Addition of Clomiphene Citrate to a Low-Dose Gonadotropin-Releasing Hormone (GnRH)-Antagonist Protocol in Poor...

To evaluate whether the addition of clomiphene citrate (CC) to a low-dose recombinant follicle-stimulating hormone (FSH) (r-FSH) gonadotropin-releasing hormone (GnRH)-antagonist protocol improves clinical outcomes in women with poor ovarian response (POR) compared with a standard high-dose antagonist regimen.

This prospective cohort study included 31 women with POR according to the Bologna criteria who underwent two sequential in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) stimulation cycles: a standard-dose r-FSH protocol (300 IU/day), followed by a low-dose r-FSH protocol (150 IU/day) combined with CC (100 mg/day, cycle days 3-7). Each patient served as her own control. The primary outcome was the ongoing pregnancy rate. Secondary outcomes included follicle number, metaphase II (MII) oocytes, embryos, fertilization rate, biochemical and clinical pregnancy, and miscarriage. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and Fisher's exact tests.

The number of follicles ≥ 17 mm and the number of mature oocytes retrieved were comparable between the standard-dose and CC/low-dose protocols (3.00 vs 2.90 follicles, p=0.665; 2.19 vs 2.06 MII oocytes, p = 0.462). Fertilization rates (27/68 (39.7%) vs 35/64 (54.7%), p = 0.116), total embryos (27 (0.87) vs 35 (1.13), p = 0.101), transferred embryos, and biochemical or clinical pregnancy rates did not differ significantly between protocols. No ongoing pregnancies occurred in the standard group, while three (3/31) were achieved after CC/low-dose stimulation (0% vs 9.7%, p = 0.238).

In women with POR, adding CC to a low-dose GnRH-antagonist protocol results in comparable ovarian response and pregnancy outcomes to a standard high-dose regimen, with the potential advantages of lower gonadotropin use and reduced cost. CC-based mild stimulation represents a viable alternative following an unsuccessful high-dose cycle.