Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment

Abstract

Women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility were randomly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH (r-hFSH; Gonal-F) and recombinant human LH (r-hLH; Luveris) (n = 212) starting on day 6 of FSH stimulation until human chorionic gonadotrophin (HCG) at a daily fixed dose of 150 IU r-hLH, or with r-hFSH alone (n = 219). There was no significant difference in the number of metaphase II oocytes retrieved (10.3 versus 10.4) in patients treated with r-hFSH and r-hLH versus r-hFSH alone; however, more embryos were transferred in the LH-supplemented group (2.9 versus 2.8, P = 0.037). Overall, the implantation rates were 22.9 versus 27.0% in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively (NS). The respective numbers of MII oocytes retrieved in patients <35 or >or=35 years were 11 versus 8.3 (P = 0.010) for patients treated with r-hFSH alone, and 10.7 versus 9.3 (NS) for those given supplemental r-hLH (150 IU) from day 6. Implantation rates in patients <35 years treated with r-hFSH were higher (30.7%) than those receiving r-hFSH and r-hLH, (23.5%) (P = 0.068). In patients >or=35 years, the implantation rates were 21.7% for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7% when treated with FSH alone (NS). Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol, but women >or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH.

Recombinant luteinizing hormone supplementation to recombinant follicle-stimulation hormone during induced ovarian stimulation in the GnRH-agonist protocol: A meta-analysis

“…Four trials fulfilled the inclusion criteria [2,[8][9][10]. In 3 trials, the pituitary down-regulation with GnRH-a started in the mid-luteal phase of the preceding cycle and in 1 trial in the beginning of the menstrual cycle.…”

“…Marrs et al [9] The study included (n = 431) normoovulatory women aged 18-40 with serum/plasma FSH ≤ 11.2 mIU/ml; presence of both ovaries; male partner with a diagnosis of male factor infertility; and a requirement for ICSI. Exclusion criteria included: clinically significant systemic disease; smoking more than 10 cigarettes per day; any contraindication to pregnancy; serum/plasma LH:FSH ratio >2; and more than two previous ICSI cycles in which gonadotrophin stimulation was used.…”

Efficacy of Low-Dose Human Chorionic Gonadotropin (hCG) in a GnRH Antagonist Protocol

“…Marrs et al and Humaidin et al reported that rLH supplementation seems to benefit treatment outcome for women above 35 years of age (27,28). While use of LH appears beneficial in patients with lowbasal LH levels or in the late follicular phase of COS, appropriate dosages remain under discussion.…”

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

“…The study population consisted of ICSI patients with major indications for ART such as tubal infertility or unexplained infertility and/ or partners with semen abnormalities. Average patient age was 33 years (range [31][32][33][34][35][36][37][38][39][40][41][42]. All patients were with regular menstrual cycles of 25-32 days, presumed to be ovulatory.…”

“…However, in women above 35 years of age, poor responders, or with more severe pituitary GnRH-a suppression, stimulation with r-LH in the mid/late-follicular phase could be associated with improved results [6,12,24,34,37,40,41,47]. In a recent meta-analysis study it has been suggested that the supplementation with r-LH in patients of advanced reproductive age stimulated with r-FSH, may improve implantation and clinical pregnancy without affecting metaphase II (Met II) yield [31].…”