Expanded carrier screening (ECS) is increasingly offered within assisted reproductive technologies (ART), particularly as a component of donor gamete selection. As genomic testing options rapidly evolve, the complexity of interpreting ECS results presents significant challenges for donor gamete recipients and the healthcare professionals supporting them. At the same time, regulatory frameworks and professional guidelines have not kept pace with these technological developments, resulting in gaps between clinical practice and formal guidance. This paper aims to summarise current practice, highlight emerging issues arising from the integration of ECS into gamete selection, and provide recommendations to facilitate informed decision-making.

A 38-year-old woman conceived after intracytoplasmic sperm injection and frozen-thawed double blastocyst transfer. First-trimester ultrasonography suggested monochorionic diamniotic twins, but discordant external genitalia were identified at 21 weeks of gestation. Delivery at 37 weeks resulted in phenotypically normal female and male infants. Placental histopathology confirmed monochorionic diamniotic placentation. Postnatal multimodal genetic evaluation, including G-banding, single nucleotide polymorphism array, and buccal cell X/Y fluorescence in situ hybridization, demonstrated mixed 46,XX/46,XY cell lines in peripheral blood, consistent with predominantly blood-limited chimerism. Single nucleotide polymorphism array analysis demonstrated admixture of two independently derived genomes and findings inconsistent with a primary dispermic mechanism. These results supported a diagnosis of monochorionic dizygotic twinning with predominantly blood chimerism, most likely reflecting intertwin cell exchange. This case highlights the value of integrating tissue-specific genetic findings with postnatal phenotypic and clinical assessment to interpret predominantly blood-limited chimerism in MCDZ twins.

Clinical rotations and clerkship experiences during medical school, including Obstetrics and Gynecology (OBGYN), play a significant role in shaping specialty choice. Reproductive medicine is becoming an increasingly important component of women's health with advances in assisted reproductive technologies, fertility preservation, and infertility care. Despite these developments, exposure to Reproductive Endocrinology and Infertility (REI) during medical education remains inconsistent, potentially limiting awareness of this evolving subspecialty. This review synthesizes the available literature on REI educational experiences, mentorship initiatives, and clinical exposure during medical school and their association with student interest in OBGYN and reproductive medicine careers. Available evidence suggests that structured REI curricula, clinical experiences, and mentorship are associated with greater student knowledge, awareness of career pathways, and interest in reproductive medicine. Although the evidence remains limited, expanding REI exposure may broaden awareness of the diversity of the field of OBGYN and has the potential to strengthen recruitment into reproductive medicine.

In bovine in vitro embryo production (IVEP), optimizing oocyte quality and yield per donor serves as the cornerstone for improving blastocyst development and field efficiency. This study evaluated the impact of naturally occurring ovarian structures on follicular dynamics, oocyte quality, and embryo development during random-day ovum pick-up (OPU) in Holstein heifers (n = 78). Donors were divided into three groups based on ovarian patterns: Group I (corpus luteum [CL]; n = 43), Group II (only antral follicles [AF]; n = 20), or Group III (CL + dominant follicle [CL + DF]; n = 15). Follicles (3-8 mm) were aspirated, and serum progesterone (P4) and estradiol (E2) levels were measured. Group I had a significantly higher usable (A + B+C) oocyte count (7 vs. 3) and total oocyte count (10 vs. 5) than Group III (P < 0.05). The mid-sized follicle pool was lower in Group III than in Group II (11 vs. 13; P < 0.05). Mature oocytes, cleaved zygotes, and blastocyst counts were significantly lower in Group III than in Groups I and II (P < 0.05). Group I achieved a higher cleavage rate than Group III (77.60 vs. 62.06; P < 0.05). Crucially, the blastocyst formation rate was significantly higher in Groups I (49.59%) and II (45.45%) than in Group III (22.20%; P < 0.05). On the OPU day, donors with serum P4 > 1 ng/mL exhibited a higher yield of B-quality oocytes than did those with P4 < 1 ng/mL (1.5 vs. 1.0; P < 0.05). In conclusion, a dominant follicle during random-day OPU is closely associated with a lower antral follicle pool, compromised oocyte quality, and reduced embryo development. Consequently, avoiding active follicular dominance during donor management might represent a supportive strategy to optimize IVEP efficiency under commercial field conditions.

The average age of childbirth in the UK in 2022 was 30.9 years, having increased by over 3 years in the past 2 decades, and 4 years since 1980. Although a woman's fertility declines markedly in her late-30s and early-40s, more women are now starting their family at this stage of their lives. Related to this, increasing numbers of women are storing their eggs (oocytes) to give them the potential opportunity to have a baby in the future. The number of egg freezing cycles accounts for 5% of in vitro fertilisation (IVF) cycles but the number of cycles using stored eggs is much lower. The use of a technique of rapid freezing called vitrification gives success rates almost as good as using fresh eggs. The reasons behind the increase in egg freezing are complex, but the most common reason given by women storing eggs is that they do not have a partner and are concerned that by the time they do find themselves in a relationship within which they wish to start a family, they may not be able to do so. This paper addresses the growing use of egg freezing and how it may have been promoted. It is essential that women are very clearly informed about the likely success rates of egg freezing, particularly as it is primarily provided by the private sector, with the associated concerns of financial costs and inappropriate or inaccurate marketing. Its success is strongly dependent on the age of the woman at the time of freezing her eggs, with much higher success rates in those under the age of 35 years. The relevant legislation changed in 2022 and now allows women to store eggs for 55 years, although consent for this needs to be renewed every 10 years. This now supports the better success rates when women store eggs at a younger age. We conclude that elective egg freezing provides women with an opportunity to act on the age-related drop in their fertility. At present, most women who are doing this are already in their later 30s when the success rates are limited. We strongly support the need for improved and continuing education of both women and men regarding the decline in female fertility with age.

Primary neurologic involvement represents one of the most serious manifestations of systemic autoimmune diseases, yet the influence on pregnancy outcomes remains poorly characterized across disorders. To describe neurologic disease activity and maternal-fetal outcomes in pregnancies occurring after the onset of systemic autoimmune-associated neurologic involvement. A retrospective case series was conducted within the Mass General Brigham healthcare system (2010-2025), including women with systemic autoimmune disease and objectively characterized neurologic involvement who experienced pregnancy following neurologic disease onset. Neurologic disease activity across the peripartum period and associated maternal and fetal outcomes were explored. Thirteen patients with systemic lupus erythematosus (SLE; 38 pregnancies), 20 with Sjögren's disease (SJD; 45 pregnancies), and 5 with sarcoidosis (14 pregnancies) met inclusion criteria; no eligible Behçet's disease cases were identified. In SLE, central nervous system involvement occurred in 69.2%, while neurologic worsening occurred during pregnancy in 38.5% and postpartum in 23.1%. Among 25 viable SLE deliveries, hypertensive disorders of pregnancy occurred in 24.0% and preterm delivery in 20.0%. In SJD, peripheral nervous system involvement occurred in 90.0% and autonomic dysfunction in 55.0%; neurologic worsening occurred during pregnancy in 5.0% and postpartum in 30.0%. Among 33 viable SJD deliveries, preterm delivery occurred in 9.1% and hypertensive disorders of pregnancy in 6.1%. Among 5 patients with sarcoidosis, peripheral and central nervous system involvement occurred in 60.0% and 40.0%, respectively; among 9 viable deliveries, hypertensive disorders of pregnancy occurred in 33.3% and preterm delivery in 22.2%. Medication exposures were heterogeneous across diseases and reproductive stages. Peripartum women with systemic autoimmune diseases and related neurologic involvement represent a clinically heterogeneous and medically complex population. Distinct disease-specific neurologic phenotypes may influence patterns of obstetric morbidity and postpartum neurologic vulnerability, highlighting the need for prospective multicenter studies with standardized neurologic phenotyping and longitudinal postpartum follow-up.

The meiotic spindle is essential for accurate chromosome segregation during oocyte maturation and fertilization, and its alteration might be considered a major contributor to age-related aneuploidy and reproductive failure. Spindle formation is inherently vulnerable to errors and contributes to the unusually high frequency of chromosome segregation defects observed in human eggs. Human oocytes are particularly prone to aneuploidy; the presence of an abnormal chromosome number, which represents one of the leading causes of infertility, recurrent pregnancy loss, implantation failure, and congenital disorders in neonates. Previous studies have reported a U-shaped relationship between maternal age and aneuploidy rates, with relatively higher rates observed in both very young females and in women of advanced maternal age. Conversely, aneuploidy rates appear comparatively lower during the intervening reproductive-age period, particularly between approximately 25 and 35 years of age. Because most aneuploid embryos fail to develop successfully after fertilization, chromosome segregation errors in oocytes have profound consequences for female reproductive success. Aneuploidy primarily arises from defects during meiotic chromosome segregation. Faithful chromosome segregation depends on the accurate assembly and function of the meiotic spindle, a dynamic microtubule-based structure that aligns and separates homologous chromosomes during meiosis I and sister chromatids during meiosis II. Growing evidence indicates that chromosome mis-segregation results from the combined effects of impaired sister chromatid cohesion, altered kinetochore architecture, defective microtubule dynamics, weakened spindle assembly checkpoint activity, and age-related metabolic decline. Together, these defects compromise spindle integrity and reduce the fidelity of chromosome separation. Furthermore, the intrinsic instability of the acentrosomal spindle increases the likelihood of incorrect microtubule-kinetochore attachments, a defect that becomes more prevalent with maternal aging due to progressive deterioration of chromosome organization and kinetochore function. This review summarizes the current understanding of the molecular mechanisms regulating meiotic spindle assembly and function in human oocytes and examines how their disruption contributes to chromosome segregation errors and embryonic aneuploidy. We discuss the interplay between spindle abnormalities and upstream cellular defects, distinguish meiotic from post-zygotic origins of chromosomal abnormalities, and evaluate the clinical significance of spindle assessment in assisted reproductive technologies. Finally, we critically examine emerging strategies aimed at preserving chromosome segregation fidelity, including approaches targeting mitochondrial function and spindle regulation, while distinguishing interventions supported by mechanistic evidence from those that remain preclinical or speculative.

Background and Objectives: Augmented reality (AR), mixed reality (MR), computer vision, artificial intelligence (AI), and three-dimensional (3D) modeling may be particularly relevant in fertility-preserving gynecologic surgery, where disease must be treated while uterine architecture, reproductive anatomy, and future fertility potential are preserved. This scoping review mapped and appraised the current evidence, with emphasis on myomectomy, adenomyomectomy, and endometriosis surgery. Materials and Methods: A scoping review with narrative synthesis was conducted and reported according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, and Google Scholar were searched from database inception to 16 May 2026. Records were appraised with design-appropriate instruments: Joanna Briggs Institute (JBI) principles, Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I), randomized-trial risk-of-bias domains, and structured feasibility criteria. Results: Of 528 records identified, 20 were included. Eleven involved application of the technology in the care of patients; of these, only two were comparative-one retrospective matched case-control study of AR-assisted myomectomy and adenomyomectomy, and one single-center randomized controlled trial of 3D-printed model-assisted myomectomy. The remaining nine were enabling technologies validated on image datasets, operative video, ex vivo models, or animal models. Only one study reported a reproductive outcome-pregnancy rates in a retrospective matched series of 34 patients, which did not differ between groups-and no study reported live birth, obstetric, or long-term reproductive-safety outcomes. Conclusions: Current evidence supports technical feasibility and preoperative planning value but does not demonstrate improvement in reproductive outcomes; here "fertility-preserving" denotes the clinical context of the surgery rather than a demonstrated reproductive benefit. Adequately powered controlled studies reporting fertility-relevant endpoints are required.

Background and Objectives: Endometriosis is a chronic inflammatory disease associated with impaired fertility, but the extent to which its systemic inflammatory profile differs from that observed in infertile women without endometriosis remains incompletely understood. This study aimed to characterize and compare the systemic inflammatory profiles of women with endometriosis, infertile women without endometriosis, and healthy controls by evaluating serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). In addition, the study explored the IL-6/TNF-α ratio as an indicator of inflammatory balance and evaluated its relationship with ovarian reserve. Materials and Methods: This observational comparative study included 87 women divided into three groups: healthy controls (n = 29), women with endometriosis (n = 29), and infertile women without endometriosis (n = 29). Serum IL-6, TNF-α, and hs-CRP concentrations were determined specifically for the present study, whereas the corresponding clinical and embryological data were retrieved from medical records. Group comparisons were performed using the Kruskal-Wallis test followed by Dunn's post hoc test with Holm correction. The IL-6/TNF-α ratio was calculated as an exploratory indicator of inflammatory balance. Associations between inflammatory biomarkers and anti-Müllerian hormone (AMH) concentrations were assessed using Spearman's correlation analysis. Results: Significant differences in serum inflammatory biomarkers were observed among the three groups. IL-6 concentrations were significantly increased in both women with endometriosis and infertile women without endometriosis compared with healthy controls, whereas TNF-α concentrations were significantly elevated only in infertile women without endometriosis compared with both healthy controls and women with endometriosis (adjusted p < 0.001 for both comparisons). Differences in hs-CRP were more modest but remained significant overall. Women with endometriosis exhibited a significantly higher IL-6/TNF-α ratio than infertile women without endometriosis, suggesting distinct inflammatory patterns between these conditions. No significant correlations were identified between circulating inflammatory biomarkers and AMH concentrations. Conclusions: Women with endometriosis and infertile women without endometriosis exhibit distinct systemic inflammatory profiles rather than simply different levels of inflammation. The IL-6/TNF-α ratio may provide additional information regarding the balance of inflammatory pathways beyond the isolated evaluation of individual cytokines. Larger prospective studies integrating systemic and local inflammatory biomarkers with assisted reproductive outcomes are warranted to validate these findings and further explore their clinical relevance.

Male infertility represents a major clinical challenge. Despite standard genetic testing (karyotyping, Y-chromosome azoospermia factor (AZF) microdeletion testing, and CFTR variant analysis), the molecular cause remains unidentified in a substantial proportion of patients. These patients are consequently diagnosed with idiopathic male infertility. This review provides a comprehensive overview of the current evidence regarding the application of whole-exome sequencing (WES) in the molecular diagnosis and clinical management of idiopathic male infertility. WES can identify pathogenic variants associated with quantitative spermatogenic defects, qualitative abnormalities of sperm motility and morphology, and pre-testicular causes related to hypogonadotropic hypogonadism. When defining the cohort strictly as patients with true idiopathic non-obstructive azoospermia (NOA) who remain undiagnosed after standard testing, the pooled diagnostic yield of WES is approximately 10-15%. Estimates vary due to differences in cohort selection, variant interpretation, and the range of genes analysed. Establishing a precise molecular diagnosis improves genetic counselling, helps predict the likelihood of successful sperm retrieval via testicular sperm extraction (TESE) or microdissection TESE (micro-TESE), and informs treatment planning for assisted reproductive technologies. However, routine clinical implementation remains limited by the high frequency of variants of uncertain significance, the absence of standardised diagnostic pipelines, unequal access to testing, and ethical concerns. Emerging "all-in-one" diagnostic strategies, multi-omics integration, and whole-genome or long-read sequencing hold promise for improving genomic diagnostics. However, broader adoption will ultimately require ongoing standardisation and functional validation of identified variants.