Growth hormone alleviates oxidative stress and improves the IVF outcomes of poor ovarian responders: a randomized controlled trial

Abstract

Background: Oxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/ or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders. Methods: This study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared. Results: Endometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group (P < 0.05). Moreover, compared to those in the non-POR group, FF malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI) and ROS levels in GCs were significantly higher, whereas superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were significantly lower in the POR-C group (P < 0.05). Furthermore, compared with those in the POR-C group, the FF TAC was significantly increased in the POR-GH group, and TOS, OSI and intracellular ROS levels were significantly reduced (P < 0.05).

Growth Hormone Cotreatment for Low-Prognosis Patients According to the POSEIDON Criteria

“…GH is reported to be capable of enhancing the functional mitochondria in oocytes (8), improving the proliferation and differentiation of granulosa cells (9,10) and increasing the endometrial blood perfusion as well (11). In seeking an effective approach to tackle the challenges of POR, GH has been explored in many related studies (8,(12)(13)(14) and utilized clinically for patients with POR during the ovarian stimulation for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) as well. Thus, it is crucial to ascertain the validity and specific effects of GH supplementation on the management of patients with POR.…”

The Effect of Growth Hormone on In Vitro Fertilization Outcomes During Ovarian Stimulation: A Matched Cohort Study

“…It also corroborates the more recent ndings by Li and Gong in their randomized controlled trials to look at GH use in the setting of history of poor embryo development and poor responder patients respectively. Both studies supported the use of GH in IVF cycles [15,17]. This is contrast to the ndings by Zhu, et al who found that live birth rate was not improved with the use of GH as adjuvant treatment.…”

“…Safderin had an arm receive 2.5mg/day as well though this did not start until day 8 and another arm that received 0.1mg/day from cycle day 3 of the previous cycle [18]. Gong et al, administered 4IU/day (1.3mg) starting from Day 4 of the previous cycle [17]. In the LIGHT study, 12 IU/day (4mg) from day of stimulation [14].…”

“…Several studies have since been published with inconsistent results [15][16][17][18][19]. Because of the inconsistencies in study ndings, both ASRM and ESHRE have failed to support the universal use of GH in the ovarian stimulation protocol of poor responder patients [20,21].…”

Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology

“…These modules reflected melatonin's effects on endocrine and immune regulation, anti-apoptosis, and ovarian function improvement. In addition, exogenous growth hormone administration has been shown to improve oocyte and embryo quality in IVF treatment of women with poor OR (80,81). The functional modules analysis showed that melatonin is closely related to the synthesis, secretion, and action of GH, which also supports the function of melatonin in improving OR.…”