Abstract

Growth hormone (GH) has been shown to improve implantation and live birth rates in women of >40 years of age treated by in vitro fertilization (IVF). This effect was initially attributed to a GH effect on oocyte quality, but later studies showed that GH can also improve uterine receptivity for embryo implantation. As to younger women with previous failures of embryo implantation after IVF, data reported in the literature are ambiguous. This retrospective study focused on this latter category of women, comparing the numbers and morphological appearance of oocytes recovered from women with two previous IVF failures, aged between 30 and 39 years and treated with GH, with a comparable group of women without GH treatment. These results were complemented with the analysis of morphological markers of zygote and embryo quality and IVF clinical outcomes in both groups. The oocytes, zygotes and embryos from women treated with GH showed better morphological scores, and their uterine transfer resulted in more implantations, pregnancies and live births, as compared with the untreated group. It is concluded that the improvement of IVF outcomes in women with previous repeated IVF failures by exogenous GH administration is, at least partly, related to an increase in oocyte developmental potential. The statistically evident improvement of oocyte and embryo quality is the main finding of this study. Its weakness is its retrospective nature.

Highlights

  • Exogenous growth hormone (GH) administration has been introduced to protocols of ovarian stimulation for in vitro fertilization (IVF) since the late 1980s and shown to improve IVF clinical outcomes [1,2,3,4,5,6,7], in agreement with observations on a positive relationship between Growth hormone (GH) concentration in follicular fluid aspirated from ovaries of patients treated by IVF and the treatment outcomes [8, 9]

  • There is solid evidence indicating that GH co-treatment during ovarian stimulation can enhance IVF outcomes in women aged >40 years [12, 13], and in some younger women with previous repeated IVF failures [14], low response to high-dose stimulation [15, 16] and poor oocyte and embryo quality [14]

  • Some studies have suggested an effect of GH on oocyte quality rather than quantity, through an improvement of cytoplasmic maturation with consequent reduction of aneuploidy caused by errors in the first and the second meiotic divisions [12, 14], while others showed an effect on the number of retrievable oocytes, mediated by an increase in follicle-stimulating hormone (FSH)- Luteinizing hormone (LH)- and bone morphogenetic protein (BMP)- receptor density, as well as the density of its own receptors in granulosa cells, by GH treatment [13]

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Summary

Introduction

Exogenous growth hormone (GH) administration has been introduced to protocols of ovarian stimulation for in vitro fertilization (IVF) since the late 1980s and shown to improve IVF clinical outcomes [1,2,3,4,5,6,7], in agreement with observations on a positive relationship between GH concentration in follicular fluid aspirated from ovaries of patients treated by IVF and the treatment outcomes [8, 9]. In spite of these encouraging initial data, some subsequent studies failed to find an improvement of IVF clinical outcomes after the inclusion of GH in the ovarian stimulation protocol [10, 11]. These data suggest that GH treatment cannot improve IVF outcome in all patients with poor response to ovarian stimulation and open the question of how to identify patients who can benefit from this treatment. A recent study reported an increase in the number of total retrieved, mature and fertilized oocytes, available embryos and high-quality embryos in all women with poor ovarian response treated with GH, independently of their age, but a significant increase in the implantation and pregnancy rate was found only in the older patients [17]

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