CONTEXT:Intracytoplasmic sperm injection (ICSI) is increasingly used in assisted reproductive technology (ART), even in cases without male factor infertility. Its true benefit in such scenarios remains uncertain. AIMS:To determine whether ICSI provides any embryological or clinical advantage over conventional in vitro fertilization (IVF) in cycles without male factor infertility, using donor sperm and sibling oocytes. METHODS:This retrospective cohort study included 52 women treated at Lis Maternity and Women's Hospital (2018-2024). Each patient underwent split-cycle fertilization with both ICSI and IVF using donor sperm, with sibling oocytes serving as internal controls. Embryological outcomes (fertilization, morphology, Gardner grading, morphokinetics) and clinical outcomes (fresh and frozen embryo transfers, cumulative pregnancy rates) were compared. Cycles in which embryos from both methods were transferred were excluded. KEY RESULTS:ICSI achieved a higher fertilization rate than did IVF (87.5%, 45.05%); however, no significant differences were observed in embryo quality on the basis of morphology and Gardner criteria. Morphokinetic analysis showed higher Day 3 cleavage grading in ICSI embryos (79.80% vs 71.43% IVF), but these advantages did not translate into improved pregnancy outcomes, such as clinical pregnancy rates (33.33% ICSI, 18.6% IVF). CONCLUSION:Among women without known infertility factors undergoing ART with donor sperm, ICSI did not confer clinical advantages over conventional IVF, despite higher fertilization rates. IMPLICATIONS:Given the higher cost, invasiveness, and frequent overuse of ICSI, its application should be reserved for cases with clear indications.

Klinefelter syndrome (KS), marked by testicular heterogeneity, provides a rationale for testicular sperm extraction in azoospermic men, yet large-scale evaluations of predictive and reproductive outcomes remain limited. This retrospective study included 79 karyotype-confirmed KS patients who underwent conventional testicular sperm extraction (cTESE) and microdissection testicular sperm extraction (micro-TESE) between February 2001 and August 2024. Clinical, hormonal, histological, embryological, and reproductive data were analyzed, with successful sperm retrieval (SR) defined as the presence of at least one spermatozoon. SR was achieved in 40.5% of patients and was significantly associated with larger testicular volumes (left: P = 0.018; right: P = 0.028), lower follicle-stimulating hormone (mean ± standard deviation [s.d.]: 29.06 ± 14.49 IU l -1vs 38.22 ± 16.97 IU l -1 ; P = 0.016), and lower luteinizing hormone levels (mean ± s.d.: 16.41 ± 7.46 IU l -1vs 20.65 ± 9.59 IU l -1 ; P = 0.047). These parameters also correlated with the number of frozen sperm vials. Among those with SR, 46 embryo transfer cycles were conducted, involving 79 embryos. Fertilization, cleavage, and blastulation rates were 50.3%, 80.7%, and 40.2%, respectively. Good-quality embryos were observed in 45.1% on day 3 and 55.0% on day 5, with clinical pregnancy and live birth rates of 39.1% and 39.5% per transfer. These findings indicate that favorable hormonal profiles and testicular characteristics are predictive of SR success and that reproductive outcomes among KS patients with sperm retrieval are comparable to those in non-KS populations. Overall, the results support the continued use of testicular sperm extraction as a viable path to genetic parenthood in this population.

To evaluate whether combining microdissection testicular sperm extraction (microTESE) with trifocal testicular sperm extraction (TESE) in a single session improves sperm retrieval and cryopreservation outcomes in men with nonobstructive azoospermia. Retrospective cohort study of 93 men with nonobstructive azoospermia (out of 176 consecutive men with azoospermia) who underwent both microTESE and trifocal TESE sequentially during the same procedure was analyzed. Specimens from each technique were processed and analyzed separately to enable within-patient comparison. Sperm retrieval rates, quantitative sperm yield, and cryopreserved vials were measured. Histopathological patterns were classified. Statistical significance was set at p < 0.05. Sperm retrieval was successful in 59 of 93 patients, resulting in an overall retrieval rate of 63.4

Abstract Objective The aim of this study was to report three cases of early severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing a GnRH antagonist protocol triggered with GnRH agonist (GnRH-a), leading to hospitalization and the need for peritoneal drainage. Additionally, a review of the existing literature on this topic is provided. Design This is a retrospective case series and a literature review. Setting This study was conducted at obstetrics and gynecology department of tertiary academic referral hospitals, Israel. Participants This study included three patients presented with severe OHSS symptoms, including abdominal distension, ascites, and hemoconcentration. Main outcome measures The main focus of the treatment was to address the symptoms and prevent any further complications. The outcome was the complete recovery of the patients. Results The presented cases detail instances of severe OHSS following oocyte retrieval, utilizing GnRH-a for triggering. Case 1 involved a 33-year-old patient with a history of polycystic ovary syndrome (PCOS), Case 2 featured a 22-year-old patient with familial adenomatous polyposis (FAP), and Case 3 included a 41-year-old patient with a history of depressive disorder. All patients receiving supportive care, including infusions and medications, exhibited gradual improvement during hospitalization, with complete resolution observed during the 20-day post-hospitalization check-up. Conclusions These three cases highlight the occurrence of severe early OHSS following a GnRH antagonist protocol triggered with GnRH-a in the absence of human chorionic gonadotropin (hCG) administration for trigger or luteal-phase support. Clinicians must be aware that a GnRH-a trigger followed by a freeze-all approach does not guarantee the complete elimination of OHSS in all patients.

OBJECTIVE:To compare the number and outcomes of elective fertility preservation (FP) before and after the Covid-19 outbreak. METHODS:This retrospective study of 574 women who underwent elective FP between 01/2017-12/2021 included 123 women who underwent the procedure before and 451 who underwent it after the Covid-19 outbreak. The change in the number of women who underwent the procedure each month before and after the pandemic was calculated. The ovarian stimulation outcomes were compared between the two groups. RESULTS:The post-Covid-19 group included significantly more single women compared to the pre-Covid-19 group (93.8% vs. 91.1%, p = 0.024). A progestin-primed ovarian stimulation protocol was followed only among the women in the post-Covid-19 group (18.8% vs. 0%, p<0.001), and their gonadotropin dose was significantly lower than that of the women in the pre-Covid-19 group (3164.6±842.87 mIU/mL vs. 3426.5±1080.63 mIU/mL, p=0.014). There were no significant group differences in ovarian stimulation duration (p=0.069), peak estradiol level (p=0.606), number of retrieved and mature oocytes (p=0.545 and p=0.364, respectively), oocyte maturity rate (p=0.719) or the number of women who cryopreserved embryos (p=0.861). High levels of basal FSH and low antral follicle counts correlated negatively with the total numbers of retrieved and mature oocytes. CONCLUSIONS:A rapid and sustained increase in elective FP after the outbreak of the Covid-19 pandemic that significantly surpassed pre-pandemic levels was observed. There was no significant difference in FP outcomes between the two time periods.

What are the clinical and laboratory insights into posthumous sperm retrieval (PHSR) under wartime circumstances? Viable sperm was retrieved in 89% of cases, with successful retrieval up to 37 hours post-mortem, influenced by time to retrieval and cause of death. Posthumous sperm retrieval (PHSR) has evolved significantly since its first description in 1980, gaining traction in reproductive medicine. Despite its increasing acceptance, regulatory frameworks vary widely, and the scientific literature remains sparse regarding optimal practices. Following the tragic events of October 7, 2023, Israel implemented temporary regulatory amendments to streamline PHSR, allowing families timely access to this procedure. A retrospective cohort study of 28 posthumous sperm retrieval cases conducted under wartime conditions, analyzing demographic, clinical, and laboratory data, including time to retrieval and sperm viability. The study included 28 deceased individuals, primarily soldiers, with an average age of 25.6 years. Sperm viability was assessed at retrieval and post-cryopreservation. Cooling conditions and cause of death (e.g., blast injuries, gunshot wounds) were recorded, and multivariate analyses identified predictors of viability. Viable sperm was retrieved in 25 cases (89%). Median fresh viability was 41%, and post-thaw viability was 25%. Retrieval within 12 hours predicted higher viability. Cooling slowed viability deterioration but did not yield statistically significant differences. The study’s findings may not be generalizable to non-wartime scenarios or cases with different regulatory or cultural contexts. Viability outcomes were influenced by uncontrolled variables such as individual physiology and environmental conditions. This study highlights the importance of timely PHSR and tailored protocols based on circumstances like cause of death. It underscores the need for regulatory clarity and research to optimize outcomes and support bereaved families. No

BACKGROUND:Cryopreservation is widely used in assisted reproductive technologies. While fresh sperm undergoes gradual time-dependent deterioration, it remains unclear whether thawed sperm exhibits a more accelerated decline. OBJECTIVES:To directly compare the rate of deterioration in sperm motility, vitality, and DNA fragmentation between fresh washed and thawed sperm samples over time. MATERIALS AND METHODS:This prospective study included semen samples from 50 males. Samples were split into two groups: Washed (freshly washed sperm) and Thawed (washed, cryopreserved for at least 2 weeks, and thawed). Sperm parameters, including motility, vitality, and DNA fragmentation index (DFI), were assessed immediately after processing (Time 1) and again after 75 min incubation at room temperature (Time 2). Additionally, control experiments tested whether cryoprotectant exposure alone could account for deterioration by comparing washed samples incubated with washing versus freezing medium (10 patient samples), and by assessing post-thaw washing (10 donor samples). RESULTS:Total sperm motility declined significantly more in thawed samples (29 ± 16%) compared to fresh washed samples (17 ± 9%, p < 0.0001). Vitality similarly deteriorated more in thawed samples (21 ± 14%) versus fresh washed samples (7 ± 5%, p < 0.0001). DNA fragmentation increased significantly only in thawed samples (p = 0.0331), reaching clinically critical levels (mean DFI 34 ± 13% at Time 2), compared to fresh samples which remained within normal range (12 ± 5%). Motility grade transitions differed markedly, with thawed samples showing direct transitions from Grade A motility to immotility, unlike fresh washed samples, which transitioned gradually from Grade A to Grade B. In additional control experiments, cryoprotectant exposure alone did not induce deterioration, and post-thaw washing did not improve metrics. DISCUSSION:Thawed sperm exhibited accelerated deterioration across all measured parameters, highlighting cumulative stress from cryopreservation. The rapid decline underscores the need to minimize the interval between thawing and insemination. CONCLUSION:Thawed spermatozoa demonstrate significantly greater susceptibility to time-dependent deterioration compared to fresh washed samples, advocating for immediate use post-thaw to optimize reproductive outcomes.

Can a novel surgical technique using motorized pipette filtration improve ovarian tissue transplantation outcomes in assisted reproduction? The use of a motorized pipette system with precise filtration (0.45μm) in ovarian tissue transplantation led to successful IVF treatment. Ovarian tissue cryopreservation and transplantation are established fertility preservation methods for cancer patients. While successful pregnancies have been reported following IVF treatment, technical challenges persist in the transplantation phase. Single case report of ovarian tissue transplantation with 4-year follow-up through three IVF pregnancies. A 27-year-old patient diagnosed with medulloblastoma underwent ovarian tissue cryopreservation before cancer treatment. Eight oocytes were also cryopreserved but failed to achieve pregnancy. At age 31, following confirmation of post-treatment menopause, she underwent ovarian tissue transplantation using a Scilogex Levo Plus motorized pipette system with 0.45μm filters, followed by IVF treatment. Following transplantation and IVF treatment, the patient achieved three pregnancies: first resulting in early miscarriage, second in live birth, and third ongoing pregnancy. These outcomes demonstrate sustained graft function and successful fertility restoration through combined surgical technique and assisted reproduction. Single case report limits generalizability. Long-term follow-up of graft function and additional cases using this technique in conjunction with IVF are needed. This case demonstrates successful fertility restoration in a cancer survivor using a novel transplantation technique combined with IVF. Multiple pregnancies from a single transplant suggest effective tissue preservation and revascularization supporting assisted reproduction. No

Changing sperm donors after unsuccessful intrauterine insemination (IUI) cycles is a common yet understudied practice. This study evaluates whether switching sperm donors impacts the number of IUI cycles required to achieve pregnancy. This retrospective cohort study analyzed 312 women undergoing donor sperm IUI at Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, from 1992 to 2020. Participants were divided into two groups: Group A (conceived using only one donor) and Group B (switched donors after initial unsuccessful attempts). The primary outcome was the number of IUI cycles until pregnancy. Statistical analyses included t-tests, ANOVA, and multivariate analysis of covariance (MANCOVA). Women in Group A required fewer cycles (mean 3.78 ± 1.90) to achieve pregnancy compared to Group B (mean 6.07 ± 2.95, P < .001). However, after switching donors, the mean number of cycles needed in Group B (2.23 ± 1.61) was significantly lower than the total cycles required by Group A (P < .001). Cumulative live birth rates were higher in Group A (50.5

RESEARCH QUESTION:What are the experiences, needs and preferences of women with a history of sexual trauma undergoing fertility treatment? DESIGN:Women survivors of sexual violence who were previously referred for, underwent or were undergoing fertility treatment were invited to participate in an online survey. Respondents were asked about which screening tool they preferred to gather information about the history of sexual violence, and to rate the significance of specific triggers related to fertility treatment. RESULTS:A total of 155 women responded to the survey. The preferred screening tool for a history of sexual violence was an intake form (76 women [63%]) followed by direct questioning (20 women [16.5%]). Only 11 women (9%) preferred not to be screened for a history of sexual violence. The triggers with the highest intensity were arm and leg fixation during egg retrieval (66.2% and 66.8% of women respectively graded the trigger as 5/5). Past pregnancy was associated with a reduction in the intensity of triggers, but this was of small magnitude (5.8%). Although 65 women (59%) preferred a female physician to carry out fertility-related procedures, most women accepted the treating physician regardless of gender as long as the physician was trained in trauma-informed care. CONCLUSION:Not all triggers related to infertility treatment can be completely avoided; however, a discussion with patients about what may pose a trigger and how to decrease the severity of that trigger is important.

Does the use of GnRH agonist trigger versus hCG trigger affect the length of the subsequent follicular phase in women? A retrospective cohort study analyzing 196 women undergoing controlled ovarian stimulation with freeze-all for PGT-M at a university-affiliated fertility center; 132 received GnRH agonist trigger, and 64 received hCG trigger. The GnRH agonist group demonstrated a significantly longer subsequent follicular phase compared to the hCG group (18.98 ± 3.54 vs. 16.06 ± 3.13 days, P < .001), with extended follicular phase occurring in 90.2

STUDY QUESTION:What are the clinical and logistical predictors of sperm viability in posthumous sperm retrieval (PHSR), and how do post-mortem interval (PMI), body refrigeration, and mechanism of death affect outcomes? SUMMARY ANSWER:Shorter PMI and body refrigeration significantly enhance post-mortem sperm viability, with the mechanism of death modulating viability patterns in a time-dependent manner. WHAT IS KNOWN ALREADY:PHSR has gained increasing prominence in reproductive medicine, yet technical aspects remain under-researched. Key questions regarding optimal timing, storage conditions, and cause of death effects on sperm quality lack systematic investigation. STUDY DESIGN, SIZE, DURATION:Retrospective observational study of 28 PHSR procedures performed between October 2023 and December 2024 at a tertiary academic medical center. PARTICIPANTS/MATERIALS, SETTING, METHODS:Twenty-eight deceased men aged 19-37 years whose families requested PHSR. Unilateral testicular biopsy was performed, followed by sperm viability assessment and cryopreservation. Fresh and post-thaw sperm viability were analyzed as functions of PMI, body refrigeration, and mechanism of death using linear regression and multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE:Viable sperm were successfully retrieved in 25 of 28 cases (89%) up to 37 h post-mortem under optimal conditions. Median fresh sperm viability was 42.0% (quartile 1-quartile 3 [Q1-Q3] 38.0-52.0%), declining to 27.0% (Q1-Q3: 20.0-32.0%) following cryopreservation, representing a median reduction of 39% (Q1-Q3: 32-48%). Linear regression showed a time-dependent viability decline of ∼2% per hour post-mortem. Refrigeration was associated with preserved viability at extended PMIs, with all successful retrievals beyond 14 h occurring in refrigerated bodies. Blast injuries showed higher initial viability than gunshot wounds but a more rapid decline over time. A multivariate model incorporating PMI, refrigeration, and mechanism of death explained 59.2% of the variance in sperm viability. LIMITATIONS, REASONS FOR CAUTION:Limited sample size (n = 28) and unique wartime circumstances may limit generalizability. Documentation of intermediate storage conditions was challenging under combat conditions. Long-term outcomes and fertilization success require further investigation. WIDER IMPLICATIONS OF THE FINDINGS:These findings provide evidence-based benchmarks for PHSR protocols and practical guidance for clinical decision-making and family counseling. The quantitative relationships identified can inform timing decisions and optimize retrieval success rates. STUDY FUNDING/COMPETING INTEREST(S):This study received no external funding. All authors declare no competing interests. TRIAL REGISTRATION NUMBER:N/A.

Study question Does thawed sperm deteriorate more rapidly than washed sperm over time? Summary answer Thawed sperm deteriorates more rapidly than washed sperm over time, with significant declines in motility and vitality and a greater increase in DNA fragmentation. What is known already Intrauterine insemination (IUI) treatments are performed using either washed sperm from a partner or thawed donor sperm. While most procedures occur on-site, some patients opt for off-site insemination. In such cases, thawed sperm samples are prepared in the laboratory and transported to the physician for the procedure. It is known that human spermatozoa is effected by time. However the magnitude of decline over time in thawed human spermatozoa compared to fresh sperm remains unknown. This raises the question regarding the effect of time on different parameters of thawed sperm, compared to fresh washed sperm. Study design, size, duration This prospective study was conducted between 2021-2024 and analyzed sperm samples from 50 men referred for semen analysis. Participants/materials, setting, methods Sperm samples from 50 men were collected, following, each sample sperm was subdivided and analyzed in two comparable ways to answer the main study question. Samples were liquefied for 20 minutes at 37 °C and assessed for motility, vitality, and DNA fragmentation (DFI). Each ejaculate was subdivided into two groups: (A) washing only, (B) washed, frozen, and thawed. Sperm quality was evaluated immediately after preparation (Time 1) and again 75 minutes later (Time 2). Main results and the role of chance Time significantly impacted sperm quality, with thawed sperm showing greater deterioration than washed sperm. Motility declined by 16.87% ± 8.58 in washed sperm versus 28.7% ± 15.55 in thawed sperm (P < 0.001). Vitality dropped by 7.04% ± 5.47 in washed samples and 21.02% ± 13.73 in thawed samples (P < 0.001). DFI increased significantly in both groups (P < 0.0001), with -60.62% ± 65.54 in washed samples and -65.16% ± 57.46 in thawed samples. Notably, thawed samples showed a steeper and more detrimental rise in DFI compared to washed samples (P = 0.0221), emphasizing the adverse impact of thawing on DNA integrity. Further analysis of motility grades revealed that the reduction in grade A motility was similar between the two groups, averaging approximately 32% (P = 0.3). However, washed sperm primarily transitioned from Grade A to Grade B, while thawed sperm showed a sharper decline, shifting to Grade C. Limitations, reasons for caution This study was limited by a single measurement (75 minutes), further research should explore additional time intervals. Additionally, while sperm quality is a viable and important index, it does not fully attest to clinical testing such as pregnancy outcome which should be incorporated in future investigations. Wider implications of the findings Thawed sperm deteriorates more rapidly than washed sperm, emphasizing the importance of minimizing delays between thawing and intrauterine insemination (IUI). These findings may inform clinical guidelines for sperm handling to optimize fertility treatment success. Trial registration number No

This study investigated whether the difference between endometrial thickness in the frozen embryo transfer (FET) cycle and the preceding fresh stimulated cycle predicts clinical pregnancy in women with thin endometrium. A retrospective analysis of 335 cycles in 227 women (age < 43) with endometrium < 8 mm in the FET cycle was conducted. Endometrial thickness was assessed using the ratio (ETfrozen/fresh) and absolute difference (ETfresh-frozen) between the maximal endometrial thickness measured during the stimulated IVF cycle and that measured in the FET cycle. We hypothesized that a smaller difference and higher ratio during FET will be associated with higher pregnancy rate. No embryo implantation occurred in women with an FET endometrial thickness < 5.9 mm and an ETfrozen/fresh < 0.86. Cycles with a positive beta-human chorionic gonadotropin (ß-hCG) showed a significantly lower mean ETfresh-frozen (1.89 ± 1.78 vs 2.30 ± 1.81, p = 0.03), and a significantly higher ETfrozen/fresh ratio (0.82 ± 0.17 vs. 0.77 ± 0.15, p = 0.024). Endometrial thickness in the FET cycle normalized to the preceding stimulated cycle is associated with implantation and may constitute a novel predictor of FET success in women with thin endometrium.

Abstract Introduction Several studies assessed the sensitivity and specificity of plasma concentrations of hormones such as FSH and AMH as biomarkers that can predict the presence of sperm cells, prior to testicular sperm extraction (TESE) in azoospermic men. However, the literature contains conflicting reports in this context. Objective To evaluate the potential of hormonal profile as a non-invasive predictor of mature sperm cells' presence in the testis of azoospermic men, and to assess if the source of these hormones- testicular or peripheral blood makes any difference. Methods Clinical data, hormonal profile, and histological classification of 57 azoospermic men were analyzed. They were categorized into 4 following groups by their testicular pathologies: obstructive azoospermia, hypospermatogenesis, spermatocyte maturation arrest, and Sertoli cells only. The level of hormones was measured by the enzyme-linked immunosorbent assay. Statistical analyses tested the predictability of hormone values for sperm retrieval. Results Overall, 28 patients (49%) had spermatozoa detected. FSH and Inhibin B measurements were statistically significantly different between the 4 groups with different testicular pathologies (p<0.001). AMH, FSH and Inhibin B were found to be independent predictor for positive sperm retrieval (p<0.05). However, a decision tree with random forest classifying the predictive ability of the variables to indicate the presence of sperm produced low accuracy. There was no significant difference between the hormone levels of peripheral blood source and testicular blood source hormone levels. Conclusions AMH, FSH, and Inhibin B are optional markers for positive sperm retrieval in TESE. Increasing the research group may contribute to their ability to predict the presence of mature sperm cells in the testis of azoospermic men. Disclosure No.

On September 5, 2010, the Israeli Parliament passed a law that allows Israeli female residents to donate their oocytes to infertile Israeli female residents. This law includes unique restrictions that do not exist in other countries. Our aim was to characterize Israeli oocyte donors and recipients and the outcomes of the oocyte donation program as regulated by national law. This retrospective study included 26 financially compensated volunteer donors (mean age 29 ± 3.52 years) and 69 recipients (mean age 44.6 ± 3.53 years) who underwent 30 intracytoplasmic sperm injection cycles and 166 embryo transfers (ETs) in our unit between March 2016 and November 2020. Stringent legal caveats unique to Israel (e.g., Jewish/Moslem donor only to Jewish/Moslem recipient, only unmarried donor, eggs in one cycle restricted to ≤ 3 recipients, donated sperm only from non-Jewish donors, and more) were meticulously applied. Sociodemographic characterizations of donors and recipients were reviewed, and pregnancy and obstetric outcomes were determined. Variables that were significant in achieving live births among the recipients were examined. Twenty-five donors and all 69 recipients were Jewish, and most were unmarried and childless. The main indication for seeking egg donation was age ≥ 40 years/perimenopause (80

The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. A retrospective cohort study of 37–45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342

STUDY QUESTION:Can the BlastAssist deep learning pipeline perform comparably to or outperform human experts and embryologists at measuring interpretable, clinically relevant features of human embryos in IVF? SUMMARY ANSWER:The BlastAssist pipeline can measure a comprehensive set of interpretable features of human embryos and either outperform or perform comparably to embryologists and human experts in measuring these features. WHAT IS KNOWN ALREADY:Some studies have applied deep learning and developed 'black-box' algorithms to predict embryo viability directly from microscope images and videos but these lack interpretability and generalizability. Other studies have developed deep learning networks to measure individual features of embryos but fail to conduct careful comparisons to embryologists' performance, which are fundamental to demonstrate the network's effectiveness. STUDY DESIGN, SIZE, DURATION:We applied the BlastAssist pipeline to 67 043 973 images (32 939 embryos) recorded in the IVF lab from 2012 to 2017 in Tel Aviv Sourasky Medical Center. We first compared the pipeline measurements of individual images/embryos to manual measurements by human experts for sets of features, including: (i) fertilization status (n = 207 embryos), (ii) cell symmetry (n = 109 embryos), (iii) degree of fragmentation (n = 6664 images), and (iv) developmental timing (n = 21 036 images). We then conducted detailed comparisons between pipeline outputs and annotations made by embryologists during routine treatments for features, including: (i) fertilization status (n = 18 922 embryos), (ii) pronuclei (PN) fade time (n = 13 781 embryos), (iii) degree of fragmentation on Day 2 (n = 11 582 embryos), and (iv) time of blastulation (n = 3266 embryos). In addition, we compared the pipeline outputs to the implantation results of 723 single embryo transfer (SET) cycles, and to the live birth results of 3421 embryos transferred in 1801 cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS:In addition to EmbryoScope™ image data, manual embryo grading and annotations, and electronic health record (EHR) data on treatment outcomes were also included. We integrated the deep learning networks we developed for individual features to construct the BlastAssist pipeline. Pearson's χ2 test was used to evaluate the statistical independence of individual features and implantation success. Bayesian statistics was used to evaluate the association of the probability of an embryo resulting in live birth to BlastAssist inputs. MAIN RESULTS AND THE ROLE OF CHANCE:The BlastAssist pipeline integrates five deep learning networks and measures comprehensive, interpretable, and quantitative features in clinical IVF. The pipeline performs similarly or better than manual measurements. For fertilization status, the network performs with very good parameters of specificity and sensitivity (area under the receiver operating characteristics (AUROC) 0.84-0.94). For symmetry score, the pipeline performs comparably to the human expert at both 2-cell (r = 0.71 ± 0.06) and 4-cell stages (r = 0.77 ± 0.07). For degree of fragmentation, the pipeline (acc = 69.4%) slightly under-performs compared to human experts (acc = 73.8%). For developmental timing, the pipeline (acc = 90.0%) performs similarly to human experts (acc = 91.4%). There is also strong agreement between pipeline outputs and annotations made by embryologists during routine treatments. For fertilization status, the pipeline and embryologists strongly agree (acc = 79.6%), and there is strong correlation between the two measurements (r = 0.683). For degree of fragmentation, the pipeline and embryologists mostly agree (acc = 55.4%), and there is also strong correlation between the two measurements (r = 0.648). For both PN fade time (r = 0.787) and time of blastulation (r = 0.887), there's strong correlation between the pipeline and embryologists. For SET cycles, 2-cell time (P < 0.01) and 2-cell symmetry (P < 0.03) are significantly correlated with implantation success rate, while other features showed correlations with implantation success without statistical significance. In addition, 2-cell time (P < 5 × 10-11), PN fade time (P < 5 × 10-10), degree of fragmentation on Day 3 (P < 5 × 10-4), and 2-cell symmetry (P < 5 × 10-3) showed statistically significant correlation with the probability of the transferred embryo resulting in live birth. LIMITATIONS, REASONS FOR CAUTION:We have not tested the BlastAssist pipeline on data from other clinics or other time-lapse microscopy (TLM) systems. The association study we conducted with live birth results do not take into account confounding variables, which will be necessary to construct an embryo selection algorithm. Randomized controlled trials (RCT) will be necessary to determine whether the pipeline can improve success rates in clinical IVF. WIDER IMPLICATIONS OF THE FINDINGS:BlastAssist provides a comprehensive and holistic means of evaluating human embryos. Instead of using a black-box algorithm, BlastAssist outputs meaningful measurements of embryos that can be interpreted and corroborated by embryologists, which is crucial in clinical decision making. Furthermore, the unprecedentedly large dataset generated by BlastAssist measurements can be used as a powerful resource for further research in human embryology and IVF. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by Harvard Quantitative Biology Initiative, the NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (award number 1764269), the National Institute of Heath (award number R01HD104969), the Perelson Fund, and the Sagol fund for embryos and stem cells as part of the Sagol Network. The authors declare no competing interests. TRIAL REGISTRATION NUMBER:Not applicable.

Objective: To compare recombinant FSH (rFSH) with highly purified-human menopausal gonadotrophin (hphMG) on ovarian response in women undergoing elective fertility preservation (FP). Methods: This retrospective study included 456 women who underwent elective FP with gonadotropinreleasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS) protocols between 01/201712/2021. Only the first treatment cycle of each woman was included. 341 women were stimulated with rFSH and 115 with hp-hMG, and the ovarian stimulation outcomes were compared. A multivariate linear regression assessed the impact of age, basal FSH, antral follicle count (AFC) and protocol and gonadotropin types on the outcomes. Results: Women in the rFSH group were significantly younger, and their AFC was significantly higher than those in the hp-hMG group (35.50 +/- 2.12 vs. 35.99 +/- 2.13years, p=0.034 and 13.76 +/- 6.08 vs. 11.84 +/- 6.06, p=0.002). There were no significant group differences in the amount (p=0.645) and duration (p=0.265) of FSH stimulation. The estradiol level was significantly lower for the rFSH group compared to the hp-hMG group (2547.18 +/- 1648.21pg/ mL vs. 3468.02 +/- 2497.69pg/mL, p<0.001), while the progesterone level was significantly higher (1.33 +/- 0.75 ng/mL vs. 1.01 +/- 0.52ng/mL, p=0.001). The numbers of retrieved and MII oocytes were significantly higher for the rFSH group compared with the hp-hMG group (16.82 +/- 10.95 vs. 13.25 +/- 9.66, p=0.02, and 13.22 +/- 9.13 vs. 9.76 +/- 7.11, p=0.005), while the maturity rates were comparable (p=0.103). Conclusions: Patients in the rFSH group had higher numbers of both retrieved and MII oocytes when undergoing elective FP.