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P/TGMS (Photo/thermo-sensitive genic male sterile) lines are crucial resources for two-line hybrid rice breeding. Previous studies revealed that slow development is a general mechanism for sterility-fertility conversion of P/TGMS in Arabidopsis. However, the difference in P/TGMS genes between rice and Arabidopsis suggests the presence of a distinct P/TGMS mechanism in rice. In this study, we isolated a novel P/TGMS line, ostms19, which shows sterility under high-temperature conditions and fertility under low-temperature conditions. OsTMS19 encodes a novel pentatricopeptide repeat (PPR) protein essential for pollen formation, in which a point mutation GTA(Val) to GCA(Ala) leads to ostms19 P/TGMS phenotype. It is highly expressed in the tapetum and localized to mitochondria. Under high temperature or long-day photoperiod conditions, excessive ROS accumulation in ostms19 anthers during pollen mitosis disrupts gene expression and intine formation, causing male sterility. Conversely, under low temperature or short-day photoperiod conditions, ROS can be effectively scavenged in anthers, resulting in fertility restoration. This indicates that ROS homeostasis is critical for fertility conversion. This relationship between ROS homeostasis and fertility conversion has also been observed in other tested rice P/TGMS lines. Therefore, we propose that ROS homeostasis is a general mechanism for the sterility-fertility conversion of rice P/TGMS lines.

PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women

The ex situ population of the endangered black-footed ferret (Mustela nigripes) has been experiencing declines in reproductive success over the past 30 years of human-managed care. A potential cause may be environmental-dependent inbreeding depression with diet being one of the contributing factors since ferrets are not fed their natural diet of prairie dogs. Here, we generated and analyzed semen proteome and transcriptome data from both wild and ex situ ferrets maintained on various diets. We identified 1757 proteins across all samples, with 149 proteins unique to the semen of wild ferrets and forming a ribosomal predicted protein-protein interaction cluster. Wild ferrets also differed from ex situ ferrets in their transcriptomic profile, showing enrichment in ribosomal RNA processing and potassium ion transport. Successful fertility outcomes documented for ex situ ferrets showed the strongest association with the semen transcriptome, with enrichment in genes involved in translation initiation and focal adhesion. Fertility also synergized with the effect of diet on differentially expressed transcriptomes, mainly affecting genes enriched in mitochondrial function. Our data and functional networks are important for understanding the causes and mechanisms of declining fertility in the ex situ ferret population and can be used as a resource for future conservation efforts.

Purpose of reviewFertility concerns are common among young women diagnosed with breast cancer, as systemic therapy increases the risk of premature ovarian insufficiency and delays family planning. Here, we review the impact of systemic therapies, including chemotherapy, endocrine therapy, HER-2 directed therapy, PARP inhibitors, and immunotherapy, on ovarian reserve.Recent findingsWith an improved understanding of disease biology, fewer women are treated with gonadotoxic chemotherapy. There are limited data on the fertility impact of novel targeted treatments and immunotherapy, though preclinical and preliminary studies suggest an impact on fertility is possible. Notably, a recent study investigated the outcomes in women who interrupted adjuvant endocrine therapy to attempt pregnancy.SummaryFurther research is needed to characterize the fertility impact of novel therapies in breast cancer. Individualized fertility counseling should be offered to all women to discuss the possible impact of therapy on ovarian reserve and options for fertility preservation and timing of pregnancy.

OBJECTIVE: To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality. STUDY DESIGN: Retrospective cohort study of all births (19,350,344) and infant deaths from 2014-2018 in the United States. The exposure was mode of conception-spontaneous vs fertility treatment. The outcome was neonatal (

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Understanding the evolutionary mechanisms underlying the maintenance of individual differences in behavior and physiology is a fundamental goal in ecology and evolution. The pace-of-life syndrome hypothesis is often invoked to explain the maintenance of such within-population variation. This hypothesis predicts that behavioral traits are part of a suite of correlated traits that collectively determine an individual's propensity to prioritize reproduction or survival. A key assumption of this hypothesis is that these traits are underpinned by genetic trade-offs among life-history traits: genetic variants that increase fertility, reproduction and growth might also reduce lifespan. We performed a systematic literature review and meta-analysis to summarize the evidence for the existence of genetic trade-offs between five key life-history traits: survival, growth rate, body size, maturation rate, and fertility. Counter to our predictions, we found an overall positive genetic correlation between survival and other life-history traits and no evidence for any genetic correlations between the non-survival life-history traits. This finding was generally consistent across pairs of life-history traits, sexes, life stages, lab vs. field studies, and narrow- vs. broad-sense correlation estimates. Our study highlights that genetic trade-offs may not be as common, or at least not as easily quantifiable, in animals as often assumed.

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Background: Before pregnancy is recognized, ovulation, fertilization, and implantation must all occur. Physical activity and sedentary behavior may impact pregnancy success by altering each or all of these processes. The aim of this review was to review the association between physical activity and sedentary behavior with spontaneous female and male fertility. Method: PubMed/MEDLINE, Web of Science, CINAHL, SPORTDiscus, and Embase were searched from inception to August 9, 2021. Eligible studies included randomized controlled trials or observational studies, published in English, describing an association between physical activity or sedentary behavior (exposures) and spontaneous fertility (outcome) among women or men. Results: Thirty-four studies from 31 unique populations were included in this review (12 cross-sectional studies, 10 cohort studies, 6 case–control studies, 5 randomized controlled trials, and one case–cohort study). Of the 25 studies among women, the majority identified mixed results (n = 11) or no association (n = 9) between physical activity and female fertility. Seven studies reported on female fertility and sedentary behavior, and 2 found sedentary behavior was associated with decreased female fertility. Of the 11 studies among men, most of the studies (n = 6) found that physical activity was associated with increased male fertility. Two of the studies reported on male fertility and sedentary behavior, and neither identified an association. Conclusions: The association between spontaneous fertility and physical activity in both men and women remains unclear, and the association with sedentary behavior remains largely unexplored. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is defined as onset of menopause characterized by amenorrhea, hypergonadotropism, and hypoestrogenism, before the age of 40 years. The POI is increasing, which seriously affects the quality of patients' life. Due to its diversity of pathogenic factors, complex pathogenesis and limited treatment methods, the search for finding effective treatment of POI has become a hotspot. Stem cells are characterized by the ability of self-renewal and differentiation and play an important role in the regeneration of injured tissues, which is therapy is expected to be used in the treatment of POI. The aim of this review is to summarize the pathogenic mechanisms and the research progress of POI treatment with stem cells from different sources. [ABSTRACT FROM AUTHOR]

Recent research has established existence of a correlation between women's education and fertility, suggesting that they share similar risk factors. However, in many studies, the two variables were analysed separately, which could bias the conclusions by undermining the apparent correlations of such paired outcomes. In this article, the univariate and bivariate Poisson regression models were applied to nationally representative sample of 24,562 women from the 2015-16 Malawi demographic and health survey to examine the risk factors of women's education levels and fertility. The R software version 4.1.2 was used for the analyses. The results showed that estimates from the bivariate Poisson model were consistent with those obtained from the separate univariate Poisson models. The sizes of estimates of coefficients, their standard errors, p-values, and directions were comparable in both bivariate and univariate Poisson models. Using either the univariate or bivariate Poisson model, it was found that the age of a woman at first sexual experience, her current age, household wealth index, and contraceptive usage were significantly associated with both the woman's schooling and fertility. The study further revealed that ethnicity, religion, and region of residence impacted education level only and not fertility. Similarly, marital status and occupation impacted fertility only and not education. The study also found that higher education levels were linked to a lower number of children, with a strong negative correlation of -0.62 between the two variables. The study recommends using bivariate Poisson regression for analysing paired count response data, when there is an apparent covariance between the outcome variables. The results suggest that efforts by policymakers to achieve the desired women's sexual and reproductive health in sub-Saharan Africa should be intertwined with improving women's and girls' education attainment in the region. [ABSTRACT FROM AUTHOR]

Artificial insemination (AI) success in bovine reproduction is vital for the cattle industry's economic sustainability and for advancing the understanding of reproductive physiology. Identify high-fertile animals' fertility is a complex task due to multifactorial traits, including hormonal, age-related, and body condition factors. Early high-fertility identification is crucial for timely interventions and enhancing AI success. In this study, we present the potential use of Fourier-transform infrared (FTIR) spectroscopy on blood serum for early identification of high-fertile Nellore female cows for AI protocols. Blood serum FTIR spectra were obtained from Nellore female cows before AI. FTIR spectra underwent data analysis and the results demonstrated successful discrimination between animals that exhibit pregnant and non-pregnant diagnoses 30 days after AI. FTIR spectra revealed consistent vibrational modes, emphasizing Amide I and II bands. Principal Component Analysis (PCA) effectively segregated groups based on molecular information. Linear SVM with C = 10 and 4 PCs achieved 100% accuracy in the group classification. This innovative approach using FTIR spectroscopy and ML algorithms offers a promising means of high-fertile cow identification, potentially improving AI outcomes in Nellore cattle. The study presents valuable insights into advancements in reproductive management practices for this economically significant breed. [ABSTRACT FROM AUTHOR]

The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis. [ABSTRACT FROM AUTHOR]

In this paper, we combine administrative data for Spain from 2010 to 2018 with meteorological data, to identify the effect of daily mean temperature on fertility. We demonstrate for Spain that hot days (≥25°C) decrease the total fertility rate nine months after exposure. Moreover, we do not observe any substantial heterogeneities in the effect of heat by mother’s age, mother’s educational attainment, sex of the newborn, climatic area, or air conditioning penetration. Our results suggest that climate change may be altering the seasonal distribution of births and affect fertility rates in a context with low fertility and rapid population ageing. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusion This article aims to compare adult sibling ties of stepsiblings to the ties of full and half‐siblings in divorced families, widowed families, and single‐parent families.Siblings are one of the most stable sources of attachment and companionship over the life course and function as important providers of practical and emotional support when going through important life transitions. Due to a steep rise in divorce over the past decades and accompanied increases in remarriage and multipartner fertility, many adults nowadays not only have full siblings, but also half‐siblings and stepsiblings.Using a new module on adult sibling relationships and random‐ and fixed‐effects modeling (OKiN, N = 4506 dyads nested in N = 1742 respondents), we examine the quality of full, half, and stepsibling ties in adulthood and test the main mechanisms driving a potential stepgap in sibling ties: (1) the (absence) of a shared genetic relatedness and (2) the amount of time shared in the same parental household.The weaker bonds adults, on average, have with their stepsiblings compared to their biological (full and half) siblings are largely explained by the shorter period of time they have lived together during childhood. Nevertheless, a substantial gap remains.Our results confirm that a stepgap in sibling closeness, contact, and support is visible, but substantially reduced once shared time is considered. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Human childrearing is cooperative, with women often able to achieve relatively high fertility through help from many individuals. Previous work has documented tremendous socioecological variation in who supports women in childrearing, but less is known about the intracultural correlates of variation in allomaternal support. In the highly religious, high‐fertility setting of The Gambia, we studied whether religious mothers have more children and receive more support with their children.We randomly sampled 395 mothers and 745 focal children enrolled in the Kiang West (The Gambia) Longitudinal Population Study cohort. Structured interviews asked mothers who and how often people invest in their children, and about their religious practices. Data were collected at participants' homes on electronic tablet‐based long‐form surveys and analyzed using the Bayesian hierarchical models.Religiosity was weakly associated with women's higher age‐adjusted fertility. Maternal religiosity was negatively related to maternal investment in focal children, but positively associated with total allomaternal support. Specifically, a woman's religiosity was positively associated with allomaternal support from matrilineal kin, other offspring, and affinal kin, but unrelated to paternal, patrilineal, and non‐kin investment.These results suggest that higher fertility among religious mothers may be supported by high levels of investment from biological and affinal kin. Matrilineal kin, other siblings, and affinal kin seem to be the most responsive to a woman's religiosity. Our findings cast doubt on interpretations of women's religious behaviors as signals of fidelity, and instead suggest they may be part of strategies to enable collective allomaternal resources and higher relative fertility. [ABSTRACT FROM AUTHOR]

Background: Social problems related to infertility are associated with a significant psychological burden for the involved couple. Previous studies have shown the positive effects of couple interactions on the psychological health of these couples; however, the specific conditions of participating in assisted reproductive treatments (ART) might influence the effect of couple collaboration. Therefore, the present study aimed to evaluate the relationship between couple collaboration, well-being during infertility, and the psychological indicators of infertile couples undergoing fertility treatment. Methods: This cross-sectional study was conducted on 200 ART volunteer couples. Couple collaboration and well-being during infertility were evaluated using a validated researcher-made questionnaire, and the level of depression, anxiety, and stress was evaluated using the DASS-21 questionnaire in both couples. Statistical analysis was performed using the plug-in application PROCESS macro for SPSS and AMOS software. Results: The results showed that couple collaboration was correlated with the level of depression, anxiety, and stress. Moreover, depression, anxiety, and stress levels were correlated with well-being during infertility. The direct and indirect effect of couple collaboration on the depression level was significant; however, the direct effect of couple collaboration on the level of anxiety and stress was not significant, and the effect of couple collaboration on these indicators was mediated by well-being during infertility. The fit index of the equation modelling showed a good fit of the relationship path between the variables of couple collaboration, well-being during infertility, and psychological indicators (CMIN = 4.196, p = 0.260). Conclusion: The results of this study show that the specific conditions of participating in ART may affect the direct effects of couple interaction on an infertile couple's levels of anxiety and stress. These results suggest that in order to develop mental health programs for infertile couples, strategies based on couple collaboration that are associated with higher well-being during infertility should be developed and presented. Plain English Summary: Social problems related to infertility are associated with a significant psychological burden for the involved men and women. Previous studies have shown the positive effects of couple interactions on the psychological health of these couples. However, the specific conditions of participating in assisted reproductive treatments (ART) might influence the effect of couple collaboration. Therefore, the present study aimed to evaluate the relationship between couple collaboration, well-being during infertility, and the psychological indicators of infertile couples undergoing fertility treatment. This cross-sectional study was conducted on 200 ART volunteer couples. Couple collaboration, well-being during infertility and the level of depression, anxiety, and stress were evaluated using validated questionnaires. The results showed that the direct and indirect effect of couple collaboration on the depression level was significant; however, the direct effect of couple collaboration on the level of anxiety and stress was not significant, and the effect of couple collaboration on these indicators was mediated by well-being during infertility. The results of this study show that the specific conditions of participating in ART may affect the direct effects of couple interaction on an infertile couple's levels of anxiety and stress. These results suggest that in order to develop mental health programs for infertile couples, strategies based on couple collaboration that are associated with higher well-being during infertility should be developed and presented. [ABSTRACT FROM AUTHOR]

Background: Now affecting one in six couples in Canada, infertility is defined as a lack of conception after 12 or more months of regular, unprotected heterosexual intercourse. Infertility is associated with immense psychological burden, particularly for individuals assigned female at birth. Yet existing psychological interventions are not specialized to this population and have been shown to be only marginally effective at relieving distress related to infertility. Thus, a new online self-directed psychological intervention was co-created with a panel of women experiencing infertility, and ultimately consisted of six 10-min video modules addressing the cognitive, emotional, and interpersonal aspects of infertility-related distress. Methods: In the current study, 21 women experiencing reduced quality of life related to infertility were recruited to participate in a one-arm pre-post pilot testing the feasibility, acceptability, and preliminary efficacy of the program. Participant adherence and retention were monitored, and participants rated the credibility of the program and the helpfulness of each module as well as provided feedback on the content and format of the program. Pre-to-post changes in fertility quality of life, anxious symptoms, depressive symptoms, and relationship satisfaction were examined. Results: The program modules were highly rated by participants, with average helpfulness ratings ranging from 7.5 to 8.2/10. Two participants became pregnant and therefore stopped prematurely, 79% of the remaining participants completed all six modules, and participants reported completing 52.8 (SD = 82.0) min of homework per week. Participants perceived the intervention as highly credible and generally approved of the format, length, and speed; however, 68% of participants had recommendations for additional content to be included in the intervention. While relationship satisfaction did not change significantly over time, large pre-to-post improvements in fertility quality of life, depression, and anxiety were observed (p <.001; Cohen's ds = 0.9–1.3). Conclusions: This self-directed intervention was well received and has the potential to be highly effective in reducing infertility-related distress, informing future development and optimization. Trial registration: ClinicalTrials.gov, NCT05103982. [ABSTRACT FROM AUTHOR]

Cryopreservation of metaphase II (MII) oocytes is crucial to preserve female fertility. However, the existing vitrification technology just provides partial cryogenic protection for oocytes and must use high concentrations of toxic penetrating cryoprotective agents (CPAs, up to 4.8 M). Here, a multi‐scale ice inhibition platform is proposed, which effectively suppresses ice crystal morphology, ice recrystallization (IR), temperature gradient, and devitrification. This platform achieves mouse oocyte survival rate of 98.6% using the low concentration of CPA (3.1 M) while also possessing batch oocyte cryopreservation ability. In contrast, recovered oocytes show a much more modest variation of genes compared with the conventional method (85 vs. 1396 genes), retaining normal fertilization, embryonic development, and birth to healthy offspring. Diverging from the conventional vitrification method with partial cryogenic protection capability, this platform introduces full‐cycle ice inhibition, offering promising prospects for achieving high‐quality and scalable fertility preservation. [ABSTRACT FROM AUTHOR]

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusion This work investigates the potential associations between maternal major depressive disorder (MDD) and daughters' family formation behaviors, specifically the timing of marriage and first birth.Family and life course research has established the importance of intergenerational ties and linked lives for children's health, education, social life, and transition to adulthood more broadly. However, mothers' MDD has remained a relatively understudied factor shaping young people's family formation behaviors.The analyses used a sample of 1127 linked mother–father–daughter triads from the Chitwan Valley Family Study (CVFS) in Nepal. Discrete‐time event‐history models at the month level were run to assess whether daughters' differential exposure to maternal MDD was prospectively associated with entry into marital unions and parenthood.Although there was no relationship between maternal lifetime MDD and daughters' family formation, results showed that being first exposed to maternal MDD during childhood, specifically between the ages of 0 and 10, increased the monthly odds of transitioning to parenthood by more than 80%. Additional findings showed that an increased pace of getting married was a primary determinant of accelerated childbearing.Daughters' exposure to mothers' depression was associated with daughters' family formation transitions. The timing of exposure, however, was a particularly important driver of that association. We argue that the study of parents' mental ill‐health provides untapped opportunity for future intergenerational research. [ABSTRACT FROM AUTHOR]

Technological change and globalization have caused unprecedented transformations of labour markets, resulting in a growing division between workers who perform cognitive vs non-cognitive tasks. To date, only few studies have addressed the fertility effects of these long-term structural changes. This study fills that gap. We measure the cognitive task content of occupations using data from the Employment Survey of the German Federal Institute for Vocational Education and Training, which we link to individual histories from the German Socio-Economic Panel 1984–2018. We find that women and men with non-cognitive jobs are increasingly less likely to enter parenthood; this is reflected in lower first-birth intensities but also in higher probabilities of childlessness compared with workers in highly cognitive jobs. These findings imply that structural shifts in the labour market are exacerbating disparities between low-skilled and highly skilled individuals, not only within the labour market but also in the realm of family formation. [ABSTRACT FROM AUTHOR]

Introduction: Nirogacestat is a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors. In the phase 3 DeFi study (NCT03785964) of nirogacestat, ovarian toxicity (OT) was identified as a safety signal among females of reproductive potential (FORP). This analysis further describes the incidence, presentation, and resolution of OT. Methods: Patients were randomized to twice‐daily oral nirogacestat (150 mg) or placebo, taken in continuous 28‐day cycles. Investigator‐identified OT in FORP was based on abnormal reproductive hormone values or perimenopausal symptoms (or both). Adverse event follow‐up was conducted to assess OT resolution. Post hoc analyses included return of menstruation and return of follicle‐stimulating hormone (FSH) to within normal limits (WNL) (≤20.4 mIU/mL). Results: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of 36) receiving nirogacestat and 0% (0 of 37) receiving placebo. As of October 24, 2022, investigators reported OT resolution in 78% (21 of 27) of patients, with median OT duration of 19.1 weeks. Off‐treatment resolution was reported in all 11 patients (100%) who stopped nirogacestat treatment; of these, all nine with available menstruation information experienced return of menstruation and eight had FSH WNL at last reported assessment. Resolution was reported in 10 of 14 (71%) while on nirogacestat; of these, all 10 experienced return of menstruation and seven had FSH WNL. Two patients were lost to follow‐up. Conclusion: Most FORP treated with nirogacestat experienced OT, with the majority resolving, including all who stopped treatment, suggesting that OT is transient. In the phase 3 DeFi study of nirogacestat, a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors, ovarian toxicity was identified as a safety signal in most females of reproductive potential. The majority (78%) of ovarian toxicity events resolved, including in 100% of patients who stopped nirogacestat for any reason, suggesting that ovarian toxicity with nirogacestat is transient. [ABSTRACT FROM AUTHOR]

This study aimed to investigate if washing ram sperm from seminal plasma (SP) could be an effective tool to extend sperm lifespan in medium-term preservation in liquid form to optimize ovine artificial insemination protocols. To this end, in Experiment 1 SP was added to a sperm model without previous contact with this substance (ram epididymal sperm) at the beginning or the end of a 48-hour preservation protocol at 5 °C (n = 13). Sperm motility and kinetic parameters and sperm functionality in terms of sperm viability, apoptosis, mitochondrial activity and reacted acrosomes were assessed after 6 h of storage at 15 °C (standard liquid preservation method) and 24 and 48 h at 5 °C. Extended sperm showed better results after 48 h when stored in the absence than in the presence of SP in most sperm quality parameters. Moreover, the final SP supplementation of this experimental group resulted in the highest sperm motility and kinetic parameters, viability and mitochondrial activity. These results suggested that initial SP deprivation could be beneficial in a medium-term ram sperm preservation protocol in liquid form, as well as a final supplementation. Therefore, we conducted Experiment 2 to evaluate the effect of SP removal from freshly ejaculated ram semen under the same storage conditions as in Experiment 1 (n = 12). Surprisingly, SP withdrawal impaired sperm functionality, leading to increased apoptosis and decreased mitochondrial activity after 24 and 48 h at 5 °C. Conversely, SP supplementation at the end of the preservation protocol of the ejaculate processed as usual had a positive effect on sperm quality and fertility. To summarize, SP absence was beneficial for a medium-term preservation protocol (up to 48 h at 5 °C) of ram epididymal sperm, but the same preservation protocol for ram ejaculated sperm revealed a possible failure of the SP removal method in avoiding the sperm-SP interaction effect. Meanwhile, SP supplementation of ram semen at the end of the preservation protocol increased in vitro sperm quality and fertility after artificial insemination. [ABSTRACT FROM AUTHOR]

Background Study design Objective Materials and methods Results Discussion and conclusion Microsurgical vasoepididymostomy is an effective surgical method for treating epididymal obstructive azoospermia but the surgical outcomes can be affected in some non‐vasectomized epididymal obstructive azoospermia patients with concurrent vas‐deferens obstruction. This study aimed to explore the clinical characteristics and surgical outcomes in non‐vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas‐deferens obstruction.Retrospective study.To explore the clinical characteristics and surgical outcomes in non‐vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas‐deferens obstruction, aiming to identify predictive factors for concurrent vas‐deferens obstruction and evaluate the efficacy of microsurgical vasoepididymostomy in patients with epididymal obstructive azoospermia and concurrent short‐segment vas‐deferens obstruction.A retrospective analysis of 225 epididymal obstructive azoospermia cases was conducted at the First Affiliated Hospital of Fujian Medical University from November 2016 to March 2023. All patients underwent a comprehensive preoperative evaluation. During surgery, the vas deferens were assessed to determine the presence and extent of obstruction. Depending on the obstruction length, either a standard microsurgical vasoepididymostomy was performed, or the obstructed segment was resected followed by microsurgical vasoepididymostomy. If the remaining length post‐resection was insufficient for anastomosis, the procedure was discontinued. Data on patient clinical characteristics, operative findings, and outcomes were collected and analyzed. Logistic regression was used to identify predictive factors for concurrent vas‐deferens obstruction, and comparative analysis assessed patency and pregnancy rates between patients with and without concurrent vas‐deferens obstruction.Of the 225 patients in the study, 77 (34.22%) presented with epididymal obstructive azoospermia and concurrent vas‐deferens obstruction. Logistic regression analysis revealed that “the history of epididymitis” was a significant predictive factor for epididymal obstructive azoospermia patients with concurrent vas‐deferens obstruction (odds ratio = 9.06, p < 0.001). The average length of vas deferens obstruction amenable to microsurgical vasoepididymostomy post‐resection was 1.31 ± 0.54 cm (range from 0.50 to 2.50 cm). In contrast, cases unsuitable for microsurgical vasoepididymostomy presented an average obstruction length of 15.26 ± 5.79 cm (p < 0.001). The patency rates were 82.17% in epididymal obstructive azoospermia patients without concurrent vas‐deferens obstruction and 74.14% in those with concurrent vas‐deferens obstruction. The pregnancy rates followed a similar trend, at 34.11% and 34.48%, respectively. These differences were not statistically significant (p > 0.05 for both). However, epididymal obstructive azoospermia patients with vas‐deferens obstruction exhibited a decreased likelihood of bilateral microsurgical vasoepididymostomy (p < 0.001).Our study identifies a noticeable occurrence of concurrent vas‐deferens obstruction in non‐vasectomized epididymal obstructive azoospermia patients, with approximately one‐third of the cases (34.22%) exhibiting vas‐deferens obstruction during surgical interventions. Notably, a small fraction (6.67%) of these individuals chose not to proceed with any microsurgical vasoepididymostomy, even on one side, due to the extensive length of the obstruction. Through logistic analysis, we have demonstrated that “the history of epididymitis” is a critical predictive factor for the presence of vas‐deferens obstruction, underscoring its significance in preoperative evaluations. Furthermore, our research confirms that microsurgical vasoepididymostomy is still an effective treatment for epididymal obstructive azoospermia patients with concurrent short‐segment vas‐deferens obstruction, achieving significant patency and favorable pregnancy rates compared to those patients without vas‐deferens obstruction. These insights are pivotal for enhancing surgical strategies and improving fertility outcomes in this patient cohort. [ABSTRACT FROM AUTHOR]

Ultrasonography is widely used to monitor pregnancy in viviparous species, but it is underutilized as a tool to characterize embryonic development in oviparous species. Currently, a multi-institutional effort is underway to rewild the endangered zebra shark (Stegostoma tigrinum) to locations where this species was previously extirpated by leveraging the reproductive efforts of aquarium sharks as a source of brood stock. Zebra sharks are oviparous and fecund, but a large percentage of their yolked eggs do not result in hatchlings. Therefore, ultrasonography represents a potential tool for distinguishing fertile eggs with developing embryos from degrading eggs, and to diagnose changes in early embryonic development predictive of poor outcomes. The objectives of the current study were to use ultrasonography to assess egg fertility, monitor early embryonic development, and identify morphological indicators that may be predictive of early embryonic mortality. Freshly laid eggs from four female zebra sharks were collected and inventoried daily at Aquarium of the Pacific. Eggs were incubated undisturbed for 2 to 4 weeks and subsequently examined weekly via ultrasound to assess fertility and monitor embryo development. Among 120 fertile eggs, embryos were identified as early as 8 days post-oviposition, with average (±SD) time to first observation at 30 ± 7 days. Morphological and behavioral abnormalities were observed for most embryos (n = 84, 70%) as early as 16 days and up to 95 days post-oviposition. Common abnormalities included: bent or curled tails, vesicle(s) at the base of the yolk stalk, and slow or weak movement. Only one embryo survived to hatch during the study and was genetically-confirmed parthenogenetic, suggesting hatching success for parthenotes is low (<1%). Ultrasonography was demonstrated to be an effective and non-invasive method to determine egg fertility, identify embryos with developmental abnormalities, and monitor embryo growth. [ABSTRACT FROM AUTHOR]

Context: Oxidative stress (OS) plays a harmful role in female reproduction and fertility. Several studies explored various dietary interventions and antioxidant supplements, such as astaxanthin (AST), to mitigate the adverse effects of OS on female fertility. Ameliorative effects of AST on female fertility and the redox status of reproductive organs have been shown in several animal and clinical studies. Objectives: The main objective of present systematic review and meta-analysis of both animal and clinical studies was to provide a comprehensive overview of the current evidence on the effects of AST on female fertility and reproductive outcomes. The effect of AST on redox status, inflammatory and apoptotic markers in reproductive organs were included as the secondary outcomes. Data sources: We systematically searched electronic databases including PubMed, Scopus, and Web of Science, until January 1, 2024, using specified search terms related to AST, female reproductive performance, and infertility, considering the diverse synonyms found in the literature for interventional studies that compared oral AST supplementation with placebo or control in human or animal models. Data extraction: Two independent reviewers extracted data on study characteristics, outcomes, and risk of bias. We pooled the results using random-effects models and assessed the heterogeneity and quality of evidence. We descriptively reported the data from animal models, as meta-analysis was not possible. Data analysis: The meta-analysis of clinical trials showed that AST significantly increased the oocyte maturation rate (MD: 8.40, 95% CI: 4.57 to 12.23, I2: 0%) and the total antioxidant capacity levels in the follicular fluid (MD: 0.04, 95% CI: 0.02 to 0.06, I2: 0%). The other ART and pregnancy outcomes and redox status markers did not show statistically significant changes. The animal studies reported ameliorative effects of AST on redox status, inflammation, apoptosis, and ovarian tissue histomorphology. Conclusion: This systematic review shows that AST supplementation may improve assisted reproductive technology outcomes by enhancing oocyte quality and reducing OS in the reproductive organs. However, the evidence is limited by the heterogeneity, risk of bias, and small sample size of the included studies. [ABSTRACT FROM AUTHOR]

Background: Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented. Specifically, shed endometrial tissues (delivered to the pelvic cavity via retrograde menstruation) reveal that a subset of stromal cells exhibiting pro-inflammatory, pro-fibrotic, and pro-senescence-like phenotypes is enhanced in endometriosis patients compared to controls. Additionally, cultured biopsy-derived endometrial stromal cells from endometriosis patients exhibit impaired decidualization, a defined differentiation process required for human embryo implantation and pregnancy. Quercetin, a senolytic agent, shows therapeutic potential for pulmonary fibrosis, a disorder attributed to senescent pulmonary fibroblasts. In rodent models of endometriosis, quercetin shows promise, and quercetin improves decidualization in vitro. However, the exact mechanisms are not completely understood. Therefore, we investigated the effects of quercetin on menstrual effluent-derived endometrial stromal cells from endometriosis patients and unaffected controls to define the signaling pathways underlying quercetin's effects on endometrial stromal cells. Methods: Menstrual effluent-derived endometrial stromal cells were collected and cultured from unaffected controls and endometriosis patients and then, low passage cells were treated with quercetin (25 µM) under basal or standard decidualization conditions. Decidualization responses were analyzed by measuring the production of IGFBP1 and PRL. Also, the effects of quercetin on intracellular cAMP levels and cellular oxidative stress responses were measured. Phosphokinase arrays, western blotting, and flow cytometry methods were performed to define the effects of quercetin on various signaling pathways and the potential mechanistic roles of quercetin. Results: Quercetin significantly promotes decidualization of control- and endometriosis-endometrial stromal cells. Quercetin substantially reduces the phosphorylation of multiple signaling molecules in the AKT and ERK1/2 pathways, while enhancing the phosphorylation of p53 and total p53 levels. Furthermore, p53 inhibition blocks decidualization while p53 activation promotes decidualization. Finally, we provide evidence that quercetin increases apoptosis of endometrial stromal cells with a senescent-like phenotype. Conclusions: These data provide insight into the mechanisms of action of quercetin on endometrial stromal cells and warrant future clinical trials to test quercetin and other senolytics for treating endometriosis. [ABSTRACT FROM AUTHOR]

Background Material and methods Results and discussion Conclusions The escalating prevalence of fertility problems in the aging population necessitates a comprehensive exploration of contributing factors, extending beyond environmental concerns, work‐related stress, and unhealthy lifestyles. Among these, the rising incidence of testicular disorders emerges as a pivotal determinant of fertility issues. Current treatment challenges are underscored by the limitations of high‐dose and frequent drug administration, coupled with substantial side effects and irreversible trauma inflicted by surgical interventions on testicular tissue.The formidable barrier posed by the blood–testis barrier compounds the complexities of treating testicular diseases, presenting a significant therapeutic obstacle. The advent of nanocarriers, with their distinctive attributes, holds promise in overcoming this impediment. These nanocarriers exhibit exceptional biocompatibility, and membrane penetration capabilities, and can strategically target the blood–testis barrier through surface ligand modification, thereby augmenting drug bioavailability and enhancing therapeutic efficacy.This review concentrates on the transformative potential of nanocarriers in the delivery of therapeutic agents to testicular tissue. By summarizing key applications, we illuminate the strides made in utilizing nanocarriers as a novel avenue to effectively treat testicular diseases.Nanocarriers are critical in delivering therapeutic agents to testicular tissue. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility‐promoting tools.To investigate the association between fertility indicators and fecundability in Danish women trying to conceive.Web‐based preconception cohort study. We analysed data from 11,328 females aged 18–49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007–2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self‐reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CIs) using proportional probabilities regression models adjusted for age, socio‐economic position, health indicators, reproductive history and gynaecological factors.Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non‐use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow‐up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31).In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator. [ABSTRACT FROM AUTHOR]

Across the globe, many species of insects are facing population decline. This is largely driven by anthropogenic changes to the environment, including the widespread exposure of invertebrates to endocrine disrupting chemicals (EDCs), which impair fertility. To test whether generations of Drosophila melanogaster born from parents exposed to a common dietary EDC, equol, could recover reproductive function, we quantified the reproductive capacity of the two subsequent generations. Using a novel suite of flow cytometry assays to assess sperm functionality in real time, we find that sperm function is compromised across three generations, even after non-exposed in individuals contribute to the breeding population. Though the sex ratio alters in response to EDC exposure, favouring the survival of female offspring, most lineages with ancestral EDC exposure exhibit persistent subfertility in both the male and female. Male offspring with ancestral EDC exposure present with reduced fertility and dysfunctional spermatozoa, whereby spermatozoa are metabolically stressed, lack DNA integrity and present with permanent epigenetic alterations. Across generations, male and female offspring demonstrate distinct patterns of reproductive characteristics, depending upon the specific lineage of EDC exposure. Our results illustrate how dietary EDCs present in agricultural plants could promote transgenerational subfertility and contribute to declining insect populations. [ABSTRACT FROM AUTHOR]

The Booroola fecunditymutation (FecB) in Small Tail Han sheep has been shown to enhance ovulation rates and litter sizes by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Despite the pituitary's role in reproductive regulation, its involvement in FecB-induced ovulation remains understudied. Our study aimed to fill this gap by analyzing pituitary tissues from FecB homozygous (BB) and wildtype (WW) ewes during luteal and follicular phases using tandem mass tag-based protein quantification and the DIABLO framework for proteomic and transcriptomic data integration. Significant differences in 277 proteins were observed across estrus periods, with network analysis highlighting the voltagedependent calcium channel L-type alpha-1C as a key convergence point in oxytocin signaling and GnRH secretion pathways. The DIABLO method revealed a strong correlation (0.98) between proteomic and transcriptomic datasets, indicating a coordinated response in FecB ewes. Notably, higher expression levels of Follicle Stimulating Hormone Subunit Beta (FSHB) and Luteinizing Hormone Subunit Beta (LHB) were found in BB ewes during the follicular phase, potentially due to elevated E2 concentrations. Furthermore, our analysis identified genes related to the Gamma-aminobutyric acid type A receptor family (GABRA2, GABRG1, GABRB1) in the pituitary, with GABRB1 showing higher expression in BB ewes. This suggests a role for GABA in modulating GnRH and gonadotropin feedback loops, potentially contributing to the FecB mutation's effect on ovulation. This study provides novel insights into the pituitary's role in fertility among FecB sheep, identifying GABA as a potential regulatory factor within the HPG axis. The findings also open avenues for discovering new biomarkers in pituitary endocrinology for sheep breeding purposes. [ABSTRACT FROM AUTHOR]

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy. Tamoxifen as adjunct therapy in premenopausal women leads to ovarian stimulation, sometimes ovulation and occasionally pregnancy with important teratogenic implications. Aromatase inhibitor therapy with or without gonadotrophin releasing hormone (GnRH) agonist leads to profound bone loss and anti-resorptive therapy is advised to prevent fracture. Tamoxifen acts to preserve bone in postmenopausal women but not premenopausal women. Pregnancy is not discouraged in young women with early breast cancer, even to the point of pausing adjunct therapy in order to conceive. However, menopausal hormone therapy is discouraged even years later. Non-hormonal therapy for menopausal symptoms in breast cancer survivors is available but, in some cases, estrogen-containing therapy may be worthy of consideration for quality of life in the informed patient. [ABSTRACT FROM AUTHOR]

Significance: Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity and optimal cell functioning. However, when challenged by endogenous or exogenous stressors, these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival, and overall organism health. Most notably, there are numerous somatic pathologies associated with a loss of proteostatic regulation, including neurodegenerative disorders, type 2 diabetes, and some cancers. Recent Advances: Lipid oxidation-derived reactive carbonyl species (RCS), such as 4-hydroxynonenal (4HNE) and malondialdehyde, are relatively underappreciated purveyors of proteostatic dysregulation, which elicit their effects via the nonenzymatic post-translational modification of proteins. Emerging evidence suggests that a subset of germline proteins can serve as substrates for 4HNE modification. Among these, prevalent targets include succinate dehydrogenase, heat shock protein A2 and A-kinase anchor protein 4, all of which are intrinsically associated with fertility. Critical Issues: Despite growing knowledge in this field, the RCS adductomes of spermatozoa and oocytes are yet to be comprehensively investigated. Furthermore, the manner by which RCS-mediated adduction impacts protein fate and drives cellular responses, such as protein aggregation, requires further examination in the germline. Given that RCS-protein adduction has been attributed a role in infertility, there has been sparked research investment into strategies to prevent lipid peroxidation in germ cells. Future Directions: An increased depth of knowledge regarding the mechanisms and substrates of RCS-mediated protein modification in reproductive cells may reveal important targets for the development of novel therapies to improve fertility and pregnancy outcomes for future generations. [ABSTRACT FROM AUTHOR]

The elevated frequency of Cesarean sections (C-sections) in OECD countries not only burdens health systems financially but also heightens the risks for mothers and infants. This study explores the feasibility of reducing C-section rates by examining the Israeli ultra-Orthodox population, noted for its large families and low C-section rates. We analyze birth data from an Israeli hospital, focusing on ultra-Orthodox mothers with husbands who are yeshiva students compared to other mothers. Our findings reveal that all else being equal, mothers married to yeshiva students exhibit a lower likelihood of undergoing a C-section and a higher propensity to seek private medical services to avoid this procedure. This behavior is attributed to their preference for large families and the desire to minimize C-sections, which may restrict the number of possible future pregnancies. These insights underscore the potential effectiveness of initiatives encouraging mothers to opt for vaginal deliveries, thereby reducing healthcare costs and maternal-infant risks. [ABSTRACT FROM AUTHOR]

Simple Summary: This study identified the protein expression profiles of horse and donkey sperm and investigated the effect of sperm proteins on sperm viability. In short, we first assessed the viability of horse and donkey sperm, revealing higher viability in donkey sperm compared to horse sperm. Subsequently, 4D-DIA protein-sequencing technology was employed to identify 3436 proteins expressed in horse sperm and 3404 proteins expressed in donkey sperm, with 73 proteins specific to horse sperm, and 41 specific to donkey sperm. Further analysis established a correlation between sperm proteins and sperm viability. These findings are significant in elucidating the reproductive variances and evolutionary relationships between horses and donkeys. The reproductive performance of horse sperm and donkey sperm has been reported to differ. Sperm proteins play a crucial role in sperm viability and fertility. Although differences between species are known, no prior study has investigated disparities in the sperm proteome between horses and donkeys. Therefore, this study characterized and compared the sperm proteomes of horses and donkeys using 4D-DIA mass spectrometry technology. We identified 3436 proteins in horse sperm and 3404 proteins in donkey sperm. Of these, 3363 proteins were expressed in both horse and donkey sperm, with 73 proteins being specifically expressed in horse sperm, and 41 in donkey sperm. According to data analysis, donkeys exhibited a greater percentage of motility and progressive movement in straight-line sperm than horses, as well as lower percentages of static and slow sperm than horses. Joint analysis of the results from the horse and donkey sperm proteomes and their CEROS II-read parameters demonstrated a possible association between sperm proteins and their sperm viability patterns. These findings suggest that there are discrepancies in the expression levels and protein compositions of horse and donkey sperm and that certain specific proteins may be responsible for the differences in performance between these two species. [ABSTRACT FROM AUTHOR]

Simple Summary: The fertility program Presynch-11-Ovsynch (Presynch-11) improved pregnancies/AI (P/AI) compared with AI following observed standing estrus + timed AI (Estrus + TAI) in first, second, and third+ parities. First parity cows that received AI following an observed standing estrus had greater P/AI compared with second and third+ parity cows. Multiparous cows treated with Presynch-11-Ovsynch had a >60% greater chance of pregnancy compared with cows receiving AI following estrus. Artificial insemination 12 h following observed standing estrus is a standard estimate of the fertility levels of cattle. The main objective of this study was to determine if controlling ovarian development with a fertility program could alter the fertility of lactating dairy cows. Lactating dairy cows (n = 1356) 60–66 days in milk (DIM) were randomly assigned to receive timed AI following Presynch-11/Ovsynch (Presynch-11) or a combination of estrus detection and timed AI using the Presynch-11/Ovsynch program (Estrus + TAI). Cows in standing estrus, following the first two cloprostenol sodium (CLO) injections, in the Estrus + TAI group were artificially inseminated using the AM/PM rule. Cows in this group that were not observed in standing estrus received Ovsynch and TAI beginning 11 d after the second CLO injection. Cows in the Presynch-11 group received two injections of 500 µg CLO 14 d apart but were not observed for estrus. The first GnRH (100 µg) of Ovsynch was administered 11 d following the second CLO injection. All cows in the Presynch-11-Ovsynch group received TAI following Ovsynch. Cows in this treatment were then assigned randomly to receive either CLO or dinoprost 7 d following the first GnRH of Ovsynch. The final GnRH of Ovsynch was administered 56 h later and TAI 16 h after the final GnRH. Pregnancies/AI (P/AI) were greater (p < 0.001) for the Presynch-11 group compared with the Estrus + TAI group (45 vs. 31%). Primiparous cows had greater fertility following observed standing estrus compared with multiparous cows. Days in milk at the first AI were greater (p < 0.01) in the Presynch-11 group vs. the Estrus + TAI group (98 vs. 80) but less variable (p < 0.01). The range of DIM at the first AI was 95 to 101 in the Presynch-11 group and 60 to 101 in the Estrus + TAI group. Within the Presynch-11 group, there were no differences in the rate of luteolysis or P/AI for the prostaglandin type at the final PGF2α of Ovsynch. Multiparous cows treated with Presynch-11 had >60% chance of pregnancy compared with multiparous cows receiving AI following standing estrus. In summary, lactating dairy cows receiving timed AI following the Presynch-11/Ovsynch program had improved fertility compared with a group of cows that received AI following standing estrus or, if not observed in estrus, timed AI. This comparison indicated that controlling ovarian development with GnRH and PGF2α positively impacted the fertility of lactating dairy cows. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently: more attention has been given to low-birth-weight calves, often without considering gestation length. Similar to human medicine, calves classified as small for gestational age (SGA) weigh below the 10th percentile at birth. The present study aimed to investigate the long-term effects on fertility, productive performance, and overall survival in Holstein Friesian (HF) heifers born SGA. We found that while SGA calves showed initial catch-up growth at six months of age, they were still significantly lighter at twelve months. SGA heifers required significantly more inseminations to conceive compared to their average (AGA) and large (LGA) counterparts. Additionally, more SGA heifers were culled during their first lactation and had lower survival rates to the second calving. SGA heifers also had a higher risk of leaving the herd prematurely. Although overall lifespan and total milk yield were similar among all groups, SGA heifers produced less milk per productive day. This study reveals that HF calves born SGA face significant long-term health and productivity challenges, emphasizing the need for further research on the economic impact of rearing SGA heifers. Recently: more attention has been given to low-birth-weight calves, often without considering gestation length. Calves can be classified as small for gestational age (SGA) when their birth weight is below the 10th percentile, similar to the definition in human medicine. While SGA babies face various health risks, it remains unclear if SGA calves face similar long-term health consequences. This study aimed to investigate the long-term effects on fertility, productive performance, and overall survival in Holstein Friesian (HF) heifers born SGA. Chi-squared analysis assessed culling and survival rates, and linear mixed-effect models evaluated the impact of gestational age group (small, average, or large for gestational age, respectively, SGA, AGA, and LGA) on growth, fertility, milk yield, and lifespan. SGA calves showed catch-up growth at six months but weighed significantly less at twelve months (p = 0.003). Age at first insemination and calving did not differ significantly, although SGA heifers required more inseminations (2.3 ± 1.50) compared to AGA and LGA heifers (1.7 ± 0.98 and 1.5 ± 0.89, respectively, p = 0.006). SGA calves tended to be culled more during the first lactation than AGA calves (25.0% vs. 11.9%, p = 0.078) and showed lower survival to second calving (p = 0.019) compared to AGA and LGA heifers. The Kaplan–Meier analysis indicated a tendency for gestational age to affect overall survival (p = 0.1), with SGA heifers having a higher risk of leaving the herd prematurely (p = 0.035, hazard ratio = 1.53). Milk yield per productive day was significantly lower in SGA heifers (21.2 ± 8.73 kg) compared to AGA and LGA heifers (26.9 ± 5.01 kg and 26.3 ± 3.38 kg, respectively, p = 0.006). This study reveals that HF calves born SGA suffer long-term consequences, although further research is needed to understand the economic impact of rearing SGA heifers. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to assess the fertility knowledge and educational experiences of graduating U.S. medical students to evaluate areas of improvement for future educational interventions. Design: Web-based cross-sectional survey. Subjects: Medical students graduating in 2023 from the University of Miami Miller School of Medicine (SOM), New York University (NYU) Grossman SOM, Wayne State University SOM, Perelman SOM at the University of Pennsylvania, and Mayo Clinic Alix SOM. Main Outcome Measures: Fertility-related knowledge and educational experiences of U.S. medical students in their final year of school. Results: In total, 117 students (14.4%) completed the survey. The average knowledge score was 78%. Twenty-three (22%) overestimated the age of most precipitous fertility decline, and 50 (52%) overestimated the chance of getting pregnant for a 40-year-old person with ovaries. One-third of students (30, 32%) incorrectly believe that physicians have equivalent infertility rates to the general population. Students were less cognizant of male fertility issues, incorrectly believing there was no negative impact on male fertility by age (43, 42%) among other factors. Seventy-five (81%) reported less than 5 hours of fertility-related education in medical school. Only one-third (32%) were satisfied or very satisfied with the fertility education they received. In an open-response question, students expressed interest in additional education on transgender and cancer patient care, fertility preservation, assisted reproductive technologies, and reproductive life planning in medicine. Conclusions: There is a need and an opportunity for medical education programs to enhance fertility education. Giving students and trainees the knowledge required to make informed decisions for their family-building purposes and improving their ability to counsel patients adequately should be a goal of future educational endeavors. The data collected in this study will serve as a guide for the development of fertility-related learning modules for medical students and trainees. [ABSTRACT FROM AUTHOR]

Data on gonadotoxicity of chemotherapies are essential to better counsel young females and males about the risk of infertility and to better indicate fertility preservation measures before cancer therapies. However, such data have not recently been reviewed for bone cancer. Therefore, a systematic literature search was conducted considering papers published since 2000. This study is part of the FertiTOX® project, which aims to improve the lack of data regarding gonadotoxicity of cancer therapies to enable more accurate counseling regarding fertility preservation. Only relapse-free women and men were included. Gonadotoxic therapy-induced suspected infertility was defined as very low anti-mullerian hormone, high gonadotropin concentration, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia. The quality of the individual studies was assessed using the Newcastle–Ottawa Scale (NOS). In total, 11 out of 831 studies were included in the review. Suspected infertility was found in 10/190 (5.1%, range 0%–66%) of female patients with osteosarcoma (six studies), in 24/46 (52.2%, range 46%–100%) of male patients with osteosarcoma (three studies), in 18/138 (13.0%, range 3%–18%) of female patients with Ewing's sarcoma (three studies), and in 34/38 (89.5%) of male patients with Ewing's sarcoma (one study). A risk calculation in relation to specific chemotherapies was not possible. Risk of suspected infertility tends to be higher in Ewing's sarcoma in which all patients received chemotherapies with alkylating agents. Two of the 11 included studies received a high NOS quality score, whereas the remaining nine studies received a low quality score, mainly because of the lack of a comparator group. Published data are too limited for precise estimation of the gonadotoxicity. However, data indicate clinically relevant risk for infertility, supporting counseling patients before chemotherapy about fertility preservation measures. [ABSTRACT FROM AUTHOR]

Purpose: Reproductive health (RH) is a critical issue among cancer survivors worldwide. However, in developing countries where RH services for patients with cancer are often lacking, reproductive concerns among adolescent and young adult (AYA) survivors remain uncertain. In this study, we assessed the reproductive concerns of AYA cancer survivors in a resource-limited context of Uganda. Methods: We collected data from AYA cancer survivors at two facilities in Uganda using an interviewer-administered questionnaire. Descriptive statistics were calculated, one-way analysis of variance was used for intergroup comparisons, and multiple regressions were used to test for predictors of reproductive concerns. Results: A total of 110 AYA cancer survivors, with a median age of 20 years (interquartile range [IQR], 18–22), were interviewed. More than half (53.6%) of the respondents were males. The median time since cancer diagnosis was 19 months (IQR, 13.0–35.0). Almost all (91.8%) respondents had a future desire to have children, but only 15.5% received reproductive counseling. The mean total score for the reproductive concern subscales was highest for the fertility concern, followed by the information-seeking and health-related concerns. Reproductive counseling, desire to have children, and respondents' age were the factors influencing reproductive concern. Conclusions: The study shows a strong desire for biological parenthood with very low reproductive counseling among AYA cancer survivors, who remain concerned about their fertility, information needs, and health. This outcome underscores the need to integrate RH services into resource-limited cancer care settings. [ABSTRACT FROM AUTHOR]