Effects of Maternal Age on Receptivity and Pregnancy Outcomes of Single Euploid Transfers: A Retrospective Cohort Study.

PURPOSE: Maternal age-related fertility decline is considered to be directly attributed to either embryonic or endometrial factors. Aneuploidy, as the dominant defect in aging embryos, has long diverted attention away from the effects of endometrial senescence. By analyzing the outcomes of euploid blastocyst transfers verified through preimplantation genetic testing for aneuploidy (PGT-A), we aimed to corroborate impaired endometrial receptivity among older women and determine whether the aging uterus also contributes to pregnancy maintenance.

METHODS

This is a single-center, real-world retrospective cohort study recruiting subfertile couples intended for PGT-A. We assessed the comprehensive correlations between maternal age and clinical outcomes, including clinical pregnancy and clinical miscarriage that represent distinct stages of pregnancy, as well as biochemical pregnancy, live birth, and maternal and neonatal events.

RESULTS

A total of 1816 subfertile couples intended for PGT-A were initially recruited, among whom 1376 obtained euploid blastocysts, leading to 2035 serial single frozen-thawed transfers. Baseline endometrial receptivity exhibited age-dependent impairment, as partially indicated by a reduction in thickness (9.409 ± 2.413 mm to 8.893 ± 2.286 mm; p = 0.0113) and unfavorable alterations in pattern (p < 0.0001). Based on the endometrial age at transfer, 256, 782, 477, 361, and 159 cycles were conducted in women aged < 30, 30-34, 35-37, 38-40, and over 40 years, respectively. Univariable analyses did not identify any discernible trend in the indicators of pregnancy progression across different age groups, independent of aneuploidy. Multivariable analyses, adjusting for embryonic and endometrial confounders, revealed that women over 35 years of age faced higher risks of poor pregnancy initiation (implantation), as evidenced by lower odds of biochemical pregnancy (0.8198 [0.6814-0.9864]) and clinical pregnancy (0.8258 [0.6851-0.9954]). Nevertheless, no such correlation was found during pregnancy maintenance, according to current findings regarding live birth and clinical miscarriage.

CONCLUSIONS

PGT-A, serving as an autologous model to control embryonic quality and study endometrial factors, seems feasible, although nonchromosomal and procedure-related factors may require further distinguishment. Advanced maternal age (AMA) is related to decreased receptivity, and endometrial aging is an independent determinant of euploid implantation. This message offers insights for profound research and appropriate counseling on AMA conditions.