Co-treatment with growth hormone of sub-optimal responders in IVF-ET

Abstract

Several growth factors augment the ovarian response to gonadotrophins and growth hormone is known to regulate the production of insulin-like growth factor-1. With this in mind, 20 women who had previously responded sub-optimally to standard ovarian stimulation regimens for in-vitro fertilization and embryo transfer (IVF-ET) were recruited into a randomized trial to study the effect of co-treatment with growth hormone (Norditropin, Novo Nordisk Gentofte A/S). Intramuscular injections of growth hormone (24 IU) or placebo were given on alternate days concurrently with the same daily dosage of gonadotrophin as administered in the patient's pretreatment cycle. Overall, there was no improvement in the ovarian response to the growth hormone-augmented regimen of stimulation although there was a tendency for the development of more follicles (P = 0.06). When the results from the patients with ultrasound-diagnosed polycystic ovaries were analysed separately, however, more follicles developed (P = 0.04), more oocytes were collected (P = 0.03) and there was a trend towards higher urinary oestrogen production following growth hormone therapy. There was no improvement in the ovarian response in patients with normal ovaries. The treatment was not associated with any adverse effects. We conclude, therefore, that in a subgroup of patients who respond sub-optimally to standard ovarian stimulation regimens for IVF-ET and who have ultrasound-diagnosed polycystic ovaries, systemic growth hormone is an effective adjunctive therapy.

The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency

“…In fact, several studies have demonstrated that GH treatment increases ovary sensitivity to gonadotropin stimulation in infertile women with hyposensitive ovaries (12)(13)(14)(15)(16)(17)(18)(19). The effect of GH administration on gonadal function in men has been poorly investigated.…”

The role of growth hormone in male infertility

“…Following the hypothesis that G H or IGF-I can facilitate granulosa cell responsiveness to gonadotrophins, a series of studies demonstrated that co-treatment with G H augmented the ovarian response to stimulation by gonadotrophins (Homburg et al. 1988;1990a;Owen et al, 1991a;Blumenfeld & Lunenfeld, 1989;Volpe et al, 1989;Menashe rt al., 1990). On the basis of the encouraging results achieved in these studies and the demonstration in pubertal boys of a Spermatogenesis requires the stimulatory effects of FSH, LH and adequate testosterone (T) concentrations (Matsumoto & Bremner, 1989).…”

Clinical Implications of Insulin-Like Growth Factors and Their Binding Proteins in Reproduction.

“…91]. Several studies have demonstrated the utility of exogenous GH to enhance ovarian responsiveness in women with previously poor responses to hMG therapy [21, [92][93][94]. GH is the primary regulator of serum IGF-I levels [3,95].…”

“…Clinical trials have demonstrated that administration of recombinant human GH in superovulation protocols for women who have previously shown poor clinical responses to hMG therapy results in significantly increased numbers of preovulatory follicles and peak E2 levels, while simultaneously reducing hMG dose requirements [21, [92][93][94]. In a randomized double-blind, placebo-controlled study with recombinant human GH and hMG given to 16 patients with amenorrhea and anovulatory infertility [21], the required dose of hMG decreases 36%, the number of days of treatment decreases 25%, and the daily effective dose decreases 19%.…”

“…The utility of adjunctive GH therapy has been assessed in patients undergoing in vitro fertilization and embryo transfer (IVF-ET) protocols which utilize recombinant human GH and hMG after pituitary suppression with a gonadotropin-releasing hormone (GnRH) agonist [92][93][94]. These studies consistently demonstrate increases in IGF-I concentrations in both serum and follicular fluid with GH cotreatment and concomitant reductions in hMG requirements in women with previously poor clinical responses to hMG therapy alone.…”