Abstract
Background: Growth hormone (GH) has long been used as adjuvant treatment in ovarian stimulation for in vitro fertilization (IVF), especially in poor responder (PR) patients. However, its clinical efficacy remains unclear, and most studies are underpowered owing to their small sample size with different regimens.Methods: Our study was divided into two parts. The first part was a parallel randomized, observational study in which 184 patients who fulfilled the criteria of poor ovarian response (POR) were enrolled and received ultra-long ovarian stimulation protocol with or without GH adjuvant therapy. For the second part, clinical data were retrospectively extracted from 163 patients classified as PRs who received 10 IU GH adjuvant therapy and 157 patients classified as normal responders (NRs) who received the same IVF protocol treatment without GH adjuvant therapy.Results: For the first part of the study, the ovarian response, the number of oocytes retrieved, and the number of available embryos transferred were all significantly higher in the GH (+) group than in the GH (–) group. The clinical pregnancy rate was significantly higher in the GH (+) group (31.9 vs. 16.7%, p = 0.0168). The miscarriage rate did not differ significantly between the groups. The ongoing pregnancy rate was also significantly higher in the GH (+) group than in the GH (–) group (26.6 vs. 14.4%, p = 0.0418). Logistic regression revealed that the chance of clinical pregnancy in the GH (+) group significant increased 2.34-fold in comparison with the GH (–) group (p = 0.018). Subgroup analysis showed that the chance of clinical pregnancy in the GH (+) group significantly increased 2.38-fold (p = 0.034). The second part of the study showed no statistical difference between the PR with GH and the NR without GH groups regarding the implantation rate (15.6 vs. 19.8%, p = 0.3254) and the clinical pregnancy rate (31.9 vs. 39.5%, p = 0.1565). The NR without GH group showed insignificantly higher chance of clinical pregnancy (OR = 1.39, p = 0.157) compared with the PR with GH group.Conclusion: Our results suggested that low-dose GH supplementation may improve ovarian response and pregnancy outcome in POR patients, particularly in patients younger than 40 years old. Moreover, the low-dose GH effect in POR patients resulted in non-inferior clinical pregnancy outcome compared with NRs.
Highlights
Controlled ovarian hyperstimulation (COH) has long been a crucial part of in vitro fertilization (IVF), along with the development of assisted reproductive technologies (ART)
Despite using different stimulation protocols and multiple treatment courses of IVF, the pregnancy outcome remains poor in Poor ovarian response (POR) patients, which is frustrating for both the patients and the clinicians
We aimed to investigate the efficacy of low-dose Growth hormone (GH) adjuvant treatment in poor responders (PRs) patients compared with normal responders (NRs) using an ultra-long ovarian stimulation protocol
Summary
Controlled ovarian hyperstimulation (COH) has long been a crucial part of in vitro fertilization (IVF), along with the development of assisted reproductive technologies (ART). POR, or poor responders (PRs), remains a significant challenge for IVF practice owing to the heterogeneity of the pathophysiology and the lack of general consensus in the definition of POR. The definition of POR was under debate without uniform agreement for decades until the European Society of Human Reproduction and Embryology conducted a consensus study and reached a definition for POR in 2011 This so-called Bologna criterion defines poor response in IVF as comprising at least two of the following three features: (i) advanced maternal age (≥40 years) or any other risk factor for POR, (ii) previous POR (≤3 oocytes with a conventional stimulation protocol), and (iii) an abnormal ovarian reserve test [antral follicular count (AFC) < 5–7 follicles or anti-mullerian hormone (AMH) < 0.5– 1.1 ng/ml]. Its clinical efficacy remains unclear, and most studies are underpowered owing to their small sample size with different regimens
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