Growth hormone supplementation improves implantation and pregnancy productivity rates for poor-prognosis patients undertaking IVF

Abstract

In a sequential crossover study of IVF conducted from 2002 to 2006, growth hormone (GH) supplementation was assessed in poor-prognosis patients, categorized on the basis of past failure to conceive (mean 3.05 cycles) due to low response to high-dose stimulation (<3 metaphase II oocytes) or poor-quality embryos. Pregnancy rates in both fresh and frozen transfer cycles and the total productivity rates (fresh and frozen pregnancies per egg collection) were compared. In all, 159 patients had 488 treatment cycles: 221 with GH and 241 without GH. These cycles were also compared with 1572 uncategorized cycles from the same period. GH co-treatment significantly improved the clinical pregnancy rate per fresh transfer (P<0.001) as well as per frozen-thawed embryo derived from GH cycles (P<0.05) creating a highly significant productivity rate (P<0.001). The effect was significant across all age groups, especially in younger patients, and was independent of stimulation modality or number of transfers. GH cycles resulted in significantly more babies delivered per transfer than non-GH cycles (20% versus 7%; P<0.001) although less than the uncategorized cycles (53%). The data uniquely show that the effect of GH is directed at oocyte and subsequent embryo quality.

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

“…However, the exact mechanism through which GH action regulates oocyte mitochondrial function remains to be elucidated, along with considerations related with the GH dosage; in this study being either 1 IU or 2.5 IU daily. Nevertheless, we can thus confirm that the administration of exogenous GH supplements, in conjunction with standard ovarian stimulation regimens, does indeed improve the quality of human oocytes, as demonstrated previously (Yovich & Stanger 2010), via a potential enhancement in mitochondrial functionality. With respect to older women, improvements in pregnancy rates have been clearly (b) Assessment of mitochondrial membrane integrity, based on cytochrome c oxidase immunolabelling.…”

“…A growing body of evidence, in both human and animal models, suggests that GH is an important regulator of ovarian steroidogenesis (Nakamura et al 2012), follicular development (Bachelot et al 2002) and oocyte maturation (Bevers & Izadyar 2002). In clinical application, we have recently demonstrated that GH supplementation together with gonadotropin-induced ovarian stimulation has lead to significant improvement in oocyte quality (Yovich & Stanger 2010). However, it is not yet clear how GH exerts its action on human oocytes.…”

“…To avoid any possibility of bias, the selection of patients who did or did not choose to undertake GH administration, the study was designed as a sequential crossover (Yovich & Stanger 2010), where patients identified as poor responders were given the option of taking GH or await the outcome of the treatment cycle then using GH on the next cycle if the first failed.…”

“…Unfortunately, w9-24% of all IVF cycles undertaken fail to respond to standard ovarian stimulation regimens, due to poor ovarian response (POR) to hormonal stimulation (Abir et al 2008). Currently, the management of POR patients represents a significant therapeutic challenge (Hazout et al 2009, Yovich & Stanger 2010, such that various alternative forms of clinical intervention have either been ineffective or lack sufficient scientific evidence necessary to support clinical application (Ubaldi et al 2005). Recently, we have demonstrated that the administration of exogenous growth hormone (GH) supplementation, in conjunction with standard ovarian stimulation regimens, resulted in significantly higher embryo implantation and clinical pregnancy rates compared with those not treated with GH (Yovich & Stanger 2010).…”

“…Currently, the management of POR patients represents a significant therapeutic challenge (Hazout et al 2009, Yovich & Stanger 2010, such that various alternative forms of clinical intervention have either been ineffective or lack sufficient scientific evidence necessary to support clinical application (Ubaldi et al 2005). Recently, we have demonstrated that the administration of exogenous growth hormone (GH) supplementation, in conjunction with standard ovarian stimulation regimens, resulted in significantly higher embryo implantation and clinical pregnancy rates compared with those not treated with GH (Yovich & Stanger 2010). These findings are supported by previous studies demonstrating the beneficial effect of GH in increasing the response of human ovary to gonadotrophins in poor-responder patients (Homburg et al 1988, Volpe et al 1989, Hazout et al 2009).…”