Growth hormone during in vitro fertilization in older women modulates the density of receptors in granulosa cells, with improved pregnancy outcomes

Regan, Sheena L.P.; Knight, P. G.; Yovich, John L.; Arfuso, Frank; Dharmarajan, Arun

doi:10.1016/j.fertnstert.2018.08.018

Cited by 78 publications

(81 citation statements)

References 71 publications

(1 reference statement)

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“…In this comparison, the (+)GH group showed a up to 2-fold increase in the likelihood of LB in the multivariate analysis, following adjustment for age, AFC and transferred embryo quality. The increased likelihood of LB in embryos previously generated under the action of GH was supported by a corresponding reduction in the miscarriage rate; this reduction was not significant, but may provide support for the premise that GH cotreatment improves oocyte maturation during folliculogenesis in the preceding stimulated cycle [32,33]. This trend for GH was also evident in our previous studies of fresh ET generated under the action of GH [12,13].…”

Section: Discussionsupporting

confidence: 60%

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis

Keane

Hinchliffe

et al. 2019

Clin Exp Reprod Med

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Objective: To determine the clinical pregnancy (CP) and live birth (LB) rates arising from frozen embryo transfers (FETs) that had been generated under the influence of in vitro fertilization (IVF) adjuvants given to women categorized as poor-prognosis. Methods: A registered, single-center, retrospective study. A total of 1,119 patients with first FETs cycle include 310 patients with poor prognosis (109 treated with growth hormone [GH], (+)GH group vs. 201 treated with dehydroepiandrosterone, (-)GH group) and 809 patients with good prognosis (as control, (-)Adj (Good) group). Results: The poor-prognosis women were significantly older, with a lower ovarian reserve than the (-)Adj (Good) group, and demonstrated lower chances of CP (p< 0.005) and LB (p< 0.005). After adjusting for confounders, the chances of both CP and LB in the (+)GH group were not significantly different from those in the (-)Adj (Good) group, indicating that the poor-prognosis patients given GH had similar outcomes to those with a good prognosis. Furthermore, the likelihood of LB was significantly higher for poor-prognosis women given GH than for those who did not receive GH (p< 0.028). This was further confirmed in age-matched analyses. Conclusion: The embryos cryopreserved from fresh IVF cycles in which adjuvant GH had been administered to women classified as poor-prognosis showed a significant 2.7-fold higher LB rate in subsequent FET cycles than a matched poor-prognosis group. The women with a poor prognosis who were treated with GH had LB outcomes equivalent to those with a good prognosis. We therefore postulate that GH improves some aspect of oocyte quality that confers improved competency for implantation.

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Section: Discussionsupporting

confidence: 60%

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis

Keane

Hinchliffe

et al. 2019

Clin Exp Reprod Med

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“…The rationale for add-on of GH to treat PORs was due to stimulation of IGF1, which has been reported to have synergistic effects with FSH on follicular development in an animal study (13). Moreover, GH treatment in older PORs increased the density of granulosa FSH and LH receptors (14). Two meta-analyses with few non-Bologna patients demonstrated statistically significant differences in CPR and LBR favoring the use of GH (24,31).…”

Section: Interpretation Of Datamentioning

confidence: 99%

“…The reasonable use of growth hormone (GH) in PORs is based on the requirement for follicular growth in animal studies (12,13). Then, GH was reported to increase the density of granulosa follicle-stimulating hormone (FSH) and luteinizing hormone receptors in older PORs (14) and enhance oocyte mitochondrial activity in older women (15). GH has been used for many years to increase the ovarian response in clinical practice (16,17).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…• GnRH analogues (3,25,26) • Androgens (25) • GH cotreatment (25,27) • Natural cycle or modified natural cycle (25) • High dose gonadotropins (25) • Glucocorticoids 3• Coenzyme Q10 (28) • Acupuncture (29) • Holistic medicine (25) • Autologous Platelet-Rich Plasma • In-vitro activation of follicles • Combination of the above (25).…”

Section: Possible Treatmentsmentioning

confidence: 99%

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

Blumenfeld

2020

Front. Endocrinol.

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The infertile patients with aging ovaries-also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in the literature, among the identified etiologies, including chromosomal and genetic etiology, metabolic, enzymatic, iatrogenic, toxic, autoimmune, and infectious causes. Although the most successful and ultimate treatment of POI/POF/POR patients is egg donation (ED), many, if not most, of these infertile women are reluctant to consent to ED upon the initial diagnostic interview, requesting alternative solutions despite the low odds for success. Despite anecdotal case reports, no unequivocal treatment proved to be successful for these patients in prospective randomized controlled trials. Nevertheless, the addition of growth hormone (GH) to ovarian stimulation in POR with GH deficiency may improve the results of controlled ovarian hyperstimulation (COH) and the IVF success. In patients with autoimmune etiology for POR/POI, the combination of glucocorticosteroids, pituitary-ovarian suppression, and COH may be successful in achieving the desired conception.

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Growth hormone during in vitro fertilization in older women modulates the density of receptors in granulosa cells, with improved pregnancy outcomes

Cited by 78 publications

References 71 publications

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis

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

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

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