Political orientation has been shown to correlate with fertility, raising the possibility that demographic processes contribute to long-term ideological change. Using data from the US General Social Survey, we analyze completed fertility across 17 birth cohorts (1898-1982) to examine how political orientation has contributed to fertility decline in the United States and whether emerging selective forces can be detected. Earlier cohorts show little difference in fertility by political orientation. From the 1943-1947 birth cohort onward, however, a pronounced divergence emerges: individuals with right-wing political orientations maintain fertility at or above replacement level, whereas fertility among left-wing individuals declines sharply to well below replacement. Applying Lande-Arnold selection gradient analyses, we find increasing directional selection that may favor right-wing political orientation over time, while education shows consistent negative associations with fertility and religiosity positive but weaker effects. Separate analysis of Black and White Americans reveals, however, that the increasingly stronger association between political orientation and fertility in more recent cohorts holds only true for whites but not for blacks. Nonetheless, these findings suggest that recent fertility decline in the United States is driven disproportionately by left-leaning individuals and point to contemporary demographic processes that may gradually shift the ideological composition of populations.
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.
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.
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.
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.
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.
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.
Testicular disorders, including male infertility and hypogonadism, are increasingly prevalent and current diagnostic tools have important limitations. The testicular microcirculation underpins testicular function. Ultrasound localisation microscopy (ULM) enables super-resolution mapping of microvascular structure and flow at clinically relevant organ depth. Prospective case-control study of ULM-assessed testicular activity in men and rodents using clinical and research ultrasound systems. Study 1 compared healthy men (n = 10) with hypogonadotrophic hypogonadism (HH) (n = 9). Study 2 included men with HH receiving testosterone (n = 11), gonadotrophins (n = 9), or no treatment (n = 12). Study 3 assessed 12-month fertility treatment response in HH (n = 7). A rodent pubertal-blockade model was also studied (n = 5). ULM markers discriminated HH from controls (vessel density p < 0.01; diameter p = 0.01; tortuosity p < 0.01) and correlated with testosterone (r = 0.53-0.67, p < 0.05) and inhibin B (r = -0.61, p < 0.01). Vessel density, diameter, area and flow-related index were reduced in azoospermia (p < 0.01). ULM distinguished HH treatment groups (vessel density p < 0.001; diameter p < 0.05), with density and diameter correlating with testosterone (r = 0.69, 0.62; p < 0.001) and inhibin B (r = 0.64, 0.65; p < 0.001). Vessel density (p < 0.001) and diameter (p < 0.01) were reduced in azoospermia irrespective of treatment. During fertility therapy, ULM parameters increased (p < 0.05) and detected testicular activation earlier than volume or inhibin B. In rodents, pubertal development showed dynamic microvascular remodelling driven by testis growth. ULM provides a treatment-responsive, biologically grounded biomarker of testicular function enabling patient stratification, early detection of therapeutic response, and potential for both refinement of clinical decision-making in HH, and application within other testicular disorders. MRC, NIHR Biomedical Research Centre Funding Scheme and the NIHR/Imperial Clinical Research Facility, Diabetes UK, BBSRC, MRC, Imperial Private Healthcare Clinical Research Fellowship Scheme, NWLP Research Grant.
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.
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%.
As a member of the Groucho/TLE family, Transducin-like enhancer of split 3 (TLE3) functions as a transcriptional co-repressor that is highly expressed in the testis. It recruits histone deacetylases (HDACs) and binds histones to mediate chromatin remodeling, thereby regulating gene expression. To investigate the physiological function of TLE3 in spermatogenesis, we generated germ cell-specific conditional knockout (cKO) mouse models using Stra8-Cre and Vasa-Cre drivers. However, Tle3 cKO male mice exhibited grossly normal development and fertility. Histological examination revealed intact testicular architecture and normal spermatogenic progression in the knockout mice. Moreover, immunofluorescence analyses of key germ cell marker proteins, including DDX4 (pan-germ cell), PLZF (undifferentiated spermatogonia), c-Kit (differentiating spermatogonia), γH2AX (meiosis recombination initiation) and PNA (acrosome in spermatids), showed normal germ cell distribution and differentiation. Furthermore, TUNEL assays for apoptosis detection revealed no significant difference between control and cKO mice. Collectively, our findings demonstrate that TLE3 is dispensable for male germ cell development and spermatogenesis.
Fertility preservation (FP) enables individuals to maintain future reproductive potential, yet population-level data on FP awareness and willingness remain limited in inland China. Previous studies have been largely descriptive without quantifying the population-level impact of modifiable determinants. This study identified independent predictors of FP awareness and willingness among college students and the general population in Henan Province, central China, and estimated the population attributable fraction (PAF) of key modifiable factors. A cross-sectional survey was conducted (May-October 2022) using stratified sampling among college students (n = 765) and general population members (n = 1,008). Two validated knowledge scoring systems (13-point and 11-point scales) were developed. Multivariable logistic regression and PAF analysis were performed. Among college students, FP awareness was 21.1% and willingness 65.3%. Knowledge score was the sole independent predictor of FP awareness (aOR = 2.22, 95%CI: 1.92-2.56; PAF = 62.8%). FP willingness was independently associated with medical major (aOR = 1.62, p = 0.003), contraceptive use (aOR = 2.06, PAF = 48.2%), and gender (aOR for female = 0.68, p = 0.024). In the general population, knowledge score (aOR = 1.86, p < 0.001) and medical background (aOR = 1.83, p = 0.003) predicted FP awareness. FP willingness was independently associated with marital status (aOR = 2.10, PAF = 39.7%) and knowledge score (aOR = 1.16, p < 0.001). Educational attainment was not independently associated with FP willingness after adjustment (aOR = 1.09, p = 0.198). Sensitivity analyses using corrected risk ratios confirmed that OR-based PAFs represent upper-bound estimates for common outcomes. Knowledge is the primary modifiable predictor of FP awareness and willingness with substantial population-level impact. If confirmed in longitudinal studies, knowledge-centered educational strategies prioritizing non-medical populations, unmarried individuals, and rural residents may substantially reduce current awareness and willingness gaps.
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.
暂无摘要（点击查看详情）
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.
An increase in genital abnormalities in boys born via assisted reproductive technologies (ART) is possibly linked to either the technical aspects of ART or parental health, regardless of the type of ART procedure. This study aimed to describe the spectrum and prevalence of genital findings in ART-conceived male infants and to identify potential modifiable factors associated with genital development in this subpopulation. An observational, exploratory/hypothesis-generating case series was conducted from August 2006 to July 2007. A total of 294 consecutively born male neonates were examined by a single urologist blinded to conception method. From this cohort, 71 infants conceived via ART were identified. Obstetrician-gynecologists retrieved detailed data on parental reproductive history and newborn health status. A nested comparative analysis was performed within the ART group, using the adjusted Wald-method and the two-sided Fisher's exact test. Forty boys (56%) in the study group had normal genitalia, whereas 31 (44%) displayed abnormalities. Singleton pregnancy was a significant protective factor for normal genitalia (p = 0.004), while a non-significant trend was observed for the absence of maternal abnormalities other than obstructive infertility (p = 0.282). Hypospadias prevalence (4.2%), in contrast to cryptorchidism and inguinal hernia, exceeded general population rates (0.06%-0.7%) and was an order of magnitude higher than in Denmark and Sweden (0.3%-0.4%). This increased prevalence was associated with male factor infertility (p = 0.041) and with maternal subfertility in the form of preterm labor (p = 0.032). The complex of penile malformations were linked to maternal endocrine infertility (p = 0.033), dizygotic twins (p = 0.014), and preterm labor (p = 0.017), with non-significant trend for threatened miscarriage (p = 0.107). This blinded case series reveals a distinct spectrum of genital findings in ART-conceived neonates, with high hypospadias prevalence. Penile development appears primarily linked to parental fertility issues and preterm labor. Singleton pregnancy is likely a strong protective factor. These findings indicate underlying parental subfertility as the potential determinant of genital malformation risk, with ART procedures as a possible confounder.
This study examined the population-level factors associated with the under-five mortality rate (U5MR) across 34 provinces in Indonesia using an ecological study design. U5MR data were obtained from BPS-Statistics Indonesia. Demographic, healthcare, and fertility-related factors were included as independent variables. An ecological study design was applied, with 34 provinces serving as the units of analysis. Hierarchical Poisson regression was used to assess the associations between the variables. All variables were log-transformed prior to the analysis. The U5MR in 2020 was 19.83 per 1,000 live births. Fertility and demographic factors were significantly associated with changes in U5MR. A 1% increase in the provincial gross domestic product (P=0.042) and the doctor-to-population ratio (P<0.001) was associated with 3% and 6% reductions in U5MR, respectively. Conversely, a 1% increase in the bed-to-population ratio (P<0.001), age-specific fertility rate (P=0.004), and total fertility rate (P<0.001) was associated with increases of 19%, 5%, and 117% in U5MR, respectively. The midwife ratio (P=0.433) and vaccine availability at primary health centers (P=0.851) were not significantly associated with U5MR. Improving the U5MR requires equitable healthcare access, addressing doctor shortages with incentive-based placements, enhancing healthcare facilities, and implementing policies to reduce teenage pregnancies through sex education and contraceptive promotion.
Subsistence agriculture in tropical smallholder farming systems of eastern Africa faces persistent productivity challenges due to low soil fertility, limited inputs, and increasing climate variability. Agroforestry can offer a sustainable strategy for smallholder systems by enhancing soil quality and influencing arbuscular mycorrhizal fungi (AMF) community composition in crop root systems. Using a canopy-based radial sampling design, we assessed the influence of Mangifera indica (mango) trees on soil properties and AMF communities in maize and cassava in southern Ethiopia. Illumina MiSeq sequencing identified 908 AMF operational taxonomic units (OTUs) from 7 families, dominated by Glomeraceae. While soil properties, including pH, total nitrogen (TN), organic carbon, and potassium, were significantly affected by the distance from mango trunks (p < 0.001), this was not the case for AMF community composition and AMF richness and diversity. Host identity, rather than distance from the mango trees, was the primary driver of AMF community composition, with distinct and host-specific assemblages in mango, maize, and cassava roots (p < 0.001). Soil nutrients influenced AMF diversity differently across host plants (p < 0.05). In maize-mango systems, TN positively affected observed richness (Sobs) and Shannon diversity (N1), whereas Olsen P negatively affected N1 and Simpson diversity (N2). In cassava-mango systems, TN increased Sobs, and Olsen P positively influenced expected richness (Sexp). Overall, these findings suggest that improvements in soil fertility associated with mango-based agroforestry systems do not necessarily translate into corresponding changes in crop-associated AMF community composition and diversity. Without demonstrating direct benefits, we at least show that mango can be effectively integrated into smallholder maize and cassava production without compromising the AMF communities, while enhancing key soil fertility indicators. Maintaining adequate nitrogen levels while avoiding excessive phosphorus inputs may help sustain stable AMF communities in agroforestry systems.
Currently, there is an increase in benign ovarian tumors, which negatively affect the fertility potential of women and cause infertility. It is relevant to study the morpho-functional state of the endometrial pattern in women with benign ovarian tumors, leading to a violation of its receptivity and, consequently, to a decrease in reproductive capabilities (the probability of successful implantation of the embryo). Adnexectomy in clinical practice is often necessary due to the lack of intact ovarian tissue. To determine the morpho-functional features of the endometrial pattern in patients of reproductive age with mature teratoma before and after unilateral adnexectomy based on the analysis of the maturity of pinopodia, the level of expression of estrogen and progesterone receptors in the endometrium. The study included 51 patients of reproductive age with benign ovarian germ cell tumor - mature teratoma. Before and 6, 12 months after unilateral adnexectomy, aspiration biopsy of the endometrium was performed during the supposed "implantation window". The qualitative and quantitative parameters of pinopodia maturity were studied, the expression of estrogen (ER) and progesterone (PR) receptors in the uterine glands and endometrial stroma were studied. In patients of late fertile period, both preoperatively and postoperatively, a decrease in the number of developed pinopodia, decreased expression of ER in the stroma, PR in the stroma and glands was found. When analyzing data in patients of middle reproductive age before surgery, no statistically significant changes were noted. After surgical treatment, a transient increase in PR expression in the stromal component was noted, an increase in the number of developed and developing pinopodia was recorded. The presence of a mature teratoma of ovary and late reproductive age explains the morpho-functional changes in the endometrium and receptivity disorders at the preoperative stage. В настоящее время наблюдается рост доброкачественных опухолей яичников (ДОЯ), которые отрицательно влияют на фертильный потенциал женщин и обусловливают инфертильность. Актуальным является исследование морфофункционального состояния эндометриального паттерна у женщин с ДОЯ, приводящими к нарушению его рецептивности и, следовательно, к снижению репродуктивных возможностей (вероятности успешной нидации эмбриона). Проведение в клинической практике аднексэктомии нередко является необходимым из-за отсутствия интактной овариальной ткани. Определить морфофункциональные особенности эндометриального паттерна у пациенток репродуктивного возраста со зрелой тератомой яичников до и после односторонней аднексэктомии на основании анализа зрелости пиноподий, уровня экспрессии эстрогеновых и прогестероновых рецепторов в эндометрии. В исследование включена 51 пациентка репродуктивного возраста с наличием доброкачественной герминогенной опухоли яичников — зрелой тератомы. До и через 6, 12 мес после односторонней аднексэктомии выполняли аспирационную биопсию эндометрия в период предполагаемого окна имплантации. Исследовали качественный и количественный параметры зрелости пиноподий, изучали выраженность экспрессии эстрогеновых (ER) и прогестероновых (PR) рецепторов в маточных железах и строме эндометрия. У наблюдаемых пациенток позднего фертильного периода как на дооперационном, так и в постоперационном этапах установлено снижение не только числа развитых пиноподий, но и экспрессии ER, PR в строме и маточных железах. При анализе данных у пациенток среднего репродуктивного возраста до оперативного вмешательства не отмечено статистически значимых изменений. После хирургического лечения выявлено транзиторное увеличение экспрессии PR в стромальном компоненте, зафиксировано увеличение числа развитых и развивающихся пиноподий. Наличие зрелой тератомы яичников, поздний репродуктивный возраст опосредованно вызывают морфофункциональные изменения эндометрия и нарушения рецептивности на до- и послеоперационном этапах.
Growth Differentiation Factor 9 (GDF9) is a key candidate gene in sheep breeding. Various mutations within GDF9 influence reproductive performance by affecting ovarian function and fertility traits in sheep. As no study has been conducted so far to explore GDF9 mutations in infertile Cholistani Buchi sheep compared with fertile one, so the current study aimed to detect the GDF9 mutations and their possible structural and functional impact using comprehensive molecular and In Silico analyses. Blood samples were collected from 108 Cholistani Buchi sheep, and DNA was extracted. PCR and Sanger Sequencing analysis were performed to detect novel or already reported mutations in Cholistani Buchi sheep. The functional and structural impacts of detected mutations were examined using Dynmut2 and the ProtParam tool. 33 genetic mutations in infertile samples while 15 mutations in fertile samples were identified. Of them, V397I, T451N, G383V, A438V, V428G, I446M, S424R, I405L, C381F, C452R, E407G, T451P, R453S, E432Q, Y442N, D410Y, A388E, and P386T are the destabilizing mutations in infertile samples having negative impact on the encoded proteins. Protein-protein interaction (PPI) and gene ontology (GO) enrichment analysis indicated that the associated partners of GDF9 have diverse biological processes (BP), cellular components (CC), and molecular functions (MF). In conclusion, we have identified 18 novel genetic mutations associated with infertility in Cholistani Buchi sheep. The findings of this study will enhance the understanding of GDF9 mutations and their potential impact on growth and litter size traits in Cholistani Buchi sheep, thus, strengthening the genetic basis for future breeding strategies.