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Purpose: To investigate cryopreserved testicular spermatozoa among patients with azoospermia. Methods: In this retrospective study spanning from October 1993 to December 2021, we examined men diagnosed with azoospermia who underwent testicular spermatozoa cryopreservation. Data from medical records included utilization and disposal of sperm samples, age at initial cryopreservation. We analyzed the data over 20 years using Kaplan–Meier curves, compared age with the log-rank test, and assessed hazard ratios (HR) with 95% confidence intervals (CI) using Cox regression analysis. Results: A total of 356 patients with a mean age of 32.1 ± 6 were included. Of these, 225 patients utilized thawed testicular sperm for fertility treatments, with 118 patients using all their frozen straws and 107 patients partially using their stored straws. Additionally, 29 patients opted for disposal (six patients partially used their testicular spermatozoa before disposal), resulting in 108 patients who neither used nor disposed of their straws. From a laboratory standpoint, nearly 90% of patients contributed a single testicular sample, which was subsequently divided and cryopreserved as straws, with a median of 4 straws per sample. Notably, in the older age group (> 35 years old), there were a significantly lower usage rate and a higher disposal rate compared to the younger age groups (p < 0.05 for both), corroborated by univariable Cox analysis. Conclusions: This extensive study unveils unique patterns in the preservation and disposal of testicular spermatozoa among azoospermic patients. Most patients utilize a significant portion of their stored samples, while older patients tend to use their testicular spermatozoa less frequently. [ABSTRACT FROM AUTHOR]

Research question: Can an optimal LH threshold algorithm accurately predict timing of ovulation for natural cycle–intrauterine insemination (NC-IUI)? Design: A retrospective cohort study (2018–2022) including 2467 natural cycles. Ovulation timing for these cycles was determined using a previously developed AI model. Two LH thresholds, low and high, were determined in the LH algorithm. Being below the low threshold meant that ovulation is likely to occur in ≥ 4 days, suggesting another daily blood test. Between the two thresholds meant that ovulation was likely in 2–3 days, suggesting IUI the next day. Above the high threshold meant that ovulation will likely occur tomorrow, suggesting performing IUI on the same day. Results: The optimal LH model with a high threshold of 40 mIU/ml and a low threshold of 11 mIU/ml succeeded in correctly predicting timing for IUI (day − 1, − 2 relative to ovulation) in 75.4% (95%CI 75.3–75.4). In 23.1% (95%CI 23.0–23.2), the algorithm predicted "error," suggesting performing insemination when in fact it would have been performed on a non-optimal day (0 or − 3). A previously described 3-hormone-based (LH, estradiol, progesterone) AI model performed significantly better in all parameters (93.6% success rate, 4.3 "error" rate). Conclusions: An LH threshold model, representing common practice, evaluating all possible high and low LH threshold combinations, was successful in accurately scheduling timing for IUI in only 75% of cases. Integrating all three hormones as performed in the AI model may have an advantage in accurately predicting the optimal time for IUI, over the use of LH only. [ABSTRACT FROM AUTHOR]

Background: The cumulus expansion process is one of the LH mediated ovulatory processes. Hyaluronan synthase 2 (HAS2) regulates the synthesis of hyaluronic acid, the main component of the cumulus expansion process. Recently, the lncRNA HAS2 antisense RNA 1 (HAS2-AS1) was identified in our global transcriptome RNA-sequencing of novel ovulation associated genes. The role of HAS2-AS1 in HAS2 regulation w.as studied previously with contradictive results in different models but not in the ovary. Taken together the induction of HAS2-AS1 and the important role of HAS2 in the cumulus expansion process, we hypothesize that HAS2-AS1 regulate HAS2 expression and function in the ovary. Therefore we undertook to study the expression, regulation, and possible functional role of HAS2-AS1 in the human ovary. Results: HAS2-AS1, located within the HAS2 gene that was highly regulated in our library. We found that HAS2-AS1 express mainly in cumulus cells (CCs). Furthermore, HAS2-AS1 showed low expression in immature CCs and a significant increase expression in mature CCs. Functional studies reveal that inhibition of HAS2-AS1 by siRNA caused decrease expression of HAS2. Furthermore, inhibition of HAS2-AS1 by siRNA results in decrease migration of granulosa cells. Conclusions: Our results suggest that HAS2-AS1 is an LH/hCG target gene that plays a positive role in HAS2 expression and thus might play a role in regulating cumulus expansion and migration. [ABSTRACT FROM AUTHOR]

Background: Sperm donation has undergone significant medical and social transformations in recent decades. This study aimed to explore Israeli students' perceptions towards sperm donation and investigate the potential influence of demographic characteristics on these perceptions. Design: The study encompassed 254 students from Tel-Aviv University, who completed an anonymous online survey in January–February 2021. This cross-sectional quantitative online survey, comprised 35 questions categorized into three sections: demographic data, assessment of prior knowledge, and perceptions of sperm donation (general perceptions related to both positive and negative stigmas associated with sperm donation, the roles and activities of sperm banks, and considerations surrounding identity disclosure versus the anonymity of sperm donors and their offspring). Results: Participants exhibited a relatively low level of prior knowledge (mean 31.2 ± 19 of 100). Scores for positive and negative stigmas ranged from 1.3 to 2.2. Notably, the statement "Donors' anonymity preservation is crucial to maintain sperm donation" received a mean of 3.7. Seeking for anonymous sperm donation identity both by recipients and offspring was ranked with low means (1.5 and 1.7, respectively). However, the pursuit of half-siblings by mothers or siblings themselves received higher ratings ranging from 2.7 to 3. Women's stigma ranking were notably lower, while men emphasized the importance of donor anonymity. Conclusions: Sperm Banks hold a position of medical authority rather than being perceived as being commercial entity. The preservation of donor anonymity is widely accepted as a crucial element, prioritized over the requests for identity disclosure from recipients and offspring. Demographic parameters exhibit a strong and precise effects on participants' perceptions. [ABSTRACT FROM AUTHOR]

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10–12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders. [ABSTRACT FROM AUTHOR]

Background: The wide implementation of sperm freezing presents a growing burden on sperm banks. Objectives: To evaluate sperm freezing and usage patterns over 30 years, according to demographic parameters of age at first cryopreservation and number of children, and indication for cryopreservation. Material and methods: This retrospective, population based, cohort study included all sperm cryopreservation cases performed at a tertiary referral center from October 1993 to December 2021, among patients aged 18 years and older. First, we determined the interval between first sperm sample and use. Then, we examined sperm usage separately for: (1) age, comparing patients grouped into 5‐year age cohorts; (2) paternal status according to number of children; (3) indication, comparison among seven indications. Secondary analysis included correlations between main age groups and paternal status versus the four most common indications found. Results: During the study period 1490 men who cryopreserved sperm met the inclusion criteria. Average age at cryopreservation of the first sample was 33.9 ± 8.1 years. Average age at first sperm use was 37 ± 8.5 years. Cumulative sperm usage was 38.7% after 17.8 years. Increasing age was associated with progressive increase in sperm usage rate and shorter preservation period. Use significantly decreased with increasing number of children. Examination of seven reasons for sperm cryopreservation found the highest cumulative sperm usage was related to azoospermia (67.7%), followed by functional cryopreservation (39.3%), oligoasthenoteratospermia (27.3%), other (26.5%), patient's request (24%), cancer (19%), and systemic disease (7.2%). Secondary analysis defined specific usage patterns mainly related to age and indication, with less of an effect based on the number of children. Discussion and conclusion: After decades of cryopreservation, the paradigm of sperm cryopreservation is mostly related to cancer patients. This should be reevaluated and evolve to include broader patient‐targeted factors and perceptions. [ABSTRACT FROM AUTHOR]

Ultrasound monitoring and hormonal blood testing are considered by many as an accurate method to predict ovulation time. However, uniform and validated algorithms for predicting ovulation have yet to be defined. Daily hormonal tests and transvaginal ultrasounds were recorded to develop an algorithm for ovulation prediction. The rupture of the leading ovarian follicle was a marker for ovulation day. The model was validated retrospectively on natural cycles frozen embryo transfer cycles with documented ovulation. Circulating levels of LH or its relative variation failed, by themselves, to reliably predict ovulation. Any decrease in estrogen was 100% associated with ovulation emergence the same day or the next day. Progesterone levels > 2 nmol/L had low specificity to predict ovulation the next day (62.7%), yet its sensitivity was high (91.5%). A model for ovulation prediction, combining the three hormone levels and ultrasound was created with an accuracy of 95% to 100% depending on the combination of the hormone levels. Model validation showed correct ovulation prediction in 97% of these cycles. We present an accurate ovulation prediction algorithm. The algorithm is simple and user-friendly so both reproductive endocrinologists and general practitioners can use it to benefit their patients. [ABSTRACT FROM AUTHOR]

To develop a machine learning model designed to predict the time of ovulation and optimal fertilization window for performing intrauterine insemination or timed intercourse (TI) in natural cycles. A retrospective cohort study. A large in vitro fertilization unit. Patients who underwent 2,467 natural cycle–frozen embryo transfer cycles between 2018 and 2022. None. Prediction accuracy of the optimal day for performing insemination or TI. The data set was split into a training set including 1,864 cycles and 2 test sets. In the test sets, ovulation was determined according to either expert opinion, with 2 independent fertility experts determining ovulation day ("expert") (496 cycles), or according to the disappearance of the leading follicle between 2 consecutive days' ultrasound examinations ("certain ovulation") (107 cycles). Two algorithms were trained: an NGBoost machine learning model estimating the probability of ovulation occurring on each cycle day and a treatment management algorithm using the learning model to determine an optimal insemination day or whether another blood test should be performed. The estradiol progesterone and luteinizing hormone levels on the last test performed were the most influential features used by the model. The mean numbers of tests were 2.78 and 2.85 for the "certain ovulation" and "expert" test sets, respectively. In the "expert" set, the algorithm correctly predicted ovulation and suggested day 1 or 2 for performing insemination in 92.9% of the cases. In 2.9%, the algorithm predicted a "miss," meaning that the last test day was already ovulation day or beyond, suggesting avoiding performing insemination. In 4.2%, the algorithm predicted an "error," suggesting performing insemination when in fact it would have been performed on a nonoptimal day (0 or −3). The "certain ovulation" set had similar results. To our knowledge, this is the first study to implement a machine learning model, on the basis of the blood tests only, for scheduling insemination or TI with high accuracy, attributed to the capability of the algorithm to integrate multiple factors and not rely solely on the luteinizing hormone surge. Introducing the capabilities of the model may improve the accuracy and efficiency of ovulation prediction and increase the chance of conception. HMC-0008-21. [ABSTRACT FROM AUTHOR]

The role of prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is significantly upregulated in preovulatory human granulosa cells (GCs). We found that PGE2 efflux in cultured human GCs is mediated by ABCC4 thus regulating its extracellular concentration. The ABCC4 inhibitor probenecid demonstrated effective blocking of ovulation and affects key ovulatory genes in female mice in vivo. We postulate that the reduction in PGE2 efflux caused by the inhibition of ABCC4 activity in GCs decreases the extracellular concentration of PGE2 and its ovulatory effect. Treatment of female mice with low dose of probenecid as well as with the PTGS inhibitor indomethacin or Meloxicam synergistically blocks ovulation. These results support the hypothesis that ABCC4 has an important role in ovulation and might be a potential target for non‐hormonal contraception, especially in combination with PGE2 synthesis inhibitors. These findings may fill the gap in understanding the role of ABCC4 in PGE2 signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment and control of fertility. [ABSTRACT FROM AUTHOR]

Are IVF treatments with extremely high peak oestradiol levels and gonadotrophin releasing hormone (GnRH) agonist trigger associated with higher complication rates? A retrospective cohort study including patients from two large medical centres treated between 2019 and 2021. A study group with extremely high peak oestradiol levels (≥20,000 pmol/l on the day of ovarian stimulation, or ≥15,000 pmol/l on the previous day) and a control group with normal range oestradiol levels (3000–12000 pmol/l) that received GnRH agonist triggering. Patients were surveyed about complaints and medical care related to ovum retrieval and medical files were reviewed. Major complication rates and the need for medical assistance were compared. Several differences between the study and control group were observed because of the study design: mean age was 33.01 ± 5.14 versus 34.57 ± 4.52 (P < 0.001), mean peak oestradiol levels was 26645.34 ± 8592.57 pmol/l versus 7229.75 ± 2329.20 pmol/l (P < 0.001), and mean number of oocytes were 27.55 ± 13.46 versus 11.67 ± 5.76 (P < 0.001) for the study and control group, respectively. Major complications and hospitalization rates were similar between the study and control groups (three [1.25%] versus one [0.48%]; P = 0.62 and three [1.25%] versus two [0.96%]; P = 1.0, respectively). Thirty-six patients (15.1%) in the study group and 11 (5.3%) in the control group sought medical care after retrieval, mostly due to abdominal pain, without the need for further workup or hospitalization (P < 0.001). Extremely high oestradiol levels were not associated with thromboembolic events, higher major complication or hospitalization rates, and therefore may be considered safe. Nevertheless, patients may be informed of possible higher rates of discomfort, mostly abdominal pain. Larger studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

In the present work, we employed bioinformatics search tools to select ovulation-associated cDNA clones with a preference for those representing putative novel genes. Detailed characterization of one of these transcripts, 6C3, by real-time PCR and RACE analyses led to identification of a novel ovulation-associated gene, designated Ncoa7B. This gene was found to exhibit a significant homology to the Ncoa7 gene that encodes a conserved tissue-specific nuclear receptor coactivator. Unlike Ncoa7, Ncoa7B possesses a unique and highly conserved exon at the 5′ end and encodes a protein with a unique N-terminal sequence. Extensive bioinformatics analysis has revealed that Ncoa7B has one identifiable domain, TLDc, which has recently been suggested to be involved in protection from oxidative DNA damage. An alignment of TLDc domain containing proteins was performed, and the closest relative identified was OXR1, which also has a corresponding, highly related short isoform, with just a TLDc domain. Moreover, Ncoa7B expression, as seen to date, seems to be restricted to mammals, while other TLDc family members have no such restriction. Multiple tissue analysis revealed that unlike Ncoa7, which was abundant in a variety of tissues with the highest expression in the brain, Ncoa7B mRNA expression is restricted to the reproductive system organs, particularly the uterus and the ovary. The ovarian expression of Ncoa7B was stimulated by human chorionic gonadotropin. Additionally, using real-time PCR, we demonstrated the involvement of multiple signaling pathways for Ncoa7B expression on preovulatory follicles. [ABSTRACT FROM AUTHOR]

Multifetal pregnancy reduction (MPR) is an accepted method of reducing complications of triplet pregnancies and higher-order multifetal pregnancies. Eighty-three pregnancies that underwent early (68 weeks) transvaginal MPR were compared with 125 pregnancies that underwent late (11–14 weeks) transabdominal MPR. Rates of pregnancy loss, preterm delivery, gestational diabetes and hypertensive disorders were similar among both groups. Early MPR was associated with a lower risk for small for gestational age newborns (6.5% versus 19.2%; P = 0.034; OR 0.32; 95% CI 0.11 to 0.92) and a higher risk for single-fetus loss (6% versus 0.8%; P = 0.041; OR 10.58; 95% CI 1.1 to 101.94). Preterm delivery rates seemed to be similar between the two groups. In MPR from triplets, an apparent benefit was observed for early MPR in preterm deliveries before 37 weeks, whereas, in MPR from high-order pregnancies, a benefit was observed for late MPR in deliveries before 32 weeks. Perinatal outcomes of twin pregnancies after early and late MPR seem to be grossly similar. Optimal timing for multifetal reduction depends on other factors, namely, the selectivity of the procedure and patient's preference. [ABSTRACT FROM AUTHOR]

Purpose: To investigate factors influencing long-term utilization and disposal patterns of cryopreserved semen straws in oncological patients.This retrospective study included all men who cryopreserved semen due to cancer between October 1993 and December 2021. To assess non-used cryopreserved sperm straws, we investigated the following parameters: cryopreserved semen and usage for fertility treatments versus disposal, summarized by total non-used cases. A Kaplan–Meier curve was used to describe last usage and disposal requests over a 15-year analysis. A Log-rank test was applied to compare between age and paternal status categories.The cohort consisted of 445 patients. Of these, 55 patients utilized thawed semen for fertility treatments, and 65 opted for disposals, leaving 325 patients who neither used nor disposed of their cryopreserved straws. Our findings revealed a distinct pattern based on age, with the youngest age group (< 25 years) exhibiting significantly lower utilization and disposal rates compared to older patient groups. Additionally, men without children exhibited significantly fewer disposal requests compared to fathers. The median cryopreserved straws were 10 (interquartile range, 6 to 17), while the median used straws were only 2 (interquartile range, 2 to 6).Our study brings attention to the additional and needless burden of preservation from both patient and preserved straw perspectives. Implementing a policy based on a cost-effective approach, incorporating time and straw limits, and considering demographic characteristics, could enhance efficiency and necessitate patient consent before preservation.Methods: To investigate factors influencing long-term utilization and disposal patterns of cryopreserved semen straws in oncological patients.This retrospective study included all men who cryopreserved semen due to cancer between October 1993 and December 2021. To assess non-used cryopreserved sperm straws, we investigated the following parameters: cryopreserved semen and usage for fertility treatments versus disposal, summarized by total non-used cases. A Kaplan–Meier curve was used to describe last usage and disposal requests over a 15-year analysis. A Log-rank test was applied to compare between age and paternal status categories.The cohort consisted of 445 patients. Of these, 55 patients utilized thawed semen for fertility treatments, and 65 opted for disposals, leaving 325 patients who neither used nor disposed of their cryopreserved straws. Our findings revealed a distinct pattern based on age, with the youngest age group (< 25 years) exhibiting significantly lower utilization and disposal rates compared to older patient groups. Additionally, men without children exhibited significantly fewer disposal requests compared to fathers. The median cryopreserved straws were 10 (interquartile range, 6 to 17), while the median used straws were only 2 (interquartile range, 2 to 6).Our study brings attention to the additional and needless burden of preservation from both patient and preserved straw perspectives. Implementing a policy based on a cost-effective approach, incorporating time and straw limits, and considering demographic characteristics, could enhance efficiency and necessitate patient consent before preservation.Results: To investigate factors influencing long-term utilization and disposal patterns of cryopreserved semen straws in oncological patients.This retrospective study included all men who cryopreserved semen due to cancer between October 1993 and December 2021. To assess non-used cryopreserved sperm straws, we investigated the following parameters: cryopreserved semen and usage for fertility treatments versus disposal, summarized by total non-used cases. A Kaplan–Meier curve was used to describe last usage and disposal requests over a 15-year analysis. A Log-rank test was applied to compare between age and paternal status categories.The cohort consisted of 445 patients. Of these, 55 patients utilized thawed semen for fertility treatments, and 65 opted for disposals, leaving 325 patients who neither used nor disposed of their cryopreserved straws. Our findings revealed a distinct pattern based on age, with the youngest age group (< 25 years) exhibiting significantly lower utilization and disposal rates compared to older patient groups. Additionally, men without children exhibited significantly fewer disposal requests compared to fathers. The median cryopreserved straws were 10 (interquartile range, 6 to 17), while the median used straws were only 2 (interquartile range, 2 to 6).Our study brings attention to the additional and needless burden of preservation from both patient and preserved straw perspectives. Implementing a policy based on a cost-effective approach, incorporating time and straw limits, and considering demographic characteristics, could enhance efficiency and necessitate patient consent before preservation.Discussion: To investigate factors influencing long-term utilization and disposal patterns of cryopreserved semen straws in oncological patients.This retrospective study included all men who cryopreserved semen due to cancer between October 1993 and December 2021. To assess non-used cryopreserved sperm straws, we investigated the following parameters: cryopreserved semen and usage for fertility treatments versus disposal, summarized by total non-used cases. A Kaplan–Meier curve was used to describe last usage and disposal requests over a 15-year analysis. A Log-rank test was applied to compare between age and paternal status categories.The cohort consisted of 445 patients. Of these, 55 patients utilized thawed semen for fertility treatments, and 65 opted for disposals, leaving 325 patients who neither used nor disposed of their cryopreserved straws. Our findings revealed a distinct pattern based on age, with the youngest age group (< 25 years) exhibiting significantly lower utilization and disposal rates compared to older patient groups. Additionally, men without children exhibited significantly fewer disposal requests compared to fathers. The median cryopreserved straws were 10 (interquartile range, 6 to 17), while the median used straws were only 2 (interquartile range, 2 to 6).Our study brings attention to the additional and needless burden of preservation from both patient and preserved straw perspectives. Implementing a policy based on a cost-effective approach, incorporating time and straw limits, and considering demographic characteristics, could enhance efficiency and necessitate patient consent before preservation. [ABSTRACT FROM AUTHOR]

Background: The development of covid‐19 vaccinations represents a notable scientific achievement. Nevertheless, concerns have been raised regarding their possible detrimental impact on male fertility Objective: To investigate the effect of covid‐19 BNT162b2 (Pfizer) vaccine on semen parameters among semen donors (SD). Methods: Thirty‐seven SD from three sperm banks that provided 216 samples were included in that retrospective longitudinal multicenter cohort study. BNT162b2 vaccination included two doses, and vaccination completion was scheduled 7 days after the second dose. The study included four phases: T0 – pre‐vaccination baseline control, which encompassed 1–2 initial samples per SD; T1, T2 and T3 – short, intermediate, and long terms evaluations, respectively. Each included 1–3 semen samples per donor provided 15–45, 75–125 and over 145 days after vaccination completion, respectively. The primary endpoints were semen parameters. Three statistical analyses were conducted: (1) generalized estimated equation model; (2) first sample and (3) samples' mean of each donor per period were compared to T0. Results: Repetitive measurements revealed −15.4% sperm concentration decrease on T2 (CI −25.5%–3.9%, p = 0.01) leading to total motile count 22.1% reduction (CI −35% – −6.6%, p = 0.007) compared to T0. Similarly, analysis of first semen sample only and samples' mean per donor resulted in concentration and total motile count (TMC) reductions on T2 compared to T0 ‐ median decline of 12 million/ml and 31.2 million motile spermatozoa, respectively (p = 0.02 and 0.002 respectively) on first sample evaluation and median decline of 9.5 × 106 and 27.3 million motile spermatozoa (p = 0.004 and 0.003, respectively) on samples' mean examination. T3 evaluation demonstrated overall recovery without. Semen volume and sperm motility were not impaired. Discussion: This longitudinal study focused on SD demonstrates selective temporary sperm concentration and TMC deterioration 3 months after vaccination followed by later recovery verified by diverse statistical analyses. Conclusions: Systemic immune response after BNT162b2 vaccine is a reasonable cause for transient semen concentration and TMC decline. Long‐term prognosis remains good. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between endometrial compaction and pregnancy rates in unstimulated natural cycle frozen embryo transfers. Design: A single-center prospective cohort study. Endometrial thickness by transvaginal ultrasound and blood progesterone levels on the day of ovulation and the day of embryo transfer were evaluated in patients undergoing natural cycle frozen embryo transfer. Compaction was defined as > 5% decrease in endometrial thickness between ovulation day and day of transfer. Clinical and ongoing pregnancy rates in cycles with and without compaction were compared. Results: Seventy-one women were included, of which 44% had endometrial compaction, with similar rates when subdividing the patients by day of transfer (day 3 or day 5). Clinical and ongoing pregnancy rates were higher in the compaction group compared to the non-compaction group (0.58 vs. 0.16, P < 0.001; 0.52 vs. 0.13, P < 0.001 respectively). Subdividing by degree of compaction > 10% and > 15% revealed similar pregnancy rates as > 5%, with no added benefit to higher degrees of compaction. Conclusions: About half the patients in our study undergoing unstimulated natural cycle frozen embryo transfer experienced compaction of the endometrium, occurring as early as day 3 post-ovulation. This was significantly correlated with increased clinical and ongoing pregnancy rates. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of SARS-CoV-2 infection on pregnancy rates in frozen embryo transfer (FET) cycles. Methods: A retrospective cohort study including women under the age of 42 with documented SARS-CoV-2 infection up to 1 year prior to treatment, undergoing FET cycles in the first half of 2021, with transfer of embryos generated prior to the infection. Controls were SARS-CoV-2 non-diagnosed, non-vaccinated women matched by age, number, and day of embryo transfer. Demographic and cycle characteristics and outcomes were compared. Results: Forty-one recovered women and 41 controls were included. Pregnancy rates were 29% and 49% respectively (p = 0.070). Stratification by time from SARS-CoV-2 infection to transfer into ≤ 60 and > 60 days revealed a difference in pregnancy rates, with women in the COVID group having lower pregnancy rates if infected in proximity to the transfer (21% vs. 55%; p = 0.006). In a logistic regression model, infection was a significant variable (p = 0.05, OR 0.325, 95% CI 0.106–0.998). Logistic regression applied on the subgroup of women infected in proximity to the transfer further strengthened the univariate results, with COVID-19 remaining a significant parameter (p = 0.005, OR 0.072, 95% CI 0.012–0.450). Conclusions: In FET cycles of patients with past SARS-CoV-2 infection, in which oocytes were retrieved prior to infection, decreased pregnancy rates were observed, specifically in patients who recovered less than 60 days prior to embryo transfer. Pending further studies, in cases of FET cycles with limited number of embryos, postponing embryo transfer for at least 60 days following recovery from COVID-19 might be considered when feasible. [ABSTRACT FROM AUTHOR]

Purpose: To describe spermatozoa extraction rate by testicular sperm extraction (TESE) for posthumous sperm retrieval (PMSR) and examine harvest time impact on sperm motility; to compare long-term sperm usage between married vs. single deceased men. Methods: This retrospective study included all PMSR cases in Shamir Medical Center during 2003–2021. We evaluated sperm cryopreservation according to latency time after death. Then, we assessed sperm usage according to Israeli PMSR regulations. Results: The study included 69 (35 married and 34 singles) deceased men with average age of 30.3 ± 7.8 years. Sperm was cryopreserved in 65 cases (94.2%) after maximum and average harvest time of 40 and 16.5 ± 8.1 h, respectively. Motile sperm extraction was associated with significantly shorter harvest time compared with non-motile sperm (13.8 ± 7.3 vs. 18.7 ± 8.1 h, p = 0.046). Sperm usage among married deceased was significantly higher than single (15.6% vs. 0%, p = 0.05). Disposal requests were lower among single compared to married men relatives without reaching statistical difference. Eventually, single men had significantly higher rate of non-used cryopreserved samples (93.8% vs 69.6%, p = 0.01). Conclusion: This large long-term cohort study demonstrates high efficacy of PMSR. We found significant harvest latency time difference between motile and non-motile preserved sperm. Clinical sperm usage rate justifies the efforts for PMSR among married deceased. However, contradicting policy on the topic of single men (which implies liberal sperm preservation but rigid prevention of usage) results with high non-used sperm rate and relatives' extremely sophisticated emotional burden. [ABSTRACT FROM AUTHOR]

Objective: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes.Design: A retrospective cohort study.Setting: A tertiary university-affiliated medical center and a private medical center.Patient(s): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021.Intervention(s): None.Main Outcome Measure(s): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients.Result(s): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates.Conclusion(s): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women. [ABSTRACT FROM AUTHOR]

The effect of the mRNA-BNT162b2 vaccine administered prior to fertility treatments has been addressed in several studies, presenting reassuring results. Cycle outcomes of patients receiving the vaccine during the stimulation itself have not been previously described. This retrospective cohort study included patients who received mRNA-BNT162b2-vaccine during the stimulation of fresh IVF cycles, between January-September 2021, age matched to pre-stimulation vaccinated patients and to non-vaccinated patients. Demographics, cycle characteristics and cycle outcomes were compared between groups. A total of 132 in-treatment vaccinated patients (study group), 132 pre-treatment vaccinated and 132 non-vaccinated patients that underwent fresh IVF cycles were included. Mean time from vaccination to retrieval in the study group was 6.68 days (SD 3.74; range 0–12). Oocyte yield was similar between groups (9.35 versus10.22 and 10.05 respectively; p=0.491). A linear regression model demonstrated no effect of vaccination before or during the stimulation, on oocyte yield (p>0.999). Clinical pregnancy rates (30 % versus 30 % versus 28 %) and ongoing pregnancy rates (25 % for all groups) did not differ between groups. In a logistic regression model for clinical pregnancy rates, vaccine administration and timing of vaccination were not a significant factor. This is the first study reporting the outcome of the mRNA BNT162b2 vaccine administration during the IVF stimulation itself. The vaccine administration had no impact on fresh IVF treatment outcomes compared to pre-treatment vaccinated or non-vaccinated patients. This adds to the growing evidence of COVID-19 vaccine safety in relation to fertility treatments and enables more flexibility regarding timing of vaccine administration. • The mRNA-BNT162b2 vaccine prior to fertility treatments has been previously studied with no effect on cycle outcomes. • The effect of the vaccine administration during the stimulation itself has not been previously described. • This study reports for the first time the effect of the vaccine administered during the stimulation itself. • Cycle outcomes were similar between in-treatment vaccinated, pre-treatment vaccinated and non-vaccinated patients. • The results enable more flexibility regarding timing of vaccine administration. [ABSTRACT FROM AUTHOR]

Study Question: Does prior severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles?Summary Answer: SARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long-term negative effect on oocyte yield (>180 days postinfection).What Is Known Already: A single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes.Study Design, Size, Duration: Retrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle postinfection), between October 2020 and June 2021, matched to non-diagnosed controls.Participants/materials, Setting, Methods: Patients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle and clinical pregnancy rates, were compared between groups.Main Results and the Role Of Chance: One hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; P = 0.169) and mature oocyte rate (78% versus 82%; P = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; P = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (P = 0.018, Slope = -4.08, 95% CI -7.41 to -0.75), although the sample size was small.Limitations, Reasons For Caution: A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group.Wider Implications Of the Findings: The study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos and clinical pregnancy rates, in fresh ART cycles, except for a possible long-term negative effect on oocyte yield when retrieval occurs >180 days post-SARS-CoV-2 infection. Further studies are warranted to support these findings.Study Funding/competing Interest(s): None.Trial Registration Number: 0010-21-HMC, 0094-21-ASF. [ABSTRACT FROM AUTHOR]

Can a machine-learning model suggest an optimal trigger day (or days), analysing three consecutive days, to maximize the number of total and mature (metaphase II [MII]) oocytes retrieved during an antagonist protocol cycle? This retrospective cohort study included 9622 antagonist cycles between 2018 and 2022. The dataset was divided into training, validation and test sets. An XGBoost machine-learning algorithm, based on the cycles' data, suggested optimal trigger days for maximizing the number of MII oocytes retrieved by considering the MII predictions, prediction errors and outlier detection results. Evaluation of the algorithm was conducted using a test dataset including three quality groups: 'Freeze-all oocytes', 'Fertilize-all' and 'ICSI-only' cycles. The model suggested 1, 2 or 3 days as trigger options, depending on the difference in potential outcomes. The suggested days were compared with the actual trigger day chosen by the physician and were labelled 'concordant' or 'discordant' in terms of agreement. In the 'freeze-all' test-set, the concordant group showed an average increase of 4.8 oocytes and 3.4 MII oocytes. In the 'ICSI-only' test set there was an average increase of 3.8 MII oocytes and 1.1 embryos, and in the 'fertilize-all' test set an average increase of 3.6 oocytes and 0.9 embryos was observed (P < 0.001 for all parameters in all groups). Utilizing a machine-learning model for determining the optimal trigger days may improve antagonist protocol cycle outcomes across all age groups in freeze-all or fresh transfer cycles. Implementation of these models may more accurately predict the number of oocytes retrieved, thus optimizing physicians' decisions, balancing workloads and creating more standardized, yet patient-specific, protocols [ABSTRACT FROM AUTHOR]

Abstract Research question What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes? Design A retrospective cohort study including 146 patients aged 41 years to <44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013. Results After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P < 0.01) as factors significantly associated with the probability of a live birth. Conclusions Multiple repeat IVF cycles in women aged 41–44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable. [ABSTRACT FROM AUTHOR]

Purpose: Partial thawing of a vial of cryopreserved sperm (shaving) is sometimes applied as a measure to preserve sperm for further use, particularly in cases of very restricted sperm quantity. However, mechanical violence may disrupt the sperm-wall and lead to impaired in-vitro fertilization (IVF) outcomes.Material and methods: In a retrospective case-control study at a tertiary, university-affiliated medical center, we compared the IVF/intracytoplasmic sperm injection (ICSI) outcomes of patients who used donor sperm following partial thawing (shaving) of the vial of cryopreserved sperm (n = 99) to a control group consisting of patients for whom the vial of sperm was completely thawed before use (n = 99).Results: While no differences were observed in the rates of oocyte fertilization, the mean number of top-quality embryos (TQE) was significantly lower in the shaving group than in the complete thawing group (1.33 ± 0.17 vs. 1.87 ± 0.17, p < 0.02). Experimental analysis of aliquots from the same donors revealed significantly reduced motility in sperm samples that were shaved vs. fully thawed (6.5 vs. 37.1%, p < 0.001).Conclusions: In cases in which available cryopreserved sperm samples are limited, shaving of the vial without thawing can be used but with caution and only when absolutely necessary. Further, large prospective studies are needed to better clarify whether there is post-thawing sperm damage and to compare IVF outcomes after these two thawing methods. [ABSTRACT FROM AUTHOR]

In conclusion, the clinical and laboratory routine workup of SD is likely to exclude pre-vaccination chronic or acute disease explanation for the study results. Keywords: Covid-19 vaccination; sperm donors, spermatogenesis EN Covid-19 vaccination sperm donors, spermatogenesis 1014 1015 2 08/22/22 20220901 NES 220901 Dear Editor, We thank Mungmunpuntipantip and Wiwanitkit for their contribution to the academic discussion regarding our study "Covid-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors."1 The study is focused on sperm donors (SD) because they supply repetitive semen samples - important method to overcome natural semen parameters' fluctuations and variations. Covid-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors. [Extracted from the article]

Purpose: Surrogacy remains the only option for having a biologic child for a unique population of women with severe medical conditions. However, no study has looked at surrogacy outcome as a result of the type of ovarian stimulation of the intended mother [controlled ovarian stimulation (COH), modified natural cycle (MNC), and in vitro maturation (IVM)] for oocyte retrieval. Methods: This is a retrospective study, including all intended mothers and gestational carriers in a tertiary, university affiliated, medical center, from 1998 to 2016. Results: Fifty-two women underwent 252 oocyte retrieval cycles. The pregnancy outcome of 212 embryo transfer cycles (64 gestational carriers) was reviewed according to the origin of the embryo. The number of retrieved oocytes was significantly higher following COH ( n = 132) compared with IVM ( n = 58) and MNC cycles ( n = 62) ( p = 0.013 and p < 0.0001, respectively). Pregnancy rates for embryos transferred according to each protocol were similar. All pregnancies that ended in live births when oocytes from IVM cycles were used derived from transfers of retrieved mature and mixed mature and immature oocytes. Pregnancies that involved embryos derived solely from immature oocytes that further matured in vitro and were transferred to gestational carriers were unsuccessful. Conclusions: MNC protocol is a good option to achieve pregnancy for intended mothers using gestational surrogacy who have contraindications to COH. The yield of IVM cycles in which immature oocytes are retrieved is inconclusive. [ABSTRACT FROM AUTHOR]

Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01 μg/mL, 0.1 μg/mL, 1 μg/mL, 10 μg/mL, or 100 μg/mL) for 48 h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100 μg/mL DBP resulted in significantly lower 17β-estradiol and progesterone production (p < 0.01). It also resulted in altered mRNA expression of steroidogenic, angiogenic, and epidermal growth factor-like growth factor genes: CYP11A1 (p < 0.001), CYP19A1 (aromatase) (p < 0.001), VEGF-A (p < 0.02), BTC (p = 0.009), and EREG (p = 0.04). StAR expression was impaired after exposure to both 10 and 100 μg/mL (p < 0.03 and p < 0.001, respectively). Our results indicate that in vitro exposure of granulosa cells to high doses of DBP alters cell functions. [ABSTRACT FROM AUTHOR]

In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs) has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID) as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (<34 weeks of gestation: 8.9% versus 0%, P < 0.01 ; <37 weeks of gestation: 20.5% versus 5.1%, P< 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations. [ABSTRACT FROM AUTHOR]

Ectopic pregnancy is a known risk for patients treated with IVF. The objective of this study was to evaluate the effect of methotrexate (MTX) and laparoscopic salpingectomy as treatments of ectopic pregnancy on ovarian response during IVF cycles. Data of all women treated for ectopic pregnancy as a result of IVF treatment were evaluated; the study included women who had an unruptured ectopic pregnancy after IVF treatment that was treated with either MTX or laparoscopic salpingectomy and underwent a subsequent IVF cycle. The main outcome measures were baseline serum FSH concentrations and ovarian response in the subsequent IVF cycle after treatment of ectopic pregnancy. Of a total of 58 patients, 36 were previously treated with MTX and 22 others by salpingectomy. No significant differences were observed between the MTX and the salpingectomy groups in the parameters of ovarian response in the subsequent IVF cycle. Repeat ectopic pregnancy was encountered in one patient in each group with a total rate of 3.4% (2/58). No significant differences were found in the outcomes of the subsequent pregnancy after treatment with MTX or salpingectomy. It is concluded that neither prior MTX treatment nor salpingectomy affect ovarian response in the subsequent IVF cycle. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the prognosis of patients with a first treatment cycle that was defined as a poor ovarian response cycle according to the new ESHRE consensus criteria. The first documented cycle of poor response for a patient and all the cycles that followed were retrospectively analysed. Factors that were associated with ongoing pregnancy rates were assessed using multivariate analysis. In total, this study evaluated 1014 patients that underwent 2819 consecutive IVF cycles. As expected, patients with poor response cycles were older and had less oocytes retrieved and less embryos transferred. Multivariate analysis for ongoing pregnancy rates adjusted for patient and the cycle characteristics revealed that the intracytoplasmic sperm injection (ICSI) procedure was associated with a significant increase of 40% in ongoing pregnancy rate (adjusted success ratio 1.40, 95% CI 1.00-1.96). Age over 41 years and additional cycles with poor response, were associated with significantly less ongoing pregnancy rate. However, the cumulative pregnancy rates were 29.5% and 36.4% following five and seven cycles, respectively. In conclusion, performing ICSI may improve the ongoing pregnancy rates in poor responders. Further studies are needed to establish the number of cycles recommended in these patients. [ABSTRACT FROM AUTHOR]

Early pregnancy loss is common among women treated with assisted reproduction treatment, but whether it is a prognostic factor for success in subsequent IVF cycles is not well established. The aim of this study was to determine whether a biochemical pregnancy (BP) or spontaneous abortion (SA) affects the pregnancy rates in the following cycle. A retrospective study of 2687 women undergoing 6678 cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate (PR) per cycle was compared between patients with a pregnancy loss versus a negative β-HCG in their previous cycles. Multivariate analysis of factors affecting ongoing pregnancy rate was performed. BP and/or SA in the first three cycles did not significantly alter the chances to conceive (16.9% patients with BP and/or SA in the previous cycle versus 16.5% patients with no previous pregnancy). From cycle 4 onwards, the presence of a previous abortion (either BP or SA) was associated with better ongoing PR (23.0% versus 11.2%, P < 0.001). In conclusion, BP and/or SA in a previous cycle appears to be a positive marker for success in subsequent cycles in patients with repeated IVF failures. These results should be further investigated in this challenging group of patients. [ABSTRACT FROM AUTHOR]

This study investigated anti-Müllerian hormone (AMH) expression and secretion from cumulus granulosa cells (GC) and steroidogenesis in follicular fluids (FF) with relation to oocyte maturational stages and fertilization capacity in large preovulatory follicles. This prospective study included 53 ovulatory women undergoing intracytoplasmic sperm injection. FF and cumulus GC from 140 large preovulatory follicles were individually obtained during oocyte retrieval. Main outcome measures were oocyte maturation, fertilization and embryo quality. FF were assayed for AMH, progesterone, 17β-oestradiol and testosterone. Cumulus GC were assayed for AMH mRNA expression. AMH mRNA expression and secretion in cumulus GC in preovulatory follicles containing germinal-vesicle (GV) and metaphase-I (MI) oocytes were significantly higher than follicles containing MII oocytes (P < 0.01 and P < 0.0001, respectively). In addition, FF AMH concentrations from atretic oocytes were significantly higher than from MII oocytes. No correlation was found between AMH expression and secretion to fertilization or embryo quality. FF of MI and GV oocytes had higher concentrations of testosterone and lower progesterone/oestradiol ratios than MII oocytes, and FF of atretic oocytes contained higher testosterone concentrations than FF of MII oocytes. AMH is highly expressed in and secreted from cumulus GC of preovulatory follicles containing premature and atretic oocytes. [ABSTRACT FROM AUTHOR]

Although many Fertility Centers have adopted day 5 or 6 embryo transfer policy, yet, 30% of embryo transfers in the US are performed on day 3. This is mainly due to concerns related to longer embryo culture effect and higher rates of embryo transfer cancellation on day 5, with no effect on cumulative pregnancy rate. We conducted a retrospective cohort study comparing individual embryo transfer order rank, best embryo for fresh transfer and intention to freeze, of day-3 and day-5 embryos based on their morphology score. Day-3 embryos of each patient were ranked by embryologists for the order of transfer and intention to freeze, based on morphological score, blinded to actual blastulation outcome. The corresponding blastocysts were similarly ranked for the order of transfer and vitrification intention. Ranking was compared to test the predictive value of day-3 morphological assessment. Sixty patients with 784 day-3 embryos were included. There was only a moderate positive significant correlation between ranks on day-3 and ranks on day-5 [ r = 0.662 95% CI (0.611-0.706, p < 0.001)]. Only 25% of the best embryos for transfer on day 3 (rank = 1) were chosen for fresh transfer on day 5. A total of 441 embryos were intended to be frozen on day 3. Of those, 201 were not transferred nor vitrified on day 5-6 (45%), 3.35 embryos per patient. No significant difference was found between average day-3 rank of embryos ranked 1, 2 (3.12 vs 4.12, p = 0.074) and 3 (3.12 vs 4.08, p = 0.082) on day-5-6. To conclude, this study brings a different perspective to the comparison of day 3 and day 5 by following each embryo's putative and actual designation. Day-3 ranking of embryo morphology did not provide a reliable prediction for blastocyst formation, transfer order and vitrification intention, and may support transfer or cryopreservation of blastocysts over cleavage stage embryos.

The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and < 5 M2 oocytes was calculated. For GAST E3 levels obtaining < 5 M2 oocytes, an AUC value of 0.79 was found. For GAST E3 levels obtaining > 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain < 5 oocytes. Patients younger than 35 with GAST E3 > 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose.Trial registration number: 0304-20-ASF., (© 2024. The Author(s).)

Introduction: Sperm banks have shifted from assisting heterosexual couples with male infertility to primarily serving single women and female couples through medical services, reflecting advances in fertility treatments and societal changes., Aims: Evaluate demographic changes among single women who have applied for sperm donation during 30 years in the State of Israel., Methods: This retrospective cohort study includes 4265 single women who received sperm donation between January 1992 and December 2021, at a tertiary medical center. We divided the follow-up period into 6 groups of 5 years each. A comparison was made of the demographic characteristics of single women applying for sperm donation in different periods according to: 1) age at the beginning of the treatment; 2) ethnic origin - 7 ethnic groups., Results: The average age of single women who received sperm donation was 38.2±4.4 years. The average age of patients decreased from 39.58 years in 1997-1992 to 38.08 years in 2017-2021 (p-value<0.05). Ashkenazic Jews (38.4%) and Sephardic Jews (37.7%) were the most common ethnic origins among single women, with Arab women comprising only 0.2%. Single Jewish women of Ashkenazi descent seek sperm donation treatment almost a year earlier than their Sephardic counterparts (Arab countries and North Africa)., Conclusions: Single Israeli women opting for early sperm donation carries significant clinical, social, and economic implications. Women from conservative social backgrounds appear to be less inclined to seek sperm donation as single individuals or tend to delay this option until a later age, in contrast to women from liberal backgrounds.

Objective: To study the preference of sperm donors with identity disclosure (ID) versus anonymous donors (AD) and to understand if this selection affects clinical outcomes in an Israeli population., Methods: This retrospective study included patients who chose imported sperm donation during 2017-2021. Of these, 526 used their own (autologous) oocytes and 43 patients used donated oocytes (DO). The primary endpoint was the type of chosen donor with ID versus AD. We examined the tendency toward ID according to demographic parameters and the theoretical impact of donor-type selection on reproductive outcome and compared patients who performed cycles with autologous oocytes with those using DO., Results: Single women had a significantly higher probability of choosing sperm donors with ID than heterosexual couples (55.6% vs. 33.3%, OR 2.5, CI 95% 1.52-4.11, P < 0.001). Although not significant, same-sex couples were more likely to choose sperm donors with ID than heterosexual couples (49.1% vs. 33.3%, OR 1.93, CI 95% 0.97-3.85, P = 0.06). Sperm donor samples, 2501 vials, were imported. It was performed 698 intra-uterine insemination and 812 in vitro fertilization cycles were performed, respectively, resulting in 283 pregnancies without differences between patients who chose sperm donors with ID versus AD sperm. No significant differences were observed regarding the option for sperm donors with ID between patients using DO (44.2%) and those using autologous oocytes (51.3%)., Conclusion: While ID is important for a certain section (mainly single) of recipients, it is far from the only dominant factor during donor selection. Sperm donation type does not impact clinical outcomes., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Sperm banks initially focused on providing sperm donation (SD) to heterosexual couples grappling with severe male infertility. Notable advancements in fertility treatments and sociological trends have broadened the scope of SD toward single women and same sex female couples., Objectives: To evaluate SD recipient characteristics over the last three decades in Israel according to demographic parameters., Methods: This retrospective cohort study included 5489 women who received SD between January 1992 and December 2021 from a tertiary referral center. We divided the overall period into six groups of five years each. A comparison of demographic characteristics of women who received SD in different periods was performed according to age at the beginning of the treatment, marital status (single women and same sex female couples, heterosexual couples), and ethnic origin., Results: The average age of women who received SD was 37.02 ± 5.36 years. The average patient age rose from 35.08 years in 1992-1997 to 37.43 years in 2017-2021 (P-value < 0.01). The use of SD was more common among single women and same sex female couples compared to heterosexual couples in later years. Regarding single and same sex female couple, the percentage of SD recipients increased radically from 33% to 88.1% (P-value < 0.01)., Conclusions: Modern sperm banks treat older patients in non-heterosexual relationships. These trends encompass not only medical implications (e.g., in vitro fertilization vs. intrauterine insemination) but also delve into the personal and sociological impact experienced by both patients and offspring.

Background: Sperm banks face a continuously evolving gap between the increasing demand for sperm donation (SD) vs. limited available reserve. To improve donors' recruitment and increase supply, motivations towards SD should be investigated specifically among young men who have the potential to become donors. Our aim was to evaluate factors which increase and decrease predisposition to donate sperm among non-donor students, who represent a "potential pool" for possible donors' recruitment., Results: Ninety-three men fulfilled the questionnaire with mean age of 28.2 ± 4.5 years. The most powerful incentive to donate sperm was financial reward followed by a willingness to help others to build a family (3.8 and 3.4, respectively). The most dominant consideration to decline donation was the fear of anonymity loss and future regret (4 and 3.8). While participants' willingness for anonymous SD was fair (2.8), the open-identity donation was rated significantly lower (1.75, p < 0.01). Familiarity with recipients and offspring had lower scores (1.9-2.2) as well., Conclusions: Young single men represent a suitable cohort for anonymous donation. Financial reward and willingness to help others are important positive incentives while anonymity preservation is crucial to maintain their willingness towards SD. Regulatory shifting towards open-identity SD necessitates the establishment of an alternative "potential pool" population as a reliable source to recruit donors., (© 2023. Société d’Andrologie de Langue Française and BioMed Central Ltd.)

Ovarian follicular development and ovulation in mammals is a highly-regulated process. Most of the current knowledge of ovarian processes was obtained from the studies of non-human models. Molecular studies on human ovarian processes suffer from lack of material and appropriate research tools. Mural granulosa cells (MGCs) culture is a major tool for studying the effect of different substances but a major problem for using these primary MGCs is their unresponsiveness to hCG stimulation at the time of oocyte retrieval. It is acceptable that MGCs regain responsiveness during days in culture but when the best time is and how to accelerate the regenerative process are unknown. The aim of the current study was to establish an optimized protocol which will provide a practical and efficient tool to examine the effect of LH/hCG on different downstream targets in luteinized MGCs. hCG effects were examined according to days in culture and hCG stimulation time. As read-out, we analyzed the gene expression of known hCG targets, protein production, and progesterone secretion. Our results show that with a daily medium exchange, the strongest effect was achieved already 4 days after seeding. On day 4, hCG stimulation triggers two major patterns of gene expression. Early induced genes were highly expressed 6-8 h after hCG, while 24 h of hCG stimulation was needed for late induced genes. Based on our results, we suggest daily medium exchange for 4 days before adding hCG and examine its effect 6 and 24 h later., (Copyright © 2019 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Multifetal pregnancy reduction (MPR) of triplets to twins results in improved pregnancy outcomes compared with triplet gestations managed expectantly. Perinatal outcomes of early transvaginal MPR from triplets to twins were compared with reduction from triplets to singletons. Seventy-four trichorionic triplet pregnancies that underwent early transvaginal MPR at 6-8 weeks gestation were included. Cases were divided into two groups according to the initial procedure: reduction to twin (n = 55) or to singleton (n = 19) gestations. Infants from triplet pregnancies reduced to twins were delivered earlier (36.6 versus 37.9 weeks; P = 0.04) and had lower mean birth weights (2364 g versus 2748 g; P = 0.02) compared with those from triplets reduced to singleton gestations. The rates of pregnancy loss before 24 weeks (3.6% versus 5.3%), as well as of preterm delivery before 32 and 34 weeks of gestation (0% versus 5.3% and 7.3% versus 5.3%, respectively) were similar between the twin and singleton pregnancies. No significant difference was found in the prevalence of gestational diabetes (15.1% versus 5.6%) or gestational hypertension (24.5% versus 16.7%) between the groups. Selective reduction of triplet pregnancies to singleton rather than twin gestations is associated with improved outcomes., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Oocyte cryopreservation is an important method in the field of infertility. This procedure can benefit the cancer patient wishing to preserve fertility before initiation of any destructive chemotherapy or radiation therapy. It is a substitute for embryo cryopreservation and thereby avoids associated ethical issues. Oocyte cryopreservation technology can lead to the establishment of "oocytes banks" and provides solutions to ovarian failure patients. Technical obstacles were the main cause for the slow progress of oocyte cryopreservation. When compared to embryos and sperm cryopreservation technologies which are in common use worldwide, the reports on oocyte cryopreservation-derived pregnancies, were sporadic and with low success rates. However, in recent years we are witnessing more and more publications and increasing success rates in this important and fascinating field. Improvement in the freezing protocols and the introduction of vitrification procedures increased the survival rates and led to the birth of more then 100 healthy newborns. In the future we believe this method will be part of daily work in the fertility world. This review describes the methods available today and the clinical reports published in this field.

In vitro maturation is a new and promising technique in the field of artificial reproductive technology. This method provides an alternative treatment to the known treatments and a solution for one of the most common and disturbing problems of infertility treatment, the hyperstimulation syndrome. The method is particularly useful in cases of patients with polycystic ovarian syndrome. The physiological process of oocyte maturation requires maturation of the nucleus and maturation of the oocyte cytoplasm. In the process of in vitro maturation of the oocyte, oocytes in their late stages of maturation are aspirated from the follicles and transferred to specific culture conditions to achieve complete maturation. The process of oocyte retrieval from small and undeveloped follicles needs proper equipment and experience. Therefore, this process requires deep understanding of the physiological process of oocyte and follicles growth and maturation, proper equipment and especially good experienced laboratory support. This review aims to describe the physiological basis for the process, the recommended protocols and to report the experience published so far on success rates and treatment safety, both maternal and fetal.