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.

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.

[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.

Obstetric, neonatal and child development outcomes following assisted hatching treatment: a retrospective cohort study.

Assisted hatching (AH) involves artificial disruption of the zona pellucida prior to embryo transfer. The purpose of this study is to examine the safety of AH technique and its effect on obstetrical, perinatal and neonatal outcomes and risk of developmental delay. This is a retrospective cohort of ART cycles using laser AH technique. The study group consisted of 120 cases of AH cycles resulting in singleton pregnancies and live births compared with 113 control cases. A current phone questionnaire was conducted to assess child development in the first year of life. AH was not associated with increased risk for all obstetrical and perinatal outcomes examined including PPROM, gestational diabetes, hypertensive diseases of pregnancy, delivery by cesarean section, gestational age at delivery, low birth weight (LBW), preterm birth and neonatal Apgar score (p>.05). No significant differences were observed between AH and control group in rates and risk of congenital malformations (5.8 vs. 4.4%, respectively, OR 1.33, 95% CI 0.41-4.34) and developmental delay (19.2 vs. 12.8%, respectively, OR 1.62, 95% CI 0.74-3.52). AH did not increase the risk of obstetrical and neonatal complications in singleton pregnancies, including congenital malformations and child developmental delay. AH may therefore be considered a safe method of ART.

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.

Impact of the mode of conception on gestational hypertensive disorders at very advanced maternal age.

RESEARCH QUESTION: To study gestational hypertensive disorders in oocyte donation pregnancies compared with other modes of conception at very advanced maternal age. DESIGN: A historical cohort study of all women aged 45-47 years who gave birth to singletons at a tertiary medical centre between March 2011 and May 2018, at 24 weeks' gestation or later. Pregnancy outcomes were compared between donor oocyte (IVF-OD), IVF using autologous oocytes (IVF-A) and naturally conceived pregnancies. A multivariate logistic regression was used to evaluate the association between the mode of conception and gestational hypertensive disorders. RESULTS: The final analysis included 159, 68 and 73 patients in the IVF-OD, IVF-A and natural conception groups, respectively. The rate of gestational hypertensive disorders was significantly higher among those who conceived by IVF compared with those who conceived naturally but did not differ between the two IVF groups (27.0% for IVF-OD, 19.1% for IVF-A, P = 0.204; 5.5% for natural conception, P < 0.001 and P = 0.013 compared with IVF-OD and IVF-A, respectively). The results remained similar in a multivariate logistic regression analysis. The rate of Caesarean deliveries was significantly higher in the IVF-OD and IVF-A groups compared with the natural conception group (83.6%, 70.6% and 37.0%, respectively, P < 0.001), but other pregnancy outcomes did not differ between the groups. CONCLUSIONS: IVF pregnancies in the late fifth decade of life were associated with significantly higher rates of gestational hypertensive disorders compared with naturally conceived pregnancies. No difference existed between the two IVF groups. These results may highlight the impact of IVF itself on gestational hypertensive disorders at very advanced maternal age.

Reprogramming human endothelial cells to haematopoietic cells requires vascular induction.

Generating engraftable human haematopoietic cells from autologous tissues is a potential route to new therapies for blood diseases. However, directed differentiation of pluripotent stem cells yields haematopoietic cells that engraft poorly. Here, we have devised a method to phenocopy the vascular-niche microenvironment of haemogenic cells, thereby enabling reprogramming of human endothelial cells into engraftable haematopoietic cells without transition through a pluripotent intermediate. Highly purified non-haemogenic human umbilical vein endothelial cells or adult dermal microvascular endothelial cells were transduced with the transcription factors FOSB, GFI1, RUNX1 and SPI1 (hereafter referred to as FGRS), and then propagated on serum-free instructive vascular niche monolayers to induce outgrowth of haematopoietic colonies containing cells with functional and immunophenotypic features of multipotent progenitor cells (MPPs). These endothelial cells that have been reprogrammed into human MPPs (rEC-hMPPs) acquire colony-forming-cell potential and durably engraft into immune-deficient mice after primary and secondary transplantation, producing long-term rEC-hMPP-derived myeloid (granulocytic/monocytic, erythroid, megakaryocytic) and lymphoid (natural killer and B cell) progenies. Conditional expression of FGRS transgenes, combined with vascular induction, activates endogenous FGRS genes, endowing rEC-hMPPs with a transcriptional and functional profile similar to that of self-renewing MPPs. Our approach underscores the role of inductive cues from the vascular niche in coordinating and sustaining haematopoietic specification and may prove useful for engineering autologous haematopoietic grafts to treat inherited and acquired blood disorders.

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.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes.

OBJECTIVE: Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved. PATIENTS AND METHODS: We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients' previous IVF attempt, triggered with hCG-only. RESULTS: Patients who received the double trigger (study group) had a significantly higher number of mature oocytes - MII (6.5 versus 3.6 p < 0.008), number of embryos transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group. CONCLUSIONS: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

Do poor-responder patients benefit from increasing the daily gonadotropin dose during controlled ovarian hyperstimulation for IVF?

We aim to assess the in vitro fertilization-embryo transfer (IVF-ET) outcome in patients receiving an extremely high 450 daily dose (IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF. Moreover, in those who failed to conceive while using 450 daily dose (IU) of gonadotropins, we aim to evaluate whether increasing the daily dose gonadotropins to 600 IU will improve IVF outcome. All consecutive women, admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. Nine-hundred one consecutive IVF cycles were evaluated. While there was no between-group difference in the duration of COH, patients who conceived were significantly younger, yielded higher number of oocytes retrieved and embryos transferred and had significantly lower cancellations. In a sub-analysis, including only those patients who failed to conceive while using 450 daily dose (IU) of gonadotropins, and who underwent a subsequent IVF cycle attempt with the used of 600 IU daily dose of gonadotropins, no improvements in COH characteristics or cancellation rates were observed with increasing the daily gonadotropin dose to 600 IU. To conclude, in poor responders undergoing COH with an extremely high daily gonadotropin dose (450 IU), the most important factors that predict IVF success are female age and the number of oocytes retrieved. Moreover, patients who failed to conceive on a daily gonadotropin dose of 450 IU will not benefit from increasing the dose to 600 IU and should therefore consider the options of egg donation or adoption.

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

OBJECTIVE: We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. PATIENTS AND METHODS: All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. RESULTS: Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. CONCLUSIONS: In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

Autologous sperm usage after cryopreservation-the crucial impact of patients' characteristics.

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.

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles.

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.