No effect of maternal age on embryo implantation and live birth rates after preimplantation genetic testing for aneuploidies: retrospective analysis of 11,855 single blastocyst transfers

Abstract

Study question Does advanced maternal age affect clinical outcomes after euploid embryo transfer?

Summary answer Advanced maternal age does not significantly affect clinical outcomes after euploid embryo transfer but is associated with poorer embryo quality.

What is known already Age-related fertility decline is closely tied to increased chromosomal abnormalities and reduced oocyte yield. While PGT-A helps mitigate the effects of maternal age by selecting euploid embryos for transfer, its ability to fully address the challenges of age-related fertility decline remains unclear. Studies examining reproductive outcomes after euploid embryo transfer in older women have delivered mixed results, raising questions about the role of embryo quality and endometrial factors in determining success. A deeper understanding of age-related barriers to ART success could improve clinical decision-making and patient counseling.

Study design, size, duration This retrospective multicentre study analyzed 11,855 single euploid blastocyst transfers from autologous preimplantation genetic testing for aneuploidy (PGT-A) cycles, performed across 7 IVF centers between January 2015 and October 2024. The primary outcomes measured included: implantation (IR), clinical pregnancy (CPR), live birth (LBR), and miscarriage (MR) rates. Embryo quality was evaluated using a modified Gardner scoring system, which categorizes embryos as excellent, good or poor.

Participants/materials, setting, methods Maternal age was categorized into five groups based on SART criteria: <35 (n = 4,141), 35-37 (n = 3,320), 38-40 (n = 3,202), 41-42 (n = 988), and >42 years of age (n = 174). A multivariate mixed-effects logistic regression model analyzed the effect of maternal age on clinical outcomes, adjusting for paternal age, cycle number, biopsy day, embryo quality (fixed effects), as well as center and provider (random effect). The interaction between maternal age and embryo quality on LBR was also modeled.

Main results and the role of chance In our cohort, mean maternal age (±SD) was 35.8 (±3.8) years. As anticipated, higher maternal age was significantly associated with a lower number of embryos available for biopsy (Pearson’s R²=-0.26, p < 0.01). Multivariate analysis showed no significant impact of maternal nor paternal age on LBR, IR or CPR (p > 0.05). Embryo quality (excellent vs. good, OR = 0.55, [95%CI: 0.51-0.60] and poor, OR = 0.29, [95%CI: 0.20-0.42], p < 0.001) and day of biopsy (day 5 vs. day 6, OR = 0.86, [95%CI: 0.79-0.93] and day 7, OR = 0.29, [95%CI: 0.22-0.39], p < 0.001) were associated with reduced LBR. While the number of cycles per patient showed a trend toward significance in the univariate analysis (OR = 0.95, [95%CI: 0.91-1.00], p = 0.051), this did not hold in the adjusted analyses (OR = 0.96, [95%CI: 0.91-1.02], p = 0.173). Older patients exhibited increased rates of poor-quality embryos (3.2%, 2.2%, 3%, 5.3%, and 9.2%, <35, 35-37, 38-40, 41-42, >42 years, respectively). Interestingly, interaction analysis showed no significant decline in LBR with advancing maternal age after transferring excellent or good-quality euploid embryos. However, a notable reduction was observed in women >42 years when transferring poor quality euploid embryos (OR = 0.46, [95%CI: 0.21-1.01], p = 0.053).

Limitations, reasons for caution This study is limited by its retrospective design. Additionally, uterine factors such as adenomyosis or fibroids, which may influence reproductive outcomes, were not available in the dataset. Further prospective studies are needed to confirm these findings and explore additional factors which may influence outcomes in older patients undergoing PGT-A.

Wider implications of the findings Advanced maternal age does not compromise clinical outcomes following euploid embryo transfer, as live birth rates remained stable across age groups. The reported decline in success rates with age may primarily stem from reduced euploid embryo availability and the overall lower likelihood of obtaining a good-quality blastocyst suitable for biopsy.

Trial registration number No