PURPOSE: To compare the efficacy of modified natural cycle (mNC) preparation versus hormone replacement therapy (HRT) for endometrial preparation in recipients of donated oocytes, specifically focusing on pregnancy rates in women of advanced maternal age. METHODS: Retrospective multicenter analysis conducted between 2021 and 2024. It includes 220 cycles of fresh single blastocyst transfers resulting from oocyte donation. The participants were divided into two groups based on their endometrial preparation method: modified natural cycle (nNC) (n = 105, 47.7%) and hormone replacement therapy (HRT) (n = 115, 52.3%). Ongoing pregnancy rate was the main outcome. RESULTS: Both groups were similar in terms of donor (24.8 vs 25.1 years) and recipient age (42.3 vs 42.8 years), BMI, and the origin of the semen used. The ongoing pregnancy rate was comparable between the mNC group (44.8%) and the HRT group (40.0%), showing no significant difference (p = 0.47). The mNC group had significantly higher progesterone levels compared to the HRT group (26.45 vs. 16.63, respectively
p <
0.002). In the multivariate analysis, which accounted for factors such as donor and recipient age, BMI, semen origin, progesterone levels, and endometrial thickness, no significant differences were observed between the two groups for the main outcome of ongoing pregnancy rate. CONCLUSIONS: The use of a modified natural cycle for endometrial preparation in advanced-age recipients of fresh single blastocyst transfers from vitrified donor oocytes results in ongoing pregnancy rates equivalent to those achieved with hormone replacement therapy.