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Diminished ovarian reserve (DOR) affects a significant percentage of women, between 8-15%, and its incidence increases in women over 40, affecting more than half of them [1]. Poor responders are women with DOR who experience difficulties producing enough mature oocytes, leading to lower embryo quality and higher cycle cancellation rates [2]. The European Society for Human Reproduction and Embryology (ESHRE) introduced a standardized set of criteria named Bologna in 2011 to diagnose women with poor ovarian response [3]. At least two of the following three criteria must be present to classify a patient as POR: (i) advanced maternal age (≥ 40 years) or any other POR risk factor; (ii) a history of poor ovarian response (≤ 3 oocytes retrieved or previous cycle cancelled); and (iii) abnormal ovarian reserve test results (antral follicle count [AFC] < 5-7 follicles or Anti-Mullerian hormone [AMH] < 0.5-1.1 ng/ml). If a patient has two episodes of POR after maximal stimulation, she can be diagnosed with the condition, even if the other criteria are not met. When considering treatment strategies for stimulating ovarian function in poor responders, one potential option is to administer gonadotropin-releasing hormone (GnRH) agonists [4]. While this approach has shown promise, it can also have its limitations. For example, it may inhibit ovarian function and response and require an increased dose of gonadotropin, thus leading to early LH secretion and potentially contributing to IVF failure rates [5]. in an effort to improve outcomes, various ovarian hyper-stimulation protocols have been explored, including the use of growth hormone as an adjuvant treatment in stimulation protocols. However, an ideal protocol for poor responders has yet to be established, and more research is needed to optimize treatment strategies. Growth hormone is a hormone secreted mostly by pituitary gland, and affects cell growth, development as well as metabolism [6]. The use of growth hormone (GH) as a co-treatment for various ovarian stimulation protocols in reproductive medicine has been the subject of extensive research. GH stimulates insulin-like growth factor 1 (IGF-1) production in both the liver and ovarian follicles. IGF-1 helps regulate steroidogenesis, enhances gonadotropin effect on granulosa and theca cells, and increases ovarian sensitivity to gonadotrophins, thereby advancing early follicular development, preventing of antral follicles involution, and promoting oocyte maturation [7-9]. Furthermore, recent studies indicate that GH takes part in enhancing follicular survival and cell proliferation as well as promoting high-quality embryos and increasing implantation rate [10, 11]. However, the effect of GH administration on IVF/ICSI outcomes is still not clearly understood, with studies showing contradictory results. Although some studies have demonstrated a positive impact of GH on oocyte, endometrium, and better outcomes for embryo development, others have not replicated these results [12-15]. In conclusion, the majority of evidence suggests that GH plays an integral role in follicular development, estrogen synthesis, and oocyte maturation via IGF-1, while its effect on the efficacy of IVF or ICSI techniques remains a subject of ongoing research. The addition of growth hormone (GH) to IVF/ICSI protocols has been the subject of several recent studies, including a 2020 meta-analysis which reported improved outcomes for poor ovarian responders [16]. Since then, several new randomized controlled trials (RCTs) have been published investigating the influence of GH on IVF/ICSI outcomes. To provide a thorough understanding of the subject, our aim is to conduct a rigorous meta-analysis of the available evidence from relevant randomized controlled trials to date. |
