Stimulation and Growth of Antral Ovarian Follicles by Selective LH Activity Administration in Women

Abstract

Intensive FSH stimulation is a key tool of assisted reproduction technology but can cause severe complications through the development of an excessive number of small ovarian follicles. We tested the hypothesis that, in the late stages of ovulation induction, LH activity in the form of low-dose human CG (hCG) can stimulate and selectively modulate ovarian follicle function and growth, independently of FSH administration. Four groups of GnRH agonist-suppressed normoovulatory women (10 each group) received recombinant human FSH (r-hFSH) (150 IU/d) for 7 d followed by: group A, r-hFSH 150 IU/d alone; group B, r-hFSH 50 IU/d and hCG 50 IU/d; group C, r-hFSH 25 IU/d and hCG 100 IU/d; group D, hCG 200 IU/d alone. Despite several days of lowered or absent r-hFSH administration, 70% of hCG-treated patients successfully completed treatment. In these subjects, preovulatory E2 levels and large (>14 mm diameter) ovarian follicle development were not reduced; conversely, the number of small (<10 mm diameter) ovarian follicles was significantly decreased in groups B-D vs. group A. Low-dose hCG administration did not cause follicle luteinization. We conclude that, following FSH priming, LH activity administration can: 1) stimulate folliculogenesis for several days, in spite of rapidly declining FSH levels; and 2) hasten small follicle demise. Therefore, LH activity administration could be used to design radically novel ovulation induction regimens that, by partly or completely replacing mid-/late follicular phase FSH administration, may reduce costs and improve safety of assisted reproduction technology.

Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective

“…In the same paper, while demonstrating that he could substitute FSH with 50, 100 or 200 IU of HCG activity from day 8, Filicori also noted that nine out of the 30 patients treated with HCG had a negative treatment outcome, i.e. they did not achieve ovulation (Filicori et al, 2002).…”

“…Functional and molecular differences between HCG and LH HCG has higher binding affinity and longer half-life HCG has a higher binding affinity to the LH receptor, with 1 IU HCG having biological activity approximately 6-8 times greater than 1 IU LH. Given by subcutaneous injection, HCG exhibits a longer serum half-life (30 h), thus leading to the possibility of significant accumulation over time (Filicori et al, 2002). In their paper comparing the addition of 50 IU of HCG per day from day 8 of stimulation, Filicori et al documented the accumulation of HCG leading to HCG concentrations of 10.2 ± 3 IU/dl in patients given 50 IU HCG/day from day 8 of stimulation.…”

Human Chorionic Gonadotropin: The Pregnancy Hormone and More

“…In the absence of the use of FSH, low-dose hCG can support the development and maturation of larger ovarian follicles (≥15 mm in diameter) that have acquired granulosa cell LH/CGRs while, at the same time, it inhibits the demise of smaller follicles lacking these receptors, thus being dependent on FSH stimulation [14,20,21]. Dinopoulou et al, studied the effect of recombinant-LH and hCG in the absence of FSH on IVM, fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.…”

Randomized, Controlled Pilot Study of Low-Dose Human Chorionic Gonadotropin Administration Beginning From the Early Follicular Phase for Women With Polycystic Ovarian Syndrome Undergoing Ovarian Stimulation Using the Progesterone Protocol

“…Filicori et al confirmed that low-dose hCG can be used to stimulate the growth of large follicles and accelerate the demise of small follicles (<10 mm diameter) when administered during the mid-follicular or late follicular phase of ovarian stimulation with the gonadotropin-releasing hormone agonist (GnRH-a) protocol or the GnRH antagonist (GnRH-ant) protocol (3-7), resulting in a lower incidence of OHSS (8). Additionally, it was demonstrated that the number of small preovulatory ovarian follicles was inversely correlated with the hCG dose administered (4).…”