Growth Hormone: A Potential Treatment of Patients with Refractory Thin Endometrium: A Clinical Trial Study

Document Type : Original Article


1 Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Gynecology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Community Medicine Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Reproductive Biology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

5 Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen–Nürnberg, Erlangen, Germany


Background: Growth hormone (GH) is a potential treatment in the assisted reproductive technology (ART) to improve endometrial receptivity and thickness. In the current study, we investigated the effect of the intrauterine administration of GH on the endometrial thickness (EMT) and ART outcomes in the patients with refractory thin endometrium.
Materials and Methods: In this clinical trial study, women with a refractory thin endometrium and a history of one or more frozen embryo transfer (FET) cancellation who were referred to the infertility center of the Tabriz Al-Zahra hospital (Tabriz, Iran) and Milad Infertility Clinic (Tabriz, Iran) received intrauterine injections of GH every other day from day 14 of the menstrual cycle until the EMT reached ≥7 mm in addition to the routine endometrium preparation protocol. EMT was evaluated during the treatment and in the cases with EMT ≥7 mm, biochemical/clinical pregnancy was evaluated after embryo transfer.
Results: Thirty-one women aged 35.29 ± 6.21 years were included in this study. The mean amount of EMT was significantly increased following the GH treatment (7.03 ± 1.23 mm) vs. before treatment (5.14 ± 1.1 mm, P<0.001). The EMT reached ≥7 mm in the 65% patients (20/31). Also, the embryo transfer resulted in pregnancy in the patients, biochemical pregnancy: 9/20 (45%) and clinical pregnancy: 7/20 (35%). There was a positive correlation between EMT on the day 13 of cycle (before the treatment) and the maximum EMT (r=0.577 and P=0.001). The EMT was statistically different on the embryo transfer day between clinically pregnant and non-pregnant women (7.18 ± 0.56 vs. 6.21 ± 0.72 mm, P=0.007).
Conclusion: The intrauterine administration of GH could be an appropriate therapeutic strategy for patients with refractory thin endometrium. This treatment could significantly increase the EMT as well as implantation and pregnancy rates in these patients (registration number: IRCT20210220050429N1).


1. Toner JP, Coddington CC, Doody K, Van Voorhis B, Seifer DB, Ball GD, et al. Society for assisted reproductive technology and assisted reproductive technology in the United States: a 2016 update. Fertil Steril. 2016; 106(3): 541-546.
2. Cimadomo D, Soscia D, Vaiarelli A, Maggiulli R, Capalbo A, Ubaldi FM, et al. Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing. Hum Reprod. 2019; 34(7): 1206-1214.
3. Munné S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019; 112(6): 1071-1079.
4. Kim SM, Kim JS. A review of mechanisms of implantation. Dev Reprod. 2017; 21(4): 351-359.
5. Eftekhar M, Tabibnejad N, Tabatabaie AA. The thin endometrium in assisted reproductive technology: an ongoing challenge. Middle East Fertil Soc J. 2018; 23(1): 1-7.
6. Zadehmodarres S, Salehpour S, Saharkhiz N, Nazari L. Treatment of thin endometrium with autologous platelet-rich plasma: a pilot study. JBRA Assist Reprod. 2017; 21(1): 54-56.
7. Kim H, Shin JE, Koo HS, Kwon H, Choi DH, Kim JH. Effect of autologous platelet-rich plasma treatment on refractory thin endometrium during the frozen embryo transfer cycle: a pilot study. Front Endocrinol (Lausanne). 2019; 10: 61.
8. Garcia-Velasco JA, Acevedo B, Alvarez C, Alvarez M, Bellver J, Fontes J, et al. Strategies to manage refractory endometrium: state of the art in 2016. Reprod Biomed Online. 2016; 32(5): 474-489.
9. Keyhanvar N, Zarghami N, Bleisinger N, Hajipour H, Fattahi A, Nouri M, et al. Cell-based endometrial regeneration: current status and future perspectives. Cell Tissue Res. 2021: 384(2): 241-254.
10. Bassiouny YA, Dakhly DMR, Bayoumi YA, Hashish NM. 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. 2016; 105(3): 697-702.
11. Yu H, Gao S, Tang H, Chen H, Deng Z, Yang L, et al. Growth hormone intrauterine perfusion combined with replacement cycle in the treatment of non-response thin endometrium: report of 5 cases. Int J Clin Exp Med. 2016; 9(6): 11982-11989.
12. Du Xf, Yang Xh, Li J, Hao M, Guo Yh. Growth hormone co-treatment within a GnRH agonist long protocol improves implantation and pregnancy rates in patients undergoing IVF-ET. Arch Gynecol Obstet. 2016; 294(4): 877-883.
13. Xue-Mei W, Hong J, Wen-Xiang Z, Yang L. The effects of growth hormone on clinical outcomes after frozen–thawed embryo transfer. Int J Gynaecol Obstet. 2016; 133(3): 347-350.
14. Yang JY, Li H, Lu N, Li L, Sun XX. Influence of growth hormone supplementation in patients with thin endometrium undergoing frozen embryo transfer. Reprod Dev Med. 2019; 3(1): 49.
15. Karizbodagh MP, Rashidi B, Sahebkar A, Masoudifar A, Mirzaei H. Implantation window and angiogenesis. J Cell Biochem. 2017; 118(12): 4141-4151.
16. Cui N, Li AM, Luo ZY, Zhao ZM, Xu YM, Zhang J, et al. Effects of growth hormone on pregnancy rates of patients with thin endometrium. J Endocrinol Invest. 2019; 42(1): 27-35.
17. Chen Y, Liu F, Nong Y, Ruan J, Guo Q, Luo M, et al. Clinical efficacy and mechanism of growth hormone action in patients experiencing repeat implantation failure. Can J Physiol Pharmacol. 2018; 96(9): 929-932.
18. Altmäe S, Mendoza-Tesarik R, Mendoza C, Mendoza N, Cucinelli F, Tesarik J. Effect of growth hormone on uterine receptivity in women with repeated implantation failure in an oocyte donation program: a randomized controlled trial. J Endocr Soc. 2018; 2(1): 96-105.
19. Liu Y, Zhancai W, Xuehong Z. Meta-analysis of the effectiveness of growth hormone on patients with endometrial dysplasia during in vitro fertilization-embryo transfer. Prog Obstet Gynecol. 2014; 23(7): 560-563.
20. Boguszewski MC, Cardoso-Demartini AA, Boguszewski CL, Chemaitilly W, Higham CE, Johannsson G, et al. Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice. Pituitary. 2021: 24(5): 810-827.
21. Kim SH, Park MJ. Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab. 2017; 22(3): 145-152.
22. Liu FT, Wu Z, Yan J, Norman RJ, Li R. The potential role of growth hormone on the endometrium in assisted reproductive technology. Front Endocrinol. 2020; 11: 49.
23. Yanping X, Zhao G, Miao J, Tan J. Changes in vimentin and vascular endothelial growth factor expression in a rat model of thin endometrium established by 95% ethanol. Chin J Tissue Eng Res. 2016; 20(5): 718-722.
24. Alfer J, Happel L, Dittrich R, Beckmann MW, Hartmann A, Gaumann A, et al. Insufficient angiogenesis: cause of abnormally thin endometrium in subfertile patients? Geburtshilfe Frauenheilkd. 2017; 77(07): 756-764.
25. Eftekhar M, Aflatoonian A, Mohammadian F, Eftekhar T. Adjuvant growth hormone therapy in antagonist protocol in poor responders undergoing assisted reproductive technology. Arch Gynecol Obstet. 2013; 287(5): 1017-1021.
26. Khan MS, Shaikh A, Ratnani R. Ultrasonography and Doppler study to predict uterine receptivity in infertile patients undergoing embryo transfer. J Obstet Gynaecol India. 2016; 66(1): 377-382.
27. Zhang T, Li Z, Ren X, Huang B, Zhu G, Yang W, et al. Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles: a retrospective cohort study of 1512 IVF cycles with morphologically good-quality blastocyst. Medicine. 2018; 97(4).
28. Fang R, Cai L, Xiong F, Chen J, Yang W, Zhao X. The effect of endometrial thickness on the day of hCG administration on pregnancy outcome in the first fresh IVF/ICSI cycle. Gynecol Endocrinol. 2016; 32(6): 473-476.
29. Ma NZ, Chen L, Dai W, Bu ZQ, Hu LL, Sun YP. Influence of endometrial thickness on treatment outcomes following in vitro fertilization/intracytoplasmic sperm injection. Reprod Biol Endocrinol. 2017; 15(1): 1-7.
30. Xiang Yg, Tan L, Dong Fl. Effect of GH on the Expressions of VEGF, LIF, MMP-9 and TIMP-1 in Endometrium of Mouse. Reprod Contracept. 2007; 27(10): 639.