Skip to main content

Advertisement

SpringerLink
Log in

Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Supplementation of growth hormone (GH) during controlled ovarian stimulation (COS) has been suggested to improve ovarian response. Despite potential benefits in poor responders, multiple injections of GH during COS are inconvenient. We conducted a randomized controlled study to evaluate the efficacy and safety of sustained-release human GH in poor responders undergoing in vitro fertilization (IVF).

Methods

This was a single-center, randomized, open-label, parallel study. Infertile women who satisfied the Bologna criteria for poor responders were randomized into GH treatment and control groups. The treatment group received a sustained-release GH (Eutropin Plus® 20 mg) three times before and during COS (mid-luteal, late luteal, and menstrual cycle day 2). The baseline characteristics and IVF outcomes were compared between the two groups.

Results

A total of 127 patients were included in the analysis. The mean age was 39.6 years and mean anti-Müllerian hormone level was 0.6 ng/ml. There was no significant difference in the baseline characteristics between GH treatment and control groups. The number of follicles on the human chorionic gonadotropin triggering day (3.1 ± 2.3 vs. 2.4 ± 1.6, P = 0.043) and the proportion of metaphase II oocytes (67.5 vs. 52.3%, P = 0.030) were higher in the GH group than in controls. The percentage of clinical and ongoing pregnancy and miscarriage was not different between the two groups.

Conclusion

Supplementation of sustained-release GH before and during COS improved ovarian response, with an increase in mature oocytes in poor responders. Further studies are needed to ensure this benefit in general infertility patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Practice Committee of the American Society for Reproductive Medicine (2015) Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril 103:e9–e17

    Google Scholar 

  2. Cooper GS, Baird DD, Hulka BS, Weinberg CR, Savitz DA, Hughes CL (1995) Follicle-stimulating hormone concentrations in relation to active and passive smoking. Obstet Gynecol 85:407–411

    Article  CAS  PubMed  Google Scholar 

  3. Cooper GS, Thorp JM (1999) FSH levels in relation to hysterectomy and to unilateral oophorectomy. Obstet Gynecol 94:969–972

    CAS  PubMed  Google Scholar 

  4. van Dorp W, Blijdorp K, Laven JS, Pieters R, Visser JA, van der Lely AJ, Neggers SJ, van den Heuvel-Eibrink MM (2013) Decreased ovarian function is associated with obesity in very long-term female survivors of childhood cancer. Eur J Endocrinol 168:905–912

    Article  PubMed  Google Scholar 

  5. Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S (2010) Interventions for ‘poor responders’ to controlled ovarian hyper stimulation (COH) in in vitro fertilisation (IVF). Cochrane Database Syst Rev 1:CD004379

    Google Scholar 

  6. Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J (2003) Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update 9:61–76

    Article  CAS  PubMed  Google Scholar 

  7. Duffy JM, Ahmad G, Mohiyiddeen L, Nardo LG, Watson A (2010) Growth hormone for in vitro fertilization. Cochrane Database Syst Rev 1:CD000099

    Google Scholar 

  8. Li XL, Wang L, Lv F, Huang XM, Wang LP, Pan Y, Zhang XM (2017) The influence of different growth hormone addition protocols to poor ovarian responders on clinical outcomes in controlled ovary stimulation cycles: a systematic review and meta-analysis. Medicine 96:e6443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Saenger PH, Mejia-Corletto J (2016) Long-acting growth hormone: an update. Endocr Dev 30:79–97

    Article  PubMed  Google Scholar 

  10. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, EwgoPOR Definition (2011) ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 26:1616–1624

    Article  CAS  PubMed  Google Scholar 

  11. Hwang JS, Lee HS, Chung WY, Han HS, Jin DK, Kim HS, Ko CW, Lee BC, Lee DY, Lee KH, Shin JH, Suh BK, Yoo HW, Ji HJ, Lee JH, Bae YJ, Kim DH, Yang SW (2013) Efficacy and safety of LB03002, a once-weekly sustained-release human GH for 12-month treatment in Korean children with GH deficiency. Eur J Endocrinol 169:179–185

    Article  CAS  PubMed  Google Scholar 

  12. Bassiouny YA, Dakhly DMR, Bayoumi YA, Hashish NM (2016) Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? A randomized, controlled trial. Fertil Steril 105:697–702

    Article  CAS  PubMed  Google Scholar 

  13. Kim C-H, Park H, Moon J-W, Ahn J-W, Kim S-H, Chae H-D (2015) Efficacy of long-acting growth hormone, eutropin plus single injection on controlled ovarian stimulation and IVF outcomes in poor responders undergoing IVF. In: Abstract book. annual meeting of Korean Society of Obstetrics and Gynecology, vol 101, p 355

  14. Weall BM, Al-Samerria S, Conceicao J, Yovich JL, Almahbobi G (2015) A direct action for GH in improvement of oocyte quality in poor-responder patients. Reproduction 149:147–154

    Article  CAS  PubMed  Google Scholar 

  15. Hull KL, Harvey S (2014) Growth hormone and reproduction: a review of endocrine and autocrine/paracrine interactions. Int J Endocrinol 2014:234014

    Article  PubMed  PubMed Central  Google Scholar 

  16. Webb R, Garnsworthy PC, Gong JG, Armstrong DG (2004) Control of follicular growth: local interactions and nutritional influences. J Anim Sci 82 E-Suppl:E63–E74

    CAS  PubMed  Google Scholar 

  17. Yoshimura Y, Nakamura Y, Koyama N, Iwashita M, Adachi T, Takeda Y (1993) Effects of growth hormone on follicle growth, oocyte maturation, and ovarian steroidogenesis. Fertil Steril 59:917–923

    Article  CAS  PubMed  Google Scholar 

  18. Yoshimura Y, Ando M, Nagamatsu S, Iwashita M, Adachi T, Sueoka K, Miyazaki T, Kuji N, Tanaka M (1996) Effects of insulin-like growth factor-I on follicle growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator activity in the rabbit. Biol Reprod 55:152–160

    Article  CAS  PubMed  Google Scholar 

  19. Qiao J, Feng HL (2011) Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update 17:17–33

    Article  PubMed  Google Scholar 

  20. Schoyer KD, Liu HC, Witkin S, Rosenwaks Z, Spandorfer SD (2007) Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) in IVF patients with polycystic ovary syndrome: correlations with outcome. Fertil Steril 88:139–144

    Article  CAS  PubMed  Google Scholar 

  21. Karamouti M, Kollia P, Kallitsaris A, Vamvakopoulos N, Kollios G, Messinis IE (2008) Growth hormone, insulin-like growth factor I, and leptin interaction in human cultured lutein granulosa cells steroidogenesis. Fertil Steril 90:1444–1450

    Article  CAS  PubMed  Google Scholar 

  22. Kolibianakis EM, Venetis CA, Diedrich K, Tarlatzis BC, Griesinger G (2009) Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update 15:613–622

    Article  CAS  PubMed  Google Scholar 

  23. Du XF, Yang XH, Li J, Hao M, Guo YH (2016) Growth hormone co-treatment within a GnRH agonist long protocol improves implantation and pregnancy rates in patients undergoing IVF-ET. Arch Gynecol Obstet 294:877–883

    Article  CAS  PubMed  Google Scholar 

  24. Yovich JL, Stanger JD (2010) Growth hormone supplementation improves implantation and pregnancy productivity rates for poor-prognosis patients undertaking IVF. Reprod Biomed Online 21:37–49

    Article  CAS  PubMed  Google Scholar 

  25. de Ziegler D, Streuli I, Meldrum DR, Chapron C (2011) The value of growth hormone supplements in ART for poor ovarian responders. Fertil Steril 96:1069–1076

    Article  PubMed  Google Scholar 

  26. Tesarik J, Hazout A, Mendoza C (2005) Improvement of delivery and live birth rates after ICSI in women aged > 40 years by ovarian co-stimulation with growth hormone. Hum Reprod 20:2536–2541

    Article  PubMed  Google Scholar 

  27. Bayoumi YA, Dakhly DM, Bassiouny YA, Hashish NM (2015) Addition of growth hormone to the microflare stimulation protocol among women with poor ovarian response. Int J Gynecol Obstet 131:305–308

    Article  CAS  Google Scholar 

  28. Eftekhar M, Aflatoonian A, Mohammadian F, Eftekhar T (2013) Adjuvant growth hormone therapy in antagonist protocol in poor responders undergoing assisted reproductive technology. Arch Gynecol Obstet 287:1017–1021

    Article  CAS  PubMed  Google Scholar 

  29. Kucuk T, Kozinoglu H, Kaba A (2008) Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective, randomized, clinical trial. J Assist Reprod Genet 25:123–127

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yoon TK, Kang IS, Koong MK, Kim YS, Kim JY, Kim MJ (2017) Effect of supplementary grow hormone in poor responders. In: Poster presentation. The 72th biannual meeting of Korean Society of Obstetrics and Gynecology

  31. Huang ZH, Baxter RC, Hughes SM, Matson PL, Lieberman BA, Morris ID (1993) Supplementary growth hormone treatment of women with poor ovarian response to exogenous gonadotrophins: changes in serum and follicular fluid insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3). Hum Reprod 8:850–857

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, 566, Nonhyun-ro, Gangnam-gu, Seoul, South Korea

    Seung-Ah Choe, Myung Joo Kim, Hee Jun Lee, Jayeon Kim, Eun Mi Chang, Ji Won Kim, Han Moie Park, Sang Woo Lyu, Woo Sik Lee, Tae Ki Yoon & You Shin Kim

  2. CHA Fertility Center, Seoul Station, Seoul, South Korea

    Seung-Ah Choe, Myung Joo Kim, Jayeon Kim, Tae Ki Yoon & You Shin Kim

Authors
  1. Seung-Ah Choe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myung Joo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hee Jun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jayeon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eun Mi Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ji Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Han Moie Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sang Woo Lyu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Woo Sik Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tae Ki Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. You Shin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YSK: Project development, data collection, and supervision of the entire study process; SAC: data analysis and manuscript writing; MJK: data collection and manuscript review; HJK: data analysis; JK: data collection and manuscript review; EMC: data collection and project administration; JYK: data collection and analysis; HMP: data collection; SWL: project development and manuscript review; WSL: data collection and project administration; TKY: project administration and data collection.

Corresponding author

Correspondence to You Shin Kim.

Ethics declarations

Funding

This study was supported by a research Grant from LG Life Sciences, Seoul, Korea.

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the institutional review board (IRB number: GCI-13-37). Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choe, SA., Kim, M.J., Lee, H.J. et al. Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study. Arch Gynecol Obstet 297, 791–796 (2018). https://doi.org/10.1007/s00404-017-4613-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4613-4

Keywords

Search

Navigation