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Growth hormone co-treatment within a GnRH agonist long protocol improves implantation and pregnancy rates in patients undergoing IVF-ET

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

Abstract

Objective

The efficacy of growth hormone (GH) co-treatment within a GnRH agonist long regimen, in women with a normal ovarian response to controlled ovarian hyperstimulation (COH), for IVF was assessed.

Methods

This retrospective clinical trial was performed in a private-assisted reproduction centre. The study involved 1114 patients who responded normally to high-dose gonadotropin treatment. The study group of 556 patients was given in a daily subcutaneous injection of 4.5 IU of GH co-treatment, starting from the initial day of gonadotropin treatment and lasting for 5 days. The control group of 558 patients received the same treatment protocol without the GH co-treatment. The participants were further divided into two subgroups: age ≥35 years and age <35 years. The primary endpoint of the study was IVF-ET outcomes.

Results

The demographic characteristics did not significantly differ between the groups. The implantation rate (36.7 vs. 20.4 %, P < 0.05) and clinical pregnancy rate (57.3 vs. 30.1 %, P < 0.05) were significantly higher in the study group than in the control group. An analysis using a multivariate logistic regression model showed that GH was a significant factor for predicting pregnancy outcomes (OR 3.125, 95 % CI 2.441–4.000). Furthermore, for the ≥35-year-old group, the endometrial thickness was significantly greater (11.99 ± 2.21 vs. 11.62 ± 2.45, P < 0.05) in the study group than in the control group; in contrast, for the <35-year-old group, the high-quality embryo rate was significantly higher (71.7 vs. 68.3 %, P < 0.05) in the study group than in the control group.

Conclusion

Our study showed that co-treatment with GH in a GnRH agonist long protocol in patients who responded normally while undergoing IVF-ET could increase the implantation and pregnancy rates.

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References

  1. Nishiyama K, Sugimoto T, Kaji H, Kanatani M, Kobayashi T, Chihara K (1996) Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation. Endocrinology 137:35–41. doi:10.1210/endo

    CAS  PubMed  Google Scholar 

  2. Herrington J, Carter-Su C (2001) Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab 12:252–257. doi:10.1016/S1043-2760(01)00423-4

    Article  CAS  PubMed  Google Scholar 

  3. Hull KL, Harvey S (2001) Growth hormone: roles in female reproduction. J Endocrinol 168:1–23. doi:10.1677/joe

    Article  CAS  PubMed  Google Scholar 

  4. Homburg R, Eshel A, Abdalla HI, Jacobs HS (1988) Growth hormone facilitates ovulation induction by gonadotrophins. Clin Endocrinol (Oxf) 29:113–117. doi:10.1111/j

    Article  CAS  Google Scholar 

  5. Nakamura E, Otsuka F, Inagaki K, Miyoshi T, Matsumoto Y, Ogura K, Tsukamoto N, Takeda M, Makino H (2012) Mutual regulation of growth hormone and bone morpho genetic protein system in steroidogenesis by rat granulosa cells. Endocrinology 153:469–480. doi:10.1210/en

    Article  CAS  PubMed  Google Scholar 

  6. Slot KA, Kastelijn J, Bachelot A, Kelly PA, Binart N, Teerds KJ (2006) Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice. Reproduction 131:525–532. doi:10.1530/rep

    Article  CAS  PubMed  Google Scholar 

  7. Bachelot A, Monget P, Imbert-Bolloré P, Coshigano K, Kopchick JJ, Kelly PA, Binart N (2002) Growth hormone is required for ovarian follicular growth. Endocrinology 143:4104–4112. doi:10.1210/en

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Bevers MM, Izadyar F (2002) Role of growth hormone and growth hormone receptor in oocyte maturation. Mol Cell Endocrinol 197:173–178. doi:10.1016/S0303-7207(02)00270-8

    Article  CAS  PubMed  Google Scholar 

  10. Yungai X, Li T (2006) The effect of growth hormone on endometrial receptivity in mice. J Med Forum 27:35–37

    Google Scholar 

  11. Díaz-Gimeno P, Horcajadas JA, Martínez-Conejero JA, Esteban FJ, Alamá P, Pellicer A, Simón C (2011) A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril 95:50–60. doi:10.1016/j

    Article  PubMed  Google Scholar 

  12. Achache H, Revel A (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 12:731–746. doi:10.1093/humupd/dml004

    Article  PubMed  Google Scholar 

  13. 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. doi:10.1093/humupd/dmp026

    Article  CAS  PubMed  Google Scholar 

  14. Kyrou D, Kolibianakis EM, Venetis CA, Papanikolaou EG, Bontis J, Tarlatzis BC (2009) How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril 91:749–766. doi:10.1016/j

    Article  CAS  PubMed  Google Scholar 

  15. Wu MY, Chen HF, Ho HN, Chen SU, Chao KH, Huang SC, Lee TY, Yang YS (1996) The value of human growth hormone as an adjuvant for ovarian stimulation in a human in vitro fertilization program. J Obstet Gynaecol Res 22:443–450. doi:10.1111/j

    Article  CAS  PubMed  Google Scholar 

  16. Hughes SM, Huang ZH, Morris ID, Matson PL, Buck P, Lieberman BA (1994) A double-blind cross-over controlled study to evaluate the effect of human biosynthetic growth hormone on ovarian stimulation in previous poor responders to in vitro fertilization. Hum Reprod 9:13–18

    CAS  PubMed  Google Scholar 

  17. Boynukalın K, Güler T (2013) The use of growth hormone in in vitro fertilization. Basic Clin Sci 2:123–127

    Article  Google Scholar 

  18. Var T, Tonguc E, Dogan M, Mollamahmutoglu L (2011) Relationship between the oestradiol/oocyte ratio and the outcome of assisted reproductive technology cycles with gonadotropin releasing hormone agonist. Gynecol Endocrinol 27:558–561. doi:10.3109/09513590

    Article  CAS  PubMed  Google Scholar 

  19. Pereira GR, Lorenzo PL, Carneiro GF, Ball BA, Bilodeau-Goeseels S, Kastelic J, Pegoraro LM, Pimentel CA, Esteller-Vico A, Illera JC, Granado GS, Casey P, Liu IK (2013) The involvement of growth hormone in equine oocyte maturation, receptor localization and steroid production by cumulus-oocyte complexes in vitro. Res Vet Sci 95:667–674. doi:10.1016/j

    Article  CAS  PubMed  Google Scholar 

  20. Mendoza C, Ruiz-Requena E, Ortega E, Cremades N, Martinez F, Bernabeu R, Greco E, Tesarik J (2002) Follicular fluid markers of oocyte developmental potential. Hum Reprod 17:1017–1022. doi:10.1093/humrep/17

    Article  CAS  PubMed  Google Scholar 

  21. Folch J, Ramón JP, Cocero MJ, Alabart JL, Beckers JF (2001) Exogenous growth hormone improves the number of transferable embryos in superovulated ewes. Theriogenology 55:1777–1785. doi:10.1016/S0093-691X(01)00520-9

    Article  CAS  PubMed  Google Scholar 

  22. Moreira F, Badinga L, Burnley C, Thatcher WW (2002) Bovine somatotropin increases embryonic development in superovulated cows and improves post-transfer pregnancy rates when given to lactating recipient cows. Theriogenology 57:1371–1378. doi:10.1016/S0093-691X(01)00719-1

    Article  CAS  PubMed  Google Scholar 

  23. Lanzone A, Fortini A, Fulghesu AM, Soranna L, Caruso A, Mancuso S (1996) Growth hormone enhances estradiol production follicle-stimulating hormone-induced in the early stage of the follicular maturation. Fertil Steril 66:948–953

    Article  CAS  PubMed  Google Scholar 

  24. Silva JRV, Figueiredo JR, van den Hurk R (2009) Involvement of growth hormone (GH) and insulin-likegrowth factor (IGF) system in ovarian folliculogenesis. Theriogenology 71:1193–1208. doi:10.1016/j

    Article  CAS  PubMed  Google Scholar 

  25. Kiapekou E, Loutradis D, Drakakis P, Zapanti E, Mastorakos G, Antsaklis A (2005) Effects of GH and IGF-I on the in vitro maturation of mouse oocytes. Hormones 4:155–160. doi:10.14310/horm

    Article  PubMed  Google Scholar 

  26. 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. doi:10.1016/j

    Article  CAS  PubMed  Google Scholar 

  27. Kölle S, Stojkovic M, Reese S, Reichenbach HD, Wolf E, Sinowatz F (2004) Effects of growth hormone on the ultrastructure of bovine preimplantation embryos. Cell Tissue Res 317:101–108. doi:10.1007/s00441-004-0898-2

    Article  PubMed  Google Scholar 

  28. Kidson A, Rubio-Pomar FJ, Van Knegsel A, Van Tol HT, Hazeleger W, Ducro-Steverink DW, Colenbrander B, Dieleman SJ, Bevers MM (2004) Quality of porcine blastocysts produced in vitro in the presence or absence of GH. Reproduction 127:165–177. doi:10.1530/rep

    Article  CAS  PubMed  Google Scholar 

  29. Xingxiang M, Yingchun Su, Yingpu Sun (2009) A meta analysis of effect of growth hormone on the development of endometrium. Prog Obstet Gynecol 18:330–332

    Google Scholar 

  30. Sbracia M, Scarpellini F, Poverini R, Alò PL, Rossi G, Di Tondo U (2004) Immunohistochemical localization of the growth hormone in human endometrium and decidua. Am J Reprod Immunol 51:112–116. doi:10.1046/j

    Article  PubMed  Google Scholar 

  31. Zhang J, Tan L (2006) Effect of growth hormone on the thickness of proliferative endometrium and the expression of VEGF, EGF, IGF-I in mouse. J Med Forum 27:13–15

    Google Scholar 

  32. Yang C, Fenghua L (2012) Effect of growth hormone on the endometrium receptivity in SD mice. J Biomed Eng 3:1674–1927

    Google Scholar 

  33. Guijin Z, Bei X (2013) Progesterone regulate endometrial receptivity. J Reprod Med 22:272–275

    Google Scholar 

  34. Spiliotis BE (2003) Growth hormone insufficiency and its impact on ovarian function. Ann N Y Acad Sci 997:77–84. doi:10.1196/annals

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yi-hong Guo.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Growth hormone co-treatment within a GnRH agonist long protocol improves implantation and pregnancy rates in patients undergoing IVF-ET”. We state that we have had full control of all primary data and that agree to allow the Journal to review our data if requested.

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All procedures performed in studies involving human participants 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.

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Du, Xf., Yang, Xh., Li, J. et al. 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 (2016). https://doi.org/10.1007/s00404-016-4163-1

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  • DOI: https://doi.org/10.1007/s00404-016-4163-1

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