Intrauterine administration of human chorionic gonadotropin improves the live birth rates of patients with repeated implantation failure in frozen-thawed blastocyst transfer cycles by increasing the percentage of peripheral regulatory T cells

  • Xuemei LiuEmail author
  • Ding Ma
  • Wenjuan Wang
  • Qinglan Qu
  • Ning Zhang
  • Xinrong Wang
  • Jianye Fang
  • Zhi Ma
  • Cuifang Hao
Gynecologic Endocrinology and Reproductive Medicine



Repeated implantation failure (RIF) frustrates both patients and their clinicians. Our aim was to observe the effects of intrauterine administration of human chorionic gonadotropin (hCG) on pregnancy outcomes of patients who received frozen-thawed embryo transfer (FET).


A prospective cohort study was conducted to evaluate the impact of intrauterine administration of hCG on pregnancy outcomes in FET cycles of patients with RIF from January 1st 2016 to December 31st 2016. The treatment group (n = 153, 152 cycles) received an infusion of 500 IU of hCG diluted in normal saline 3 days before embryo transfer. The control group (n = 152, 151 cycles) received embryo transfer with a previous intrauterine injection of normal saline without hCG. Early morning fasting blood samples were obtained from each patient for the measurement of peripheral regulatory T cells (Tregs) on the day of embryo transfer. The outcome parameters including Tregs in each group were compared.


The patients in the hCG-treated group had significantly higher clinical pregnancy rates, implantation rates and live birth rates than the controls (37.5% versus 25.17%, 29.19% versus 19.4%, 26.97% versus 17.22%, respectively). They also had significantly higher percentages of peripheral Tregs than the controls (6.1 ± 0.6% versus 5.4 ± 1.0%). In addition, the clinical pregnancy rate, implantation rate and live birth rate in patients who received blastocyst transfer were significantly higher in the hCG-treated group when compared to the control group (41.38% versus 26.44%, 42.22% versus 26.14%, 33.33% versus 17.24%, respectively). We also showed that the clinical pregnancy rate, implantation rate and live birth rate were significantly higher in hCG-treated group when compared to the control group (49.12% versus 28.07%, 49.15% versus 28.07%, 40.35% versus 17.54%, respectively) of RIF patients with blastocyst transfer under 35 years, while there was on difference in patients above 35 years.


Intrauterine administration of hCG significantly improves the clinical pregnancy rate, implantation rate and live birth rate in FET cycles of patients with RIF by increasing Tregs. The treatment improves the pregnancy outcomes much more for younger RIF patients transferred blastocysts.


Human chorionic gonadotropin Tregs Embryo transfer Live birth rate 



The authors are very grateful to Mrs Nadia Sultan for the corrections of language. She is a clinical embryologist at London Women's Clinic.

Author contribution

XML: Project development, Data collection, Data analysis and Manuscript writing. DM: Data collection, Data analysis and Manuscript editing. WJW, QLQ and NZ: the specimen collection and Data management. XRW, JYF, ZM and CFH: Data collection and Manuscript writing.


This work was supported by National Natural Science Foundation of China (81601276, 81741027), the special fund for clinical research of the Chinese Medical Association (16020220638, 17020180687 and 17020160685).

Compliance with ethical standards

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Reproductive Medicine Center, Yantai Yuhuangding HospitalAffiliated Hospital of Qingdao UniversityYantaiChina

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