Recent advances in IVF have shifted the focus towards maximizing treatment efficacy and efficiency. Traditionally, IVF success has been evaluated on a cycle-by-cycle basis. Advancements such as individualized ovarian stimulation protocols, gonadotrophin-releasing hormone agonist triggers, cryopreservation techniques and embryo selection strategies, including preimplantation genetic testing for aneuploidies, have improved precision medicine in IVF, optimizing clinical outcomes. Despite these developments, certain patient groups - especially those with low ovarian response and/or advanced age - still face lower success rates per IVF cycle initiated. Considering the reproductive system's physiology, which often requires multiple attempts for success, and drawing from the experience of intrauterine insemination, a shift from a single-cycle focus to a multicycle strategy is now needed. A multicycle approach, adopting approaches such as oocyte/embryo accumulation from several stimulations or two consecutive stimulations (e.g. DuoStim), enables the advance planning of multiple attempts. It helps shorten time to pregnancy, reduces treatment discontinuation and offers support for patients facing setbacks. To be effective, this strategy must include personalized psychological counselling to manage emotional stress and prepare patients for possible failures, which are major causes of discontinuation. Evidence shows that well-informed, supported patients are more likely to persist in treatment, leading to higher cumulative success rates.

AimsTo evaluate DuoStim strategy across a decade from its clinical implementation in IVF by comparing embryological and clinical outcomes between the first and second ovarian stimulations (1st-OS and 2nd-OS) conducted within 30 days, focusing on treatment efficiency and time-to-conclusion.MethodsRetrospective single-center study (2015–2024) including 1656 poor-prognosis patients undergoing 1896 DuoStim cycles planned for ICSI and PGT-A at the blastocyst stage. Poor prognosis was defined as very advanced maternal age (≥40 years) and/or reduced ovarian reserve (AMH ≤1.2 ng/mL, AFC ≤5, or ≤3 oocytes in previous retrievals). Endpoints included all embryological, clinical and neonatal outcomes comparing 2nd-OS versus 1st-OS and cumulatively. Among 1561 concluded first DuoStim cycles, we calculated time-to-treatment-conclusion (TTC), stratified as without a live-birth (TTC-noLB) and with a live-birth (TTC-LB), and treatment discontinuation at our center after a first failed DuoStim attempt.ResultsThe use of DuoStim increased over time, reaching 34% of all cycles in 2024. The 2nd-OS yielded more oocytes and embryos than 1st-OS, while their competence was comparable. Consequently, the 2nd retrieval provided a cumulative incremental yield of 66% for cycles achieving ≥1 euploid blastocyst and 125% for cycles achieving ≥1 live birth (LB) compared with the 1st-OS alone. Median TTC was 40 days (quartile-1: 36, quartile-3: 118.5), while TTC-noLB and TTC-LB were 38 days (quartile-1: 35, quartile-3: 41.5) and 145 days (quartile-1: 112.25, quartile-3: 221), respectively. Embryological and clinical outcomes were stable across the years. Treatment discontinuation among patients without a LB after a first completed DuoStim decreased from 61% in 2015 to 44% in 2021, as second DuoStim attempts increased from 16% to 21% and transition to egg donation from 9% to 21%.ConclusionDuoStim is a multicycle stimulation strategy that represents an alternative approach for patients requiring multiple treatment opportunities within a short timeframe. It shifts IVF toward a flexible personalized journey for poor prognosis patients. By enabling two stimulations within a single ovarian cycle, it achieved a cumulative live birth rate of 28.5% per concluded cycle in our cohort, within a consistently short timeframe in terms of both TTC-noLB and TTC-LB. Overall, DuoStim represents a treatment strategy that supports rapid and effective clinical decision-making in time-sensitive patients.

Background: Male factor could contribute, alone or in combination with female factor, to the inability to conceive in a couple in more than half of cases. The effect of male factor infertility (MFI) on embryological assisted reproductive technology (ART) outcomes remains an ongoing discussion. Purpose: to evaluate the impact of MFI on embryo aneuploidy rates, to better understand the role and possible indication for Preimplantation genetic testing for aneuploidies (PGT-A), considering the role of sperm characteristics, paternal age, sperm DNA fragmentation and sperm aneuploidies. Methods: this narrative review included all available articles, published up to January 2026. Results and conclusions: Available evidence, often based on heterogeneous and old-fashioned methodologies, suggests that MFI may impair embryonic development, particularly in terms of fertilization rate and blastulation rate, more than embryo euploidy; however, a comprehensive evaluation of MFI should be integrated into clinical practice in the context of couple infertility, to also optimize the efficiency and outcomes of ART. Promising results emerged from sperm DNA fragmentation as a tool to predict embryo euploidy, but further investigations involving larger sample sizes and improved standardization are required.

OBJECTIVE:To evaluate whether artificial intelligence (AI)-based blastocyst ranking tools can outperform traditional noninvasive assessments in prioritizing euploid embryos for transfer. DESIGN:Retrospective single-center cohort study. SUBJECTS:The study included 786 preimplantation genetic testing for aneuploidy cycles performed between 2013 and 2020 after embryo culture in a time-lapse incubator (TLI). The analysis focused on 279 cycles producing ≥3 blastocysts, of which ≥1 was euploid and ≥1 aneuploid embryo. EXPOSURE:Blastocyst ranking was conducted through: static morphology on the basis of Gardner's score (control; embryologists-assigned scores from 1 [AA] to 9 [CC]); random guessing; Gardner's score plus morphodynamic parameters (time of expanding blastocyst [tEB] and embryo area at tEB in μm2); and two versions of a commercially-available AI model. The coefficient of variation (CV = SD/mean) within each cohort of blastocysts was then calculated to estimate the morphological variability perceived by each method among sibling embryos, and its association with ranking accuracy was investigated. MAIN OUTCOME MEASURES:Accuracy in prioritizing euploid blastocysts within cohorts of sibling embryos, assessed by the proportion of cycles in which a euploid embryo was ranked first, and association between intracohort CV and ranking performance. RESULTS:The AI model version-2 showed the highest rate of correctly prioritized euploid blastocysts (68%), followed by morphodynamic assessment (64%), AI model version-1 (62%), Gardner's score (58%), and random guessing (44%). Larger intracohort CVs for Gardner's scores were positively associated with prioritization of euploid embryos. No such associations were observed with AI-based CVs. CONCLUSION:The AI-powered tools can match or slightly improve traditional noninvasive assessments. However, no blastocyst ranking strategy on the basis of morphology/morphodynamics may prevent aneuploid embryos from being prioritized, even in the presence of euploid siblings.

IVF treatments should be personalized to collect an appropriate number of oocytes, taking into account the woman’s age and ovarian reserve, in order to maximize the efficacy and efficiency of the IVF process. From a scientific perspective, the ‘continuous recruitment theory’ suggests that several follicular waves are continuously recruited to grow and regress throughout one ovarian cycle. Clinically, this approach has paved the way for the theorization of a double stimulation protocol back-to-back in the same ovarian cycle (DuoStim) to rescue anovulatory waves. This protocol has been successfully adopted by several independent groups in the last decade to improve the number of oocytes in a short timeframe. Although the published data are promising for treating patients of advanced maternal age with reduced ovarian reserve and poor oocyte/embryo competence, the protocols adopted vary across studies. In this challenging population, choosing the appropriate protocol in the DuoStim context is critical to maximize the ovarian response and exploit the potential of individual follicular waves. In this regard, the administration of luteinizing hormone (LH) could be relevant to promote steroidogenesis and folliculogenesis, increase androgen production, improve pre-antral and antral follicle recruitment, and enhance the expression of follicle-stimulating hormone receptors in the granulosa cells. This review presents a step-by-step outline of all DuoStim protocols and proposes a SWOT (strengths, weaknesses, opportunities, threats) analysis of LH administration in the context of DuoStim.

Triploid and haploid conceptions are not viable and are a common occurrence in humans, where they account for 10% of all pregnancy losses. Despite the parent of origin being important in the etiology of the pregnancy, our knowledge of their causes is limited, especially at the point of conception. Using a dataset of 96,660 biopsies and a validation dataset of 44,324 from human blastocyst embryos generated by intracytoplasmic sperm injection, we estimate that 1.1% of human conceptions (n = 1,063) contain extra or missing chromosome sets in zygotes. In our cohort of intracytoplasmic-sperm-injection-derived embryos, where the risk of polyspermy is inherently lower compared to natural conception, we identify for the first time a maternal age effect, with a 1.046-per-year increased risk in triploidy/haploidy (p < 0.001). In 0.03% of couples, we identified three or more triploid/haploid embryos, suggesting a personal risk effect (p = 0.03). Genotype analysis of 41 triploid embryo biopsies and their parents shows that around one-third of maternal triploid conceptions originate in meiosis I and two-thirds in meiosis II. Seven of these embryos are inferred to have entirely failed to initiate meiotic recombination genome wide, a surprising finding suggesting that human oocytes with pervasive meiotic recombination failure that are formed during fetal development are capable of ovulation in adult life. Finally, we identify a type of genome-wide maternal isodiploidy (two maternal chromosome sets) in 0.05% of embryos (41/74,009). Collectively, our findings shed light on the biology of meiosis and the formation of human oocytes with the number of chromosome sets.

Breast cancer is one of the most common tumors among women with 10 % of cases diagnosed in reproductive age. Estrogen positive forms are characterized by an excellent long-term prognosis with the 5-year survival rate of approximately 90 %. Recently, the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in women good prognosis have been introduced. At present, there are no indications or protocols on the optimal management of conception during discontinuation of endocrine therapy for these patients. A Delphi consensus was carried out to obtain expert opinion from a global perspective to identify the optimal pathways to pursue childbearing with particular focus in strategies aimed at reducing time to live birth. The Delphi consensus was carried out involving one Scientific Coordinator and 6 additional experts. Each member of the Scientific Board suggested additional experts, resulting in a panel of 31 experts. The Scientific Board proposed 20 statements covering the following area of interest: 1) Resumption of menstrual cycle after the suspension of endocrine therapy; 2) Management of the washout period; 3) Fertility assessment; 4) Decision-making of reproductive planning; 5) Ovarian reserve evaluation; 6) Expectant management vs immediate fertility treatment; 6) Controlled ovarian stimulation protocols; 7) In vitro fertilization protocols. Eighteen statements reached the consensus This Delphi consensus provides strategies to reduce the time to live birth in breast cancer patients' candidates for discontinuation of endocrine therapy.

OBJECTIVES:The aim of this study was to investigate the ovarian response in different phases of the menstrual cycle in breast cancer women candidates for fertility preservation. DESIGN:A retrospective study was carried out, including women with breast cancer undergoing oocyte cryopreservation at the Fertility Preservation Unit of the University of Naples Federico II between 2017 and 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS:Women who started ovarian stimulation (OS) during the follicular phase (FP) were compared with those who started during the luteal phase (LP). The two study groups were further stratified according to the phase of the menstrual cycle at OS initiation: early (day 1-5, EFP) or late follicular phase (day 6-14, LFP), early (day 15-21, ELP) or late luteal phase (day 22-32, LLP). The primary outcome was oocyte recovery. RESULTS:A total of 113 women who underwent fertility preservation for breast cancer were included. No differences in oocytes retrieved and ovarian sensitivity were observed when comparing follicular and luteal phases. No differences were observed regarding oocytes retrieved and ovarian sensitivity among the four groups divided according to the menstrual cycle phase. OS was significantly shorter in the early follicular phase (9 days; 8-10) than in the other menstrual phases (LFP: 10 days, 9-11, p < 0.04; ELP: 11, 9-11, p < 0.004; and LLP: 11 days, 10-12, p < 0.001). LIMITATIONS:Our study's limitations are its small sample size and retrospective design. CONCLUSIONS:The phases of the menstrual cycle at which OS was started did not affect oocyte yield and ovarian sensitivity in women with breast cancer undergoing a random-start protocol with letrozole.

PurposeTo evaluate the performance of different embryo transfer (ET) operators in a strictly controlled scenario minimizing potential confounders.MethodsThis single-center retrospective cohort study analyzed vitrified-warmed single euploid top-quality day-5 blastocyst transfers performed in non-obese women at the same IVF center by four equally trained clinicians using a standardized ET technique. These strict inclusion criteria allowed excluding all main confounders on the primary study outcome, namely clinical pregnancy rate (CPR) per ET across different operators. Endometrial preparation protocol, maternal age at transfer, parity, and the embryologist involved were assessed as putative further confounders.ResultsOut of 8663 ETs performed between January 2013 and December 2021, 421 first single euploid top-quality blastocyst transfers were included. No significant difference in ET outcomes was observed among clinicians. Multivariate logistic regression analysis confirmed no association between ET operators and CPR. The experience-defined as the sequential number of previous ETs conducted-did not involve any increase in the CPR.ConclusionsThe ET operator does not affect ET outcomes when subject to the same training and adopting a standardized ET protocol. As the performance does not increase with experience, the initial training is crucial to standardize the procedure across clinicians. In this regard, the CPR per euploid transfer can be considered a valuable Key Performance Indicator (KPI) for quality control purposes. Larger studies are required to build a consensus on competence and benchmark values to achieve.

Objective To compare the effectiveness and cost of in-vitro fertilization (IVF) with or without preimplantation genetic testing for aneuploidy (PGT-A) when only one or two blastocysts are obtained. Methods A dataset was gathered from 1829 patients including 368 non-PGT-A and 1461 PGT-A cycles with one or two blastocysts obtained, between April 2013 and July 2022. Patients were matched 1:1 by propensity-score matching for maternal age, number of metaphase-II oocytes inseminated and number of blastocysts obtained, achieving a database of 242 patients per group. The non-PGT-A and PGT-A groups were compared for differences in live birth rate (LBR) per embryo transfer (ET), cumulative LBR per patient, miscarriage rate (MR) per clinical pregnancy, number of days between oocyte retrieval and conclusion of the IVF cycle (primary outcome), mean expenses incurred at the clinic and incremental cost-effectiveness ratio (ICER). Results More than twice as many ETs were conducted in the non-PGT-A group compared with the PGT-A group, yet the cumulative LBR per patient was similar between groups (23.6% (95% CI, 18.5-29.5%) vs 27.3% (95% CI, 21.9-33.4%)). This outcome was achieved with a higher LBR per ET (16.2% (95% CI, 12.6-20.5%) vs 41.5% (95% CI, 33.9-49.4%)) and lower MR per clinical pregnancy (30.1% (95% CI, 21.8-42.6%) vs 13.9% (95% CI, 7.5-24.0%)) in the PGT-A group. The MR per patient was also lower in the PGT-A group (9.5% (95% CI, 6.2-14.1%) vs 4.5% (95% CI, 2.4-8.2%)). The mean duration between oocyte retrieval and IVF cycle conclusion was 131 (95% CI, 113-150) days in the non-PGT-A group vs 74 (95% CI, 61-87) days in the PGT-A group (P < 0.001; power = 99.8%). The ICER of PGT-A for the months saved between oocyte retrieval and conclusion of the IVF cycle was 499 overall, ranging between 170 and 2065 according to the number of blastocysts obtained and/or maternal age. The ICER of PGT-A for prevented miscarriages was 18 968, decreasing to 3525 when calculated among patients aged >= 35 years with two blastocysts obtained. Conclusions When conducted in expert IVF clinics for patients indicated for the procedure, PGT-A is clinically valuable even when only one or two blastocysts are obtained. PGT-A reduces the number of ETs and miscarriages while the cumulative LBR per patient remains unaffected, and allows these outcomes to be achieved in a shorter timeframe. The ICER of PGT-A vs non PGT-A decreased as maternal age increased.

Which ovarian stimulation and transfer features do impact on clinical, gestational, obstetric and neonatal outcomes after vitrified-warmed euploid single blastocyst transfers? Artificial endometrial preparation involved slightly lower live-birth, higher miscarriage and risk for hypertensive gestational disorders, and larger newborns than modified-natural cycle. Enhancing IVF success requires a comprehensive evaluation of each stage along the treatment. While no conclusive evidence links ovarian stimulation features to clinical, gestational and neonatal outcomes per embryo-transfer, emerging data suggest that regimens of endometrial preparation may impact on miscarriage and live birth rates. Lately, it has been suggested that natural/modified-natural endometrial preparation may be protective against long-term obstetric complications, particularly hypertensive pregnancy disorders and large-for-gestational-age newborns. However, no robust evidence exist that demonstrated the superiority of any endometrial preparation protocol especially in the context of euploid blastocyst transfer. Retrospective observational study of 3698 vitrified-warmed euploid single blastocyst transfers conducted at a private IVF clinic (years:2013-2023) by 2361 couples. The following features were tested for associations with clinical outcomes after transfer, gestational, obstetric and neonatal outcomes per delivery: maternal age, BMI, cause of infertility, days between menses and oocyte-retrieval, duration of ovarian-stimulation, ovarian-stimulation protocol, type of hypothalamic suppression and trigger of ovulation, endometrial preparation protocol, blastocyst quality and day. Single euploid day5-7 blastocysts were transferred 2-3hours after warming. GnRH-antagonist/short-agonist/progestin-primed ovarian-stimulation were conducted, either conventional or DuoStim, with GnRH-analogues (agonist/antagonist)/progesterone hypothalamic suppression and hCG/GnRH-agonist ovulation induction. Endometrial preparation included: artificial-cycle (estradiol-valerate 6mg/daily followed by 600 mg/day micronized-progesterone) and modified-natural-cycle (10,000hCG administered when the leading follicle was >17 mm). Gestational outcomes included embryo twinning, diabetes, cholestasis, placental-abruption, uterine-atony, hypertensive-disorders, placenta-previa, premature-rupture-of-the-membranes, and intrauterine-growth-restriction. Obstetric outcomes included gestational-age and birthweight. Neonatal outcomes included mild and severe malformations. Median maternal age was 37 and 38 years at oocyte-retrieval and embryo-transfer, respectively. The median BMI was 21.5Kg/m2. They underwent 11days (median) of ovarian-stimulation, and 14days (median) separated menses from oocyte-retrieval. Generalized-estimated-equations were used to confirm associations with all outcomes adjusting for multiple observations. Ovarian-stimulation and ovarian-cycle features were not associated with any outcome. Decreasing blastocyst Gardner-quality involved lower live-birth rate per transfer (LBR), and in case of Although, no difference was reported for positive pregnancy test per transfer and biochemical pregnancy loss per positive pregnancy test, artificial rather than modified-natural cycle involved higher MR (N = 178/1100,16.2% versus 73/731,10%; OR:1.7,95%CI:1.27-2.31,p<0.001; Power=98%) and also lower LBR (N = 922/2261,40.8% versus N = 658/1437,45.8%; OR:0.83,95%CI:0.72-0.96,p=0.011; Power=91%). Additionally, artificial-cycle was associated with larger birthweight (median:3300g versus 3240g; unstandardized coefficient-B = +79g, 95%CI:+27g to 132g,p<0.001; Power=90%), higher prevalence of large-for-gestational-age and lower of small-for-gestational-age newborns (N = 139/836,16.6% versus N = 69/590,11.7% and N = 70/836,8.4% versus N = 73/590,12.4%; p < 0.001; Power=93%). Lastly, although the overall prevalence of gestational complication, and neonatal malformations was comparable, a higher prevalence of hypertensive disorders was reported after artificial-cycle endometrial preparation (N = 14/836,1.7% versus N = 3/590,0.5%; OR:3.3,95%CI:1.01-11.63,p=0.05; Power=60%). Retrospective study. Only oocyte retrievals after ovarian-stimulation were included. Pure natural cycle for endometrial preparation was not conducted. Secondary outcomes are biased by limited sample size. All data were obtained by phone interviews and 10.3% of the deliveries lacked gestational and neonatal information (N = 164/1590). No significant association was found between ovarian stimulation features and obstetric or neonatal outcomes. Conversely, modified natural-cycle preparation may involve better prognosis. While artificial-cycle remains essential for premature-ovarian-insufficiency, hypothalamic-amenorrhea, and resistance to ovulation-induction, (modified-)natural endometrial-preparation should be preferred, whenever possible. A randomized-controlled-trial in PGT-A cycles is warranted. No

The evidence that multiple follicular waves arise along an ovarian cycle opened important implications for the treatment of poor prognosis women. Based on the promising evidence of safety and efficiency from luteal phase stimulation and/or random start ovarian stimulation protocols conventionally adopted in oncologic patients, double stimulation in the same ovarian cycle (DuoStim) was theorized. DuoStim can maximize the number of oocytes retrieved per ovarian cycle, thereby increasing the chance to obtain competent embryos in the shortest possible time and reducing treatment discontinuation. Both these outcomes are crucial for patients with limited time available to conceive because of advanced maternal age and/or reduced ovarian reserve. This protocol, pioneered by a Chinese and an Italian group in humans after the intriguing evidence in animals, has been shown safe and reproducible worldwide. Cost-effectiveness analyses are required from future trials; however, the reassuring results achieved support further implementation of DuoStim for poor prognosis patients or time-sensitive conditions.

Objective: To outline oocyte competence after progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) compared to conventional GnRH-antagonist protocol. Study design: Retrospective matched case-control study involving advanced-maternal-age women undergoing ICSI with PGT-A. 89 NETA-PPOS were matched with 178 control patients based on maternal age and ovarian reserve biomarkers. Both groups underwent recombinant-FSH OS with GnRH-agonist ovulation trigger and collected >= 1 MII. In the study group, NETA (10 mg/day) was administered orally starting from day2 of the menstrual cycle. Euploid blastocyst rate per cohort of metaphase-II oocytes (EBR per MII) was the primary outcome. All other embryological and clinical outcomes were reported. Gestational age, birthweight and length were also assessed. Results: The EBR per MII was comparable among PPOS and control (13.9 % +/- 19.3 % versus 13.3 % +/- 17.9 %; the sample size allowed to exclude up to a 10 % difference). Blastocysts morphology and developmental rate were similar. No difference was reported for all clinical outcomes among the 61 and 107 vitrified-warmed euploid single blastocyst transfers respectively conducted. The cumulative live birth delivery rate per concluded cycles was also comparable (24.7 % versus 21.9 %). Neonatal outcomes were analogous. Conclusions: Oocyte competence after NETA-PPOS and standard OS is comparable. This evidence is reassuring and, because of its lower cost and possibly higher patients' compliance, supports PPOS administration whenever the patients are indicated to freeze-all (e.g., fertility preservation, PGT-A, oocyte donation). More data are required about follicle recruitment, oocyte yield, gestational and perinatal outcomes. Randomized-controlledtrials are advisable to confirm our evidence.

Abstract Background Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART. Methods Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed. Results The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data. Conclusions This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation.

In-vitro fertilization (IVF) aims at overcoming the causes of infertility and lead to a healthy live birth. To maximize IVF efficiency, it is critical to identify and transfer the most competent embryo within a cohort produced by a couple during a cycle. Conventional static embryo morphological assessment involves sequential observations under a light microscope at specific timepoints. The introduction of time-lapse technology enhanced morphological evaluation via the continuous monitoring of embryo preimplantation in vitro development, thereby unveiling features otherwise undetectable via multiple static assessments. Although an association exists, blastocyst morphology poorly predicts chromosomal competence. In fact, the only reliable approach currently available to diagnose the embryonic karyotype is trophectoderm biopsy and comprehensive chromosome testing to assess non-mosaic aneuploidies, namely preimplantation genetic testing for aneuploidies (PGT-A). Lately, the focus is shifting towards the fine-tuning of non-invasive technologies, such as "omic" analyses of waste products of IVF (e.g., spent culture media) and/or artificial intelligence-powered morphologic/morphodynamic evaluations. This review summarizes the main tools currently available to assess (or predict) embryo developmental, chromosomal, and reproductive competence, their strengths, the limitations, and the most probable future challenges.

To assess oocyte competence and embryo chromosomal constitution in phenotype-D PCOS women undergoing ICSI for PGT-A at the blastocyst stage. Retrospective study at a private IVF center. In the period 2013–2021, 58 naïve phenotype-D PCOS women (i.e., oligomenorrhea, ovarian PCO-morphology, and absence of hyperandrogenism) underwent ICSI with ejaculated sperm for PGT-A. These cases were matched to 58 controls selected from 2211 naïve women with idiopathic infertility planned for the same treatment in the same period. The matching variables were age (≈ 36 years), BMI (≈ 22), cumulus oocyte complexes (COCs) retrieved (≈ 21–23), and sperm quality (≈ 43–45

IMPORTANCE:The clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, but with mixed results, mainly because the definition of DOR used was inconsistent among trials. OBJECTIVE:To investigate adjuvant treatments and protocols involving only women with DOR according to POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria. DATA SOURCES:We conducted a systematic search using the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases to identify relevant studies published up to June 2024.The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42022346117). STUDY SELECTION AND SYNTHESIS:After duplication removal, the titles and abstracts of 4,806 articles were scrutinized, and 124 full-text articles were assessed for eligibility. In total, 38 randomized controlled trials were included in the qualitative/quantitative analysis. The following interventions were evaluated: dehydroepiandrosterone (n = 1,336); testosterone (n = 418); high- vs. low-dose gonadotropin (n = 957); delayed-start protocol with gonadotropin hormone-releasing hormone antagonist (n = 398); letrozole (n = 612); clomiphene citrate (1,113); growth hormone (311); luteal phase stimulation (n = 57); dual triggering (n = 139); dual stimulation (168); luteinizing hormone (979); oestradiol pretreatment (n = 552); and corifollitropin alfa (n = 561). MAIN OUTCOMES:The primary outcome was live birth rate or ongoing pregnancy if data on live birth were unavailable. Secondary outcomes were number of oocytes retrieved, number of metaphase II oocytes, clinical pregnancy rate and miscarriage rate. RESULTS:Testosterone supplementation is associated with higher live birth rates compared with nonsupplemented women among all interventions evaluated (odds ratio: 2.19, 95% confidence interval [CI]: 1.11-4.32, four studies, 368 patients). Testosterone (weighted mean difference [WMD] 0.88, 95% CI: 0.03-1.72; 4 studies, n = 368 patients), dehydroepiandrosterone (WMD 0.60, 95% CI: 0.07-1.13; 4 studies, n = 418 patients), and delayed started protocol (WMD 1.32, 95% CI: 0.74 to 1.89; 3 studies, n = 398 patients) significantly improved the total number of eggs collected. Lower number of oocytes retrieved is achieved in women undergoing low dose gonadotropin regimen vs high dose (WMD: -1.57, 95% CI: -2.12 to -1.17; 2 studies, n = 905 patients), The other interventions did not produce significant improvements. CONCLUSION AND RELEVANCE:Specific interventions such as testosterone seem to correlate with a better live birth rate in women with DOR; these findings should be further explored in randomized trials.