We investigated the impact of natural cycle/modified natural cycle and artificial cycle in oocyte donation pregnancies on obstetric/neonatal outcomes and placental angiogenic biomarkers. A total number of 201 singleton live births resulted from in vitro fertilization with oocyte donation were enrolled: n = 70 after natural cycle/modified natural cycle endometrial preparation and n = 131 after artificial cycle endometrial preparation. Moreover, 35 placental biopsies were collected: n = 12 after natural cycle/modified natural cycle endometrial preparation, n = 23 after artificial cycle endometrial preparation. Finally, 24 placentae from women with a spontaneous, healthy singleton pregnancy at term, who showed no signs of maternal, placental or fetal disease were used as control. We reported a lower incidence of both hypertensive disorders of pregnancy (7.1

Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15-39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet real-world access data remain limited. Methods: This multicentre, retrospective observational study analysed FP counselling for women aged 15-39 with haematological malignancies from 2015 to 2023. Counselling data were extracted from the Italian Assisted Reproductive Technology Registry (IARTR). This data collection system, known as PreFerIta, was developed within a project supported by the Italian Ministry of Health to collect data on Fertility Preservation (FP) treatments in oncology patients and/or those at risk of iatrogenic infertility, provided in seven specialised ART centres across Italy. The PreFerIta database includes data on both oocyte cryopreservation and ovarian tissue cryopreservation. Annual visits were related to the estimated regional incidence of new haematological malignancies (GBD 2023). Counselling-to-incidence ratios, absolute/relative gaps, and 95% confidence intervals (CIs) were calculated. Results: From 2015 to 2023, an estimated 4473 new haematological malignancies occurred in the catchment regions. Concurrently, 1200 FP counselling visits were recorded. While incidence modestly declined, counselling activity remained high. The counselling-to-incidence ratio increased from 17.33% in 2015 to 31.92% in 2018, stabilising between 26% and 31% thereafter (30.98% in 2023). The relative counselling gap decreased from 82.67% to 69.02%. These ratios represent lower-bound estimates of access to specialised oncofertility consultations. Conclusions: In this Italian network, approximately one in four to one in three incident haematological malignancies in young women were associated with specialised FP counselling. This reflects a substantial integration of oncofertility services into haematology care, highlighting opportunities to further strengthen referral pathways and achieve full guideline concordance.

To assess if 2.1PN-derived embryos are diploid, euploid and suitable for embryo-transfer. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading (MeSH) terms. Diploidy, confirmed by genotyping analysis, is defined as the primary outcome measure. Secondary outcomes included blastulation rates, good quality blastocysts, euploidy, clinical pregnancy, miscarriage and live birth (LB). A total of 7 studies were included in the systematic review. Six out of seven studies indicated that 2.1PN embryos have lower developmental competence than 2PN embryos, yet can still be euploid/diploid. Only one study advised against their use for embryo transfer. In our analysis of the evidence tables, 2.1PN-derived embryos showed a descriptive trend toward lower blastulation rates (− 22.50

Endometriosis and adenomyosis are estrogen-dependent inflammatory conditions frequently associated with impaired fertility. Although progesterone resistance at the tissue level is well documented, it remains unclear whether these conditions are associated with altered systemic progesterone exposure during frozen-thawed embryo transfer (FET) cycles and whether higher circulating progesterone levels are required to achieve successful reproductive outcomes. To evaluate mean serum progesterone levels on the day of FET in women with endometriosis and/or adenomyosis compared with unaffected controls, and to explore potential differences according to endometrial preparation protocol and pregnancy outcome. This retrospective single-center cohort study included 1,927 women undergoing their first single-blastocyst FET between June 2020 and December 2023. FET cycles were performed using hormone replacement therapy (HRT) or modified natural cycle (mNC) protocols. Serum progesterone was measured on the day of embryo transfer. Women were categorized into three groups: endometriosis, adenomyosis, and unaffected controls. Analyses were stratified by FET protocol. Mean serum progesterone concentrations differed between HRT-FET and mNC-FET cycles and were therefore analyzed separately. In both protocols, progesterone levels were comparable between women with endometriosis or adenomyosis and unaffected controls, and live birth rates did not differ across diagnostic groups or between endometrial preparation strategies within each group. Among women with adenomyosis undergoing HRT-FET, those achieving live birth showed higher mean progesterone levels compared with those who had no live birth (β = 1.76, 95

CONTEXT:Antimüllerian hormone (AMH) is produced by Sertoli cells and may serve as a biomarker of spermatogenesis, yet the literature lacks comprehensive comparative analyses across male fertility conditions. OBJECTIVE:This work aimed to discover how serum AMH levels differ among men with varying fertility statuses, and the relationship between AMH, spermatogenesis, and functional testicular reserve. METHODS:A cross-sectional study was conducted of 1085 White European, non-Finnish men with confirmed fertility, primary infertility, or nonazoospermic infertility. Men with confirmed fertility (n = 116), primary infertility (n = 791), and nonobstructive azoospermia (NOA) (n = 178) underwent comprehensive hormonal and semen analyses per World Health Organization 2010 criteria. Kruskal-Wallis and chi-square tests were used for group comparisons. Correlations were assessed using Spearman rank correlation. Multivariable linear regression models identified factors associated with AMH levels and sperm concentration. RESULTS:Serum AMH levels were significantly lower in men with NOA compared to fertile controls and NOA infertile men. AMH correlated negatively with age and follicle-stimulating hormone (FSH), and positively with testicular volume and sperm concentration. After adjustment, AMH showed no independent association with sperm concentration. AMH levels were significantly lower in NOA vs fertile men and primary infertility 3.8 (1.6-7.2) vs 5.1 (3.6-7.0) vs 4.9 (3.0-7.8) ng/mL; P less than .001. AMH negatively correlated with age and FSH, positively with testicular volume and sperm concentration. Age, FSH, and testicular volume were independently associated with AMH; FSH and testicular volume, not AMH, were independently associated with sperm concentration. However, the cross-sectional design limits causality, and the study faced limited ethnic generalizability. CONCLUSION:AMH reflects Sertoli cell function and testicular status rather than directly influencing spermatogenesis, potentially serving as a complementary male fertility biomarker.

BACKGROUND:Expected poor ovarian responders represent a challenging population in assisted reproduction, in whom controlled ovarian stimulation requires a careful balance between achieving an adequate oocyte yield and limiting cycle cancellation and treatment burden. Algorithm-based follitropin delta dosing has been proposed as an alternative to conventional high-dose follitropin alpha regimens, but comparative real-world data in this population remain limited. METHODS:This retrospective single-center matched cohort study included 423 women fulfilling the Bologna criteria for poor ovarian response undergoing IVF/ICSI. Ovarian stimulation was performed with either algorithm-based follitropin delta (12 mcg/day; N.=141) or follitropin alpha at a minimum daily starting dose of 225 IU (N.=282). Groups were matched for age, ovarian reserve markers, body weight, year of treatment, and recombinant LH supplementation. The primary outcome was the number of oocytes retrieved. Secondary outcomes included ovarian stimulation characteristics, progesterone (P) levels at hCG trigger, incidence of premature progesterone elevation (PPE), feasibility of fresh embryo transfer, and cumulative pregnancy outcomes. RESULTS:Follitropin delta was associated with a lower number of oocytes retrieved (IRR 0.847, 95% CI 0.733-0.979; P=0.025) and mature oocytes (IRR 0.823, 95% CI 0.703-0.963; P=0.016) compared with follitropin alpha. P levels at hCG trigger were significantly lower with follitropin delta (median 0.4 ng/mL, IQR 0.3-0.6) than with follitropin alpha (0.6 ng/mL, IQR 0.4-0.9; P<0.001), resulting in a reduced incidence of PPE (5.4% vs. 16.7%; P=0.006) and a higher likelihood of fresh embryo transfer (64.6% vs. 52.1%; P=0.023). Fertilization rates, embryo development, and cumulative pregnancy outcomes did not differ significantly between groups. CONCLUSIONS:In expected poor responders, algorithm-based follitropin delta resulted in a lower oocyte yield compared with conventional follitropin alpha dosing, while reducing PPE and increasing the feasibility of fresh embryo transfer, without a clear impact on cumulative pregnancy outcomes.

Are progesterone levels lower in women with endometriosis or adenomyosis undergoing an embryo transfer compared to unaffected? Progesterone levels before embryo transfer in women with adenomyosis and endometriosis are not significantly lower compared to controls. Endometriosis and adenomyosis are gynecological conditions associated with infertility. The hormonal environment plays a critical role in the success of embryo transfer, and progesterone levels are particularly crucial during the luteal phase. Recent clinical studies demonstrate the mechanistic pathways through which progesterone influences endometrial morphology and function, particularly in the inflammatory uterine environment characteristic of endometriosis and adenomyosis. Moreover it has been recently suggested that women affected by these conditions may have suboptimal absorption of progesterone, which could result in a lower implantation rate. We conducted a single-center prospective study on women with adenomyosis, endometriosis, or both, who underwent their first frozen embryo transfer (FET) of a blastocyst at Reproductive Medicine Center of San Raffaele Hospital in Milan from 2020 to 2024. We excluded patients receiving injective progestin supplementation to focus on vaginal absorption. Progesterone levels were analyzed on the day of embryo transfer. Patients were divided based on different ultrasound diagnosis (adenomyosis, endometriosis or both) and different endometrial preparation protocols (medicated cycle or spontaneous modified cycle). FET at the blastocyst stage was planned when an endometrial thickness > 7mm was reached, and performed on day 6 of vaginal progesterone. Our primary outcome was to compare the levels of circulating progesterone (P) sampled 10 to 5 minutes prior to FET between women affected versus not affected. 2374 patients were examined (396 had only endometriosis, 469 only adenomyosis, 128 both conditions and 1381 controls). There was no statistically significant difference in progesterone levels in any subgroup regardless of the endometrial preparation. We had the same results analyzing exclusively the group of patients who conceived; while in those who not conceive, a lower level of progesterone at FET was observed in patients with either isolated adenomyosis or adenomyosis with endometriosis compared to controls (P = 13.98 ± 5.66 vs ng/ml versus P = 15.09 ± 6.08 ng/ml and P = 13.07 ± 4.94 ng/ml vs 15.09 ± 6.08 ng/ml, p values 0.037 and 0.027, respectively). Performing multiple linear regression in the group of women with adenomyosis, we observed that circulating P level is influenced by BMI (P-value 0.007) and the dose of vaginal progesterone administered (P-value 0.047). The overall implantation rate (positive betaHCG test/FET) in the control group was 48.4% and it was comparable among women with endometriosis and/or adenomyosis (48.4%). The ongoing pregnancy rates (viable pregnancy beyond week 8 of gestation/FET) were respectively 35.3% and 34.9% , with a 15.5 % and 13.3% biochemical miscarriage rate in the two groups respectively and a 13.7% and 16.7% clinical miscarriage rate in the two groups respectively. This is a preliminary and retrospective study and the diagnosis of endometriosis and/or adenomyosis was performed using different ultrasound devices operated by various practitioners. Further large-scale, controlled studies are warranted to elucidate the underlying mechanisms by which progesterone influences implantation and pregnancy maintenance in these challenging clinical scenarios. No

Introduction:Several studies indicate that a specific genotype profile could influence ovarian sensitivity to exogenous gonadotropin. However, most of the previous studies were observational and retrospective and thereby more prone to bias. The aim of this study was to evaluate the impact of gonadotropin single nucleotide polymorphisms (SNPs) on the outcomes of in-vitro fertilization (IVF) in infertile patients undergoing their first ovarian stimulation (OS) cycle. Method:A multicenter, longitudinal, prospective, interventional cohort study was carried out in four clinical centers of medically assisted reproduction from August 2016 to November 2018. Only expected normo-responder women, estimated through standardized-computerized antral follicle count (AFC), stimulated with a fixed 150 IU daily dose of recombinant follicle-stimulating hormone (FSH), were included. The study population consisted of infertile normo-gonadotropic patients, aged between 34 and 39, at their first OS, with normal ovarian reserve (AFC between 8 and 16) measured with 3D automated ultrasonography and undergoing standardized OS protocol. Results:One hundred nineteen patients were enrolled, and the following five SNPs were studied (FSHR c.-29G>A, FSHR p.N680S, FSHB c.-211G>T, LHCGR p.S312N, and LHβ "V-LH" p.W8R). Separate and multivariate analysis of investigated polymorphisms did not show any statistical impact on the number of oocytes retrieved. However, adopting an overdominant model, heterozygosis of FSHR p.N680S SNP was associated with significantly lower duration of OS compared with homozygotic women. Considering LHCGR p.S312N polymorphism, N allele carriers required a longer duration of OS in the codominant, dominant, and log-additive models. Multivariate analysis revealed that specific genotype combinations could affect the ovarian sensitivity. A significantly higher follicle-to-oocyte index (FOI) was observed when the S or N allele of both FSHR p.N680S and LHCGR p.S312N were combined (S allele combination: difference 0.18, CI 95% 0.04-0.33, p = 0.011; N allele combination: difference 0.18, CI 95% 0.01-0.34, p = 0.037; N allele combination). Discussion:Based on our results, the combination of specific genetic variants could impact ovarian sensitivity to gonadotropin. This research adds to the controversy in the literature regarding the effect of genetic variants in IVF and ovarian response.

Extracellular vesicles (EVs) have been proven to have a crucial role in intercellular communication and have attracted significant attention in the physiology of reproduction because of their multiple functions in physiological processes essential for reproduction including gametogenesis, fertilization and embryo-endometrial cross-talk. Although EVs from the male reproductive tract have been extensively studied for their role in sperm maturation, research on female reproductive tract-derived EVs in humans is still emerging and supported by only a few studies to date. In vitro study was performed using spermatozoa from normozoospermic men and EVs isolated from follicular fluid (FF-EVs), cervicovaginal fluid collected 2 and 7 days after the LH surge (CVF-EVs LH + 2 and LH + 7, respectively) and spent medium of decidualized (dESCs-EVs) and non-decidualized (eESCs-EVs) endometrial stromal cells from healthy women of reproductive age. The principal outcome measures comprise the percentage of viable, progressively motile, and capacitated spermatozoa after treatment with FF-EVs, CVF-EVs LH + 2 and LH + 7, dESCs-EVs, and eESCs-EVs. Spermatozoa are able to capture EVs derived from all the considered tracts of the female reproductive system, with slightly varying efficiencies, albeit comparable in most cases. Incubating sperm cells with any of these EVs does not have any detrimental effect on sperm vitality, increases the percentage of spermatozoa displaying progressive motility and the percentage of acrosome-reacted spermatozoa. EVs produced and released in various regions of the female reproductive system likely contribute to spermatozoa maturation during their transit, promoting both capacitation and motility.

How do ovarian responses with follitropin delta 15 µg/day compare with follitropin alfa 225 IU/day in women undergoing ovarian stimulation using conventional dosing regimens? The ADAPT-1 trial demonstrates similar ovarian responses with follitropin delta 15 µg/day and follitropin alfa 225 IU/day as starting doses in a conventional dosing regimen. Follitropin delta, a recombinant follicle-stimulating hormone (rFSH), is currently approved for ovarian stimulation using an individualised fixed daily dose based on serum anti-Müllerian Hormone (AMH) and bodyweight (maximum 12 µg/day for first cycle and 24 µg/day in subsequent cycles). Other rFSHs, such as follitropin alfa, conventionally apply a starting dose of 150–225 IU, fixed for the initial days of stimulation, after which dose adjustments can be made. Ovarian stimulation with follitropin delta 10 µg/day provides a similar ovarian response to follitropin alfa 150 IU/day for serum oestradiol concentration and number of follicles ≥12 mm. This randomised, assessor-blinded, multicentre trial compared the efficacy and safety of follitropin delta 15 µg/day with follitropin alfa 225 IU/day in conventional dosing regimens. The primary endpoint was the number of oocytes retrieved; mean difference between treatment groups was estimated using a negative binomial regression model (treatment and serum AMH level as factors). During the follow-up period, clinical pregnancy rates from first fresh/frozen transfers within 3 months and ovarian hyperstimulation syndrome (OHSS) rates were assessed. Participants, 18–40 years, undergoing IVF/ICSI were enrolled at specialist reproductive clinics in Austria, France, Italy, Spain, and United Kingdom for ovarian stimulation if they had no contraindications for treatment with starting gonadotropin dose of 225 IU/day. Patients could enrol if they reported infertility for at least 1 year if ≤ 37 years and at least 6 months for those >37 years, and regular menstrual cycles (21–35 days). All cycles used a gonadotropin-releasing hormone (GnRH) antagonist protocol. Between August 1, 2022, and April 16, 2024, 300 of 337 screened patients were randomised to, and received, follitropin delta (n = 200) or follitropin alfa (n = 100). The two treatment groups were comparable in terms of demographics, baseline characteristics, and duration of infertility. The mean duration of treatment was ∼9 days in both groups. The mean total dose of follitropin delta was 143.7±33.6 µg and 154.3±23.1 µg (2,105±315 IU) for follitropin alfa. A total of 75% (226/300) used a human choriogonadotropin trigger for final follicular maturation. A mean of 9.9 oocytes was retrieved for both groups (estimated difference: 0.0 oocytes; 95% confidence interval [CI] –1.3,1.2). The category of 8–14 oocytes retrieved was the most common ovarian response (follitropin delta: 45.5%; follitropin alfa: 50.0%). Clinical pregnancy rates were comparable (31.6% and 31.0%; estimated difference 0.6 (95% CI –10.6, 11.8). The proportion of participants who experienced adverse events was 36.5% and 40.0%. Early OHSS (≤9 days after triggering) occurred in 2.5% and 3.0%, and all cases were Grade 3 (moderate) or lower. No participant had the stimulation cycle cancelled due to excessive ovarian response. Cumulative pregnancy rates after the first transfer were not followed up. All analyses are of descriptive nature and no formal hypothesis testing or multiplicity adjustment was applied. Treatment groups had similar ovarian responses, supporting equivalence for starting doses follitropin delta 15 µg and follitropin alfa 225 IU, with low rates of early OHSS. Ovarian stimulation cycles with follitropin delta dosed in micrograms can be planned and adjusted, leveraging the established IU dose equivalence to follitropin alfa. Yes

STUDY QUESTION:How do ovarian responses using conventional dosing for follitropin delta 15 µg/day compare with follitropin alfa 225 IU/day in women undergoing ovarian stimulation? SUMMARY ANSWER:The ADAPT-1 trial demonstrates similar ovarian responses with follitropin delta 15 µg/day and follitropin alfa 225 IU/day starting doses in a conventional dosing regimen. WHAT IS KNOWN ALREADY:Follitropin delta, a recombinant FSH (rFSH), is currently approved for ovarian stimulation using an individualized fixed daily dose based on serum anti-Müllerian hormone (AMH) and bodyweight (maximum 12 µg/day for first cycle and 24 µg/day in subsequent cycles). Other rFSHs, such as follitropin alfa, conventionally apply a starting dose of 150-225 IU, fixed for the initial days of stimulation, after which dose adjustments can be made (maximum 450 IU/day). Ovarian stimulation with follitropin delta 10 µg/day provides a similar ovarian response to follitropin alfa 150 IU/day for serum concentration and number of follicles ≥12 mm. STUDY DESIGN, SIZE, DURATION:ADAPT-1 was a randomized, accessor-blinded, multicentre trial comparing efficacy and safety of a starting dose of follitropin delta 15 µg/day with follitropin alfa 225 IU/day in conventional dosing regimens. The primary endpoint was the number of oocytes retrieved; mean difference between treatment groups was estimated using a negative binomial regression model (treatment and serum AMH level as factors). During the follow-up period, clinical pregnancies resulting from the first fresh/frozen transfers within 3 months of the start of stimulation, and ovarian hyperstimulation syndrome (OHSS) rates were assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS:Participants, 18-40 years, undergoing IVF/ICSI could enrol at specialist reproductive clinics in Austria, France, Italy, Spain, and the United Kingdom for ovarian stimulation if they had no contraindications for treatment with a starting gonadotropin dose of 225 IU/day. Patients could enrol if they reported infertility for at least 1 year if ≤37 years and at least 6 months for those >37 years, and regular menstrual cycles (21-35 days). All cycles used a GnRH antagonist protocol. MAIN RESULTS AND THE ROLE OF CHANCE:Between 1 August 2022 and 16 April 2024, 300 of 337 screened patients were randomized to, and received, follitropin delta (n = 200) or follitropin alfa (n = 100). The two treatment groups were comparable in terms of demographics, baseline characteristics, and duration of infertility. The mean duration of treatment was ∼9 days in both groups. The mean total dose of follitropin delta was 143.7 ± 33.6 µg and 154.3 ± 23.1 µg (2105 ± 315 IU) for follitropin alfa. Three-quarters (226/300) used an human Chorionic Gonadotropin trigger for final follicular maturation. A mean of 9.9 oocytes was retrieved for both groups (estimated difference: 0.0 oocytes; 95% CI -1.3, 1.2). The category of 8-14 oocytes retrieved was the most common ovarian response (follitropin delta: 45.5%; follitropin alfa: 50.0%). Clinical pregnancy rates were comparable (31.6% and 31.0%; estimated difference 0.6 (95% CI -10.6, 11.8)). Early OHSS (≤9 days after triggering) occurred in 2.5% and 3.0%, and all cases were Grade 3 (moderate) or lower. No participant had the stimulation cycle cancelled due to excessive ovarian response. LIMITATIONS, REASONS FOR CAUTION:Only pregnancies from the first fresh or cryopreserved transfer within 3 months of oocyte retrieval were recorded. Cumulative pregnancy rates after the first transfer were not followed up. All analyses are of descriptive nature and no formal hypothesis testing or multiplicity adjustment was applied. WIDER IMPLICATIONS OF THE FINDINGS:Treatment groups had similar ovarian responses, supporting equivalence for starting doses follitropin delta 15 µg and follitropin alfa 225 IU, with low rates of early OHSS. Ovarian stimulation cycles with follitropin delta in µg can be planned and adjusted, leveraging the established IU dose equivalence to follitropin alfa. STUDY FUNDING/COMPETING INTEREST(S):This trial was funded by Ferring Pharmaceuticals A/S, Kastrup, Denmark. Medical writing support for manuscript development was provided by Celia J. Parkyn, PhD, and was funded by Ferring Pharmaceuticals A/S, Kastrup, Denmark. P.Z. and R.A. have none. A.B. has received grants from Gedeon Richter, IBSA, GP Pharm & Seid, Miguel Hernandez University, Centre for Technological Development and Innovation, Valencian Innovation Agency, Regional Secretary for Industry, Trade and Consumption, and the Government Ministry of Industry and Tourism; payments from University Complutense of Madrid, Ferring Pharmaceuticals, Fentypharm, Miguel Hernandez University, Gedeon Richter, & Vall d'Hebron Hospital; travel support from Ferring Pharmaceuticals, Fentypharm, Gedeon Richter, International ESHRE Congress Organising Committee, Spanish Society of Gynaecology and Obstetrics, CROG Congress Organising Committee, & Vall d'Hebron Hospital; has a patent pending for Sperm plate (U202431456); and is Chair of the Organising Committee of the Infertility and Sterility Section of the Spanish Society of Gynaecologist (non-paid role) and equipment from Obstetrics; & equipment from Cook Medical. J.S. has received consulting fees from Ferring Pharmaceuticals. E.P. has received grants from Merck, Ferring, Theramex, Gedeon Richter, IBSA, and Organon; payments from Merck, Ferring, IBSA, and Organon; travel support from Merck, IBSA, Organon, Theramex, and Ferring; and participated in a Safety Monitoring Board or Advisory Board for Merck. M.G.S. has received patient medication from Ferring; payments from Ferring, Merck for educational events; and travel support from Ferring, Merck, Theramex, and IBSA. R.L. and S.M. are employees of Ferring Pharmaceuticals. I.E.J. was an employee of Ferring Pharmaceuticals at the time of the trial conduct. TRIAL REGISTRATION NUMBER:clinicaltrials.gov NCT05263388; Eudract 2021-001785-38. TRIAL REGISTRATION DATE:16 November 2021 (clinicaltrials.gov); 5 August 2021 (Eudract). DATE OF FIRST PATIENT’S ENROLMENT:1 August 2022.

Do premature ovarian insufficiency (POI), prior chemotherapy, and hormonal treatment affect reproductive outcomes in women seeking pregnancy who have cryopreserved oocytes for fertility preservation? At completion of oncological follow-up, 11,5% of women used cryopreserved oocytes to attempt pregnancy. POI, chemotherapy, hormonal treatment don’t reduce pregnancy success from warmed oocytes. Fertility preservation is a major issue in women with oncological pathologies, who face a risk of iatrogenic premature ovarian failure and subsequent infertility. Oocyte vitrification is an established option for women with cancer, but long-term outcome of utilization rate, oocyte warming and fertilization and reproductive outcomes are scarce. POI, chemotherapy and hormonal therapy are known to have the potential to induce multi-system long-term physical and psychological sequelae in women, but their impact on patients attempting to conceive using cryopreserved oocytes is not yet fully understood. Data were retrospectively collected between 2013 and 2024 from all women with a diagnosis of cancer who cryopreserved oocytes as a fertility preservation option in Centro Scienze della Natalità at San Raffaele Hospital, Milan. Oncological follow-up, reproductive desire and outcomes of patients were prospectively reported in a dedicated clinical database. Medical files and patient databases were used to extract data of 357 patients, who cryopreserved oocytes prior to anticancer treatment. Data from patients who returned asking for oocyte warming and subsequent IVF with fresh or frozen embryo transfers were further analyzed. Clinical pregnancy rates and live birth rates were then calculated. T-student tests and chi-square analysis were performed, with P-value<0.05 considered statistically significant. The study protocol was approved by the institutional ethics committee. A total of 357 women underwent 373 oocyte vitrifications for oncological reasons between 2013 and 2024, with a mean age of 31.1 ± 5.9 years. Of these, 294 women completed oncological follow-up, and 34 women (11.5%) later returned for oocyte warming, at an average age of 38.3 ± 4.2 years. Among those returning, 32,3% (11/34) had developed a POI, while 67,6% (23/34) were menstruating normally but failed to conceive after 6-12 months of attempts. POI patients were older (41.7±3.1 vs 36.4±3.3 years, p = 0.0005) and had fewer MII oocytes cryopreserved (6.09±3.1 vs 10.17±5.4, p = 0.02), despite no age difference at cryopreservation (34.9±3.6 vs 32.9±3.9, p = 0.2). POI patients were likely to have a lower pregnancy rate (27% vs 47%) and clinical live birth rate (27% vs 34%) compared to normally menstruating women, despite no statistical significance (p = 0.4). Twenty-three women had undergone chemotherapy, with clinical pregnancy and live birth rates of 39% and 34%, respectively, while in 11 chemo-naïve patients, clinical pregnancy and live birth rates were 45% and 27%, respectively (p = 0.2). Eight patients receiving only hormonal treatment showed the highest clinical pregnancy (75%) and live birth (50%) rates. The sample size is small and results must be confirmed by larger sample analysis. Moreover, the follow-up period varied among patients and not all cryopreserved material was used by the end of the study. This study offers valuable data on reproductive outcomes after fertility preservation, highlighting its effectiveness and challenges. It serves as a key resource for healthcare professionals, aiding personalized counseling and supporting informed decision-making on ovarian stimulation, considering both medical and emotional factors in fertility preservation. No

Identifying the optimal Window Of embryo Implantation (WOI) is important for improving pregnancy rates in Assisted Reproductive Technology (ART). During the WOI, the endometrium becomes receptive, enabling the complex communication between the embryo and endometrial tissue needed for the initiation of pregnancy. This study explores the molecular landscape of endometrial receptivity by analyzing the transcriptomic profile of Extracellular Vesicles isolated from Uterine Fluid (UF-EVs), a non-invasive alternative to traditional endometrial biopsies. RNA-sequencing of UF-EVs collected from 82 women undergoing ART with single euploid blastocyst transfer revealed 966 differentially ‘expressed’ genes (nominal p-value < 0.05) between women who achieved pregnancy (N = 37) and those who did not (N = 45). Patients who obtained a pregnancy showed a globally higher gene expression compared to the not-pregnant group. Weighted Gene Co-expression Network Analysis (WGCNA) clustered these differentially ‘expressed’ genes into four functionally relevant modules involved in key biological processes related to embryo implantation and development. A Bayesian logistic regression model, integrating gene expression modules with clinical variables, including vesicle size and history of previous miscarriages, achieved a predictive accuracy of 0.83 and an F1-score of 0.80 for pregnancy outcome prediction. This systems biology approach utilizing UF-EVs may represent an advancement over current methods that rely on endometrial transcriptomic profiles during the embryo implantation window.

This study evaluates the effects of double cryopreservation and re-biopsy on embryo viability and clinical outcomes. Studies of interest were selected from an initial cohort of 1027 potentially relevant records retrieved. PubMed was systematically searched for peer-reviewed original papers identified by keywords and medical subject heading terms. Moreover, we elaborated the evidence tables for double cryopreservation and re-biopsy separately. Data were systematically extracted, focusing on live birth, survival, clinical pregnancy, and miscarriage rates. For each study, we identified absolute numbers (numerator and denominator) related to clinical outcomes. Finally, for each outcome, we calculated the percentage change between the control and study groups. Among studies on double cryopreservation, 13 out of 22 reported no effect on clinical outcomes, suggesting contradictory results. Similarly, findings on re-biopsy were controversial, with seven out of 12 studies showing negative effects on survival and clinical outcomes, while five reported no impact. In our analysis of the evidence tables, we observed a reduction in live birth rates of 22.2

The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men. Transcriptomic profiling confirms the upregulation of genes associated with the interferon-gamma and -alpha responses in peripheral blood T cells of infertile men with oligo-astheno-teratozoospermia or non-obstructive azoospermia, with distinct T cell signatures of exhaustion and senescence discriminating the two infertile conditions. These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures and unravel the potential link between infertility and the risk of developing secondary diseases.

To assess if 1PN-derived embryos are diploid/euploid and suitable for embryo transfer. This systematic review and meta-analysis were conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. PubMed, Embase, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading (MeSH) terms: “1PN” OR “monopronucleated” OR “single pronucleus” AND “cleavage” OR “embryo quality” OR “blastocyst quality” OR “blastulation” OR “embryo development” OR “euploidy” OR “ploidy” OR “pregnancy” OR “live birth” OR “miscarriage” OR “clinical outcomes” OR “malformation.” A total of 21 studies met the inclusion criteria. Compared to 2PN-derived embryos, 1PN-derived embryos exhibited a lower blastulation rate and clinical outcomes when transferred without prior genetic testing. However, 1PN-derived embryos demonstrated similar euploidy and live birth rates following euploid blastocyst transfer, as well as comparable malformation rates to their 2PN counterparts. A non-significant trend toward a higher risk of abnormal ploidy constitution was observed in 1PN-derived embryos. Notably, pregnancy and live birth rates were significantly lower for 1PN-derived embryos from ICSI compared to those from conventional IVF. 1PN-derived embryos, though less competent than 2PNs, can lead to healthy live births. They may be cautiously utilized in clinical practice, particularly when biparental diploidy has been confirmed. Clinical trial registration. CRD42024605305.