Growth Hormone Adjuvant Therapy Research Articles

Expression of concern: “The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial” [Eur. J. Obstet. Gynecol. Reprod. Biol. 228 (2018) 161–165, ISSN 0301-2115, https://doi.org/10.1016/j.ejogrb.2018.06.035

Expression of concern: “The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial” [Eur. J. Obstet. Gynecol. Reprod. Biol. 228 (2018) 161–165, ISSN 0301-2115, https://doi.org/10.1016/j.ejogrb.2018.06.035

Clinical Outcomes of Frozen-Thawed Embryos Generated From Growth Hormone Stimulation in Expected Poor Responders.

ObjectiveThis study aimed to elucidate whether growth hormone (GH) adjuvant therapy significantly improves clinical outcomes for expected poor responders in frozen-thawed cycles.MethodsExpected poor responders undergoing controlled ovarian stimulation with or without GH adjuvant therapy, and subsequently underwent the first frozen-thawed transfer from January 2017 to March 2020 were retrospectively reviewed. Maternal age was matched at a 1:1 ratio between the GH and control groups. All statistical analyses were performed with the Statistical Package for the Social Sciences software.ResultsA total of 376 frozen-thawed cycles comprised the GH and control groups at a ratio of 1:1. The number of oocytes (7.13 ± 3.93 vs. 5.89 ± 3.33; p = 0.001), two pronuclei zygotes (4.66 ± 2.76 vs. 3.99 ± 2.31; p = 0.011), and day 3 available embryos (3.86 ± 2.62 vs. 3.26 ± 2.04; p = 0.014) obtained in the GH group was significantly higher than the control group in corresponding fresh cycles. The clinical pregnancy (30.3 vs. 31.0%; p = 0.883), implantation (25.3 vs. 26.2%; p = 0.829), early abortion (16.1 vs. 15.8%; p = 0.967), and live birth rates (20.6 vs. 20.8%; p=0.980) were comparable between the two groups in frozen-thawed cycles. Improvement in the clinical pregnancy (46.8 vs. 32.1%; p = 0.075), early miscarriage (10.3 vs. 20.0%; p = 0.449), and live birth rates (35.7 vs. 18.9%; p = 0.031) was found in the subgroup of poor ovarian responders (PORs) with good quality blastocyst transfer (≥4BB) following GH co-treatment.ConclusionsGH administration would increase oocyte quantity and quality, in turn, improve live birth rate in PORs.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; response of women categorized as poor-prognosis to recombinant growth hormone adjuvant therapy (Study 4)

In this fourth study examining the relevance of measuring the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), we have examined the influence of recombinant growth hormone (rGH) prescribed as an adjuvant on the profile. Of 1633 ART-naïve women who completed an assessment cycle (AC) workup, and which included an IGF profile, 941 women proceeded to an in-vitro fertilization ± intracytoplasmic sperm injection (IVF±ICSI) treatment cycle during the period January 2011 to December 2019. Among those women, 90 were prescribed rGH because they were classified as likely poor-prognosis cases on the basis of advanced age or evidence of severely reduced ovarian reserve parameters. These women had their IVF±ICSI treatment within 3-months of their AC and consented to a second IGF profile measurement 4-6 weeks during their rGH treatment phase. Of the 90 women prescribed rGH adjuvant, 71 used the adjuvant and 19 deferred the treatment, but still completed the second IGF-profile. The data showed that rGH caused a significant elevation in IGF-1 (p<0.0001) as well as its main binding protein, IGFBP-3 (p<0.001), albeit to a lesser degree. Consequently, the IGF ratio, considered a more reliable marker of IGF-1 activity, was shown to be significantly reduced towards the normal range (p<0.0001). The data of clinical outcomes from these 90 women as well as the entire 941 women entering the IVF±ICSI treatment are presented for comparison, noting these data are not suitable for statistical evaluation as the groupings are disparate and unmatched. Further studies are intended to show the clinical relevance of increasing the IGF-1 levels in the analytical investigation of rGH as an adjuvant in ART.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; response of women categorized as poor-prognosis to recombinant growth hormone adjuvant therapy (Study 4)

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; response of women categorized as poor-prognosis to recombinant growth hormone adjuvant therapy (Study 4)

The effect of growth hormone adjuvant therapy on assisted reproductive technologies outcomes in patients with diminished ovarian reserve or poor ovarian response

Low response of patients with diminished ovarian reserve to exogenous gonadotropins in controlled ovarian stimulation (COS) protocols is one of the important problems of reproductive endocrinology. Various treatment protocols have been developed in patients with diminished ovarian reserve (DOR) or poor ovarian response (POR). Recently, the addition of growth hormone (GH) to treatment protocols has been brought to the agenda in these patients. In this study, we aimed to investigate the effect of GH adjuvant treatment on intracytoplasmic sperm injection (ICSI) cycle results in patients with DOR or POR. This retrospective cohort study was carried out with patients who diagnosed as DOR or POR and underwent ICSI. The patients were divided into the groups according to whether GH was used. In this study, ongoing pregnancy rates and live birth rates were observed to be significantly higher in the group receiving GH compared to the control group. In addition, there was a significant increase in embryo quality in the group receiving GH. As a result, the addition of GH to COS protocols in DOR and POR patients may increase the ongoing pregnancy rate, live birth rate, embryo quality.

Growth Hormone Supplementation May Not Improve Live Birth Rate in Poor Responders.

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.

Low Dose Growth Hormone Adjuvant Treatment With Ultra-Long Ovarian Stimulation Protocol in Poor Responders Showed Non-inferior Pregnancy Outcome Compared With Normal Responders.

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.

The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial

Objectiveto detect the impact of growth hormone (GH) co-treatment to the long down regulation protocol, on the outcomes of IVF/ICSI cycles in poor responders. Study Designthis parallel open label randomized control trial was conducted in a university hospital. It included 240 females satisfying the bologna criteria for poor responders. The enrolled females were randomized into 2 groups: A (long/GH) receiving GH adjuvant therapy to the long protocol and group B (control) receiving the long protocol alone. The main outcome measure was the live birth rate (fresh, frozen and cumulative). ResultsGH supplementation improved the number of collected oocytes (5.4 ± 1.7 vs. 4.3 ± 2.1), MII oocytes (4.1 ± 2.1 vs. 2.1 ± 1.4), fertilized oocytes (4.0 ± 2.2 vs. 2.0 ± 1.2), transferred embryos (2.4 ± 0.9 vs. 1.6 ± 1.1) and cryopreserved (0.5 ± 0.7 vs. 0.2 ± 0.5). There was no significant difference in the live birth rate whether fresh (17.5% vs. 14.1%) or cumulative (18.3% vs. 14.7%). ConclusionsFurther studies are needed to know the true impact of adding GH to the induction protocols in poor responders, as there was no difference in the live birth rates between the study groups, indicating a lack of trend toward benefit from GH supplementation in poor responders.Clinical Trial Registration: NCT02338206.

Effects of growth hormone plus gonadotropins on controlled ovarian stimulation in infertile women of advanced age, poor responders, and previous in vitro fertilization failure patients

ObjectiveTo investigate the effects of growth hormone (GH) cotreatment in ovarian stimulation in infertile women of advanced age, poor responders, and patients with one or more previous IVF treatment failures. Materials and methodsWe conducted a retrospective observational study of 436 patients undergoing GH cotreatment in ovarian stimulation. The first arm included 134 infertile women of advanced age. The second arm included 236 patients with one or more IVF previous treatment failures, and the third arm included 66 younger poor responders. Main outcome measures were the number of oocytes and embryos, quality of embryos, and implantation and pregnancy rates. ResultsIn infertile women of advanced age, GH plus ovarian stimulation yielded no statistical differences in the numbers of oocytes and embryos, quality of embryo, and rates of implantation and pregnancy. In the second arm, the mature oocyte number (8.2 vs. 6.8), implantation rate (16.1% vs. 0%), and pregnancy rate (33.9% vs. 0%) in the GH cotreatment group differed significantly from those in the control group; the rate of good-quality embryos in the GH cotreatment group improved from 35.5% ± 31.1%–41.4% ± 30.6% in this arm. Similar results were observed in the third arm; in this arm, the clinical pregnancy rate was 30.3% in the GH cotreatment group and 6.1% in the control group. ConclusionNo significant differences were observed in infertile women of advanced age, which may be due to the low GH dose. The GH adjuvant therapy for patients with one or more previous IVF treatment failures and for poor responders significantly improved the oocyte and embryo numbers as well as implantation and pregnancy rates.