive care, their clinical integration should be guided by rigorous validation and cautious interpretation of the existing evidence.
Objective:This study compared serum anti-Müllerian hormone (AMH) concentrations measured in capillary fingerstick and venous samples using the automated fluorescence immunoassay system (AFIAS) AMH assay and evaluated procedure-related discomfort. Methods:We conducted a prospective paired-sample method-comparison study at Korea University Anam Hospital, Seoul, Republic of Korea, in October 2023. During a single clinic visit, paired venous and fingerstick blood samples were obtained from each participant. Serum AMH concentrations were measured with the AFIAS AMH assay, and all laboratory analyses were performed at EONE Laboratories, Incheon, Republic of Korea. Agreement between sampling methods was evaluated using Passing-Bablok regression, Bland-Altman analysis, Pearson and Spearman correlation coefficients, and the intraclass correlation coefficient (ICC). Procedure-related pain was assessed immediately after sampling using an 11-point numeric rating scale (NRS; 0=no pain, 10=worst pain imaginable). Results:Overall, 90 women aged 25-46 years provided paired samples. Mean AMH concentrations were 2.74 ng/mL (range, 0.11 to 9.99) in venous samples and 3.42 ng/mL (range, 0.17 to 11.55) in fingerstick samples. Passing-Bablok regression indicated proportional bias (y=0.123+1.175x), with no significant deviation from linearity on the cumulative sum (CUSUM) test (p=0.07). Agreement and correlation were high (ICC=0.930; Pearson r=0.982; p<0.001). Mean NRS pain scores were 2.36 for venipuncture and 2.91 for fingerstick sampling. Conclusion:Capillary fingerstick sampling may be an alternative approach for AMH measurement when improved access to testing is desired. However, because proportional bias was observed, fingerstick and venous AMH measurements should not yet be considered fully interchangeable without further validation.
Objective:Polystyrene exposure poses an increasing threat to reproductive health, and effective interventions remain limited. Jinkui Shenqi pills (JSP), a traditional Chinese medicine used to treat reproductive disorders, may protect against such damage. This study integrated network pharmacology with experimental validation to explore the mechanisms by which JSP counteracts polystyrene-induced reproductive toxicity. Methods:Potential targets related to polystyrene toxicity and bioactive components of JSP were retrieved from relevant databases. Overlapping targets were identified using VENNY 2.1. Protein-protein interaction networks were constructed using STRING, and core targets were identified with Cytoscape. Enrichment analyses were performed using DAVID. Molecular docking was used to evaluate ligand-target binding. A polystyrene-exposed mouse model was established, and tissue injury and recovery were assessed by hematoxylin-eosin (HE) staining and Western blotting (WB). Results:In-depth screening identified 111 overlapping targets, and three key molecules-AKT serine/threonine kinase 1 (AKT1), caspase-3 (CASP3), and B-cell lymphoma 2 (BCL2)-were selected for further investigation. Gene Ontology analysis highlighted phosphorylation-related processes and responses to xenobiotics, while Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment in pathways related to lipid metabolism, atherosclerosis, cancer, and phosphatidylinositol-3-kinase (PI3K)-AKT signaling. Molecular docking confirmed effective binding of sitosterol, alisol B monoacetate, acetate, and alisol to these targets. HE staining revealed polystyrene-induced damage in testicular and ovarian tissues, which was effectively alleviated by JSP administration. WB results further demonstrated that JSP upregulated the expression of core target proteins, supporting its protective role against polystyrene-induced reproductive toxicity. Conclusion:JSP mitigates polystyrene-induced reproductive toxicity by modulating AKT1, CASP3, and BCL2, supporting its potential as a protective agent.
Objective:Nandrolone, a synthetic anabolic steroid, is frequently used for muscle enhancement but is known to compromise male fertility, particularly when administered at supraphysiological doses. Conversely, royal jelly exhibits antioxidant activity and may exert protective effects on reproductive function. This study aimed to assess the histomorphological effects of nandrolone, royal jelly, and their concurrent administration on testicular architecture during pubertal development. Methods:Thirty-five male Syrian mice (4-5 weeks old, approximately 25 g) were randomly assigned to five groups (n=7): untreated control, sesame oil vehicle, nandrolone (10 mg/kg/week), royal jelly (500 mg/kg/day), and combined nandrolone plus royal jelly. On day 32, animals were euthanized, and testicular tissues were harvested for morphological and histological evaluation. Paraffin-embedded sections were stained with hematoxylin and eosin, and seminiferous tubule diameters were quantitatively assessed. Results:Nandrolone administration increased testicular weight and the gonadosomatic index relative to controls. Royal jelly similarly enhanced testicular metrics. However, co-treatment markedly reduced testicular weight, gonadosomatic index, and lumen diameter, while germinal epithelium thickness was increased. Conclusion:Nandrolone alone may not impair fertility during pubertal maturation, and royal jelly may enhance reproductive potential when administered prepubertally. Nonetheless, their combined administration appears to disrupt spermatogenic architecture, potentially impeding sperm transit through epithelial hyperplasia and delaying testicular maturation.
Turner syndrome (TS) is associated with progressive ovarian insufficiency, and fertility preservation (FP) remains difficult even in women with mosaic karyotypes. We report a live birth achieved after oocyte cryopreservation with 3.5 years of storage and preimplantation genetic testing for aneuploidy (PGT-A) in a woman with mosaic TS (45,X[4%]/46,XX[96%]). At 34 years of age, she underwent controlled ovarian stimulation for FP, which yielded nine mature oocytes that were vitrified. After 3.5 years of storage, all oocytes survived warming and were fertilized using intracytoplasmic sperm injection. Four blastocysts developed and underwent PGT-A, which identified two euploid embryos, one aneuploid embryo, and one mosaic embryo. Transfer of a single euploid blastocyst resulted in an uncomplicated term pregnancy and the delivery of a healthy male infant. To our knowledge, this is the first reported live birth in Korea achieved using cryopreserved oocytes in a woman with mosaic TS.
Objective:Asthenozoospermia, characterized by diminished sperm motility, shows substantial genetic heterogeneity. Although many familial cases of asthenozoospermia have been documented, the genetic etiology for most affected males remains unknown. Methods:This study used clinical and molecular approaches to characterize a hereditary form of asthenozoospermia. Two patients born to consanguineous parents exhibited impaired sperm motility. Whole-genome sequencing (WGS), followed by Sanger sequencing, was performed for molecular diagnosis and was coupled with three-dimensional protein modeling to characterize the identified variant. Results:WGS revealed that both affected brothers carried a pathogenic variant (c.580C>T; p.Gln194*) in dynein heavy chain domain 1 (DNHD1). Homozygous variants in DNHD1 have previously been linked to spermatogenic failure 65 (Online Mendelian Inheritance in Man [OMIM] 619712). Three-dimensional protein modeling demonstrated significant alterations in DNHD1 secondary structure that could contribute to loss-of-function. Conclusion:These findings support a role for DNHD1 in maintaining the structural and functional integrity of sperm. Accurate molecular diagnosis may facilitate genetic counseling and inform clinical management.
Objective:To evaluate the impact of blastulation speed and blastocyst quality on pregnancy outcomes in single vitrified-warmed blastocyst transfer (SVBT) cycles. Methods:A total of 736 SVBT cycles conducted between 2019 and 2021 were analyzed. Blastocysts were classified according to blastulation speed (day 5 vs. day 6) and morphological quality (top, good, average, and poor). A supplementary analysis included 395 blastocysts from 171 cycles that underwent pre-implantation genetic testing for aneuploidy between 2022 and 2023. Ongoing pregnancy rates and euploidy rates were compared across blastulation speed and quality categories. Results:In SVBT cycles, the ongoing pregnancy rate was significantly higher in the day 5 group than in the day 6 group. However, no significant difference in ongoing pregnancy rates was observed between top-quality and good-quality blastocysts prior to vitrification, irrespective of blastulation speed. Average- and poor-quality blastocysts were more frequently observed in the day 6 group than in the day 5 group. In addition, euploidy rates were significantly higher in the day 5 group than in the day 6 group. However, no significant difference in euploidy rates was detected between top- or good-grade blastocysts derived from day 5 and day 6 embryos. By contrast, significant differences in euploidy rates were observed between average- and poor-quality blastocysts from day 5 and day 6. Conclusion:Blastocyst quality has a significant influence on clinical outcomes, whereas blastulation speed appears to be comparatively less critical. For slow-developing embryos, vitrification of high-quality day 6 blastocysts may be preferable to the transfer of low-grade day 5 blastocysts, thereby providing practical clinical options for patients experiencing developmental delays.
Objective:This study investigated the association between vitamin D deficiency and polycystic ovary syndrome (PCOS), focusing on metabolic and endocrine parameters. Methods:A retrospective analysis with Mendelian randomization (MR) was conducted using clinical data from patients diagnosed with PCOS at Shanxi Provincial People's Hospital from 2019 to 2025. Variables included serum vitamin D levels, anthropometric indices, hormone profiles, and inflammatory markers. Multiple regression models were applied to control for confounders. LASSO logistic regression was used for feature selection and predictive modeling, with model performance assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. A nomogram based on logistic regression was constructed and evaluated using ROC-derived AUC values to determine classification accuracy and translational potential. Results:Patients with PCOS exhibited higher rates of vitamin D deficiency or insufficiency compared with healthy controls. Vitamin D deficiency was associated with weight gain, insulin resistance, and chronic inflammation. Vitamin D may reduce testosterone levels, suppress interleukin- 6, and influence hepatic sex hormone-binding globulin (SHBG) synthesis, thereby affecting PCOS development. MR analysis further suggested that vitamin D deficiency may worsen PCOS through insulin resistance. Body mass index and testosterone levels were positively associated with PCOS, whereas SHBG was inversely related. The nomogram derived from multivariate modeling demonstrated high predictive accuracy, reliability, and generalizability. Conclusion:Vitamin D deficiency is significantly associated with PCOS and may contribute to its pathogenesis by exacerbating metabolic dysfunction. MR findings support potential causality. Further studies should assess whether vitamin D supplementation improves clinical outcomes in PCOS.
