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The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials.

ABSTRACT: PURPOSE:The aim of this meta-analysis was to evaluate the effect of growth hormone (GH) supplementation in poor responders undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). METHODS:PubMed, MEDLINE and Cochrane Library databases were searched for the identification of relevant randomized controlled trials. Outcome measures were live birth rate, clinical pregnancy rate, miscarriage rate, cycle cancelation rate, number of retrieved oocytes and total dose of gonadotropin. RESULTS:Fifteen randomized controlled trails (RCTs) involving 1448 patients were eligible for the analysis. GH supplementation improved live birth rate (RR, 1.74; 95% CI, 1.19-2.54), clinical pregnancy rate (RR, 1.65; 95% CI, 1.31-2.08) and retrieved oocytes number (SMD, 0.72; 95% CI, 0.28-1.16), while reducing cancelled cycles rate (RR, 0.62; 95% CI, 0.44-0.85) and dose of Gonadotropin (SMD,-1.05 95% CI, -?1.62 - -0.49) for poor ovarian response patients. Besides, there was no significant difference in the miscarriage rate between GH group and control group. CONCLUSIONS:Based on the limited available evidence, growth hormone supplementation seems to improve IVF/ICSI outcomes for poor ovarian responders. Further randomized controlled trials with large sample sizes are required to clarify the effect of GH adjuvant therapy in the treatment of women with poor ovarian response.

SUBMITTER: Yang P

PROVIDER: S-EPMC7390166 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials.

Yang Peiwen P Wu Ruxing R Zhang Hanwang H

Reproductive biology and endocrinology : RB&E 20200729 1

<h4>Purpose</h4>The aim of this meta-analysis was to evaluate the effect of growth hormone (GH) supplementation in poor responders undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).<h4>Methods</h4>PubMed, MEDLINE and Cochrane Library databases were searched for the identification of relevant randomized controlled trials. Outcome measures were live birth rate, clinical pregnancy rate, miscarriage rate, cycle cancelation rate, number of retrieved oocytes and total ...[more]

PMID: 32727608

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Project description:BackgroundDehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the evidence remains inconsistent. This study aimed to investigate the efficacy of DHEA supplementation in patients with POR/DOR undergoing IVF/ICSI.MethodsPubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched up to October 2022.ResultsA total of 32 studies were retrieved, including 14 RCTs, 11 self-controlled studies and 7 case-controlled studies. In the subgroup analysis of only RCTs, DHEA treatment significantly increased the number of antral follicle count (AFC) (weighted mean difference : WMD 1.18, 95% confidence interval(CI): 0.17 to 2.19, P=0.022), while reduced the level of bFSH (WMD -1.99, 95% CI: -2.52 to -1.46, P<0.001), the need of gonadotropin (Gn) doses (WMD -382.29, 95% CI: -644.82 to -119.76, P=0.004), the days of stimulation (WMD -0.90, 95% CI: -1.34 to -0.47, P <0.001) and miscarriage rate (relative risk : RR 0.46, 95% CI: 0.29 to 0.73, P=0.001). The higher clinical pregnancy and live birth rates were found in the analysis of non-RCTs. However, there were no significant differences in the number of retrieved oocytes, the number of transferred embryos, and the clinical pregnancy and live birth rates in the subgroup analysis of only RCTs. Moreover, meta-regression analyses showed that women with lower basal FSH had more increase in serum FSH levels (b=-0.94, 95% CI: -1.62 to -0.25, P=0.014), and women with higher baseline AMH levels had more increase in serum AMH levels (b=-0.60, 95% CI: -1.15 to -0.06, P=0.035) after DHEA supplementation. In addition, the number of retrieved oocytes was higher in the studies on relatively younger women (b=-0.21, 95% CI: -0.39 to -0.03, P=0.023) and small sample sizes (b=-0.003, 95% CI: -0.006 to -0.0003, P=0.032).ConclusionsDHEA treatment didn't significantly improve the live birth rate of women with DOR or POR undergoing IVF/ICSI in the subgroup analysis of only RCTs. The higher clinical pregnancy and live birth rates in those non-RCTs should be interpreted with caution because of potential bias. Further studies using more explicit criteria to subjects are needed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD 42022384393.

Project description:IntroductionThe results of a recent meta-analysis showed that adding recombinant human luteinising hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) for ovarian stimulation was beneficial in poor responders, resulting in a 30% relative increase in the clinical pregnancy rate compared with r-hFSH monotherapy. However, a limitation of the meta-analysis was that the included studies used heterogeneous definitions of poor ovarian response (POR). Furthermore, the use of r-hLH supplementation during ovarian stimulation is a topic of ongoing debate, and well-designed, adequately powered, multicentre, randomised controlled trials in this setting are warranted. Therefore, the objective of the ESPART trial is to explore the possible superiority of a fixed-dose combination of r-hFSH plus r-hLH over r-hFSH monotherapy in patients with POR, as per a definition aligned with the European Society of Human Reproduction and Embryology (ESHRE) Bologna criteria.Methods and analysisPhase III, randomised, single-blind, parallel-group trial in women undergoing in vitro fertilisation and/or intracytoplasmic sperm injection. Approximately 946 women aged 18-<41 years from 18 countries will be randomised (1:1) to receive a fixed-dose combination of r-hFSH plus r-hLH in a 2:1 ratio (Pergoveris) or r-hFSH monotherapy (GONAL-f). The primary end point is the total number of retrieved oocytes per participant. Secondary end points include: ongoing pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate and clinical pregnancy rate. Safety end points include: incidence and severity of ovarian hyperstimulation syndrome, and of adverse events and serious adverse events.Ethics and disseminationThe study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki, with the International Conference on Harmonisation-Good Clinical Practice guidelines and all applicable regulatory requirements. All participants will provide written informed consent prior to entry. The results of this study will be publically disseminated.Trial registration numbersClinicalTrials.gov identifier: NCT02047227; EudraCT Number: 2013-003817-16; Clinical Trial Protocol Number: EMR200061-005 V.3.0, 15 April 2014.

Project description:Backgrounds: Growth hormone (GH) was used for many years to increase ovarian response in poor ovarian responders (PORs). Although meta-analysis suggested that GH therapy improve early clinical outcomes, the benefit of GH usage on chance of live birth was still widely debated. This study was to determine whether or not GH supplementation influences the live birth rate (LBR). Methods: A total of 3,080 expected PORs receiving and not receiving (control) GH adjuvant therapy at Peking University Third Hospital from January 2017 to March 2018 were retrospectively analyzed. The basal characteristics of patients were compared using analysis of variance (continuous variables) and categorical variables were evaluated with a chi-square test. Logistic regression analyses were used to evaluate potential associations of LBR with GH treatment while adjusting other confounding factors. Results: No statistically significant differences existed in miscarriage rate (5.3 vs. 12.5%; p = 0.076) and LBR (37.7 vs. 34.5%; p = 0.426) in young expected PORs (< 35 years of age). Moreover, no significant differences existed in the miscarriage rate (25.6 vs. 23.3%; p = 0.681), and LBR (17.8 vs. 17.9%; p = 0.977) in the old expected PORs (≥35 years of age). Logistic regression suggested that GH adjuvant therapy did not improve the LBR in young (OR, 1.27; 95% CI, 0.88-1.85; p = 0.203) and elderly expected PORs (OR, 1.20; 95% CI, 0.82-1.76; p = 0.342), while GH was not associated with risk of miscarriage in young (OR, 0.37; 95% CI, 0.11-1.24; p = 0.108) and elderly expected PORs (OR, 0.91; 95% CI, 0.43-1.93; p = 0.813). In subgroup analysis, GH treatment significantly increased the day 3 embryos available rate in the subgroup of young PORs with the long down-regulation (63.11 vs. 49.35%; p = 0.004), while significantly reduced the risk of miscarriage in the subgroup of young PORs with GnRH antagonist protocol (0.00 vs. 12. %; p = 0.023). There was no significant difference for LBR in PORs with GnRH antagonist (<35 years [35.19 vs. 28.45%; p = 0.183]; ≥35 years [12.96 vs. 14.03%; p = 0.707]), GnRH-a long (<35 years [33.33 vs. 36.99%; p = 0.597]; ≥35 years [17.44 vs. 20.28%; p = 0.574]) and long down-regulation (<35 years [58.82 vs. 41.90%; p = 0.193]; ≥35 years [43.33 vs. 25.30%; p = 0.065]). Conclusions: Growth hormone treatment may not improve live birth rate in expected poor responders.

Dataset Information

The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials.

Publications

The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials.

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