Human growth hormone (HGH) increasingly appears to be yet another “fashion of the moment,” as more and more IVF centers use it almost as a routine. It used to be rare to see patients who had been on HGH during their cycles; now, it happens almost every day. What makes this evolving practice appear rather peculiar is the fact that nothing has appeared in the literature to suggest that HGH really makes any difference in IVF outcomes.
We recently addressed the utilization of HGH in IVF, pointing out that adequate studies that would support routine HGH use in IVF are mostly lacking. Existing literature suggests, and does so with only relatively weak evidence, that HGH supplementation in women with very small oocyte yields may marginally improve egg numbers. Currently, however, there is absolutely no evidence that HGH improves IVF pregnancy and live birth chances.
Absence of evidence, of course, does not necessarily mean absence of positive effects on IVF outcomes. It, indeed, appears reasonable to assume that more eggs will result in more embryos and more embryos in better pregnancy and live birth rates. After all, after maternal age, number of available embryos for transfer represents the second most important positive predictor of pregnancy and live birth chances in IVF. But a good hypothesis does not replace evidence and, especially since HGH is quite expensive, one has to wonder about the sudden explosion in HGH utilization in IVF practice, with not even animal data being available to support its routine use.
How to use HGH in IVF cycles
What make this surge in utilization further suspicious is how HGH is used. Colleagues who prescribe HGH to their patients, quite obviously, often do not know why they prescribe it and, therefore, how to prescribe it. In almost all these cases, HGH supplementation is given just during IVF cycle stimulation. Only rarely, supplementation may be started 1-2 weeks before cycle start. Yet, HGH acts through IGF-1, produced in the liver, and this action, like androgen supplementation, is synergistic to FSH activity on granulosa cells (and, therefore, follicle growth) primarily at small growing follicle stages up to small pre-antral follicles.
Like in androgen supplementation, the follicles that benefit from HGH supplementation still require at least 6-8 weeks before they reach the gonadotropin-dependent stage and, therefore, become available in an IVF cycle. Practically, this means that HGH supplementation, like androgen supplementation, must be started at least 6-8 weeks before IVF cycle start. Supplementing with HGH only during IVF cycles or starting just 1-2 weeks before a cycle start, therefore, is unlikely to yield the intended results.
It is also unknown how much HGH should be given on a daily basis. Following published formulas, CHR prescribes between 3-6 IU s.c. per day for at least 8 weeks prior to IVF cycle start. CHR is currently conducting a registered clinical trial of HGH supplementation, but progress has been slow because women are understandably hesitant to be randomized. If patients do not wish to be randomized, they have the option of receiving HGH off-label under an experimental consent.
Who may benefit from HGH for IVF
Though physicians at CHR routinely utilize HGH in selected patients, only a small minority of CHR’s patients receive this treatment. Furthermore, it is usually only as last resort in attempts to improve egg numbers. Besides costs, side effects are another reason for cautious utilization. The two most frequent side effects of HGH we have observed have been edema (swelling) in feet and hands and joint pain. Both usually respond quickly to lower dosing of HGH and/or discontinuation of the medication. Fully informed consent, therefore, should be an absolute prerequisite for the utilization of HGH in female infertility.