STUDY QUESTION Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes? SUMMARY ANSWER Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit

STUDY QUESTION What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)? SUMMARY ANSWER Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts

STUDY QUESTION Is it feasible to safely determine metabolic imaging signatures of nicotinamide adenine dinucleotide [NAD(P)H] associated auto-fluorescence in early embryos using a light-sheet on-a-chip approach? SUMMARY ANSWER We developed an optofluidic device capable of obtaining high-resolution 3D images of the NAD(P)H autofluorescence of live mouse embryos using a light-sheet on-a-chip device as

STUDY QUESTION Are reproductive factors associated with biological aging, and does biological aging mediate the associations of reproductive factors with premature mortality? SUMMARY ANSWER Multiple reproductive factors are related to phenotypic age acceleration (PhenoAge-Accel), while adherence to a healthy lifestyle mitigates these harmful effects; PhenoAge-Accel mediated the associations between

Access to state-of-the-art ART can be viewed as a marker of societal development. The recent Alabama Supreme Court ruling represents a major local setback in the access to state-of-the-art ART. If this isolated local incident becomes a national trend, the USA will lose ground in this emerging area of healthcare, and its citizens will be left with substandard treatment options for the redress of infertility

STUDY QUESTION Does the downregulation of cell division cycle 42 (CDC42) protein in endometrial stroma lead to endometrial senescence in patients with recurrent implantation failure (RIF), and what is the potential mechanism? SUMMARY ANSWER CDC42 deficiency causes endometrial stromal senescence and decidualization defects, impairing uterine receptivity of RIF patients, via activation of Wnt signaling

STUDY QUESTION Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle? SUMMARY ANSWER In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and

STUDY QUESTION What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands? SUMMARY ANSWER This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient

STUDY QUESTION Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? SUMMARY ANSWER Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. WHAT IS KNOWN ALREADY EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation

STUDY QUESTION Can more reliable time cut-offs of embryo developmental incompetence be generated by combining time-lapse technology (TLT), artificial intelligence, and preimplantation genetics screening for aneuploidy (PGT-A)? SUMMARY ANSWER Embryo developmental incompetence can be better predicted by time cut-offs at multiple developmental stages and for different ranges of maternal age. WHAT IS KNOWN

STUDY QUESTION What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS? SUMMARY ANSWER We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial

STUDY QUESTION Is there an association between male or female epigenetic age acceleration (EAA) or deceleration (EAD) and fecundability? SUMMARY ANSWER We do not find compelling evidence of an association between EAA or EAD and fecundability. WHAT IS KNOWN ALREADY Prior research has shown that female accelerated epigenetic aging is associated with unfavorable clinical fecundity outcomes and use of

STUDY QUESTION Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue? SUMMARY ANSWER We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions. WHAT IS KNOWN ALREADY The in vitro growth of oocytes

STUDY QUESTION In addition to chromosomal euploidy, can the transcriptome of blastocysts be used as a novel predictor of embryo implantation potential? SUMMARY ANSWER This retrospective analysis showed that based on differentially expressed genes (DEGs) between euploid blastocysts which resulted and did not result in a clinical pregnancy, machine learning models could help improve implantation rates

STUDY QUESTION What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? SUMMARY ANSWER Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated

STUDY QUESTION Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? SUMMARY ANSWER Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1)

STUDY QUESTION Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. WHAT IS KNOWN ALREADY Our previous study suggested a link between

STUDY QUESTION Compared to the ‘single biopsy + single vitrification’ approach, do ‘double biopsy + double vitrification’ or ‘single biopsy + double vitrification’ arrangements compromise subsequent clinical outcomes following euploidy blastocyst transfer? SUMMARY ANSWER Both ‘double biopsy + double vitrification’ and ‘single biopsy + double vitrification’ led to reduced live birth/ongoing pregnancy

STUDY QUESTION Can oocyte functionality be assessed by observing changes in their intracytoplasmic lipid droplets (LDs) profiles? SUMMARY ANSWER Lipid profile changes can reliably be detected in human oocytes; lipid changes are linked with maternal age and impaired developmental competence in a mouse model. WHAT IS KNOWN ALREADY In all cellular components, lipid damage is the earliest manifestation

STUDY QUESTION What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? SUMMARY ANSWER Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. WHAT IS KNOWN ALREADY Oestrogen enhances cervical mucus secretion while progesterone inhibits it. STUDY DESIGN, SIZE, DURATION Observational study. Daily

STUDY QUESTION Are 24-h movement composition and time reallocations between the movement behaviours (moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep) differentially associated with cardiometabolic markers in women with polycystic ovary syndrome (PCOS) relative to women without PCOS? SUMMARY ANSWER There was no difference in 24-h movement

This Directions article examines the mechanisms by which a father’s age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health

STUDY QUESTION What is the involvement of ovarian stroma in the anti-Müllerian hormone (AMH) signaling pathway and which stromal cells are involved? SUMMARY ANSWER Mouse and human ovaries show high expression of AMH receptor II (AMHR2) in the stromal fibroblasts surrounding the follicles and activation of the post-AMHR2 pathway by recombinant AMH was evidenced by increased phosphorylation of SMAD1

STUDY QUESTION What are the implications of the presence cytoplasmic strings (Cyt-S) and their quantity and dynamics for the pre-implantation development of human blastocysts? SUMMARY ANSWER Cyt-S are common in human embryos and are associated with faster blastocyst development, larger expansion, and better morphological quality. WHAT IS KNOWN ALREADY Cyt-S are dynamic cellular projections connecting

STUDY QUESTION What is the impact of male age- and sperm-related factors on embryonic aneuploidy? SUMMARY ANSWER Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy. WHAT IS KNOWN ALREADY While the effect of maternal age on embryo chromosomal aneuploidy

STUDY QUESTION Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility? SUMMARY ANSWER The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility. WHAT IS KNOWN ALREADY Underpowered studies suggested that face-to-face interventions

STUDY QUESTION Can novel genetic factors contributing to early embryonic arrest in infertile patients be identified, along with the underlying mechanisms of the pathogenic variant? SUMMARY ANSWER We identified a heterozygous variant in the SPRY4 (sprouty RTK signaling antagonist 4) in infertile patients and conducted in vitro and in vivo studies to investigate the effects of the variant/deletion, highlighting

The current article provides an ethical reflection on the moral status of the human embryo, which is a crucial factor in determining permissible actions involving embryos and the extent of their protection. It advocates for the extension of the research period for embryos to 28-days post fertilization. It also states that integrated embryo-like structures (ELSs) should not currently be given the same

STUDY QUESTION Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? SUMMARY ANSWER Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. WHAT IS KNOWN ALREADY Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice

STUDY QUESTION Does the prevalence of 12-month infertility in Burkina Faso, Côte d’Ivoire, Kenya, and Uganda differ between women trying to conceive and the broader population of women exposed to unprotected sex, and how are prevalence estimates affected by model assumptions and adjustments? SUMMARY ANSWER Estimates of 12-month infertility among tryers ranged from 8% in Burkina Faso to 30% in Côte

STUDY QUESTION What is the natural history of elective autologous sperm cryostorage prior to gonadotoxic treatment? SUMMARY ANSWER We estimate large sample median times to transfer for use, to the man’s death or to discard of sperm, and their determinants, as the key operational outcomes of sperm cryostorage. WHAT IS KNOWN ALREADY No large sample studies of the natural history of sperm cryostorage

STUDY QUESTION Is there an association between premature ovarian insufficiency (POI) and severe autoimmune diseases before and after POI diagnosis? SUMMARY ANSWER Women with POI had at least one hospital-treated autoimmune disorder preceding POI diagnosis 2.6 times more often compared with matched female controls, and a 2- to 3-fold risk for these diseases for several years after POI diagnosis. WHAT

STUDY QUESTION What is the relative length variance of the luteal phase compared to the follicular phase within healthy, non-smoking, normal-weight, proven normally ovulatory, premenopausal women with normal-length menstrual cycles? SUMMARY ANSWER Prospective 1-year data from 53 premenopausal women with two proven normal-length (21–36 days) and normally ovulatory (≥10 days luteal) menstrual cycles

STUDY QUESTION How do surrogates think, feel, and reflect on their experiences of being a surrogate over time? SUMMARY ANSWER Despite continuing to require physical, emotional, and interpersonal labour, surrogates in this study reflected positively on their experiences of being a surrogate decades later. WHAT IS KNOWN ALREADY Research on families created through surrogacy shows that it can be a positive

STUDY QUESTION Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? SUMMARY ANSWER The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and

STUDY QUESTION What are the experiences and outcomes of donor conceived adults who are actively searching for, open to contact with, or not searching for donor connections? SUMMARY ANSWER Most participants were actively searching or open to contact, and 67% had found or been found by a connection; finding or not finding experiences were complex. WHAT IS KNOWN ALREADY There is variation among donor

STUDY QUESTION Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER Larger embryonic crown–rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN Preterm birth, SGA, and congenital anomalies are the most prevalent adverse

STUDY QUESTION Can a functional in vitro model, containing the main cellular components of the uterine wall, be generated from cells derived from patient tissues? SUMMARY ANSWER We present a three-dimensional (3D) physiologically relevant, organ-on-a-chip model of the uterine wall containing primary endometrial and myometrial cellular participants, generated from human uterine tissue. WHAT IS KNOWN

STUDY QUESTION What are the current national medically assisted reproduction (MAR) data collection systems across EU Member States, and how can these countries contribute to a unique, cycle-by-cycle registry for the European Monitoring of Medically Assisted Reproduction (EuMAR) project? SUMMARY ANSWER The study identified significant variation in MAR data collection practices across Member States,

STUDY QUESTION Which decision-making factors influence family building among permanently infertile couples? SUMMARY ANSWER Ethical, legal, and financial considerations outweigh genetic relatedness in decision-making, favouring domestic gestational surrogacy, if this were possible, over international options. WHAT IS KNOWN ALREADY Permanent infertility affects 4-5% of people in the fertile age. Their

STUDY QUESTION How do transfeminine adolescents and their parents experience fertility preservation via testicular sperm extraction (TESE)? SUMMARY ANSWER Participants experienced the TESE process positively when provided with appropriate guidance to navigate the decisional dilemma between preserving future biological parenthood and the pressure to start puberty suppression early. WHAT IS KNOWN ALREADY

STUDY QUESTION Is there an association between male creatinine levels and time to pregnancy (TTP) in couples planning pregnancy? SUMMARY ANSWER Low and high male creatinine concentrations were associated with reduced couple fecundity. WHAT IS KNOWN ALREADY Abundant evidence suggests male creatinine dysfunction is associated with infertility in males with kidney diseases. However, the association of

STUDY QUESTION What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY Chemotherapy and radiotherapy to

STUDY QUESTION What is the molecular landscape underlying the functional decline of human testicular ageing? SUMMARY ANSWER The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing. WHAT IS KNOWN ALREADY Testicular ageing is known to cause male age-related

STUDY QUESTION Does advanced male partner’s age impact live birth rates (LBRs) in IVF treatment when female partner’s age is factored in? SUMMARY ANSWER In fresh IVF cycles LBRs decline with male partner’s age ≥40 years when the female partner is aged 35–39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is

STUDY QUESTION Are there neurobiological changes induced by endometriosis? SUMMARY ANSWER Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis. WHAT IS KNOWN ALREADY Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied

STUDY QUESTION Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C? SUMMARY ANSWER CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C. WHAT IS KNOWN ALREADY Since the beginning of IVF, embryo culture has been performed at

STUDY QUESTION Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans? SUMMARY ANSWER Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding. WHAT IS KNOWN ALREADY In male mice, the Calr3-knockout has been

STUDY QUESTION Are Sertoli cells (SCs) from adult Klinefelter men (47,XXY) capable of proliferating in vitro and maintaining their main phenotypical and functional characteristics as do SCs from adult 46,XY patients? SUMMARY ANSWER Isolated SCs from patients with Klinefelter syndrome (KS) can be expanded in vitro while maintaining their characteristics and a stable karyotype, similar to SCs from 46

STUDY QUESTION Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS? SUMMARY ANSWER This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts. WHAT IS KNOWN ALREADY An early alert

STUDY QUESTION Does RXFP2 disruption impair male fertility? SUMMARY ANSWER We identified biallelic variants in RXFP2 in patients with male infertility due to spermatogenic arrest at the spermatid stage, supporting a role of RXFP2 in human spermatogenesis, specifically in germ cell maturation. WHAT IS KNOWN ALREADY Since RXFP2, the receptor for INSL3, plays a crucial role in testicular descent during

STUDY QUESTION Is virtual reality (VR) an effective non-pharmacological tool to reduce procedural pain during hysterosalpingography (HSG)? SUMMARY ANSWER An HSG with VR does not reduce procedural pain scores compared to an HSG without VR. WHAT IS KNOWN ALREADY An HSG is often experienced as painful and uncomfortable. VR has been proven successful to reduce acute procedural pain during a variety of

STUDY QUESTION Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women’s all-cause and cause-specific

STUDY QUESTION Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children’s neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives

STUDY QUESTION How were the logbook and curriculum for the Nurses and Midwives Certification Programme of ESHRE developed? SUMMARY ANSWER The logbook and corresponding curriculum for the ESHRE Nurses and Midwives Certification Programme were based on an extensive literature review, an international expert panel, and a survey of Belgian and Dutch nurses and midwives (N&M) working in reproductive medicine

STUDY QUESTION Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? SUMMARY ANSWER Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. WHAT IS KNOWN