Effects of progestin-primed ovarian stimulation protocol plus clomiphene citrate in patients with low basal LH levels: a randomized controlled trial

Infertile patients with low basal luteinizing hormone (LH) levels have low oocyte retrieval rate, but whether progestin-primed ovarian stimulation (PPOS) protocol with clomiphene citrate (CC) could enhance oocyte retrieval rate in these patients remains unclear. This prospective randomized controlled trial was performed between January 2018 and February 2021, included 230 infertile patients with low basal LH levels (LH < 2.27 mIU/mL). In study group, 115 patients received human menopausal gonadotropin (hMG) 150 or 225 IU/d + CC 50 mg/d + medroxyprogesterone acetate (MPA) 10 mg/d from the third day of menstruation. In control group, 115 patients received hMG 150 or 225 IU/d + MPA 10 mg/d from the third day of menstruation. Viable embryos were cryopreserved for later transfer. The primary outcome measure was the oocyte retrieval rate. CC contributed to LH secretion. The hMG+MPA+CC group showed a decreased oocyte retrieval rate (0.71 ± 0.22 vs. 0.76 ± 0.18, mean difference (MD) -0.06 (-0.11 to -0.01); P = 0.043) and a decreased number of cryopreserved embryos (2.89 ± 2.43 vs. 3.90 ± 2.39, MD -0.89 (-1.50 to -0.28); FDR- P = 0.035). Two groups had similar number of retrieved oocytes (8.83 ± 5.41 vs. 10.69 ± 5.85, MD -0.99 (-2.27 to 0.29); FDR- P = 0.213) and oocyte utilization rate (0.40 ± 0.25 vs. 0.46 ± 0.24, MD -0.07 (-0.14 to -0.01); FDR- P = 0.084). Two groups had comparable cumulative clinical pregnancy rates (61.05% vs. 77.67%, hazard ratio (HR) 0.74 (0.53 to 1.06); P = 0.101; FDR- P = 0.214) and cumulative live birth rates (53.68% vs. 66.02%, HR 0.77 (0.53 to 1.13); P = 0.183; FDR- P = 0.214). CC contributed to LH secretion, but PPOS protocol with CC resulted in a lower oocyte retrieval rate in patients with low basal LH levels. PPOS protocol with CC should be used cautiously in these patients. ChiCTR number: ChiCTR1800014440. URL: https://www.chictr.org.cn/showproj.html?proj=24573 . Date of registration: 2018/01/13. Date of enrollment of the first subject: 2018/1/17.