Efficacy of different gonadotropin combinations to support ovulation induction in WHO type I anovulation infertility: clinical evidences of human recombinant FSH/human recombinant LH in a 2:1 ratio and highly purified human menopausal gonadotropin stimulation protocols

Abstract

Background: The World Helath Organization (WHO) Group I anovulation, or hypogonadotropic hypogonadism (HH), is characterized by reduced hypothalamic/pituitary activity which results in abnormally low serum FSH and LH levels and negligible estrogen activity.

Aim: To compare the efficacy of human recombinant FSH (r-hFSH) plus human recombinant LH (r-hLH) in a 2:1 ratio with highly purified human menopausal gonadotropin (hMG-HP) urinary extract, containing LH-like activity, in women with HH.

Subjects and methods: This two-arm randomized open-label study included 35 HH women (aged 25-36 yr) attending our Center. Eighteen patients received 150 IU hMG-HP (150 IU FSH + 150 IU LH-like activity) and seventeen received 150IU r-hFSH/75IU rhLH daily for a maximum of 16 days. Ovulation was induced by a single administration of hCG on the day after the last hMG-HP or r-hFSH/r-hLH.

Results: The primary efficacy endpoint was ovulation induction as measured by follicle ≥17 mm, pre-ovulatory estradiol (E 2 ) ≥400 pmol/l and mid-luteal phase progesterone (P 4 ) ≥25 nmol/l. Secondary efficacy endpoints included E 2 levels/follicle at mid-cycle, number of follicles at mid-cycle and pregnancy rate (PR). Following a total of 70 cycles, 70% of r-hFSH/r-hLH treated patients met the primary endpoint vs 88% in hMG-HP group (p=0.11). However, PR in r-hFSH/r-hLH group was 55.6% compared to 23.3% in hMG-HP group (p=0.01).

Conclusions: The primary endpoint achievement did not correlate with PR. This study has shown the superiority of LH compared to hCG in supporting FSH-induced follicular development in HH women.

Trial registration: ClinicalTrials.gov NCT01623570.