Effect of Growth Hormone on Uterine Receptivity in Women With Repeated Implantation Failure in an Oocyte Donation Program

A Randomized Controlled Trial

Signe Altmäe; Raquel Mendoza-Tesarik; Carmen Mendoza; Nicolas Mendoza; Francesco Cucinelli; Jan Tesarik

Disclosures

J Endo Soc. 2018;2(1):96-105. 

In This Article

Abstract and Introduction

Abstract

Background and Objective Administration of growth hormone (GH) during ovarian stimulation has been shown to improve success rates of in vitro fertilization. GH beneficial effect on oocyte quality is shown in several studies, but GH effect on uterine receptivity is not clear. To assess it, we studied whether GH administration can improve the chance of pregnancy and birth in women who experienced repeated implantation failure (RIF) using donated oocyte programs.

Design and Study Population A total of 105 infertile women were enrolled in the randomized controlled trial: 70 women were with a history of RIF with donated oocytes, and 35 infertile women underwent the first oocyte donation attempt. Women receiving donated oocytes were treated with progressively increasing doses of oral estradiol, followed by intravaginal progesterone after previous pituitary desensitization with gonadotropin-releasing hormone agonist. Thirty-five RIF patients were treated with GH (GH patients), whereas the rest of the 35 RIF patients (non-GH patients) and 35 first-attempt patients (positive control group) were not.

Results RIF patients receiving GH showed significantly thicker endometrium and higher pregnancy and live birth rates as compared with RIF patients of non-GH study group, although these rates remained somewhat lower as compared with the non-RIF patients of the positive control group. No abnormality was detected in any of the babies born.

Conclusion Our data of improved implantation, pregnancy, and live birth rates among infertile RIF patients treated with GH indicate that GH improves uterine receptivity.

Introduction

Administration of growth hormone (GH) during ovarian stimulation has been shown to improve success rates of in vitro fertilization (IVF) treatment,[1,2] and especially in women with poor ovarian response.[3–6] It is widely assumed that this improvement is related to the beneficial effects of GH on oocyte quality, as suggested by the observations of a higher number of oocytes collected, higher fertilization rate, and a higher number of embryos reaching the transfer stage in GH-treated patients.[3,5–8] Furthermore, ovarian costimulation with GH has been shown to increase pregnancy rate,[2,9,10] implantation rate,[1,2,11] and live birth rate.[1,4] Additionally, a recent meta-analysis of GH costimulation in controlled ovarian stimulation demonstrates significant increase in clinical pregnancy and live birth rates among poor ovarian responders.[5]

Growth hormone (GH) is a peptide hormone secreted by the anterior pituitary gland in pulsatile manner, and it has important roles in cell growth and metabolism throughout the body. GH receptor is expressed in human oocytes and cumulus cells,[12,13] and GH has been shown to promote in vitro nuclear maturation of denuded human oocytes.[14] In addition to its direct effect on the oocytes and/or cumulus cells, GH may also influence oocyte quality indirectly, through activation of insulin-like growth factor-I synthesis or promotion of follicle-stimulating hormone–induced ovarian steroidogenesis (reviewed in[15]).

The data published on the beneficial effect of GH on assisted reproduction outcomes do not exclude the possibility that this effect is due, at least in part, to an action of GH on the uterus, enhancing the receptivity of endometrium for the implanting embryo. In fact, the uterus is a site of both GH production and GH action.[15] Indeed, GH has been shown not only to increase embryonic development in superovulated cows, but also to improve posttransfer pregnancy rates when given to embryo recipients.[16] In humans, the first study indicating GH beneficial effect on endometrium has been published recently, in which it was shown that simultaneous administration of GH with hormone-replacement therapy could improve clinical outcomes after frozen embryo transfer by increasing endometrial blood perfusion and expression of cytokines related to endometrial receptivity.[17] Further studies of GH effects on human uterine receptivity are clearly warranted before any clinical recommendations/adjustments in infertility treatment protocols could be done.

In the current study, we used a model of oocyte donation to evaluate the possible beneficial effects of GH on uterine receptivity. Oocyte donation usually enables very high success rates, but some patients can suffer repeated implantation failure (RIF) even with the use of this approach. In general, RIF is diagnosed when good-quality embryos repeatedly fail to implant. In this study, patients who had undergone two failed oocyte donation attempts at our center were considered as RIF patients. They were randomly assigned to two groups, as follows: patients in one group received GH treatment during endometrium preparation with estradiol, and those in the other group underwent a standard protocol without GH (non-GH group). The results of both RIF groups were compared with a group of supposedly good-prognosis patients undergoing their first oocyte donation attempt (positive controls).

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