ABCC4 is a PGE2 efflux transporter in the ovarian follicle: A mediator of ovulation and a potential non-hormonal contraceptive target.

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.

An artificial intelligence-based approach for selecting the optimal day for triggering in antagonist protocol cycles.

RESEARCH QUESTION: 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? DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Sperm Donors' Identity Disclosure: Is It REALLY Crucial? For Whom?

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.

Israeli students' perceptions regarding sperm donation: dilemmas reflections with dominant demographic effect.

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.

Cryopreserved testicular spermatozoa among patients with azoospermia.

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.

Intrauterine insemination timing models-LH can only take you so far.

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.

[THE EFFECT OF ETHNICITY ON THE AGE OF SINGLE PATIENTS APPLYING FOR SPERM DONATION].

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.

Treatment safety of ART cycles with extremely high oestradiol concentrations using GnRH agonist trigger.

RESEARCH QUESTION: Are IVF treatments with extremely high peak oestradiol levels and gonadotrophin releasing hormone (GnRH) agonist trigger associated with higher complication rates? DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Critical Demographic Changes among Sperm Donation Recipients Over Three Decades.

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.

IVF under COVID-19: treatment outcomes of fresh ART cycles.

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.

What can we learn about posthumous sperm retrieval after extra long-term follow-up?

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.

The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles.

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.

Endometrial compaction is associated with increased clinical and ongoing pregnancy rates in unstimulated natural cycle frozen embryo transfers: a prospective cohort study.

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.

Suspension of fertility treatment during the COVID-19 pandemic: views, emotional reactions and psychological distress among women undergoing fertility treatment.

RESEARCH QUESTION: What are the views and emotional reactions of patients towards the suspension of fertility treatment during the COVID-19 pandemic, and what are the factors affecting their psychological distress? DESIGN: A cross-sectional study conducted in an academic fertility centre. Online questionnaires were distributed between 18 April 2020 and 23 April 2020 to patients whose treatment cycle had been postponed or discontinued. The outcome measures included agreement with the reproductive society guidelines to postpone treatments; willingness to resume treatments, given the choice; patients' emotional reactions; and psychological distress level, measured by the Mental Health Inventory validated scale. A multivariate linear regression was conducted to identify factors associated with psychological distress. RESULTS: Because of the small number of male respondents, only women were included in the analysis (n = 181). Forty-three per cent expressed disagreement with the guidelines and 82% were willing to resume treatments, given the choice. Sadness and anxiety were the most common emotional reactions expressed towards the guidelines. In the multivariate analysis, COVID-19-related anxiety (B = 0.145, P = 0.04) and disagreement with treatment suspension (B = -0.44, P = 0.001) were found to be significantly associated with patients' psychological distress. Background characteristics of patients did not contribute significantly to their distress. CONCLUSIONS: Suspension of fertility treatment during the initial phase of the COVID-19 pandemic was associated with patients' negative emotional reactions. Anxiety related to COVID-19 and disagreement with treatment suspension were found to be significantly associated with psychological distress among women undergoing fertility treatment, regardless of their background characteristics. Our findings suggest the need to monitor the mental health of patients and provide psychological support should a shutdown of fertility care re-occur.

NF-κB-miR-155 axis activation mediates ovulation-induced oncogenic effects in fallopian tube epithelium.

The fallopian tube secretory epithelial cells (FTSECs) are the cell-of-origin of most high-grade serous ovarian carcinomas (HGSOC). FTSECs are repeatedly exposed to inflammation induced by follicular fluid (FF) that is released with every ovulation cycle throughout a woman's reproductive years. Uninterrupted ovulation cycles are an established risk factor for HGSOC. Stimuli present in the FF induce an inflammatory environment which may cause DNA damage eventually leading to serous tumorigenesis. With the aim of elucidating possible mechanistic pathways, we established an 'ex vivo persistent ovulation model' mimicking the repeated exposure of human benign fallopian tube epithelium (FTE) to FF. We performed mass spectrometry analysis of the secretome of the ex vivo cultures as well as confirmatory targeted expressional and functional analyses. We demonstrated activation of the NF-κB pathway and upregulation of miR-155 following short-term exposure of FTE to human FF. Increased expression of miR-155 was also detected in primary HGSOC tumors compared with benign primary human FTE and corresponded with changes in the expression of miR-155 target genes. The phenotype of miR-155 overexpression in FTSEC cell line is of increased migratory and altered adhesion capacities. Overall, activation of the NF-κB-miR-155 axis in FTE may represent a possible link between ovulation-induced inflammation, DNA damage, and transcriptional changes that may eventually lead to serious carcinogenesis.

Fertility patients under COVID-19: attitudes, perceptions and psychological reactions.

STUDY QUESTION: What are the perceptions of infertility patients and the factors correlating with their psychological distress, following suspension of fertility treatments during the Corona Virus Disease-19 (COVID-19) pandemic? SUMMARY ANSWER: Most patients preferred to resume treatment given the chance regardless of background characteristics; higher self-mastery and greater perceived social support were associated with lower distress, while feeling helpless was associated with higher distress. WHAT IS KNOWN ALREADY: Infertility diagnosis and treatment frequently result in significant psychological distress. Recently published data have shown that clinic closure during the COVID-19 pandemic was associated with a sharp increase in the prevalence of anxiety and depression among infertile patients undergoing IVF and was perceived as an uncontrollable and stressful event. Personal resources play an important protective role in times of crisis, helping reduce levels of distress. STUDY DESIGN, SIZE, DURATION: This cross-sectional questionnaire study included patients whose fertility treatment was suspended following the COVID-19 pandemic, in a tertiary hospital. The survey was delivered to 297 patients within 12 days at the beginning of April 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: The self-administered questionnaire included items addressing: (i) patients' demographic characteristics, (ii) anxiety related to COVID-19 infection risk and level of social support, (iii) patients' perceptions of the new guidelines and description of subsequently related emotions and (iv) two validated scales assessing levels of emotional distress and self-mastery. Multivariate analysis was conducted to assess factors alleviating or increasing emotional distress during the COVID-19 pandemic. MAIN RESULTS AND THE ROLE OF CHANCE: There were 168 patients who completed the survey, giving a response rate of 57%. Study variables in the regression model explained 38.9% of the variance in psychological distress experienced by patients during treatment suspension. None of the background characteristics (e.g. age, marital status, parity, economic level or duration of treatments) had a significant contribution. Feeling helpless following the suspension of treatments was associated with higher distress (P < 0.01). Higher self-mastery and greater perceived social support were associated with lower distress (P < 0.01). Despite the ministry of health's decision, 72% of patients wished to resume treatment at the time of survey. LIMITATIONS, REASONS FOR CAUTION: This was a cross-sectional study, thus information about patients' characteristics prior to the COVID-19 pandemic was not available. The length and implications of this pandemic are unknown. Therefore, the ability to draw conclusions about the psychological consequences of the crisis is limited at this point of time. WIDER IMPLICATIONS OF THE FINDINGS: Personal resources play an important protective role in times of crisis, helping to reduce levels of distress. Study findings suggest that attention should be paid to strengthening and empowering patients' personal resources together with directly confronting and containing feelings of helplessness. In line with the European Society for Human Reproduction and Embryology (ESHRE) guidelines, especially at this time of high levels of distress, it is imperative to offer emotional support to reduce stress and concerns. Furthermore, as the pandemic is stabilizing, resumption of treatment should be considered as soon as appropriate according to local conditions. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the IVF unit of the Shamir Medical Center. All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Does double trigger (GnRH-agonist + hCG) improve outcome in poor responders undergoing IVF-ET cycle? A pilot study.

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36 h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36 h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34 h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups' differences in patients' demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1 ± 0.9 vs. 0.3 ± 0.8 and 0.5 + 0.7; p<.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.

The expected cumulative incidence of live birth for patients starting IVF treatment at age 41 years or older.

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.

Comparison of effects of thawing entire donor sperm vial vs. partial thawing (shaving) on sperm quality.

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.

Outcome of immature oocytes collection of 119 cancer patients during ovarian tissue harvesting for fertility preservation.

PURPOSE: Few clinical options for fertility preservation are available to females with cancer, and data about clinical outcomes is limited. Potential supplementary approaches to fertility preservation include retrieval of immature oocytes followed by in vitro maturation (IVM) and storage. The aim of this study was to evaluate post-thawing outcomes of immature oocytes collected both by transvaginal aspiration and from excised ovarian tissue. METHODS: We conducted a retrospective cohort study of patients treated in a single tertiary center. We reviewed the records of 119 cancer patients who underwent ovarian tissue cryopreservation and immature oocyte harvesting for fertility preservation. All embryos and oocytes that were frozen and thawed were included in the study. Post-thawing outcomes were evaluated. RESULTS: Thirty-five stored embryos from eight patients were thawed. Twenty-nine embryos survived (82% survival rate) and were transferred. Six oocytes were thawed, two oocytes survived, and no oocytes were fertilized. Only one PCOS patient became pregnant, resulting in the normal delivery of a healthy baby. CONCLUSIONS: Although a relatively high number of mature oocytes and embryos can be stored with the combined procedure, the limited rate of pregnancies represents a poor reproductive outcome. Therefore, this approach should be reserved for special groups with limited options.