"Blame it on my youth": when very young age appears to be associated with poorer embryo development in oocyte donors

Abstract Study question Is a very young donor’s age associated with different blastocyst usable rate and embryo quality? Summary answer Donors <20 years old have a significantly lower blastocyst usable rate but comparable average embryo quality than donors >25. What is known already Embryo development and quality in IVF cycles are affected by increasing female age. However, some authors also described a lower fertilization rate and reduced number of top-quality embryos in very young infertile patients <25 years old as compared to patients aged 25-35. It has even been reported that live birth rates are significantly lower in oocyte recipients when the donors’ age is < 25. Still, the mechanisms underlying these apparently poorer outcomes in very young women remain speculative given that data on embryo development and quality in vitro are scarce. Study design, size, duration Retrospective-observational study of 1274 oocyte donor’s and 1738 oocyte recipient’s cycles with blastocyst transfer carried out in 2016-2022 in the Fertility Unit of a tertiary University Hospital. Cycles with vitrified oocytes, severe male factor or cleavage-stage embryo transfer were excluded. The main parameters analyzed were blastocyst usable rate (% fertilized oocytes that became a blastocyst suitable for transfer/freezing) and blastocyst quality based on 2015 ASEBIR-scoring system (considering day of development and morphology):D5A, D5B, D5C, D6B, D6C. Participants/materials, setting, methods Cycles were categorized according to donor’s age (Group A: <20, Group B: 20-25, Group C: ≥26). Oocyte donors were aged 18-34. Recipients were aged 18-50. Blastocyst usable rate and embryo quality were compared across groups according to donor’s age. For multivariable analysis, a generalized logistic linear mixed model was applied to estimate the odds for every endpoint, taking Group C as a reference group. Donor and recipient were treated as random factors to avoid the repeated-observation effect. Main results and the role of chance A total of 1274 oocyte donor’s cycles and 1738 oocyte recipient’s cycles were analyzed. Mean age was 26.1 ± 4.3 years old for donors, 42.6 ± 3.8 for recipients, and 43.3 ± 5.7 for male partners. Mean donors’ AMH was 3.8 ± 2.1ng/ml, mean number of mature oocytes (MII) retrieved was 15.8 ± 7.7, and mean total dose of gonadotropins was 1413.1 ± 885.4 units. ICSI technique was used in 75.6% of the cycles. The distribution of cycles by donor age was Group A: n = 55 cycles (4.3%), Group B: n = 532 cycles (41.8%) and Group C: n = 687 cycles (53.9%). Blastocyst usable rate was significantly different according to donors’ age: 33.2% (176/530) for Group A, 42.9% (2580/6016) for Group B and 43.5% (3109/7147) for Group C. Regression analysis, adjusting for confounding factors (AMH, MII, gonadotropins total dose, male age, insemination technique), has shown a significantly lower blastocyst usable rate in very young donors Group A (OR: 0.63; CI 95%; 0.48-0.83) as compared to Group C. Although similar differences were observed in the proportion of top-quality blastocysts (D5A+D5B) in the bivariate analysis A: 19.2% (102/530), B: 24.6% (1480/6016) and C: 24.4% (1742/7147), no significant differences were found after adjustment for confounding factors. Limitations, reasons for caution The main limitation of this study is its retrospective design; still multiple adjustments for confounding factors have been performed in order to minimize the risk of confounding bias. Wider implications of the findings Our finding of a lower blastocyst usable rate in very young donors may be associated with a higher aneuploidy embryo rate in this group, previously reported, advocating for further studies with PGT-A and basic research to decipher the underlying molecular mechanisms. Trial registration number not applicable