Comparison of clomiphene citrate + letrozole add-on versus classical ovarian stimulation protocols in diminished...

To investigate if there is any benefit of adding clomiphene citrate (CC) + letrozole to controlled ovarian stimulation (COS) cycles on the total gonadotropin dose in POSEIDON group 4 diminished ovarian reserve (DOR) patients.

A total of 61 DOR patients who underwent 150 COS cycles between 2020 and 2023 in our center were investigated retrospectively. The patients were divided into three main subgroups: group A, group B, and group C. In group A, gonadotropin stimulation started after the completion of 5 days of co-treatment with CC (50 mg twice daily) and letrozole (2.5 mg twice daily). In group B, patients received gonadotropins after completing 5 days of letrozole (2.5 mg twice, daily), and in group C, patients started gonadotropins only.

Mean age was higher in groups A and B. Body mass index, previous parity, and mean AMH levels were similar between the groups. Day 2 antral follicle count was significantly lower in group A (0.90, 1.45 and 1.53; p = 0.017). The need for gonadotropins was lower in group A compared to groups B and C (p = 0.131, and p = 0.029; respectively). Cycle cancellation rates, follicle count on trigger day, number of mature oocytes, number of cleavage stage embryos, and number of blastocyst stage embryos were similar between the groups.

CC + letrozole co-treatment before starting gonadotropin stimulation in POSEIDON group 4 DOR patients might reduce the need for gonadotropins, with similar live birth rates in COS cycles.