Abstract
Abstract Study question Does oocyte vitrification impair clinical outcomes in women of advanced maternal age (AMA, >35 years old)? Summary answer Up to the age of 39 years, clinical outcomes were comparable amongst cycles using fresh and vitrified oocytes. What is known already Primarily recommended for young women, oocyte vitrification is the most efficient method for elective fertility preservation. Nevertheless, various social and economic circumstances often compel women to undergo fertility preservation when already at an AMA. Recent studies in mouse suggest that AMA increases the vulnerability of oocytes to molecular and subcellular damage during vitrification, ultimately compromising embryo viability and implantation potential. However, the effects of oocyte vitrification on human preimplantation development and clinical outcomes in women of AMA currently remain unknown. Study design, size, duration This is a retrospective cohort single-center study. We compared outcomes of 1268 patients undergoing their first fresh ICSI cycle using autologous fresh (n = 1087) or vitrified oocytes (n = 181), performed between January 2019 and October 2022. All vitrified oocytes were obtained following elective fertility preservation for age-related fertility decline. Outcomes were stratified according to maternal age at oocyte pick-up: control group (≤35) and AMA groups (36-37, 38-39 and ≥40 years). Participants/materials, setting, methods We compared outcomes between fresh and vitrified oocytes across matching maternal age groups. These included fertilization rates, proportion of viable embryos on day 3, clinical pregnancy and live birth rates. Univariate and multivariate analyses (2-contrast linear and logistic regression) were used to establish correlations. Analyses were adjusting for sperm origin (partner or donor), day of transfer (3 or 5), number of embryos transferred and endometrial age. All p values <0.05 were considered significant. Main results and the role of chance Sperm donation and homologous cycles were equally distributed among the study groups (45% sperm donor and 55% male partner across the entire cohort). In our cohort, blastocyst transfer was performed less frequently in older women, 23.8% for women ≥40 years compared to 45.6% for women ≤35 years (p < 0.0001). When comparing oocyte status across matching maternal age groups, fertilization rates were ∼10% lower when vitrified oocytes were used (p < 0.05). Our adjusted analysis confirmed this negative impact of oocyte vitrification on fertilization rates. Oocyte vitrification also affected ongoing cleavage, as the proportion of viable embryos on day 3 was significantly lower across all groups when vitrified oocytes were used (p < 0.05). Nevertheless, this effect did not translate to clinical pregnancy rates, which were comparable across all maternal age groups regardless of oocyte status. As expected, live birth rate decreased steadily with advancing maternal age (from 38.5% in women ≤35 to 15.0% in women ≥40). While our adjusted analysis showed a negative effect of oocyte vitrification on live birth rates for patients ≥40 (OR: 0.60, 95%CI: 0.18-2.06), we observed no such effect in AMA patients ≤39 years. Limitations, reasons for caution The main limitation of this study is its retrospective design. The low number of women ≥40 undergoing fertility presentation (n = 39) warrants careful interpretation. Our results cannot be generalized to all patient populations and indications for fertility preservation. Wider implications of the findings Clinical outcomes were comparable between fresh and vitrified oocytes up to the age of 39 years. While oocyte vitrification before 35 years old remains the most established and effective method for preventing age-related fertility decline, our findings offer a valuable clinical resource for counselling AMA patients considering elective fertility preservation. Trial registration number Not applicable
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