Elective egg freezing patients may benefit from increasing the maximal daily gonadotropin dose above 300IU.

OBJECTIVE: Nowadays, patients attempting social/elective egg freezing has spread globally. Ovarian stimulation (OS) with high daily gonatotropin doses, are commonly offered to this group of patients, aiming to achieve the maximal oocytes cohort with minimum IVF cycle attempts. We aim to assess the IVF-ET outcome, and specifically the oocyte yield, of patients undergoing two successive IVF cycle attempts for elective egg freezing (EEF), and whether changing the daily gonadotropin dose in the second IVF cycle attempt, affect the outcome. PATIENTS AND METHODS: All women admitted to our IVF unit for social/EEF, who underwent 2 consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300 IU were included. Ovarian stimulation characteristics, duration of OS, number of retrieved oocytes, number of mature oocytes were assessed and compared between the 1st and the 2nd IVF cycle attempts, and between the different daily gonadotropin doses and the oocyte yields in the 2nd cycle attempt (increase, decrease or no change). MAIN OUTCOME MEASURES: Oocytes and mature oocytes yield in the 2nd as compared to the 1st IVF cycle attempt. RESULTS: A reduced oocyte yield in the 2nd cycle attempt was observed in those who highly responded in the 1st attempt, regardless the daily dose in the 2nd cycle attempt (whether it was increased, no change and decreased). Moreover, the proportion of patients with same or more oocytes in the 2nd IVF cycle attempt was significantly lower in patients with high peak E2 levels, compared to those with peak E2 levels < 9175 pmol/L. Among patients with high peak E2 (> 9175 pmol/L), those who achieved a lower oocytes yield in the 2nd IVF cycle attempt had lower basal Day-3 FSH/LH ratio (1.5 + 0.5 vs 1.8 + 0.8, p < 0.03) and higher oocyte (range: 7-28, median:10; vs range: 2-15, median:7) and mature oocytes yields. With a cut-off of 9 oocytes, 78.8% of those with > 9 oocytes and 61.8% of those with < 9 oocytes will achieve lower/higher oocytes yield in the 2nd IVF cycle attempt, respectively. CONCLUSIONS: Ovarian stimulation with high daily gonatotropin doses (300 IU) should be offered to patients attempting social/EEF. Moreover, in their 2nd IVF cycle attempt, those with high peak E2 (> 9175 pmol/L) in the 1st attempt, and basal Day-3 FSH/LH ratio < 1.5 and/or more than 9 oocytes retrieved, should receive same OS protocol with no change in the daily gonadotropin dose.

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.

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.

Absence of AGG Interruptions Is a Risk Factor for Full Mutation Expansion Among Israeli FMR1 Premutation Carriers.

Introduction: Fragile X syndrome (FXS) is a common form of X-linked intellectual and developmental disability with a prevalence of 1/4000-5000 in males and 1/6000-8000 in females. Most cases of the syndrome result from expansion of a premutation (55-200 CGGs) to a full mutation (>200 CGGs) repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. The risk for full mutation expansions increases dramatically with increasing numbers of CGG repeats. Recent studies, however, revealed AGG interruptions within the repeat area function as a "protective factor" decreasing the risk of intergenerational expansion. Materials and Methods: This study was conducted to validate the relevance of AGG analysis for the ethnically diverse Israeli population. To increase the accuracy of our results, we combined results from Israel with those from the New York State Institute for Basic Research in Developmental Disabilities (IBR). To the best of our knowledge this is the largest cohort of different ethnicities to examine risks of unstable transmissions and full mutation expansions among FMR1 premutation carriers. Results: The combined data included 1471 transmissions of maternal premutation alleles: 369 (25.1%) stable and 1,102 (74.9%) unstable transmissions. Full mutation expansions were identified in 20.6% (303/1471) of transmissions. A total of 97.4% (388/397) of transmissions from alleles with no AGGs were unstable, 79.6% (513/644) in alleles with 1 AGG and 46.7% (201/430) in alleles with 2 or more AGGs. The same trend was seen with full mutation expansions where 40% (159/397) of alleles with no AGGs expanded to a full mutation, 20.2% (130/644) for alleles with 1 AGG and only 3.2% (14/430) in alleles with 2 AGGs or more. None of the alleles with 3 or more AGGs expanded to full mutations. Conclusion: We recommend that risk estimates for FMR1 premutation carriers be based on AGG interruptions as well as repeat size in Israel and worldwide.

Cigarette smoking and hormones.

PURPOSE OF REVIEW: The purpose is to provide a summary of the effects of cigarette smoking on steroid hormone metabolism and how it affects female fertility. RECENT FINDINGS: Components of tobacco smoke such as polycyclic aromatic hydrocarbons lead to transcriptional upregulation of a number of genes, including members of the cytochrome P450 (CYP) family, in particular CYP1B1 and CYP1A1. In humans, CYP1A1 and CYP1A2 are the primary enzymes catalyzing the 2-hydroxylation of estradiol. This pathway shunts available estrogen away from the more estrogenically potent 16α-hydroxylation to the production of catechol estrogens, mainly 2 and 4 hydroxyestradiol. SUMMARY: Smoking has multiple effects on hormone secretion and metabolism. These effects are mainly mediated by the pharmacological action of tobacco alkaloids (nicotine and its metabolite cotinine). A strong body of evidence indicates that the negative effects of cigarette smoking on fertility compromises nearly every system involved in the reproductive process.

Disparity in post-treatment maternal circulating magnesium sulfate levels between twin and singleton gestation: Is this the missing link between plurality and adverse outcome?

OBJECTIVE: Magnesium sulfate (MgSO4) administered to women at risk for preterm delivery decreases the risk of cerebral palsy in their children. However, the neuroprotective effect of MgSO4 has not been shown in twin gestations. Thus, the aim of this study was to determine the maternal serum levels of magnesium in twin vs. singleton pregnancies following intravenous treatment of MgSO4. METHODS: Case control study including two groups of pregnant women who received intravenous MgSO4: (1) twin gestations (n=83) and (2) singleton pregnancies (n=83). Maternal serum magnesium levels 6 and 24 h after initiation of treatment were determined in both groups. RESULTS: Maternal serum levels of magnesium were significantly lower among patients with twin gestations compared to those with singleton ones 6 h after initiation of treatment (4.6 vs. 4.8 mg/dL, P=0.003). In addition, the rate of pregnant women who obtained therapeutic levels 6 h after initiation of treatment was significantly lower in twin gestations than in singleton ones (36% vs. 58%, P=0.008). Multiple regression analysis revealed that twin gestations were independently and significantly associated with low maternal serum magnesium levels. CONCLUSIONS: Maternal serum concentrations of magnesium are lower in twin pregnancies than in singleton ones following MgSO4 treatment, which might explain the decreased neuroprotective effect of MgSO4 reported in twin pregnancies.