STUDY QUESTION Does Cushing’s syndrome (CS) differently affect the gonadotrope axis and testicular functions (GA/TF) according to the hypercortisolism intensity and underlying etiology? SUMMARY ANSWER Endogenous cortisol excess caused by CS leads to varying degrees of hypogonadotropic hypogonadism (HH) with more severe GA/TF impairment and altered spermatogenesis in men with intense hypercortisolism

STUDY QUESTION What are the effects of male anxiety and depression on IVF outcomes? SUMMARY ANSWER Men with anxiety had lower final total motile sperm counts (fTMSC) during IVF compared to men without anxiety; however, there were no differences in live birth rates (LBRs). WHAT IS KNOWN ALREADY Studies have shown that male anxiety causes low sperm motility, worse sperm morphology, and increased DNA

STUDY QUESTION Can maternal serum levels of soluble programmed cell death-1 (sPD-1) and its ligand (sPD-L1) serve as biomarkers for missed miscarriage (MM)? SUMMARY ANSWER Serum sPD-L1 levels are significantly decreased in MM patients and may serve as a potential predictive biomarker for miscarriage. WHAT IS KNOWN ALREADY Programmed cell death-1 (PD-1) and its ligand (PD-L1) comprise important immune

STUDY QUESTION Are human ovarian aging and the age-related female fertility decline caused by oxidative stress and mitochondrial dysfunction in oocytes? SUMMARY ANSWER We found oxidative damage in oocytes of advanced maternal age, even at the primordial follicle stage, and confirmed mitochondrial dysfunction in such oocytes, which likely resulted in the use of alternative energy sources. WHAT IS KNOWN

STUDY QUESTION What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? SUMMARY ANSWER Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. WHAT IS KNOWN ALREADY Reproductive factors have been

STUDY QUESTION Are there associations between natural or surgical menopause and incident dementia by age at menopause? SUMMARY ANSWER Compared to age at menopause of 46–50 years, earlier natural menopause (≤40 and 41–45 years) was related to higher risk of all-cause dementia, while a U-shape relationship was observed between age at surgical menopause and risk of dementia. WHAT IS KNOWN ALREADY Menopause

STUDY QUESTION Are there any differences in physical and psychosocial well-being among women undergoing modified natural cycle frozen embryo transfer (mNC-FET) with or without vaginal progesterone as luteal phase support (LPS)? SUMMARY ANSWER Women undergoing mNC-FET with vaginal progesterone supplementation were more likely to experience physical discomfort but there was no difference in psychosocial

STUDY QUESTION How does the number of children in women with primary ovarian insufficiency (POI) compare to the number for control women across their reproductive lifespans? SUMMARY ANSWER Approximately 14% fewer women with POI will have children, but for those able to have children the median number is 1 less than for age-matched controls. WHAT IS KNOWN ALREADY Women with POI are often identified

STUDY QUESTION Does a chemically defined maturation medium supplemented with FGF2, LIF, and IGF1 (FLI) improve in vitro maturation (IVM) of cumulus–oocyte complexes (COCs) obtained from children, adolescents, and young adults undergoing ovarian tissue cryopreservation (OTC)? SUMMARY ANSWER Although FLI supplementation did not increase the incidence of oocyte meiotic maturation during human IVM, it

STUDY QUESTION Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? SUMMARY ANSWER Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. WHAT IS KNOWN ALREADY Endometriosis is associated with a

STUDY QUESTION Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment? SUMMARY ANSWER SC in human blastocyst is associated with reduced euploid embryo and pregnancy rates. WHAT IS KNOWN ALREADY SC of the human blastocyst is a phenomenon that was revealed relatively recently following the clinical application of time-lapse monitoring in IVF laboratories. The ploidy and

STUDY QUESTION Can machine learning predict the number of oocytes retrieved from controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER Three machine-learning models were successfully trained to predict the number of oocytes retrieved from COH. WHAT IS KNOWN ALREADY A number of previous studies have identified and built predictive models on factors that influence the number of oocytes retrieved

In the past decade, scientific developments in human germline genome editing (GGE) have reinvigorated questions about research ethics, responsible innovation, and what it means to do good in the field of reproductive biology and medicine. In recent years, it has become part of the ethical debate on GGE whether categorical objections about (un)naturalness, dignity, respect for the gene pool as common

STUDY QUESTION Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? SUMMARY ANSWER As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. WHAT IS KNOWN ALREADY Subjects

Transgender and nonbinary people with female birth sex may utilize testosterone therapy for masculinization. Individuals interested in reproduction using their own gametes should be offered fertility preservation prior to starting testosterone. However, logistical and practical barriers prevent many from accessing fertility preservation options prior to starting testosterone. Some of these transmasculine

In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about the intersection of age and male reproduction. Our current understanding is that advancing age brings forth a progressive decline in male fertility accompanied by a reduction in circulating testosterone levels and the

STUDY QUESTION In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? SUMMARY ANSWER We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with

STUDY QUESTION What are the differences in gene expression of cumulus cells (CCs) between young women with diminished ovarian reserve (DOR) and those of similar age with normal ovarian reserve (NOR)? SUMMARY ANSWER Gene expression and metabolome profiling analysis demonstrate that the de novo serine synthesis pathway (SSP) is increased in the CCs of young women with DOR. WHAT IS KNOWN ALREADY The incidence

During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies

STUDY QUESTION What are the experiences of single men using egg donation and surrogacy as a route to parenthood? SUMMARY ANSWER The fathers mainly had a positive relationship with the surrogate and simultaneously exercised agency, and experienced challenges, during the process of surrogacy. WHAT IS KNOWN ALREADY Little is known about single men’s experiences of egg donation and surrogacy arrangements

STUDY QUESTION Which patients might benefit from insemination of delayed-matured oocytes? SUMMARY ANSWER Delayed-matured oocytes had a ≥50% contribution to the available cohort of biopsied blastocysts in patients with advanced maternal age, low maturation, and/or low fertilization rates. WHAT IS KNOWN ALREADY Retrieved immature oocytes that progress to the MII stage in vitro could increase the number

STUDY QUESTION Is exposure to toxic metal cadmium associated with increased endometriosis prevalence among a nationally representative sample of the US population? SUMMARY ANSWER Concentrations of urinary cadmium, a long-term biomarker (10–30 years) of cadmium exposure, were associated with an increased prevalence of endometriosis. WHAT IS KNOWN ALREADY Cadmium exhibits estrogenic properties and may

STUDY QUESTION Can anti-Müllerian hormone (AMH) help predict how many oocytes will be retrieved following double stimulation (DuoStim)? SUMMARY ANSWER A simple clinical tool can use serum AMH values to predict ovarian response following DuoStim in IVF cycles. WHAT IS ALREADY KNOWN The knowledge that multiple follicular waves arise during a single ovarian cycle has led to the introduction of unconventional

STUDY QUESTION Could inhibition of the checkpoint kinase (CHEK) pathway protect human oocytes and even enhance the anti-tumour effects, during chemotherapy? SUMMARY ANSWER CHEK inhibitors prevented apoptosis of human oocytes induced by chemotherapy and even enhanced the anti-tumour effects. WHAT IS KNOWN ALREADY CHEK inhibitors showed ovarian protective effects in mice during chemotherapy, while their

STUDY QUESTION What is the association between past infertility and the type and timing of menopause in midlife women? SUMMARY ANSWER Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. WHAT IS KNOWN ALREADY Infertility is

STUDY QUESTION Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)? SUMMARY ANSWER For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers

STUDY QUESTION Are there some characteristics that render individuals more susceptible to report menstrual changes following the Coronavirus disease 2019 (COVID-19) vaccination? SUMMARY ANSWER We found that 30% of menstruating women reported menstrual changes following COVID-19 vaccination and several potential risk factors including stress, vaccine concerns, severe COVID-19 infection, and immediate

STUDY QUESTION Does chemotherapy exposure affect IVM potential of immature oocytes retrieved from the ovarian cortex following ovarian tissue cryopreservation (OTC) for fertility preservation? SUMMARY ANSWER The IVM potential of oocyte retrieved from ovarian cortex following OTC is not affected by prior exposure to chemotherapy but primarily dependent on patient's age, while successful retrieval of

STUDY QUESTION Does the meteorological season at the time of oocyte retrieval affect live birth rates in subsequent frozen embryo transfers? SUMMARY ANSWER Frozen embryo transfers resulting from oocytes retrieved in summer have 30% increased odds of live birth compared to frozen embryo transfers resulting from oocytes retrieved in autumn, regardless of the season at the time of embryo transfer. WHAT

STUDY QUESTION Are the extracellular vesicles (EVs) secreted by the maternal endometrium uptaken by human embryos and is their miRNA cargo involved in implantation and embryo development? SUMMARY ANSWER Data suggest that EVs secreted by human endometrial epithelial cells are internalized by human blastocysts, and transport miRNAs to modulate biological processes related to implantation events and early

STUDY QUESTION Does a public online IVF success prediction calculator based on real-world data help set patient expectations? SUMMARY ANSWER The YourIVFSuccess Estimator aided consumer expectations of IVF success: one quarter (24%) of participants were unsure of their estimated IVF success before using the tool; one half changed their prediction of success after using the tool and one quarter (26%)

STUDY QUESTION Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis? SUMMARY ANSWER Compared to reference women, the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis. WHAT IS KNOWN ALREADY Endometriosis is associated with pain and reduced

Study question What are the reproductive treatment outcomes in women who underwent elective oocyte cryopreservation (EOC) returning to our clinic with a desire for a child? Summary answer Whether to warm oocytes or to first use fresh oocytes for ART depends on age upon returning, but both strategies resulted in favourable reproductive outcomes. What is known already Most affluent countries have observed

Study question Does blastocyst-stage embryo transfer in fresh and frozen cycles improve the cumulative live birth rate (cLBR) compared with cleavage-stage embryo transfer in IVF/ICSI treatments? Summary answer In good prognosis IVF patients (≥4 available embryos), a blastocyst-stage transfer policy did not result in a significant higher cLBR compared to cleavage-stage transfer policy. What is known

Study question Can an artificial intelligence (AI) improve the speed and accuracy of identifying sperm in complex testicular tissue samples? Summary answer Trained AI can identify sperm in real-time instantly with higher accuracy, not only reducing strain on embryologists but increasing sample coverage in a shorter time. What is known already Non-obstructive azoospermia (NOA) is a form of severe male-factor

Study question Does exogenous progesterone for luteal phase support in natural cycles affect the biochemical, clinical pregnancy, livebirth or miscarriage rates in women with unexplained infertility (UI)? Summary answer Progesterone luteal support lead to an increase in livebirth rate from 7% to 15.3% and a decrease in miscarriage rates from 40% to 20%. What is known already Unexplained infertility

Study question What is the time required in men who have suffered a mild Covid-19 infection, for the seminal parameters to be restored to the pre-Covid values? Summary answer The effect of Covid-19 infection on the concentration and sperm motility is clearly confirmed and is maintained over time, at least beyond 100 days. What is known already Although several studies have been performed on the effect

Study question What is the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes? Summary answer Impaired markers of ovarian reserve in childhood HL survivors substantiate risk of a reduced fertile life span. Pregnancy outcomes seem reassuring at a young age. What is known already Childhood Hodgkin Lymphoma (HL) is nowadays highly curable with survival

Study question Is double-strand DNA break repair functional in human preimplantation embryos and what implications might a deficiency have for genome editing performed at early developmental stages? Summary answer CRISPR-Cas9 succeeds in generating DNA breaks with high efficiency, but these often remain unresolved, indicating that early human embryos are deficient in DNA repair. What is known already

Study question Does adenomyosis impact reproductive and neonatal outcomes? Summary answer Adenomyosis increases risk of infertility and pregnancy/delivery complications. Increased surveillance may aid in prevention and/or decreasing risk of maternal and neonatal morbidity and mortality. What is known already Patients with adenomyosis experience greater adverse obstetric and gynecological events which

Study question Is polycystic ovary syndrome (PCOS) associated with epithelial ovarian cancer and borderline ovarian tumors? Summary answer Overall, no association between PCOS and epithelial ovarian tumors was seen, however, we observed an increased risk of ovarian cancer among postmenopausal women with PCOS. What is known already Few studies have investigated the association between PCOS and epithelial

STUDY QUESTION What clinical and laboratory differences emerge from parallel direct comparison of embryos reaching the blastocyst stage between Days 4, 5, 6, and 7 (Days 4–7)? SUMMARY ANSWER Increasing times to blastocyst formation are associated with a worse clinical outcome and perturbations in developmental patterns appear as early as the fertilization stage. WHAT IS KNOWN ALREADY Previous evidence

STUDY QUESTION Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)? SUMMARY ANSWER The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation

STUDY QUESTION Is there a relationship between pregnancy termination history and metabolic syndrome (MetS), and if so, is the relationship moderated by physical activity (PA)? SUMMARY ANSWER Induced abortion, and both miscarriage and induced abortion, increased the risk of MetS, while leisure PA attenuated the effects of induced abortion, and both miscarriage and induced abortion, on the risk of MetS

STUDY QUESTION Do expectant parents experience increased anxiety and depression during pregnancies conceived through ART compared to spontaneous conception? SUMMARY ANSWER Among all expectant parents in the sample, those who conceived through ART reported overall lower levels of anxiety and depression in pregnancy compared to expectant parents who conceived spontaneously, while in the subsample of

STUDY QUESTION Does 8 weeks of daily low-dose hCG administration affect androgen or inhibin B levels in serum and/or follicular fluid (FF) during the subsequent IVF/ICSI cycle in women with low ovarian reserve? SUMMARY ANSWER Androgen levels in serum and FF, and inhibin B levels in serum, decreased following 8 weeks of hCG administration. WHAT IS KNOWN ALREADY Recently, we showed that 8 weeks of low-dose

Study question Is the vaginal or faecal microbiome different between primary RPL (pRPL) and secondary RPL (sRPL) patients, and is it related to reproductive outcome after referral? Summary answer Before pregnancy, the vaginal microbiome differed between pRPL and sRPL, and the faecal microbiome was altered in those who did not achieve pregnancy after follow-up. What is known already RPL is a heterogeneous

Study question Does ovarian endometriosis deteriorate embryo quality in terms of morphokinetic parameters determined by time-lapse images? Summary answer Embryos from ovarian endometriosis patients accelerate their early developmental events but decelerate after t5. Completion of late developmental events were significantly delayed in endometriosis group. What is known already Endometriosis may affect

Study question What are the transcriptomic differences between child and adult ovarian follicles in the human cortex? Summary answer Our results suggest that human ovarian cortical follicles show marked differences before and after puberty, with the greatest differences being present in the secondary stage. What is known already The ovaries and their main functional structures, follicles, are important

Study question Is a combination of parenteral methotrexate and oral gefitinib more effective than methotrexate alone in the treatment of tubal ectopic pregnancy? Summary answer In women with a tubal ectopic pregnancy, adding oral gefitinib to parental methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. What is known already Current treatment of tubal

Study question Can microRNA expression in blastocoel fluid (BF) predict embryo implantation potential? Summary answer Up-regulation of miR-106, miR-373, miR-301, miR-320 and miR-525-3p represents the molecular signature characterizing the embryos with high implantation capability. What is known already The discovery of DNA within the BF and in spent embryo culture media, has caused increased interest

Study question Does intraovarian administration of platelet rich-plasma (PRP) increase ovarian response in women with poor ovarian response (POR) undergoing IVF treatment? Summary answer In patients with low ovarian response, the number of oocytes and embryos is higher in the 4 cycles after PRP administration compared to pre-PRP cycles. What is known already The number of oocytes after controlled ovarian

Study question How should men with globozoospermia be managed in Assisted Reproductive Technologies (ART)? Summary answer IMSI (intracytoplasmic morphologically selected sperm injection), without oocyte activators (OA) allows to obtain a live birth, even when there is a mutation of DPY19L2 gene. What is known already Globozoospermia is a rare syndrome found in less than 0.1% of the infertile population

Study question Can centrifugation-free sperm separation device be used to simplify and standardize the selection of high-quality spermatozoa? Summary answer Centrifugation-free CA0 sperm separation device minimizes inter- and intra-operator variability and yields spermatozoa with comparable fertilizing properties in a variety of semen conditions. What is known already Centrifugation-based sperm separation

Study question Is it safe to have a pregnancy in women with prior history of hormone receptor-positive early breast cancer? Summary answer Pregnancy following breast cancer treatments in young women with history of hormone receptor-positive disease is safe with no detrimental effect on patients’ prognosis. What is known already Breast cancer is the most common malignancy diagnosed in women of reproductive

Study question What can we learn from 3D reconstructions of cleavage-stage embryos derived from Hoffman modulation contrast (HMC) time-lapses? Summary answer A simple spatial biomarker extracted from 3D embryo reconstructions at the t4 and t8 stages is associated with blastulation, blastocyst quality, pregnancy and live birth. What is known already Several works have demonstrated significant associations

Study question Are there differential transcriptomic profiles of the receptive phase endometria in infertile women with different infertility diagnoses? Summary answer Endometrium-related pathologies such as endometriosis and RIF seemed to share similar endometrial molecular profiles in mid-secretory phase,while samples from unexplained infertility were similar to controls. What is known already Successful

Study question Investigating estradiol in relation with other sperm parameters might reveal new correlations which would help our understanding of male idiopathic infertility Summary answer Statistical significance was found in a series of correlations of E2 levels and sperm, hormonal and health parameters What is known already Male infertility is a rising major health concern, with sperm counts decreasing

Study question Does a Decision-Aid for those considering elective egg-freezing impact decisional conflict, the decision-making process, and quality of the decision made, compared to existing information? Summary answer The Decision-Aid significantly reduced decisional conflict and improved preparedness for decision-making. What is known already Elective egg-freezing offers women the potential to extend

Study question Can progestins be used to prevent spontaneous LH surge during ovarian stimulation (OS) without affecting the euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes? Summary answer Progestin Primed Ovarian Stimulation (PPOS) (conducted with norethisterone acetate) and conventional-OS with GnRH-antagonist show similar EBR per MII-oocytes What is known already PPOS is a novel OS protocol