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Abstract Context Powerful demographic trends toward reproductive aging of human populations, older age at first childbirth, and lower birth rates will profoundly influence the health, vitality, and economies of human societies and deserve greater attention in health policy and research. Evidence Acquisition Information on birth rates, fertility rates, and outcomes of assisted reproductive technologies were obtained from databases of government agencies (census data, Centers for Disease Control and Prevention). Evidence Synthesis Fecundity declines with advancing age, especially in women >35 years and men >50 years. Advanced parental age adversely affects pregnancy outcomes for the mother and the offspring and increases the offspring’s risk of chromosomal disorders, neurodegenerative diseases, and birth defects. Because of increased life expectancy, today people will spend a major portion of life in a period of reproductive senescence; diseases associated with reproductive senescence will influence the health and well-being of middle-aged and older adults. Inversion of the population age pyramid will affect health care costs, retirement age, generational distribution of wealth, and the vitality of societies. Actions can be taken to mitigate the societal consequences of these trends. An educational campaign to inform young people about the trade-offs associated with postponement of childbirth will enable them to make informed choices. Some repositioning of research agenda and health care policies is needed to address the public health threat posed by reproductive aging. Conclusion The consequences of low fertility rates and delayed parenthood on our nation’s health, vitality, and economic growth should be considered when crafting research, health, and economic policies. Reproductive aging will profoundly influence health, vitality, and economies of human societies; redirection of health and economic policies is needed to mitigate its adverse societal consequences.

Encapsulated microRNAs (i.e., miRNAs within the extracellular vesicles, i.e., EV-miRNAs) have been detected in follicular fluid in both animal and human studies and different profiles have been associated with IVF cycle characteristics. However, limited studies to date have investigated other IVF outcomes, including fertilization status and embryo quality on day three”. In this cohort, we performed a cross-sectional analysis on 126 women who contributed follicular fluid from a single follicle during a single IVF cycle. One hundred and ninety-two EV-miRNAs were assessed by univariable fold-change and multivariable logistic regression analyses. Hsa-miR-92a and hsa-miR-130b, were over-expressed in follicular fluid samples from oocytes that failed to fertilize compared to those that were normally fertilized. Additionally, hsa-miR-888 was over-expressed and hsa-miR-214 and hsa-miR-454 were under-expressed in samples that resulted in impaired day-3 embryo quality compared to top-quality day-3 embryos. After adjusting for confounders as BMI, smoking and total motile sperm, associations of these EV-miRNAs remained significant. In-silico KEGG pathway analyses assigned the identified EV-miRNAs to pathways of follicular growth and development, cellular signaling, oocyte meiosis, and ovarian function. Our findings suggest that EV-miRNAs may play a role in pathways of ovarian function and follicle development, which could be essential for understanding the molecular mechanisms that could lead to a successful pregnancy and birth.

A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.

Introduction Since 2017, women with absolute uterine infertility due to Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome have been eligible to participate in a uterine transplantation clinical trial conducted by Foch Hospital in France. The aim of this study is to assess the psychological state of potential candidates, including recipients, their partners, and their living‐related donors. Material and Methods Sixteen potential uterus transplant candidates, including recipients, partners, and living‐related donors, participated in the study. The psychological evaluation of these candidates was conducted using three validated questionnaires: the Dyadic Adjustment Scale (DAS‐16), the Hospital Anxiety and Depression Scale (HADS), and the Fertility Quality of Life (FertiQoL) questionnaire. Results No depression symptoms were observed in any participant according to the HADS. Most recipients did not exhibit signs of anxiety; however, three partners and three donors reported moderate to high anxiety levels. A positive correlation was found between the recipient's psychological distress related to infertility (FertiQoL) and the anxiety scores of their donors. The emotional aspect of infertility was identified as the most distressing factor for the recipients. Conclusions While the overall psychological state of the participants was generally good, anxiety was notably present among donors and partners. Therefore, providing psychological support throughout the uterine transplantation process is essential for not only the recipients but also their partners and donors. Psychological evaluation of potential candidates for the uterus transplantation French Trial shows that providing psychological support is essential throughout all the process until explanation.

Infertility affects 17% of the global population, yet fertility awareness remains low, particularly among younger individuals and men. This study assessed fertility awareness and attitudes toward infertility prevention among French adults of childbearing age, focusing on gender differences. Conducted via social media from March to May 2023, the survey included 322 participants aged 18–43 who had not consulted assisted reproduction centers. Most respondents were women (84%), under 33 (59%), from high socio-professional backgrounds (58%), in relationships (78%), and childless (59%). Significant gender differences emerged regarding desired ages for having a first (women: 30.7 ± 3.5 years vs. men: 32.8 ± 3.8 years; p = .06) and last child (women: 36.7 ± 3.6 years vs. men: 39.8 ± 4.5 years; p = .001). Only 55.8% of men correctly identified the female fertility window, compared to 64.1% of women (p = .023). Men also showed lower awareness of the timing of female fertility decline (p = .043) and underestimated the prevalence of assisted reproductive technologies among heterosexual couples (p = .001). In addition, men were less likely to discuss fertility with their doctor (15.4% vs. 35.9%; p = .004) or express interest in infertility prevention consultations (53.9% vs. 60.8%; p = .048). These findings suggest a gender gap in fertility awareness, with men generally less informed and engaged in reproductive health discussions. While the small sample size limits generalizability, the results underscore the need for targeted educational efforts to improve fertility knowledge and encourage proactive reproductive health behaviors across genders.

PurposeTo determine the expected out-of-pocket costs of IVF with preimplantation genetic testing for aneuploidy (PGT-A) to attain a 50%, 75%, or 90% likelihood of a euploid blastocyst based on individual age and AMH, and develop a personalized counseling tool.MethodsA cost analysis was performed and a counseling tool was developed using retrospective data from IVF cycles intended for PGT or blastocyst freeze-all between January 1, 2014 and August 31, 2017 (n = 330) and aggregate statistics on euploidy rates of > 149,000 embryos from CooperGenomics. Poisson regression was used to determine the number of biopsiable blastocysts obtained per cycle, based on age and AMH. The expected costs of attaining a 50%, 75%, and 90% likelihood of a euploid blastocyst were determined via 10,000 Monte Carlo simulations for each age and AMH combination, incorporating age-based euploidy rates and IVF/PGT-A cost assumptions.ResultsThe cost to attain a 50% likelihood of a euploid blastocyst ranges from approximately $15,000 U.S. dollars (USD) for younger women with higher AMH values (≥ 2 ng/mL) to > $150,000 for the oldest women (44 years) with the lowest AMH values (< 0.1 ng/mL) in this cohort. The cost to attain a 75% versus 90% likelihood of a euploid blastocyst is similar (~ $16,000) for younger women with higher AMH values, but varies for the oldest women with low AMH values (~ $280,000 and > $450,000, respectively). A typical patient (36–37 years, AMH 2.5 ng/mL) should expect to spend ~ $30,000 for a 90% likelihood of attaining a euploid embryo.ConclusionsThis tool can serve as a counseling adjunct by providing individualized cost information for patients regarding PGT-A.

Aims/hypothesis Disorders of the reproductive system, including hypogonadism and reduced fertility, are an under-recognized complication of diabetes. Based on experimental data in mice, hyperglycemia and obesity may modify epigenetic marks in sperm and impact health and development of offspring, but data are more limited in humans. Thus, we sought to study the impact of type 2 diabetes and glycemic control on sperm quality and DNA methylation. Methods In this prospective cohort study, we recruited 40 men with BMI greater than 25 kg/m 2 including 18 with type 2 diabetes, 6 with prediabetes, and 16 normoglycemic controls. Assessments were repeated after 3 months in 9 men with type 2 diabetes and 7 controls. We analyzed reproductive hormones, sperm concentration and motility, and sperm DNA methylation (MethylationEPIC BeadChip). Results Men with type 2 diabetes had higher levels of follicle-stimulating hormone (FSH), but similar testosterone levels and sperm quality as controls. Sperm DNA methylation was stable with repeat sampling at 3 months in men with and without type 2 diabetes. We identified differential methylation at 655 of 745,804 CpG sites in men with type 2 diabetes versus controls (FDR < 0.05). Of these, 96.5% showed higher methylation in type 2 diabetes, with a mean difference in DNA methylation (beta value, β) of 0.16 ± 0.004 (16 ± 0.4%). Ontology analysis of differentially methylated loci revealed annotation to genes regulating synaptic signaling, actin, cAMP-dependent pathways, and G protein-coupled receptor pathways. 24% of probes differentially regulated in men with type 2 diabetes versus control overlapped with probes associated with HbA1c, suggesting additional factors beyond glycemic control contributed to diabetes-associated differences in DNA methylation. Conclusions/interpretation Men with type 2 diabetes showed higher DNA methylation levels in sperm relative to normoglycemic controls with similar BMI. Whether these differences are reversible with glucose-lowering treatment or may contribute to post-fertilization transcriptional regulation warrants further investigation. Trial registration NCT03860558

Background An oocyte undergoes two rounds of asymmetric division to generate a haploid gamete and two small polar bodies designed for apoptosis. Chromosomes play important roles in specifying the asymmetric meiotic divisions in the oocytes but the underlying mechanism is poorly understood. Results Chromosomes independently induce spindle formation and cortical actomyosin assembly into special cap and ring structures in the cortex of the oocyte. The spindle and the cortical cap/ring interact to generate mechanical forces, leading to polar body extrusion. Two distinct force-driven membrane changes were observed during 2 nd polar body extrusion: a protrusion of the cortical cap and a membrane invagination induced by an anaphase spindle midzone. The cortical cap protrusion and invagination help rotate the spindle perpendicularly so that the spindle midzone can induce bilateral furrows at the shoulder of the protruding cap, leading to an abscission of the polar body. It is interesting to note that while the mitotic spindle midzone induces bilateral furrowing, leading to efficient symmetric division in the zygote, the meiotic spindle midzone induced cytokinetic furrowing only locally. Conclusions Distinct forces driving cortical cap protrusion and membrane invagination are involved in spindle rotation and polar body extrusion during meiosis II in mouse oocytes.

Preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy is widely applied in in vitro fertilization (IVF) to identify aneuploid embryos. However, potential safety concerns regarding biopsy and restrictions to only those embryos suitable for biopsy pose limitations. In addition, embryo mosaicism gives rise to false positives and false negatives in PGT-A because the inner cell mass (ICM) cells, which give rise to the fetus, are not tested. Here, we report a critical examination of the efficacy of noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) in the spent culture media of human blastocysts by analyzing the cell-free DNA, which reflects ploidy of both the TE and ICM. Fifty-two frozen donated blastocysts with TE biopsy results were thawed; each of their spent culture medium was collected after 24-h culture and analyzed by next-generation sequencing (NGS). niPGT-A and TE-biopsy PGT-A results were compared with the sequencing results of the corresponding embryos, which were taken as true results for aneuploidy reporting. With removal of all corona-cumulus cells, the false-negative rate (FNR) for niPGT-A was found to be zero. By applying an appropriate threshold for mosaicism, both the positive predictive value (PPV) and specificity for niPGT-A were much higher than TE-biopsy PGT-A. Furthermore, the concordance rates for both embryo ploidy and chromosome copy numbers were higher for niPGT-A than TE-biopsy PGT-A. These results suggest that niPGT-A is less prone to errors associated with embryo mosaicism and is more reliable than TE-biopsy PGT-A.

PurposeTo evaluate the use of preimplantation genetic testing (PGT) and live birth rates (LBR) in the USA from 2014 to 2017 and to understand how PGT is being used at a clinic and state level.MethodsThis study accessed SART data for 2014 to 2017 to determine LBR and the CDC for years 2016 and 2017 to identify PGT usage. Primary cycles included only the first embryo transfer within 1 year of an oocyte retrieval; subsequent cycles included transfers occurring after the first transfer or beyond 1 year of oocyte retrieval.ResultsIn the SART data, the number of primary PGT cycles showed a significant monotonic annual increase from 18,805 in 2014 to 54,442 in 2017 (P = 0.042) and subsequent PGT cycles in these years increased from 2946 to 14,361 (P = 0.01). There was a significant difference in primary PGT cycle use by age, where younger women had a greater percentage of PGT treatment cycles than older women. In both PGT and non-PGT cycles, the LBR per oocyte retrieval decreased significantly from 2014 to 2017 (P<0001) and younger women had a significantly higher LBR per oocyte retrieval compared to older women (P < 0.001). The CDC data revealed that in 2016, just 53 (11.4%) clinics used PGT for more than 50% of their cycles, which increased to 99 (21.4%) clinics in 2017 (P< 0.001).ConclusionsA growing number of US clinics are offering PGT to their patients. These findings support re-evaluation of the application for PGT.