Pregnancy And Neonatal Outcomes Of hMG Stimulation With Or Without Letrozole In Endometrial Preparation For Frozen–Thawed Embryo Transfer In Ovulatory Women: A Large Retrospective Cohort Study

OBJECTIVE: Frozen–thawed embryo transfer enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred in subsequent cycles into a more “physiologic environment”. This study aimed to investigate the clinical effect of letrozole use or hMG stimulation on pregnancy and neonatal outcomes in ovulatory patients undergoing FET. METHODS: This study includes a total of 5901 FET cycles with letrozole use (n = 1569), HMG (n =1827) or letrozole + HMG (n = 2505). In the letrozole group, 2.5 mg of letrozole was administered on menstrual cycle day 3 to 5 for 3 days for patients, and then follicle growth was monitored beginning on day 10. If the follicular diameter was ≥14 mm on the 10th day, no other ovarian stimulation drugs were needed. If the follicular diameter was <14 mm on the 10th day, 150 IU human menopausal gonadotropin (hMG) was added to stimulate follicle growth every two days (hMG + letrozole group). In hMG stimulation group, a total of 150 IU of hMG was injected every two days to stimulate development of follicles from cycle day 10 to 12. RESULTS: Compared with the patients undergoing hMG stimulation, the group receiving letrozole or letrozole+HMG stimulation exhibits significantly higher clinical pregnancy rates per transfer (hMG: 47.02% vs letrozole: 52.07% vs letrozole+HMG: 52.26%) and implantation rates (hMG: 31.76% vs letrozole: 34.36% vs letrozole+HMG: 34.24%). In addition, the letrozole group was associated with a statistically significantly lower incidence of miscarriage (hMG: 14.78% vs letrozole: 10.53% vs letrozole+HMG: 14.13%) and ectopic pregnancies (hMG: 1.83% vs letrozole: 0.97% vs letrozole+HMG: 1.58%) than the letrozole + HMG and HMG groups. Neonatal outcomes are similar among the three groups. CONCLUSION: Our data demonstrate that the letrozole use may improve clinical pregnancy outcomes and decrease the risk of ectopic pregnancies and miscarriage in ovulatory patients who receive FET cycles.