STUDY QUESTION What are the unrecognized risk factors for recurrent implantation failure (RIF) as defined in the ESHRE recommendation? SUMMARY ANSWER Anti-Müllerian hormone (AMH) is the strongest predictor for RIF, followed by chronic endometritis (CE), intrauterine adhesions, and BMI. WHAT IS KNOWN ALREADY Advanced age is a well-known risk factor for implantation failure, and the definition of RIF

STUDY QUESTION What is the association between insulin resistance (IR), metformin treatment, and the outcomes of IVF in IR infertile women without polycystic ovarian syndrome (non-PCOS)? SUMMARY ANSWER IR among non-PCOS infertile women was associated with worse IVF outcomes compared to insulin-sensitive (IS) infertile women, and metformin treatment prior to embryo transfer (ET) was associated with

STUDY QUESTION Does definitive occlusion of uterine arteries have a short- or long-term impact on ovarian reserve markers in reproductive-age women undergoing laparoscopic myomectomy? SUMMARY ANSWER Preventive definitive uterine artery occlusion (UAO) during laparoscopic myomectomy reduces intraoperative blood loss but does not impact serum AMH levels after short- and long-term follow-up in reproductive-age

STUDY QUESTION What methods are used by sexual and gender minority (SGM) parents to build their families? SUMMARY ANSWER SGM parents used diverse methods to build their families, which varied both by gender identity and age. WHAT IS KNOWN ALREADY Despite experiencing significant barriers to becoming parents, 63% of SGM adults aged 18–35 years old are considering having children or expanding their family

Infertility, affecting one in six couples worldwide, poses significant health and social challenges. While both male and female factors contribute to infertility, male infertility causes remain underexplored, with about 34% of cases classified as unexplained. A few studies focus on the role of lipids in male fertility, and some lipids are rising as key players in spermatozoa. This review highlights

STUDY QUESTION Is it feasible to detect minimal residual disease (MRD) in cryopreserved testicular tissue (TT) from (pre)pubertal boys diagnosed with acute leukemia using molecular biology techniques? SUMMARY ANSWER This pilot study demonstrates the feasibility of detecting MRD in cryopreserved TT, which could guide the choice of the safest techniques for fertility restoration. WHAT IS KNOWN ALREADY

STUDY QUESTION Are serum estradiol and progesterone levels higher in women treated with programmed cycle (PC) FET compared to women treated with a gonadotrophin-stimulated (gSC) FET or a modified natural cycle (mNC) FET during early pregnancy? SUMMARY ANSWER Estradiol and progesterone levels are higher on the day of embryo transfer in women treated with PC compared to those treated with a mNC or gSC

STUDY QUESTION What is the validity of published administrative health data case definitions of polycystic ovary syndrome (PCOS) compared with reference standards? SUMMARY ANSWER Due to the limited number of eligible studies, drawing definitive conclusions is challenging; however, this review highlights significant gaps and variability in current PCOS case definitions, underscoring the need for standardized

Polycystic ovarian syndrome (PCOS) is a common female endocrinologic condition that affects both the metabolic and reproductive systems and is the most frequent cause of anovulatory infertility. It is also associated with a range of psychiatric outcomes in individuals, including bulimia nervosa, schizophrenia, bipolar disorder, depression, anxiety, and personality disorders. At the same time, evidence

STUDY QUESTION Can a reliable assay be developed to quantify DNA accessibility in human sperm to help with the assessment of pre-implantation development affected by dense packaging of mammalian sperm's genetic material? SUMMARY ANSWER We adapted NicE-view, an assay that directly labels accessible DNA, for use in human sperm and applied it to examine spermatozoa from infertile individuals with distinct

STUDY QUESTION What is the optimal stage (immature vs mature) and most efficient vitrification technique (semi-automated vs manual) to ensure the safety of the rescue-IVM (r-IVM) procedure for oocyte cryopreservation? SUMMARY ANSWER Human oocytes should be cryopreserved after r-IVM at the mature stage (r-MII oocytes) by semi-automated or manual vitrification. WHAT IS KNOWN ALREADY r-IVM of immature

STUDY QUESTION What is the minimum effective dose of SHR7280, a novel oral GnRH antagonist, to prevent a premature LH surge in women undergoing controlled ovarian hyperstimulation for ART? SUMMARY ANSWER SHR7280 at 200 mg once every 12 h (Q12h) was the minimal effective dose to suppress an LH surge and was associated with high-quality embryos, and a high clinical pregnancy rate. SHR7280 was well-tolerated

STUDY QUESTION Are maternal folate and vitamin B12 concentrations associated with first-trimester placental growth? SUMMARY ANSWER Maternal folate concentrations and commencement of folic acid supplements prior to conception, as compared to following conception, are positively associated with first-trimester placental volume (PV), whereas no associations were found for maternal vitamin B12 concentrations

STUDY QUESTION Which proteins are involved in the transition of human oocytes from the germinal vesicle (GV) to metaphase I (MI) phase? SUMMARY ANSWER A total of 2369 proteins were identified, including 149 with significantly differential expression, 79 with upregulated expression in MI oocytes and 70 with downregulated expression. WHAT IS KNOWN ALREADY During oocyte maturation, maternal proteins and

STUDY QUESTION Do severely impaired sperm concentrations (oligozoospemia) in male factor infertility affect embryo aneuploidy rates and clinical results after IVF oocyte donation cycles? SUMMARY ANSWER Severe oligozoospermia (SO) in IVF cycles utilizing donor oocytes does not significantly affect embryo euploidy rates or IVF outcomes or cumulative live birth rates (CLBRs). WHAT IS KNOWN ALREADY SO

The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression

STUDY QUESTION Can fast vitrification (FV) and fast warming (FW) protocols effectively reduce oocyte exposure times to cryoprotectants while maintaining survival, developmental potential, and laboratory efficiency compared to a standard protocol? SUMMARY ANSWER FV and FW protocols significantly reduce exposure times compared to a standard protocol without compromising oocyte integrity or developmental

STUDY QUESTION Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height? SUMMARY ANSWER We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche. WHAT IS KNOWN ALREADY Dietary patterns have been sparsely examined in relation to age at menarche and no studies

STUDY QUESTION Does leukocyte-derived Oncostatin-M (OSM) regulate the ovulatory process in human dominant follicles? SUMMARY ANSWER Leukocyte-derived OSM activates key signaling pathways in human preovulatory granulosa cells and modulates steroidogenesis, prostaglandin synthesis, and tissue remodeling in human ovulatory follicles. WHAT IS KNOWN ALREADY Leukocytes are essential regulators of ovulation

STUDY QUESTION What is the association between endometriosis and the type and age of menopause? SUMMARY ANSWER Women with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally. WHAT IS KNOWN ALREADY Endometriosis is associated with reduced ovarian reserve

STUDY QUESTION How do hematological characteristics affect ovarian reserve, ovarian response to ovarian stimulation, and fertility outcomes? SUMMARY ANSWER Although lymphoma characteristics impact serum AMH levels, they do not affect, per se, the response to ovarian stimulation and the number of mature oocytes recovered at the time of fertility preservation; in addition, fertility in survivors of hematologic

STUDY QUESTION What are the current recommended criteria for morphological assessment of oocytes, zygotes, and embryos? SUMMARY ANSWER The present ESHRE/Alpha Scientists in Reproductive Medicine consensus document provides several novel recommendations to assess oocyte and embryo morphology and rank embryos for transfer. WHAT IS KNOWN ALREADY A previous Alpha Scientists in Reproductive Medicine/ESHRE

STUDY QUESTION Does the transcriptome of preconceptional endometrium in the proliferative phase show a specific profile in women with recurrent pregnancy loss (RPL)? SUMMARY ANSWER A specific differential gene expression signature in endometrial samples for women experiencing RPL compared with IVF control women was identified including an RPL subgroup characterized by upregulation of immune-related

Thyroid disorders are among the most prevalent of medical conditions, especially in women, with the prevalence of both hypo- and hyper-thyroidism being 10-fold more common in women than in men. Thyroid hormones play a key role in subfertility associated with ovulatory dysfunction and miscarriages. While overt thyroid disorders are more often clinically diagnosed, subclinical hypothyroidism (SCH) poses

STUDY QUESTION Are preconception sleep characteristics associated with pregnancy loss and adverse pregnancy outcomes? SUMMARY ANSWER Preconception sleep characteristics were not associated with pregnancy loss, but earlier sleep midpoints were associated with lower risk of adverse pregnancy outcomes, while social jetlag >1 h was associated with greater risk of a composite of adverse pregnancy outcomes

STUDY QUESTION Is there an increased risk of immunological diseases among endometriosis patients, and does a shared genetic basis contribute to this risk? SUMMARY ANSWER Endometriosis patients show a significantly increased risk of autoimmune, autoinflammatory, and mixed-pattern diseases, including rheumatoid arthritis, multiple sclerosis, coeliac disease, osteoarthritis, and psoriasis, with genetic

STUDY QUESTION Can a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth? SUMMARY ANSWER We developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation

STUDY QUESTION In patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS; population), is the presence of functional endometrium (FE) in uterine remnants (URs) (exposure), compared with the absence of FE in UR/absence of UR (comparison), associated with a higher prevalence of endometriosis (outcome)? SUMMARY ANSWER The aggregate prevalence of endometriosis was considerably higher in MRKHS patients

STUDY QUESTION How updated expression and genomic data combined with a disease/disorder-specific classification system can be used to correct a gene model for a better evaluation of the pathogenicity of variants found in patients? SUMMARY ANSWER By combining available genomic and transcriptomic data from several species and a quantitative classification framework with primary ovarian insufficiency

STUDY QUESTION To what extent are there racial and ethnic disparities in fecundability in North America? SUMMARY ANSWER In a North American preconception cohort study, we observed large differences in fecundability across racial and ethnic groups. WHAT IS KNOWN ALREADY Several studies in the United States (USA) have shown that Black women tend to wait longer for fertility treatment and are less likely

STUDY QUESTION What were the rates of utilization, effectiveness, and safety for assisted reproductive technology (ART) throughout the world in 2017 and 2018, and what trends were observed? SUMMARY ANSWER The total reported number of ART fresh and frozen cycles conducted in 83 participating countries was 2 913 498 in 2017 and 3 303 505 in 2018, with 5-year trends including an increasing proportion

STUDY QUESTION Can a core outcome set be developed through a global consensus to standardize outcome selection, collection, comparison, and reporting in future male infertility trials? SUMMARY ANSWER A minimum dataset, known as a ‘core outcome set’, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. WHAT IS KNOWN

STUDY QUESTION Does COVID-19 vaccination affect the risk of pregnancy-induced hypertension (PIH) in women undergoing ARTs, and does this risk differ based on vaccine type (inactivated vs recombinant) and timing relative to embryo transfer? SUMMARY ANSWER Women who received inactivated COVID-19 vaccines before undergoing ART had a significantly increased risk of developing PIH, particularly when vaccinated

Advances in reproductive medicine and genetic technologies now offer prospective parents the option to test IVF embryos for genetic predispositions to complex diseases, such as coronary heart disease and psychiatric disorders, through polygenic embryo screening (PES). However, limited clinical data on its real-world use leaves parents facing complex decisions based on probabilistic risk scores, requiring

STUDY QUESTION Do corifollitropin alfa (CFA) and follitropin beta (FSH-B) have different effects on oocyte yield and live birth rates (LBRs) after IVM in women with polycystic ovaries? SUMMARY ANSWER In patients who underwent IVM, one injection of CFA resulted in lower oocyte retrieval rates, but similar cumulative LBRs compared to three injections of FSH-B. WHAT IS KNOWN ALREADY IVM involves the maturation

STUDY QUESTION Does the restoration of regulatory T cells (Tregs) suppress the progression of endometriosis? SUMMARY ANSWER Adoptive transfer of Tregs suppresses the progression of endometriosis and reduces the levels of helper T (Th)-cell-related and proinflammatory cytokines in mice. WHAT IS KNOWN ALREADY Endometriosis is a chronic inflammatory gynecological disease, which involves multiple immune

Ovariostasis is a reversible and temporary suspension of the cyclic ovarian activity, characterized by anovulation and hypogonadotropinemia (low serum concentrations of FSH and LH), which can be observed in case of pregnancy or hypothalamic amenorrhea or medically obtained through the administration of combined hormonal contraceptives, progestin-only pills, or GnRH analogues. Ovariostasis effectively

STUDY QUESTION Is preimplantation genetic testing for mitochondrial DNA (mtDNA) disorders (PGT-mt) feasible at early compaction and blastocyst stages? SUMMARY ANSWER Pathogenic mtDNA variants segregate evenly among cell types and various lineages of a given embryo during preimplantation development, supporting the relevance of genetic analyses performed on Day 4 blastomere and on Day 5 or 6 trophectoderm

STUDY QUESTION How does adenomyosis affect live birth rates (LBRs) in women undergoing ART compared to a matched control population? SUMMARY ANSWER Women with adenomyosis, matched with controls for age, blastocyst count, and top-quality blastocyst count, exhibited reduced LBR following IVF/ICSI treatment. WHAT IS KNOWN ALREADY Adenomyosis, a benign uterine disorder, is believed to hinder implantation

STUDY QUESTION Do the diagnostic delay and symptoms differ between endometriosis patients with advanced disease, defined as endometriosis involving the vagina, intestine, rectovaginal septum, or bladder (eVIRB), compared to patients without endometriosis in these locations (non-eVIRB)? SUMMARY ANSWER Patients with advanced endometriosis had a significantly longer diagnostic delay, an earlier onset

STUDY QUESTION Is being born of a young mother associated with worse gynecologic health, as indicated by a bilateral oophorectomy or hysterectomy before age 40? SUMMARY ANSWER Daughters of mothers younger than 25 did not have reduced parity but did have a higher risk of having bilateral oophorectomy or hysterectomy before age 40, particularly if their mother was younger than 20 years at their birth

STUDY QUESTION What is the effectiveness of swim-up (SU) and density gradients (DG) for sperm preparation in infertile couples undergoing IUI? SUMMARY ANSWER In infertile couples undergoing IUI, SU and DG did not result in statistically significant different live birth rates. WHAT IS KNOWN ALREADY SU and DG are the two most commonly used techniques for sperm preparation in infertile couples undergoing

STUDY QUESTION What is the optimal sperm concentration threshold for screening Y-chromosome microdeletions (YCMs) in male infertility patients? SUMMARY ANSWER This study identified three clinically relevant screening thresholds: an receiver operating characteristic (ROC)-optimal cutoff at 0.45 million sperm/ml, a high-sensitivity cutoff at 8 million sperm/ml, and a cost-effective threshold at 1 million

STUDY QUESTION Is patient consent to research associated with the distribution of population characteristics and study outcomes in ART cohort studies? SUMMARY ANSWER The distribution of population characteristics in the patient consent subset differs from that in the non-consent subset and is not fully representative of the general ART population; thus, study results of population subsets requiring

STUDY QUESTION Do IVF outcomes differ in patients over the age of 40 using donor oocytes? SUMMARY ANSWER Even with the use of donor oocytes, maternal age appears to have an impact on live birth (LB) rate and perinatal outcomes. WHAT IS KNOWN ALREADY Maternal age has a significant impact on the outcome of IVF, mainly attributed to age-related oocyte chromosomal factors. STUDY DESIGN, SIZE, DURATION

STUDY QUESTION What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults? SUMMARY ANSWER Our findings show dysregulation of plasma metabolomic profiles in adolescents and young adults with endometriosis, revealing systemic elevation of fatty acyls and ceramides in endometriosis cases compared to controls. WHAT IS KNOWN ALREADY Endometriosis is a gynecologic

STUDY QUESTION Which phenotypes can be confidently linked to a genetic etiology in males with congenital hypogonadotropic hypogonadism (CHH) resulting in absent or arrested puberty? SUMMARY ANSWER In this systematic review and reclassification of the disease-causing potential of gene variants using the recommendations of the American College of Medical Genetics and Genomics (ACMG) and the Association

In recent years, an increased interest in the efficacy of intrauterine infusion of autologous platelet-rich plasma (PRP) in women with repeated implantation failure (RIF) has resulted in the publication of 13 randomized controlled trials (RCTs) and 11 meta-analyses. Although these meta-analyses support an increase in pregnancy rates after intrauterine infusion of autologous PRP, the low quality of