INFERTILITY CASE REPORT
Dr Padmaja Pala
Habsiguda, hyderabad, telangana, india, Bengaluru Jan 28, 2020
The aim of the study was to assess the effectiveness of adjuvant growth hormone therapy in In Vitro Fertilization (IVF) in order to retrieve mature oocytes in women with low Anti-Mullerian Hormone (AMH) of 1–2 ng/ml.
All the data were retrospectively analyzed from 60 IVF cycles among women with AMH 1–2 ng/ml, where 27 women were given growth hormone, and 33 women were not, over a period of 1 year (February 2018 to January 2019).
Growth hormone was administered by a daily subcutaneous injection of 0.5 mg from day 1 of ovarian stimulation until the day of Human Chorionic Gonadotropin (HCG) triggering. The average number of mature oocytes retrieved were compared between the groups.
Among 60 cases, growth hormone was given in 27 cases; 9 cases stimulated with Human Menopausal Gonadotropin (HMG), and the average number of mature oocytes retrieved was 3.55. Eighteen cases stimulated with recombinant Follicle-stimulating Hormone (FSH) for the ﬁrst 5 days followed by HMG till trigger, and the average number of mature oocytes retrieved was 2.88.
Growth hormone was not given in 33 cases; 18 cases stimulated with HMG, and the average number of mature oocytes retrieved was 3.27. Fifteen cases stimulated with recombinant FSH for the ﬁrst 5 days followed by HMG till trigger, and the average number of mature oocytes retrieved was 5.8.
There was no signiﬁcant difference in the average number of mature oocytes retrieved from women given with adjuvant growth hormone in IVF cycles with low AMH.
Growth hormone, IVF (in vitro fertilization), low AMH (Anti-Mullerian Hormone), Mature oocytes.
In 1988, the ﬁrst report of the use of growth hormone as an adjuvant to gonadotropins for ovarian stimulation was published.1 This showed that in patients with ovulatory infertility due to hypogonadotropic–hypogonadism, co-treatment with growth hormone sensitized the ovary to treatment with HMG in both in vivo and in vitro fertilization cycles. The prognosis for treatment by IVF is highly dependent upon ovarian response and the quality of oocytes retrieved, both factors determining the number of good quality embryos. An extraordinary resurgence of interest then occurred at the end of the ﬁrst decade of the millennium, that growth hormone plays an important role in ovarian function, sensitizing the ovary to gonadotropin stimulation, stimulating follicular development, estrogen production and oocyte maturation.
Both ovarian steroidogenesis and folliculogenesis are under the inﬂuence of gonadotropins. It has been suggested that growth hormone may act as a co-gonadotropin and have a role in the follicular selection and maturation.7 Growth hormone may activate cells directly by its receptor but also indirectly by inducing the production of Insulin-like Growth Factor I (IGF-1). Patients undergoing IVF receive various adjuvant therapies in order to enhance the success rate, particularly for those who are categorized as poor responders according to the Bologna criteria.9 Some of the adjuvant therapies being steroid supplementation - DHEA or testosterone, immune therapy - IV immunoglobulin and growth hormone, the true beneﬁt is actively debated.
MATERIALS AND METHODS
It was a retrospective study, performed at Padmaja Fertility Centre, Habsiguda, Hyderabad, over a period of 1 year from February 2018 to January 2019. This study included 60 women undergoing IVF with AMH 1-2 ng/ml. The study population was divided into 4 groups:
Growth hormone was given in 27 cases:
A) 9 cases stimulated with HMG
B) 18 cases stimulated with recombinant FSH for the ﬁrst 5 days followed by HMG till trigger Growth hormone was not given in 33 cases:
C) 18 cases stimulated with HMG
D) 15 cases stimulated with recombinant FSH for the ﬁrst 5 days followed by HMG till the trigger
All cases underwent Gonadotropin-releasing Hormone (GnRH) antagonist conventional ovarian stimulation. Growth hormone was co-administered in 27 cases by a daily subcutaneous injection of 0.5 mg from day 1 of ovarian stimulation until the day of HCG trigger. The average number of mature oocytes retrieved were compared between the groups.
Our cases were divided into 4 groups, who did not differ signiﬁcantly in the gynaecological background, with AMH range 1–2 ng/ml.
Among 60 cases,
Growth hormone was given in 27 cases:
9 cases stimulated with HMG - an average number of mature oocytes retrieved was 3.55. Eighteen cases stimulated with recombinant FSH for the ﬁrst 5 days followed by HMG till trigger - the average number of mature oocytes retrieved were 2.88.
Growth hormone was not given in 33 cases:
18 cases stimulated with HMG - an average number of mature oocytes retrieved was 3.27. Fifteen cases
Over 25 years ago, Owen et al., concluded that growth hormone co-treatment improved the ovarian response to ordinary ovarian stimulation protocols.11 This was supported by studies of Homberg, et al., demonstrating that growth hormone administration raises ovarian sensitivity to the gonadotropins.¹² Despite numerous recent studies, the applicability of growth hormone adjuvant treatment in IVF cycles remains controversial.13 Growth hormone is reported to modulate the activity of FSH on granulose cells by upregulating the local synthesis of IGF-1, which ampliﬁes the effect of gonadotropin action.
According to the European Society of Human Reproduction and Embryology (ESHRE), there is still no strong evidence that adjunctive treatment with growth hormone in IVF shall improve results.15 In one retrospective study by Rajesh et al., on 20 growth hormone deﬁcient women, embryo quality improved after growth hormone supplementation.
In our study, growth hormone adjuvant therapy in IVF cycles in low AMH cases did not improve the number of matures oocytes retrieved. Although necessity is the mother of invention, taking into consideration, it seems necessary to conduct a large study to know the use and effectiveness of the growth hormone and its safety for further recommendation to be applied in clinical practice.
1. Homburg R et al. Growth Hormone facilitates Ovulation Induction by gonadotropins. Clin Endocrinol. 1988;29(sup1):113–17.
2. Homburg R et al. The re-growth of growth hormone in fertility treatment: a critical review. Hum Fertil (Camb). 2012;15(sup4):190-3.
3. Ob'edkova K et al. Growth hormone co-treatment in IVF/ICSI cycles in poor responders. Gynecol Endocrinol. 2017;33(sup1):15-17.
4. Adashi EY et al. Insulin-like growth factor as intraovarian regulators of granulose cell growth and function. Endocr Rev. 1985;6(sup3)400-420.
5. Yoshimura Y et al. Effects of Insulin-like growth factor on follicle growth, oocyte maturation and Ovarian Steroidogenesis and plasimogen activator activity. Biol Reprod. 1996;55(sup1):152-160.
6. Homburg R et al. The re-growth of growth hormone in fertility treatment: a critical review. Hum Fertil (Camb). 2012;15(sup4):190-3.
7. Franks S. Growth Hormone and ovarian function, Bailliere’s clinical endocrinology and metabolism. 1998;12(sup2):331-340.
8. Florini JR et al. Growth Hormone and Insulin-like growth factor system in myogenesis. Endocr Rev. 1996;17(sup5):481-517.
9. Keane KN et al. Single-centre retrospective analysis of growth hormone supplementation in IVF patients classiﬁed as poor-prognosis. BMJ Open. 2017;7(sup10):e018107.
10. Ferraretti AP et al. ESHRE consenses on the deﬁnition of poor response to ovarian stimulation for IVF: The Bologna Criteria. Hum Reprod. 2011;26(sup7):1616-24.
11. Owen EJ et al. Co-treatment with Growth Hormone of suboptimal responders in IVF-ET. Hum Reprod. 1991;6:524-8.
12. Homburg R et al. The re-growth of growth hormone in fertility treatment: a critical review. Hum Fertil (Camb). 2012;15(sup4):190-3.
13. De Zieglar D et al. The value of Growth Hormone supplements in ART for poor Ovarian responders. Fertil Steril. 2011;96(sup5):1069–76.
14. Hsu C et al. Concomitant effects of Growth Hormone on the secretion of Insulin-like Growth factor-1 and progesterone by cultured porcine granulosa cells in vitro. Endocrinology. 1998;120:198–207.
15. European Society of Human Reproduction and Embryology. Still, no strong evidence that adjunctive treatment with human growth hormone in IVF improves results: Study ﬁnds supplementation results no better than placebo [internet]. Science Daily. 2016 [cited 18 Oct 2019] Available from: www.sciencedaily.com/releases/2016/07/160704101107.htm
16. Rajesh H et al. Growth Hormone deﬁciency and supplementation at in-vitro fertilization. Singapore Medical Journal. 2007;48(sup6):514–518.
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