Growth Hormone and Reproduction: Lessons Learned From Animal Models and Clinical Trials

Abstract

Growth Hormone (GH) has been considered as a therapeutic option to increase the number of growing follicles during Assisted Reproductive Technology (ART) for more than 30 years. In this review the biological rationale for therapeutic GH usage is explained through evidence in animal models, aiming to put this into a clinical context. First, we explain the GH—Insulin like Growth Factor (IGF)-1—gonadal axis and its role in reproduction. Evidence suggests that GH can stimulate the secretion of IGF1 not only in the liver but also in the peripheral target structures, including the ovary. Moreover, IGF-1 can be secreted locally under the influence of stimuli other than GH. In the case of the ovary, steroid hormones, gonadotropins or the combination of both seems to be involved. Even more interesting, the ovary itself can secret GH locally and exert a paracrine action modulating the intracellular signaling pathway of GH, i.e., not by the systemic pathway where GH binds to the extracellular domain of the GH receptor. Finally, these aspects from animal models are put into clinical perspective by discussing results and shortcomings of studies and meta-analyses in order to put forth the state-of-the-art rationale for therapeutic GH usage in modern ART.

Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues

“…Other investigations using knock-out animal models have provided further evidence to indicate that GH influenced reproduction, but was not completely essential for generating offspring. For example, while the absence of functional GHR was reported to cause an increase in systemic GH levels, a decrease in circulating IGF-1 level (but still present), and a delay in puberty onset with a reduced number of ovarian follicles, these animals could still reproduce, but with a smaller litter size (21–24). Several studies have confirmed that GHR knock-out resulted in a delay in puberty onset, and this echoes the delayed puberty that is observed in human disorders such as Laron dwarfism where GHR is dysfunctional (25, 26).…”

The Evolving Concept of Poor-Prognosis for Women Undertaking IVF and the Notion of Growth Hormone as an Adjuvant; A Single-Center Viewpoint

“…Where a freeze-all option is contemplated, there should be at least 2 high-grade embryos cryopreserved, otherwise the case can be classified as poor-prognosis, warranting GH therapy. With respect to the dosage and duration of GH therapy, our experience over more than 12 years indicates that 1 IU daily is sufficient to produce a response (e.g., raising IGF-1 levels) but an optimum response with respect to oocyte quality probably requires 4–6 months to cover the full period of folliculogenesis from the earliest stage of primary follicle recruitment being at least 20 weeks prior to the ovulatory cycle, when paracrine controls over oocyte development are strongest (80). We acknowledge there may be both logistic and financial problems to such a prolonged treatment schedule, hence a compromise treatment proposal could be a six-week schedule, beginning Day 2 of the menstrual cycle preceding the IVF cycle.…”

Growth hormone alleviates oxidative stress and improves oocyte quality in Chinese women with polycystic ovary syndrome: a randomized controlled trial

“…Growth hormone (GH), a peptide secreted by adenohypophysis cells, can reduce OS in some types of cells 19 , 20 ; for this reason, GH has been widely applied to treat pathologies associated with OS, such as burns over large areas, obesity, Alzheimer’s disease and multiple sclerosis 21 . GH bound to the GH receptor (GHR) augments the effects of gonadotropin on GCs and thecal cells, and may improve follicle development and steroidogenesis 22 . Therefore, exogenous GH administration might improve oocyte quality and IVF outcomes among older women and/or patients with poor ovarian response 23 .…”