STUDY QUESTION Do sexual, relational, and psychological functioning of male partners of women with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome differ from male partners of women without MRKH syndrome? SUMMARY ANSWER Male partners of women with MRKH syndrome did not significantly differ in sexual functioning but reported higher relational satisfaction and less anxiety than the control group. WHAT

STUDY QUESTION Are live birth rates (LBRs) per woman following flexible progestin-primed ovarian stimulation (fPPOS) treatment non-inferior to LBRs per woman following the conventional GnRH-antagonist protocol in expected suboptimal responders undergoing freeze-all cycles in assisted reproduction treatment? SUMMARY ANSWER In women expected to have a suboptimal response, the 12-month likelihood of live

STUDY QUESTION Does the risk of childhood cancer following ARTs vary by sex? SUMMARY ANSWER In this registry-based study, some childhood cancers showed positive sex- and age-specific associations in children conceived using certain ART modalities, which were not evident in overall combined analyses. WHAT IS KNOWN ALREADY The relationship between ART and risk of childhood cancer has shown diverse outcomes

STUDY QUESTION How are the changing maternal age structure and population growth expected to shape future twinning rates in low-income countries? SUMMARY ANSWER With maternal age at birth projected to shift toward older ages, twinning rates are also estimated to increase in most low-income countries by 2050 and even more by 2100. WHAT IS KNOWN ALREADY Many of the sub-Saharan African and South Asian

STUDY QUESTION How can we best achieve tissue segmentation and cell counting of multichannel-stained endometriosis sections to understand tissue composition? SUMMARY ANSWER A combination of a machine learning-based tissue analysis software for tissue segmentation and a deep learning-based algorithm for segmentation-independent cell identification shows strong performance on the automated histological

STUDY QUESTION To what extent are self-reported diagnoses of food allergies associated with fecundability, the per-cycle probability of conception? SUMMARY ANSWER Fecundability was not appreciably associated with self-reported food allergy diagnoses, number of food allergies, age at first diagnosis, or time since last allergic reaction. WHAT IS KNOWN ALREADY Food allergies are atopic diseases that

STUDY QUESTION Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART? SUMMARY ANSWER Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator. WHAT IS KNOWN

STUDY QUESTION Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis? SUMMARY ANSWER A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis. WHAT IS KNOWN ALREADY Endometriosis poses intricate medical challenges for affected individuals and their physicians

STUDY QUESTION Does one-step warming (OW), a simplified embryo warming protocol, adversely affect survival and developmental potential in vitrified cleavage or blastocyst stage embryos compared to standard multi-step warming (SW)? SUMMARY ANSWER OW showed no detrimental effects on survival and developmental potential compared to SW in cleavage and blastocyst stage embryos. WHAT IS KNOWN ALREADY While

The extensive use of bisphenols in the plastics industry globally is a major growing concern for human health. Bisphenol compounds are easily leached out from plastic containers to food, beverages, and drinking water and contaminate the natural environment. Daily exposure of bisphenol compounds increases their load and impairs various organs, including the reproductive system. Bisphenol compounds directly

STUDY QUESTION Can antinuclear antibodies (ANA) affect the subsequent live birth rate (LBR) in patients with unexplained recurrent pregnancy loss (RPL) in the absence of antiphospholipid antibodies (aPL)? SUMMARY ANSWER Women with unexplained RPL have a high probability of live birth following a positive pregnancy test (>70%), being similar between those with positive and negative ANA testing, regardless

STUDY QUESTION Is it possible to predict an euploid chromosomal constitution and identify a transcriptomic profile compatible with extended embryonic development from RNA sequencing (RNA-Seq) data? SUMMARY ANSWER It has been possible to obtain a karyotype comparable to preimplantation genetic testing for aneuploidy (PGT-A), in addition to a transcriptomic signature of embryos which might be suggestive

STUDY QUESTION How does pre-diagnosis use of hospital care differentiate between women later diagnosed with endometriosis and age-matched controls without a diagnosis? SUMMARY ANSWER Women with hospital-diagnosed endometriosis had more frequent hospital contacts in the 10 years leading up to the diagnosis compared to women without a diagnosis of endometriosis, and the contacts were related to registered

STUDY QUESTION How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease? SUMMARY ANSWER For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data—International Classification of Diseases (ICD) 9 codes—and surgically confirmed diagnoses among participants who

STUDY QUESTION Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes? SUMMARY ANSWER Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity. WHAT IS KNOWN ALREADY Somatic cancer-driver mutations

STUDY QUESTION To what extent is male physical activity (PA) associated with fecundability (per-cycle probability of conception)? SUMMARY ANSWER Preconception levels of vigorous, moderate, or total PA were not consistently associated with fecundability across Danish and North American cohorts, but there was suggestive evidence that bicycling with a ‘soft, comfort seat’ was associated with reduced fecundability

STUDY QUESTION What is the cost per live birth after live donor uterus transplantation in a Swedish clinical trial setting? SUMMARY ANSWER The total cost per child, from a health care perspective, was calculated to be €124 894 and if only surgically successful transplants are considered, the total cost per live birth was €107 120. WHAT IS KNOWN ALREADY Uterus transplantation has proved to be a feasible

STUDY QUESTION Does adjuvant growth hormone (GH) therapy in GnRH antagonist cycles improve reproductive outcomes in the general IVF population? SUMMARY ANSWER Empiric adjuvant GH therapy in GnRH antagonist cycles does not improve IVF stimulation results or reproductive outcomes, including implantation, miscarriage, and clinical pregnancy rates. WHAT IS KNOWN ALREADY Previous evidence regarding the

STUDY QUESTION Do the infertility core outcome set and standardized definitions affect the outcome selection for randomized controlled trials, and what aspects should be further improved in the future? SUMMARY ANSWER Intrauterine pregnancy demonstrated the highest uptake level, whereas others were low, especially in neonatal outcomes; as time progresses, the target sample size increases, and with prospective

STUDY QUESTION What is the governmental fiscal impact of a new assisted reproduction subsidy scheme based on projected lifetime net taxes attributed to resulting live births in Taiwan? SUMMARY ANSWER We estimate that the new fertility reimbursement scheme has generated favorable lifetime fiscal gains for the Taiwanese government, resulting in a return on investment (ROI) of NT$5.6 for every NT$1.0

Artificial intelligence (AI) has the potential to standardize and automate important aspects of fertility treatment, improving clinical outcomes. One promising application of AI in the fertility clinic is the use of machine learning (ML) tools to assess embryos for transfer. The successful clinical implementation of these tools in ways that do not erode consumer trust requires an awareness of the ethical

STUDY QUESTION Is there an increased risk of reproductive or colon cancer in women with Turner syndrome and their family members? SUMMARY ANSWER Our data suggest that there is an increased risk for sigmoid colon cancer in women with Turner syndrome and an increased prostate cancer risk in second- and third-degree male relatives. WHAT IS KNOWN ALREADY Turner syndrome has been associated with lower risk

STUDY QUESTION What role do sphingolipids have in mediating human sperm capacitation? SUMMARY ANSWER Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion. WHAT IS KNOWN ALREADY Bioactive sphingolipids, such as S1P

STUDY QUESTION What is the predictive value of oligomenorrhea and other PCOS diagnostic characteristics in adolescence (age 15–18 years) for future fertility and cardiovascular and metabolic health at adult age? SUMMARY ANSWER Adolescents with oligomenorrhea are more often treated to conceive but are as likely to have as much children as those with regular periods, while persisting oligomenorrhea may

STUDY QUESTION To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies? SUMMARY ANSWER HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between

STUDY QUESTION What is the association between infertility with or without fertility treatment and incident onset of systemic autoimmune rheumatic disease (SARD) among women who give birth? SUMMARY ANSWER Women who experienced infertility but did not use fertility treatment had a higher incidence of SARD up to 9 years after delivery than those who did not experience infertility, even after accounting

STUDY QUESTION Are there differences in psychosocial and physical wellbeing among women and male partners undergoing modified natural cycle (mNC) frozen embryo transfer (FET) in immediate compared to postponed cycles after ovarian stimulation (OS) and oocyte pick-up (OPU)? SUMMARY ANSWER Significantly more women in the immediate group reported physical symptoms than women in the postponed group whilst

STUDY QUESTION Does exposure to particulate matter (PM) air pollution prior to oocyte retrieval or subsequent frozen embryo transfer (FET) affect the odds of live birth? SUMMARY ANSWER Live birth rates are lower when particulate matter (PM2.5 and PM10) levels are higher prior to oocyte retrieval, regardless of the conditions at the time of embryo transfer. WHAT IS KNOWN ALREADY Exposure to air pollution

The immune system plays a major role in ovarian physiology by regulating the ovarian follicle pool through complex signaling of different growth factors, cytokines, and chemokines. These may promote follicle activation and further growth but could also trigger follicle atresia and clearance of aging or damaged cells within the ovarian cortex. Moreover, extraglandular steroidogenesis potentially occurring

Grading of blastocyst morphology is used routinely for embryo selection with good outcomes. A lot of effort has been placed in IVF to search for the prize of selecting the most viable embryo to transfer (‘the golden fleece of embryology’). To improve on morphology alone, artificial intelligence (AI) has also become a tool of interest, with many retrospective studies being published with impressive

STUDY QUESTION What is the composition of currently available commercial human embryo culture media provided by seven suppliers, for each stage of human preimplantation embryo development? SUMMARY ANSWER While common trends existed across brands, distinct differences in composition underlined the absence of a clear standard for human embryo culture medium formulation. WHAT IS KNOWN ALREADY The reluctance

STUDY QUESTION Is there a difference in the use of endocrine endometriosis therapy in endometriosis patients with and without endometrioma? SUMMARY ANSWER Patients with endometriomas received significantly less endocrine endometriosis treatment (present intake in 42.5%) compared to patients with other forms of endometriosis and without endometriomas (present intake in 52.1%). WHAT IS KNOWN ALREADY

STUDY QUESTION What is the transcriptomic response of human blastocysts following internalization of extracellular vesicles (EVs) secreted by the human endometrium? SUMMARY ANSWER EVs secreted by the maternal endometrium induce a transcriptomic response in human embryos that modulates molecular mechanisms related to embryo development and implantation. WHAT IS KNOWN ALREADY EVs mediate intercellular

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