This study translates and validates an Assamese version of the Infertility Stigma Instrument-Female (ISI-F) among women seeking Medically Assisted Reproduction (MAR) in Assam, India. The translated ISI-F was administered among 188 Assamese-speaking women in two healthcare facilities. Exploratory factor analysis (EFA), reliability assessment, and confirmatory factor analysis (CFA) were carried out. Convergent validity was examined using Spearman correlations between ISI-F and the Fertility Quality of Life (FertiQOL) subscales. EFA yielded a refined 15-item scale with four factors: Social Withdrawal, Perceived Social Pressure, Experienced Stigma, and Avoidant Coping, explaining 44.36% of the variance. The scale had acceptable reliability (Cronbach's α = 0.728; McDonald's ω = 0.911). CFA demonstrated a better fit to the four-factor Assamese model (RMSEA = 0.051; CFI = 0.92; TLI = 0.90) than the original ISI-F structure. ISI-F scores were significantly and negatively correlated with FertiQOL domains, supporting the convergent validity. Mean stigma score (44.6 ± 9.11) indicated moderate perceived infertility stigma. The Assamese version of the ISI-F is a reliable and culturally appropriate tool for measuring infertility stigma among MAR treatment seekers in Assam, India. The revised factor structure reflects context-specific distinctions between social pressure, experienced stigma, and coping responses.
Chemotherapy regimens in high-grade osteosarcoma have markedly improved survival rates, currently reaching approximately 70%. Concerns persist regarding a long-term effect on fertility. Despite the systematic application of many fertility preservation techniques, few studies specifically address fertility in survivors. Our goal was to assess fertility in patients treated for pediatric and young adult osteosarcoma in a long-term follow-up period. This study was retrospective analysis of osteosarcoma survivors treated at our center from 1980 to 2005. All followed a standardized chemotherapy protocol. In cases where contact could not be established at the time of the follow-up for their osteosarcoma, telephone interviews were conducted, querying about pregnancy desires and difficulties. In case of difficulties, we further investigated about the possible reasons behind them. Of 116 consecutive patients initially enrolled, 104 were contacted; 67 (36 women, 31 men) desired pregnancy. Mean age at the beginning of treatment was 16.9 (4 to 33) years. The mean age at the end of follow-up was 46.8 (31 to 64) years, with an average follow-up period of 359 (156 to 480) months. Among the 36 women desiring pregnancy, only 1 (2.7%) faced fertility challenges due to chemotherapy. Of the 31 men desiring pregnancy, 4 (12.9%) experienced difficulties due to azoospermia secondary to chemotherapy and in two cases, the cause is unknown because no fertility studies were conducted for the couple. No discernible chemotherapy dosage differences were found between patients with fertility issues and those without. Survivors of pediatric and young adult osteosarcoma exhibit a high success rate in achieving normal conception and childbirth, aligning with the general population. To inform pediatric and adolescent patients with osteosarcoma, as well as their parents, about the high success rate associated with achieving a normal conception and childbirth should be the standard.
Paclobutrazol (PBZ), a triazole-based plant growth retardant, is widely employed in agriculture and horticulture to control plant height and promote root growth. However, its persistence and mobility in the environment raise concerns regarding its bioavailability and toxicity in aquatic ecosystems. In this study, we investigated the reproductive toxicity of PBZ in zebrafish (Danio rerio), a well-established model for aquatic toxicology and vertebrate reproductive research. Adult zebrafish were exposed to PBZ (0, 0.1, 1 ppm) for 2, 4, 6, or 8 weeks. After exposure, breeding was conducted using exposed or unexposed pairs to assess maternal, paternal, and combined effects on reproduction. Fertilization and hatching rates were quantified, and gonads were processed for histological evaluation. Chronic PBZ exposure significantly reduced fertilization and hatching success in both sexes, especially at higher concentrations and longer exposure durations. Histological examination revealed a reduction in testicular cyst area without significant changes in gonadosomatic index (GSI). In ovaries, structural integrity remained largely intact, although a mild increase in atretic follicles was observed. These findings demonstrate that PBZ impairs zebrafish reproductive success through subtle but consequential gonadal disruptions and suggest potential risks to aquatic biodiversity and population sustainability.
Male infertility, particularly severe oligozoospermia, presents a significant challenge in reproductive health, often associated with high oxidative stress and poor lifestyle practices. This case report highlights the potential therapeutic role of a structured yoga regimen in improving semen quality, reducing stress, and enhancing quality of life in a male with long-standing infertility. The novelty lies in documenting comprehensive improvements across semen parameters and psychological well-being following a nonpharmacological intervention. A 30-year-old Indian male diagnosed with severe oligozoospermia presented with a four-year history of primary infertility. His 30-year-old Indian female partner had no identifiable reproductive abnormalities. The couple sought consultation at a tertiary care centre. The male patient reported a high-stress lifestyle due to his occupation as an architectural researcher involving extensive travel and irregular routines. He underwent a six-month structured yoga intervention (five days per week) comprising guided sessions involving breathing exercises, meditation, and specific physical postures, supervised by a certified yoga therapist. Pre- and post-intervention assessments included semen analysis, sperm DNA integrity, oxidative stress markers in seminal fluid, and quality of life using a standardized assessment tool. Post-intervention, the patient exhibited notable improvements in semen parameters, including increased sperm count and motility, reduced morphological abnormalities, and decreased seminal oxidative stress levels leading to sperm DNA fragmentation index decline. Improvements were also observed in quality-of-life scores across physical, psychological, social, and environmental domains. Following these outcomes, intrauterine insemination was advised as a fertility treatment option. This case illustrates the potential of yoga as an adjunctive, noninvasive therapy for managing male infertility, particularly in individuals with stress-related reproductive dysfunction. The structured yoga program led to substantial improvement in semen quality and quality of life, suggesting a mind-body connection that may influence reproductive health. This single case provides preliminary insight into the potential link between lifestyle factors and reproductive health, though broader studies are required. Further studies involving larger cohorts are needed to validate and expand upon these promising results.
CAR T-cell therapy has become a highly effective treatment for hematological malignancies, and emerging evidence indicates promising benefits for non-oncohematological conditions. As its clinical use broadens, understanding long-term outcomes and late complications is crucial. One critical yet understudied area is fertility, for which current evidence remains limited and no formal guidelines provide direction for patients undergoing CAR T-cell therapy. To address this gap, we conducted a cross-sectional survey on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT) focusing on current practices, existing challenges, and reported reproductive outcomes. Questionnaires were distributed electronically (via SurveyMonkey) between Jan 8, 2025 and April 18, 2025 to 247 EBMT-affiliated centers assessing current fertility-related practices and procedures around CAR T-cell therapy. A second, complementary questionnaire was circulated between Dec 23, 2025 and April 9, 2026 to gather detailed information on reported pregnancies following CAR T treatment. 99 of 247 (40%) centers answered and were included in the analysis. At data censoring, 24 pregnancies were reported in 19 patients, resulting in 18 live births, 2 ongoing pregnancy (one with twins), and 4 miscarriages. Eighteen pregnancies occurred in female CAR T-cell recipients, and six were reported by male recipients through their partners. In patients achieving pregnancy, B cell lymphoma was the most common indication for treatment. Pregnancies in the female cohort occurred naturally in 83% of cases (15/18). Among patients with data, the median time between CAR T-cell infusion and delivery or miscarriage was 3 years (range 4 months-6 years). Although both low- and high-grade Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported among these patients, these events did not appear to influence pregnancy outcomes, acknowledging the small sample size. While most centers (52/63, 83%) reported offering fertility counselling before CAR T-cell infusion, 11 centers (17%) indicated that they do not routinely inform patients of the potential reproductive risks. Most centers (79%) offered fertility preservation procedures to male and female patients. The most common barriers to fertility preservation referral were the urgency of initiating bridging therapy to CAR T-cell infusions due to active or rapidly progressive disease in aggressive disease and extensive prior chemotherapy exposure, defined as more than three previous treatment lines. For female patients, the predominant approaches were oocyte cryopreservation (63%) and ovarian tissue cryopreservation (59%). Among male patients, semen collection and cryopreservation was the most frequently used method (93%). Endocrinologic follow-up practices after CAR T-cell therapy varied substantially across centers. We report the largest series of pregnancies and live births after CAR T in patients with hematological malignancies and autoimmune diseases, and the first within Europe. As CAR T-cell therapy is increasingly administered earlier in the treatment algorithms and to younger populations, integrating standardized fertility counselling and preservation strategies into routine care will be essential. The reproductive success highlights the urgent need for robust research and formalized guidelines in this evolving field. None.
Inadequate nutrition of the dams, even if recognized as a possible cause of infertility, it is usually underestimated during the common diagnostical procedures (i.e., clinical examination, vaginal cytology, ultrasound, blood and urine analysis). Although the diet may meet adult maintenance requirements, several nutrients can be suboptimal during the pre-gestation period and may influence reproductive performance. This case report describes the use of an oral supplement to increase fertility in a German Sheperd breeding center experiencing prolonged secondary anoestrus. Fifteen German Shepherd bitches with secondary anoestrus (>12 months) underwent standard reproductive workup (vaginal cytology, hormone assays, ultrasound, and semen testing of sires). Abdominal ultrasound of the bitches did not present any signs of cystic endometrial hyperplasia (CEH). Similarly, metabolic disorders (hypothyroidism and Cushing's disease) were ruled out. It was hypothesized that the kennel diet might have provided suboptimal bioavailability of nutrients; as such the nutritional plan was reviewed, and a multi-component "fertility mix" (liquid and powder phases dosed daily at 0.8 g/kg0.75 and 0.4 g/kg0.75, respectively) was added to the usual complete maintenance ration. Within 6 months of supplementation, 12/15 bitches resumed cyclicity and were confirmed pregnant or gave birth; whereas three underweight bitches with chronic enteropathies did not resume cyclicity. The diagnostic approach to infertility is complex and involves both male and female factors, while dietary adequacy is often overlooked. Nutrients such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, folic acid, vitamin E, selenium, and zinc may influence ovarian steroidogenesis and antioxidant systems, and maintenance diets may not always be optimal for bitches intended for reproduction. These observations are hypothesis-generating; baseline and follow-up nutrient biomarkers were not obtained and no untreated control group was available, precluding causal inference.
Embryo development and pregnancy establishment require successful interaction between the oocyte and sperm and proper activation of developmental signaling pathways. In the bovine, the successful execution of this biological equation requires, on one hand, maternal determinants such as the intrinsic quality of the oocyte and molecules secreted by the endometrium epithelium critical to sustain embryo development. In contrast, paternal contributions encompass both visible sperm characteristics assessed by routine semen evaluation and hidden traits that escape conventional laboratory assessment of sperm quality. Paternal contributors extend beyond DNA delivery, as sperm also transfer a diverse array of molecules critical for reproduction. For instance, sperm can deliver proteins that could have short- and long-term consequences for sperm functionality, organelles that can be used to assemble the cytoskeleton machinery of the developing embryo, and other molecules that can regulate critical processes in reproduction to ensure the survival of different mammalian species. Taken together, paternal contributors can significantly influence fertility, with their impact manifesting at events occurring around fertilization with or without subsequent effects on embryo development and with or without consequences for pregnancy establishment, leading to the divergence in fertility observed among males.
Adenomyosis is a chronic reproductive condition that impairs fertility and is characterized by endometrial tissue invading the myometrium. Despite advances in MRI and 3D ultrasound for diagnosis, there is still no consensus on optimal fertility management. The choice between uterus-sparing surgery and direct IVF, including the ideal timing for each approach, remains a subject of ongoing debate. This narrative review analyzed relevant studies retrieved from PubMed, Scopus, and Web of Science, focusing on uterine morphology, hormonal and surgical therapeutic responses, and IVF/ICSI outcomes in women with adenomyosis. Infertility in adenomyosis is associated with JZ remodeling, inflammation, hypercontractility, and impaired endometrial receptivity. Poor prognostic markers include JZ thickness ≥8.5 mm, uterine volume 90-130 mL, and MUSA direct features. These features are linked to lower live birth rates (aRR=0.62; 95% CI 0.43-0.88; P=0.007) and higher miscarriage risk (aRR=2.88; 95% CI 1.49-5.57; P=0.002), with larger uterine volume (>130 cm3) and thicker JZ significantly correlating with pregnancy failure and reduced cumulative live birth in Kaplan-Meier analyses. Assessment of JZ morphology, uterine volume, and MUSA features is crucial for individualized treatment planning in women with adenomyosis and infertility. Based on observational data, a pragmatic approach may include: 1) medical therapy with GnRH agonists for 3-6 cycles for uterine volumes 100-200 mL and JZmax 8.5-16 mm, followed by IVF; 2) consideration of uterus-sparing surgery for volumes >200 mL and JZmax >16 mm in highly selected patients, then IVF with an ultra-long protocol; and 3) direct IVF for volumes <100 mL and JZmax <8.5 mm, preferably using an ultra-long protocol with a freeze-all and HRT-FET strategy. These proposals are intended as a clinically oriented framework derived from current observational evidence rather than as formal guideline recommendations.
Angiotensin II receptor antagonists (ARBs), such as losartan, are widely prescribed for the management of hypertension and various cardiovascular disorders. However, their potential effects on female fertility remain largely unexplored. This study aimed to investigate the impact of losartan on ovarian function and fertility in female Wistar albino rats. Rats were orally administered low (0.7 mg/kg) and high (1.4 mg/kg) doses of losartan daily for 1 month. Following the treatment period, ovaries were collected, weighed, fixed, and subjected to comprehensive analysis for markers associated with folliculogenesis and steroidogenesis. Specifically, histopathological, immunofluorescence, RT-PCR, and in silico analyses were performed on ovarian tissues. The results demonstrated a significant reduction in fertility rates, accompanied by notable alterations in follicular development and ovarian histoarchitecture. Furthermore, losartan treatment led to a decreased expression of Cyp19 while concurrently increasing the expression of estrogen receptor genes, Esr1 and Esr2, and insulin-like growth factor 1 (Igf1). Crucially, the mRNA expression levels of anti-Müllerian hormone (Amh), a reliable indicator of ovarian reserve, were disrupted. Biochemical analyses revealed reduced glutathione levels and increased malondialdehyde levels, further indicating oxidative stress and ovarian cellular damage, consistent with the observed histopathological findings. In silico docking studies provided insights into potential molecular mechanisms, revealing interactions between losartan, microRNA-129-1-3p, and the mRNA expression levels of Esr1 and Esr2, which may contribute to the observed molecular changes. These findings collectively underscore the detrimental impact of losartan on ovarian health and highlight the urgent need for further comprehensive research into its effects on female reproductive health.
Spermiogenesis dysfunction is a major cause of male infertility; however, the underlying molecular mechanisms involved remain incompletely elucidated. Although transmembrane protein 67 (TMEM67), a ciliary transition zone protein implicated in ciliopathies, is highly enriched in mouse testes, its cell type-specific functional relevance in spermatogenesis is unclear. Here, we generated germ cell-specific (Stra8-Tmem67f/f) and Sertoli cell-specific (Amh-Tmem67f/f) Tmem67 knockout mice to investigate the function of TMEM67 in spermatogenesis and male fertility. Amh-Tmem67f/f mice maintained normal fertility and exhibited normal spermatogenesis, with no significant differences in testicular histology or sperm count, morphology, or motility compared with wild-type (WT) controls. However, Stra8-Tmem67f/f males were completely infertile, manifesting severe oligoasthenoteratozoospermia (OAT) characterized by a drastic reduction in sperm count, total loss of sperm motility, and global sperm malformation. Further investigations revealed that TMEM67 deletion did not impair spermatogonial proliferation or meiosis, but instead disrupted key spermiogenic events, including manchette dynamics, acrosome biogenesis, and flagellum development. Proteomic analysis indicated that TMEM67 knockout altered the expression of numerous spermiogenesis-related proteins. Furthermore, our experiments confirmed that TMEM67 deficiency led to profound perturbations in both the expression levels and subcellular localization of key spermiogenic regulators in the testis. Collectively, our findings demonstrate that TMEM67 is indispensable for spermiogenesis and male fertility, revealing its critical role in coordinating manchette function, axonemal integrity, and spermiogenesis-related protein regulation, providing novel insights into OAT pathogenesis.
Is there an association of co-occurring hypospadias and congenital heart defects (CHD) with method of conception? There is a small excess risk for co-occurring hypospadias and CHD among boys conceived through in vitro fertilization (IVF) not fully explained by other risk factors. We previously reported a higher prevalence of major CHDs among boys born with hypospadias. Our previous analyses leveraged 3.7 million pregnancies recorded through birth defect registries in 11 US states but could not evaluate the role of IVF in the risks for these pregnancy outcomes. Simultaneously, in registry data linked to fertility parameters, we observed excess risk for hypospadias and CHD with conception by IVF. The rarity of co-occurring birth defects requires large sample sizes with key information on both IVF treatment parameters and maternal characteristics to differentiate their roles in birth defects. We conducted a population-based study of live births in four US states (Massachusetts, New York, North Carolina, and Texas) from 2004 to 2018 and linked to IVF cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). Information on the treatment cycle included the use of autologous or donor oocytes, fresh or frozen embryos, male infertility diagnosis, and the use of ICSI. Non-IVF births were sampled 10:1 at the time of IVF births. For the purposes of evaluating isolated and co-occurring hypospadias and CHD, our study included 731 838 boys born over the study period. State birth defect registries reporting British Pediatric Association codes were used to identify major birth defects. We formed four outcome groups: (i) boys with CHD alone, (ii) boys with hypospadias alone, (iii) boys with both (hypospadias-CHD), and (iv) boys without birth defects (comparison group). We used unadjusted and adjusted logistic regression to associate IVF conception with each outcome group relative to the common comparison group. Adjustments in each outcome model included backward elimination for birth year, plurality, maternal race/ethnicity, age, education, diabetes, hypertension, and parity. We additionally calculated the prevalence of CHD and hypospadias by IVF treatment parameters. Among 731 838 boys, we identified 267 who had both hypospadias and a major CHD, 65 conceived through IVF and 202 controls. We observed strong unadjusted associations of IVF with hypospadias (OR 1.49, 95% CI 1.37-1.62), CHD (OR 1.64, 95% CI 1.49-1.81), and hypospadias-CHD (OR 2.63, 95% CI 1.39-4.69). The associations of IVF with isolated hypospadias and isolated CHD were attenuated, but not fully explained, after adjustment for key covariates (hypospadias adjusted OR 1.15, 95% CI 1.03-1.28; CHD adjusted OR 1.14, 95% CI 1.003-1.29). The adjusted association of IVF with hypospadias-CHD suggests a stronger association than for either defect alone (OR 2.16, 95% CI 1.17-3.99), and calculating the observed-expected multiplicative effect supports an excess risk for hypospadias-CHD co-occurrence among boys conceived through IVF (observed ratio 1.65 > expected ratio 1). Among boys with hypospadias, 4.4% (95% CI 4.0-4.8) of boys conceived without IVF also had a CHD, whereas 6.9% (95% CI 5.8-8.0) of boys conceived using IVF also had a CHD. We found that prevalence of CHD was highest among boys with the most severe form of hypospadias among those conceived with IVF (14.1% with CHD, 95% CI 5.5-22.6) or naturally conceived (10.8% with CHD, 95% CI 6.6-15.0). Calculating number needed to screen (NNS) suggests that incorporating information on hypospadias and method of conception could allow for targeted CHD screening opportunities (NNS range: 8-99). Description of fertility treatment parameters suggests the prevalence of hypospadias or CHD among boys conceived using frozen embryos (autologous or donor oocytes) is 2.8%, and is 2.7% among boys whose fathers were diagnosed with male infertility. For co-occurring hypospadias-CHD, the prevalence was highest among boys conceived using donor oocytes (both fresh or frozen embryos) and among boys whose fathers were diagnosed with male infertility, though the absolute risk remained low (0.09-0.12%). When further evaluating male infertility by the use of ICSI, we found that ICSI use increased the risk for isolated or co-occurring defects regardless of an underlying diagnosis of male infertility. Based on the rarity of co-occurring birth defects (0.08% prevalence of hypospadias-CHD among boys conceived using IVF), we were not able to fully evaluate IVF treatment parameters or subfertility for their role in the co-occurrence of hypospadias and CHD. However, we adjusted for maternal characteristics related to both birth defect risks and fertility. We further sought to characterize treatment parameters that warrant follow-up in future studies of health outcomes among children conceived using IVF. The use of IVF is associated with increased risk for co-occurrence of two of the most common birth defects in boys, hypospadias and CHD, but the absolute risk remains low. Additional investigations of combinations of birth defects, other childhood outcomes in relationship to method of conception, and mechanisms to explain these associations are warranted. This project was supported by grant R01 HD112081 from the National Institute of Child Health and Human Development, USA (Barbara Luke and Philip Lupo, Multiple Principal Investigators). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any State Departments of Health which contributed data. M.L.E. declares stock/shares from their role as advisor to Swim Club, VSeat, Doveras, Legacy, Illumicell, Hannah, and HisTurn. E.W. is employed by Redshift Technologies, Inc., which is the data vendor for SART, and has received consulting fees from SART. The other authors declare no competing interests. N/A.
White adipose tissue is now recognized as an active endocrine organ that secretes numerous bioactive molecules known as adipokines. These proteins regulate essential physiological processes, including energy metabolism, inflammation, and reproduction, while disturbances in their secretion are linked to conditions such as infertility, obesity, and diabetes. Omentin-1, also termed intelectin-1, is a secreted trimeric lectin conserved across mammals. In addition to systemic actions that improve insulin sensitivity, enhance glucose uptake, and suppress oxidative stress and inflammation, omentin-1 exerts important functions within the female reproductive system. It is expressed in the hypothalamus, pituitary gland, ovary, oocyte, and placenta, where it influences cell proliferation, apoptosis, and hormone production. Through these actions, omentin-1 contributes to hormonal homeostasis, follicular development, oocyte maturation, luteal function - integrating energy balance with female fertility. Altered circulating or local levels of omentin-1 have been observed in polycystic ovary syndrome, endometriosis, ovarian and endometrial cancers, preeclampsia, and gestational diabetes. This review aims to summarize current knowledge on omentin-1 expression and function in the female reproductive system within hypothalamus - pituitary - ovary axis and its role in reproductive pathologies.
The variability observed in bull field fertility cannot be fully explained by conventional semen analysis. Work by our group and others has shown that ejaculates are highly heterogeneous and contain distinct sperm subpopulations (SSPs) that differ in motility, functionality, and susceptibility to processes such as cryopreservation, with recent evidence indicating differential interactions within the female reproductive tract (FRT). Therefore, these SSPs have the potential to influence sperm survival and the uterine and oviductal environments, which not only influence fertilization but also early embryo development success. This review discusses key sperm-related processes within the FRT, including molecular changes, penetration into the uterine glands, sperm reservoir formation, and, in particular, the role of the immune response and endometrial priming in fertility. Comparative studies between high- and low-fertility bulls offer valuable models for the investigation of the mechanisms behind fertility variation, providing indications of the relevance of some SSPs. By summarizing the existing knowledge on SSPs, this review aims to provide a framework for understanding sperm behavior within the FRT and highlights the need to better understand sperm heterogeneity and its role in successful pregnancy establishment.
Nutrition has a profound impact on male reproductive well-being through its influence on molecular mechanisms involved in spermatogenesis, sperm function, and endocrine regulation. Elucidation of these nutrition-fertility relationships at the molecular level may inform future research directions, although clinical application remains uncertain. The review critically assesses how nutritional interventions regulate gene expression, protein synthesis, and cellular signaling pathways controlling sperm concentration, motility, morphology, and DNA integrity. This review discusses molecular mechanisms connecting nutritional components to male fertility results. Micronutrients such as vitamins C, D, E, zinc, selenium, and folate have been implicated in oxidative stress regulation through molecular processes, primarily based on preclinical and observational evidence. Zinc has been primarily shown in experimental and observational studies to act as a cofactor in enzymes of testosterone biosynthesis, preserve sperm membrane phospholipid integrity through metallothionein binding, and modulate flagellar dynein ATPase activity; however, randomized controlled evidence remains limited. In mechanistic and animal studies, Omega-3 fatty acids, particularly DHA, are incorporated into sperm membrane phospholipids in mechanistic and animal models, increasing membrane fluidity and influencing mitochondrial respiratory chain efficiency through cardiolipin modification; while human interventional findings remain heterogeneous. Mechanistic data indicate that Vitamin C quenches hydroxyl radicals as an electron donor, whereas coenzyme Q10 facilitates efficient mitochondrial electron transport, together inhibiting oxidative damage to sperm DNA; although clinical benefits are not consistently demonstrated. However, diets high in processed foods and saturated fats have been associated with increased lipid peroxidation and inflammatory signalling, which may adversely influence spermatogenesis, potentially involving epigenetic regulation. A scoping narrative literature review was conducted using PubMed, Scopus, and Web of Science (January 2000-March 2025). Human, animal, and in vitro studies examining nutritional exposures, molecular mechanisms, and semen parameters were included. This review synthesizes molecular evidence linking nutrition to male fertility through defined biochemical and cellular pathways. By critically evaluating supportive, null, and context-dependent findings, it highlights where mechanistic data align with clinical observations and where translation remains limited. This study identifies key gaps in long-term adaptation, nutrient-gene interactions, and dose-response relationships, underscoring the need for well-designed clinical trials incorporating validated molecular biomarkers. The existing literature is predominantly derived from preclinical and observational studies, with limited high-quality randomized controlled trials. Future research integrating nutrigenomics and epigenetic mechanisms will be essential to determine whether targeted nutritional strategies can be reliably applied in male reproductive health before routine clinical implementation can be recommended.
Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare uterine neoplasm characterized by ambiguous histopathological features and unpredictable clinical behavior. Management is particularly challenging in young, nulliparous women, where the standard approach of hysterectomy conflicts with fertility preservation. We report a case of a young nulliparous woman who underwent fertility-preserving robotic myomectomy with bilateral uterine artery ligation for a presumed atypical leiomyoma, later diagnosed as STUMP on histopathology. This case highlights the diagnostic limitations of preoperative assessment, the intraoperative decision-making involved in fertility-sparing surgery, and the role of robotic-assisted techniques in optimizing surgical precision and uterine preservation. In the absence of standardized management guidelines, treatment of STUMP requires individualized decision-making, balancing oncologic risk with reproductive goals. Careful patient selection, multidisciplinary evaluation, and long-term surveillance are essential. This case supports the feasibility and safety of a conservative robotic approach in selected patients.
In the 66 years since the introduction of clomiphene citrate, the 64 years since the first pregnancy using menotrophin stimulation and the 48 years since the birth of the first baby conceived through IVF, the procedures that have been developed to help millions of families to overcome infertility have become increasingly safe and effective. Our ability to provide access to the much larger population of underserved and unserved has, however, lagged far behind. As declining fertility rates bring renewed attention to access to fertility care, the challenge for reproductive medicine is to leverage the progress made in developing safe and effective treatment and make it universally available to those patients in need. This requires a strategy to address both cost of care and treatment capacity constraints, challenges made less daunting due to recent innovation and technology.
Pollution of the environment and infertility are two current worldwide health problems that plague people everywhere. Hexavalent chromium has been linked to reproductive toxicity, as seen by a decrease in sperm motility, count, and testosterone levels, as well as an increase in sperm abnormalities. The current study assessed the fertility effect of chitosan-saponinbentonite nanocomposite (CSB NC) against potassium dichromate-induced reproductive toxicity in male rats. The 49 rats were placed into seven groups of seven rats each. All groups, except for control, were administered K2Cr2O7 at a dosage of 10 mg/kg body weight via subcutaneous injection as a single dose. The treated groups administered saponin, chitosan, bentonite, or CSB NC (30 and 60 mg/kg, orally). Fourier transform infrared, X-ray diffractometer, and transmission electron microscopy were used to confirm the NC of CSB. Follicle stimulating hormone, luteinizing hormone, testosterone, glutathione reduced, and catalase all rose, whereas malondialdehyde and nitric oxide fell in response to CSB NC administration. Sperm count, motility, and semen fructose were all enhanced by the CSB NC, whereas sperm abnormalities were reduced. Histologically, the effects of K2Cr2O7 on testicular shrinkage, degenerative alterations, and disorganized germinal cell layers were reversed after oral administration of CSB NC. Restoration of sex hormonal balance and semen quality after administration of CSB NC may be related to Cr- adsorption properties. The chromium adsorption properties and antioxidant activity of CSB NC mitigate chromium-induced reproductive toxicity in male rats as it increases the sperm motility to about 43%.
Routine semen analysis provides limited diagnostic and prognostic insight into male reproductive potential, contributing to the increasing use of sperm DNA fragmentation (SDF) testing in fertility evaluation. However, the clinical application of SDF testing appears to outpace the strength and consistency of the supporting evidence. This opinion paper critically appraises SDF testing through established screening, diagnostic, and prognostic test-performance frameworks, drawing on published observational studies, meta-analyses, and international guideline statements across natural conception and ART. The available evidence indicates that SDF testing does not meet the criteria for population-level screening or for routine diagnostic or prognostic use in unselected infertile populations and is frequently applied beyond its validated scope. Interpretation is further limited by assay heterogeneity, lack of standardization, variable thresholds, reliance on surrogate outcomes, and the limited effectiveness of available interventions. Routine implementation therefore risks overdiagnosis, unnecessary interventions, and premature escalation to assisted reproduction without proven benefit. When applied selectively within an aetiology-driven framework, particularly in defined subgroups, SDF testing may provide adjunctive risk stratification rather than deterministic clinical guidance. All stakeholders must be made aware of these limitations before the test is offered, interpreted, or used to modify treatment.
Severe asthenoteratozoospermia (ATZ) is a major cause of male infertility and is frequently associated with defects in sperm flagellar architecture. DNAH12 encodes a dynein heavy chain of the inner dynein arm (IDA); however, the spectrum of sperm structural abnormalities associated with DNAH12 mutations in humans remains incompletely characterized. Whole-exome sequencing (WES) was performed in two infertile men with severe ATZ. Sperm from patients and fertile controls were examined by immunofluorescence (IF) staining for DNAH12 and related axonemal proteins, hematoxylin and eosin (H&E) staining for sperm head and tail morphology, and transmission electron microscopy (TEM) for ultrastructural evaluation. The developmental expression pattern of DNAH12 was analyzed using integrated single-cell transcriptomic datasets. Intracytoplasmic sperm injection (ICSI) outcomes were assessed to evaluate reproductive potential. In this study, two novel homozygous loss-of-function (LoF) variants in DNAH12 (c.5442dupT and c.6286C > T) were identified. DNAH12 deficiency in patient sperm was accompanied by loss of DNAH1, DNALI1, RSPH9, and SPAG6 and disruption of the classical "9 + 2" axonemal structure. Although H&E staining and TEM revealed marked abnormalities in both flagellar and head morphology, the acrosomal region and key functional markers of the sperm head remained preserved. Single-cell analyses showed stage-specific DNAH12 expression from secondary spermatocytes to round spermatids, consistent with roles in early flagellar assembly and sperm head morphogenesis. Both patients achieved normal fertilization and embryo development following ICSI. These findings expand the DNAH12-related spectrum of male infertility and support ICSI as an effective reproductive option for affected individuals.
Buffaloes are integral to the agricultural economies of numerous countries, providing essential contributions to milk and meat production, as well as draught power. Fertility in buffaloes is a complex quantitative trait that significantly affects both production and economic efficiency. Therefore, elucidating the genetic architecture underlying reproductive traits in buffaloes is critical for the development of sustainable breeding programs aimed at enhancing reproductive performance. This review provides an overview of the genetic basis of buffalo reproduction, summarizing recent advances in the estimation of genetic parameters for reproductive traits. It also consolidates information on genomic regions and candidate genes associated with reproductive traits, identified through genome-wide association studies (GWAS), selection signature analysis, and transcriptome profiling. Additionally, this review discusses the functional enrichment analysis and molecular networks among these candidate genes.