A direct action for GH in improvement of oocyte quality in poor-responder patients

Abstract

Declining female fecundity at later age and the increasing tendency for women to delay childbirth have lead to a drastic rise in the number of women seeking assisted reproductive technology. Many women fail to respond adequately to standard ovarian stimulation regimens, raising a significant therapeutic challenge. Recently, we have demonstrated that the administration of GH, as an adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing the oocyte quality. However, the mechanism(s) by which GH facilitated this improvement is yet to be understood. This study aimed to determine these potential mechanism(s) through the use of immunofluorescent localisation of GH receptors (GHRs) on the human oocyte and unbiased computer-based quantification to assess and compare oocyte quality between women of varying ages, with or without GH treatment. This study demonstrates for the first time, the presence of GHRs on the human oocyte. The oocytes retrieved from older women showed significant decrease in the expression of GHRs and amount of functional mitochondria when compared with those from younger patients. More interestingly, when older patients were treated with GH, a significant increase in functional mitochondria was observed in their oocytes. We conclude that GH exerts a direct mode of action, enabling the improvement of oocyte quality observed in our previous study, via the upregulation of its own receptors and enhancement of mitochondrial activity. This result, together with recent observations, provides scientific evidence in support of the use of GH supplementation for the clinical management of poor ovarian response.

Six‐week pretreatment with growth hormone improves clinical outcomes of poor ovarian responders undergoing in vitro fertilization treatment: A self‐controlled clinical study

“…The ovary can respond directly to GH because GHR are present in ovarian follicles . Alternatively, the actions of GH may be indirectly mediated by both IGF‐I and IGF‐II, which are synthesized within the ovary.…”

“…However, in GH receptor (GHR) and GH‐binding protein knockout mice, IGF‐I treatment is not able to rescue either fertility or ovarian responsiveness to exogenous gonadotropins, indicating that the effect of GH is independent of IGF‐I . GH could also improve developmental potential of the preimplantation embryo by promoting GHR expression and the functional viability of mitochondria …”

Factors affecting pregnancy outcomes following the surgical removal of intrauterine adhesions and subsequent in vitro fertilization and embryo transfer

“…Improving the pregnancy outcome of patients with DORs is a goal of many researchers. Weall et al have demonstrated that the use of growth hormone (GH) during the ovulation induction process can improve the ovarian response, the clinical pregnancy rate and the live birth rate of patients with DORs (18). IVF treatment together with androgen administration or a modulator in patients with DORs can improve the clinical pregnancy rate, reduce the total amount of GH used, and improve the pregnancy outcome (19).…”

Oocyte mitochondrial function and reproduction

“…COH causes mitochondrial abnormalities in granulosa cells of Rhesus monkeys [68]. Growth hormone improves oocyte quality and increases the number of functional mitochondria when applied as part of a COH protocol in aged women with poor ovarian response [69]. The widespread use of ART necessitates extensive studies on the effects of these techniques on oocyte quality and mitochondrial function.…”