Risk factors for poor oocyte yield and oocyte immaturity after GnRH agonist triggering.

STUDY QUESTION: What are the potential risk factors for poor oocyte recuperation rate (ORR) and oocyte immaturity after GnRH agonist (GnRHa) ovulation triggering? SUMMARY ANSWER: Lower ovarian reserve and LH levels after GnRHa triggering are risk factors of poor ORR. Higher BMI and anti-Müllerian hormone (AMH) levels are risk factors of poor oocyte maturation rate (OMR). WHAT IS KNOWN ALREADY: The use of GnRHa to trigger ovulation is increasing. However, some patients may have a suboptimal response after GnRHa triggering. This suboptimal response can refer to any negative endpoint, such as suboptimal oocyte recovery, oocyte immaturity, or empty follicle syndrome. For some authors, a suboptimal response to GnRHa triggering refers to a suboptimal LH and/or progesterone level following triggering. Several studies have investigated a combination of demographic, clinical, and endocrine characteristics at different stages of the treatment process that may affect the efficacy of the GnRHa trigger and thus be involved in a poor endocrine response or efficiency but no consensus exists. STUDY DESIGN, SIZE, DURATION: Bicentric retrospective cohort study between 2015 and 2021 (N = 1747). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients aged 18-43 years who underwent controlled ovarian hyperstimulation and ovulation triggering by GnRHa alone (triptorelin 0.2 mg) for ICSI or oocyte cryopreservation were included. The ORR was defined as the ratio of the total number of retrieved oocytes to the number of follicles >12 mm on the day of triggering. The OMR was defined as the ratio of the number of mature oocytes to the number of retrieved oocytes. A logistic regression model with a backward selection method was used for the analysis of risk factors. Odds ratios (OR) are displayed with their two-sided 95% confidence interval. MAIN RESULTS AND THE ROLE OF CHANCE: In the multivariate analysis, initial antral follicular count and LH level 12-h post-triggering were negatively associated with poor ORR (i.e. below the 10th percentile) (OR: 0.61 [95% CI: 0.42-0.88]; P = 0.008 and OR: 0.86 [95% CI: 0.76-0.97]; P = 0.02, respectively). A nonlinear relationship was found between LH level 12-h post-triggering and poor ORR, but no LH threshold was found. A total of 25.3% of patients suffered from oocyte immaturity (i.e. OMR < 75%). In the multivariate analysis, BMI and AMH levels were negatively associated with an OMR < 75% (OR: 4.34 [95% CI: 1.96-9.6]; P < 0.001 and OR: 1.22 [95% CI: 1.03-1.12]; P = 0.015, respectively). Antigonadotrophic pretreatment decreased the risk of OMR < 75% compared to no pretreatment (OR: 0.72 [95% CI: 0.57-0.91]; P = 0.02). LIMITATIONS, REASONS FOR CAUTION: Our study is limited by its retrospective design and by the exclusion of patients who had hCG retriggers. However, this occurred in only six cycles. We were also not able to collect information on the duration of pretreatment and the duration of wash out period. WIDER IMPLICATIONS OF THE FINDINGS: In clinical practice, to avoid poor ORR, GnRHa trigger alone should not be considered in patients with higher BMI and/or low ovarian reserve, balanced by the risk of ovarian hyperstimulation syndrome. In the case of a low 12-h post-triggering LH level, practicians must be aware of the risk of poor ORR, and hCG retriggering could be considered. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

What importance do donors and recipients attribute to the nuclear DNA-related genetic heritage of oocyte donation?

STUDY QUESTION: How do oocyte donors and recipients perceive the genetic link related to the transfer of nuclear DNA between donors and offspring? SUMMARY ANSWER: Whether they are donors or recipients, individuals attach great importance to the transmission of their genetic heritage, since 94.5% would opt for the pronuclear transfer method to preserve this genetic link in the context of oocyte donation. WHAT IS KNOWN ALREADY: Since 1983, the use of oocyte donation has increased worldwide. Performed in France since the late 1980s and initially offered to women with premature ovarian insufficiency, its indications have progressively expanded and now it is proposed in many indications to prevent the transmission of genetically inherited diseases. This has resulted in an increase in the waiting time for access to oocyte donation due to the difficulty in recruiting oocyte donors in French ART centres. Several articles have discussed how to fairly distribute donor oocytes to couples, but few have interviewed women in the general population to record their feelings about oocyte donation, as either the donor or recipient and the importance given to the genetic link between the oocyte donors and the children born. Mitochondrial replacement therapy (MRT) is a technique originally developed for women at risk of transmitting a mitochondrial DNA mutation. Recently, MRT has been considered for embryo arrest and oocyte rejuvenation as it could help females to reproduce with their own genetic material through the transfer of their oocyte nucleus into a healthy donor oocyte cytoplasm. STUDY DESIGN, SIZE, DURATION: We conducted an opinion survey from January 2021 to December 2021, during which 1956 women completed the questionnaire. Thirteen participants were excluded from the analysis due to incomplete responses to all the questions. Consequently, 1943 women were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We specifically developed a questionnaire for this study, which was created and distributed using the Drag'n Survey® software. The questionnaire consisted of 21 items presented alongside a video created with whiteboard animation software. The aim was to analyse whether certain factors, such as age, education level, marital status, number of children, use of ART for pregnancy, video viewing, and knowledge about oocyte donation, were associated with feelings towards oocyte donation, by using a univariate conditional logistic regression model. This statistical method was also used to assess whether women would be more inclined to consider oocyte donation with the pronuclear transfer technique rather than the whole oocyte donation. All parameters found to be statistically significant in the univariate analysis were subsequently tested in a multivariate model using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Most women were concerned about the biological genetic contribution of the donated oocyte (94.8%). The most common reason for a women's reluctance to donate their oocytes was their unwillingness to pass on their genetic material (33.3%). Nearly 70% of women who were initially hesitant to donate their oocytes indicated that they would reconsider their decision if the oocyte donation was conducted using donated cytoplasm and the pronuclear transfer technique. Concomitantly, >75% of the respondents mentioned that it would be easier to receive a cytoplasm donation. The largest proportion of the population surveyed (94.5%) expressed their support for its legalization. LIMITATIONS, REASONS FOR CAUTION: In this study, a substantial portion of the responses came from individuals with medical or paramedical backgrounds, potentially introducing a recruitment bias among potential donors. The rate of missing responses to the question regarding the desire to become an oocyte donor was 13.6%, while the question about becoming an oocyte cytoplasm donor had a missing response rate of 23%. These missing responses may introduce a bias in the interpretation of the data. WIDER IMPLICATIONS OF THE FINDINGS: This study was the first to demonstrate that, for the French population studied, the combination of oocyte cytoplasm donation with pronuclear transfer could offer a promising approach to enhance the acceptance of oocyte donation for both the donor and the recipient. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

What is the threshold of mature oocytes to obtain at least one healthy transferable cleavage-stage embryo after preimplantation genetic testing for fragile X syndrome?

STUDY QUESTION: What are the chances of obtaining a healthy transferable cleavage-stage embryo according to the number of mature oocytes in fragile X mental retardation 1 (FMR1)-mutated or premutated females undergoing preimplantation genetic testing (PGT)? SUMMARY ANSWER: In our population, a cycle with seven or more mature oocytes has an 83% chance of obtaining one or more healthy embryos. WHAT IS KNOWN ALREADY: PGT may be an option to achieve a pregnancy with a healthy baby for FMR1 mutation carriers. In addition, FMR1 premutation is associated with a higher risk of diminished ovarian reserve and premature ovarian failure. The number of metaphase II (MII) oocytes needed to allow the transfer of a healthy embryo following PGT has never been investigated. STUDY DESIGN, SIZE, DURATION: The study is a monocentric retrospective observational study carried out from January 2006 to January 2020 that is associated with a case-control study and that analyzes 38 FMR1 mutation female carriers who are candidates for PGT; 16 carried the FMR1 premutation and 22 had the full FMR1 mutation. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 95 controlled ovarian stimulation (COS) cycles for PGT for fragile X syndrome were analyzed, 49 in premutated patients and 46 in fully mutated women. Only patients aged ≤38 years with anti-Müllerian hormone (AMH) >1 ng/ml and antral follicle count (AFC) >10 follicles were eligible for the PGT procedure. Each COS cycle of the FMR1-PGT group was matched with the COS cycles of partners of males carrying any type of translocation (ratio 1:3). Conditional logistic regression was performed to compare the COS outcomes. We then estimated the number of mature oocytes needed to obtain at least one healthy embryo after PGT using receiver operating characteristic curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, in the FMR1-PGT group, the median number of retrieved and mature oocytes per cycle was 11 (interquartile range 7-15) and 9 (6-12), respectively. The COS outcomes of FMR1 premutation or full mutation female carriers were not altered compared with the matched COS cycles in partners of males carrying a balanced translocation in their karyotype. Among the 6 (4-10) Day 3 embryos obtained in the FMR1-PGT group, a median number of 3 (1-6) embryos were morphologically eligible for biopsy, leading to 1 (1-3) healthy embryo. A cutoff value of seven MII oocytes yielded a sensitivity of 82% and a specificity of 61% of having at least one healthy embryo, whereas a cutoff value of 10 MII oocytes led to a specificity of 85% and improved positive predictive value. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective, analyzing a limited number of cycles. Moreover, the patients who were included in a fresh PGT cycle were selected on ovarian reserve parameters and show high values in ovarian reserve tests. This information could influence our conclusion. WIDER IMPLICATIONS OF THE FINDINGS: The results relate only to the target population of this study, with a correct ovarian reserve of AMH >1 and AFC >10. However, the information provided herein extends knowledge about the current state of COS for FMR1 mutation carriers in order to provide patients with proper counseling regarding the optimal number of oocytes needed to have a chance of transferring an unaffected embryo following PGT. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.