Comparing the clinical outcomes of high purified-human menopausal gonadotropin initial usage with mid follicle phase supplementation during ovarian stimulation in modified ultra-long protocols

Abstract

Objective To explore the effect of high purified-human menopausal gonadotropin (HP-hMG) supplement from initial or from mid follicle phase during ovarian stimulation on the clinical outcomes at GnRHa modified ultra-long protocol. Methods Retrospective analysis was performed on 454 patients who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatment after modified ultra-long GnRH agonist down-regulation and HP-hMG supplement during ovarian stimulation. According to the serum LH level on gonadotropin (Gn) stimulation day, patients were divided into two groups: initial supplement group (group A) and the mild follicle phase supplement group (group B). In group A with serum LH<1.2 IU/L on Gn stimulation day, recombinant FSH (r-FSH) was used combined with HP-hMG from day one of controlled ovary stimulation (COS) until hCG injection day. In group B with LH≥1.2 IU/L on Gn stimulation day, r-FSH was alone for initial COS, HP-hMG was added from the day 6 of stimulation to hCG injection day. Clinical outcomes of two groups were analyzed in subgroup patients according to the age (≤35 years old, 36-40 years old), including total dosage of Gn used, stimulation day of Gn, hormone levels on hCG injection day, the status of oocytes retrieved, embryo quality, implantation rate, clinical pregnancy rate, live birth rate, miscarriage rate, ovarian hyperstimulation syndrome (OHSS) rate, etc. Results For those patients who were younger than 35 years old, HP-hMG initial usage could lead to lower progesterone level on hCG injection day, higher fertilization rate, but need more dosage of Gn compared with those who added HP-hMG from mid follicle phase. The implantation rate was 58.2% vs 42.4%, the clinical pregnancy rate was 80.1% vs 61.7%, the live birth rate was 68.9% vs 49.5% in groups A, B respectively with statistical significances (P<0.05). For those older patients who were 36-40 years old, the clinical pregnancy rate was 61.9% vs 26.3%, live birth rate was 47.6% vs 15.8% in groups A, B, respectively with statistical significances (P<0.05). The miscarriage rate, the mild and severe OHSS rate were similar in the two groups regardless age. Conclusion HP-hMG supplementation from the beginning of COS rather than the late half follicular phase can lower the progesterone level, and improve implantation rate, clinical pregnancy rate, live birth rate after GnRH agonist modified ultra-long protocol. Key words: Modified ultra-long protocol; High purified-human menopausal gonadotropin (HP-hMG); Luteinizing hormone (LH) activity