Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 4/2019

01-04-2019 | Ectopic Pregnancy | Gynecologic Endocrinology and Reproductive Medicine

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

Authors: Xuemei Liu, Ding Ma, Wenjuan Wang, Qinglan Qu, Ning Zhang, Xinrong Wang, Jianye Fang, Zhi Ma, Cuifang Hao

Published in: Archives of Gynecology and Obstetrics | Issue 4/2019

Login to get access

Abstract

Introduction

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).

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
go back to reference Macklon N (2017) Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertil Steril 108(1):9–14CrossRefPubMed Macklon N (2017) Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertil Steril 108(1):9–14CrossRefPubMed
2.
go back to reference Simon A, Laufer N (2012) Repeated implantation failure: clinical approach. Fertil Steril 97(5):1039–1043CrossRefPubMed Simon A, Laufer N (2012) Repeated implantation failure: clinical approach. Fertil Steril 97(5):1039–1043CrossRefPubMed
3.
go back to reference Licht P, Fluhr H, Neuwinqer J, Wallwiener D, Wildt L (2007) Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol Cell Endocrinol 269(1–2):85–92CrossRefPubMed Licht P, Fluhr H, Neuwinqer J, Wallwiener D, Wildt L (2007) Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol Cell Endocrinol 269(1–2):85–92CrossRefPubMed
4.
go back to reference Tsampalas M, Gridelet V, Berndt S, Foldart JM, Geenen V, Perrier d’Hauterive S (2010) Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. J Reprod Immunol 85(1):93–98CrossRefPubMed Tsampalas M, Gridelet V, Berndt S, Foldart JM, Geenen V, Perrier d’Hauterive S (2010) Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. J Reprod Immunol 85(1):93–98CrossRefPubMed
5.
go back to reference da Ju H, Yi SW, Sohn WS, Lee SS (2015) Acquired uterine vascular abnormalities associated with persistent human chorionic gonadotropin: experience at a Korean teaching hospital. Taiwan J Obstet Gynecol 54(6):654–659CrossRef da Ju H, Yi SW, Sohn WS, Lee SS (2015) Acquired uterine vascular abnormalities associated with persistent human chorionic gonadotropin: experience at a Korean teaching hospital. Taiwan J Obstet Gynecol 54(6):654–659CrossRef
6.
go back to reference Lopata A, Hay DL (1989) The potential of early human embryos to form blastocysts, hatch from their zona and secrete HCG in culture. Hum Reprod 4(8 suppl):87–94CrossRefPubMed Lopata A, Hay DL (1989) The potential of early human embryos to form blastocysts, hatch from their zona and secrete HCG in culture. Hum Reprod 4(8 suppl):87–94CrossRefPubMed
7.
go back to reference Bourdiec A, Bedard D, Rao CV, Akoum A (2013) Human chorionic gonadotropin regulates endothelial cell responsiveness to interleukin 1 and amplifies the cytokine-mediated effect on cell proliferation, migration and the release of angiogenic factors. Am J Reprod Immunol 70(2):127–138CrossRefPubMed Bourdiec A, Bedard D, Rao CV, Akoum A (2013) Human chorionic gonadotropin regulates endothelial cell responsiveness to interleukin 1 and amplifies the cytokine-mediated effect on cell proliferation, migration and the release of angiogenic factors. Am J Reprod Immunol 70(2):127–138CrossRefPubMed
8.
go back to reference Palomino WA, Argandona F, Azua R, Kohen P, Devoto L (2013) Complement C3 and decay-accelerating factor expression levels are modulated by human chorionic gonadotropin in endometrial compartments during the implantation window. Reprod Sci 20(9):1103–1110CrossRefPubMedPubMedCentral Palomino WA, Argandona F, Azua R, Kohen P, Devoto L (2013) Complement C3 and decay-accelerating factor expression levels are modulated by human chorionic gonadotropin in endometrial compartments during the implantation window. Reprod Sci 20(9):1103–1110CrossRefPubMedPubMedCentral
9.
go back to reference Strug MR, Su R, Young JE, Dodds WG, Shavell VI, Diaz-Gimeno P et al (2016) Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial. Hum Reprod 31(7):1552–1561CrossRefPubMedPubMedCentral Strug MR, Su R, Young JE, Dodds WG, Shavell VI, Diaz-Gimeno P et al (2016) Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial. Hum Reprod 31(7):1552–1561CrossRefPubMedPubMedCentral
10.
go back to reference Wirleitner B, Schuff M, Vanderzwalmen P, Stecher A, Okhowat J, Hradecky L et al (2015) Intrauterine administration of human chorionic gonadotropin does not improve pregnancy and life birth rates independently of blastocyst quality: a randomised prospective study. Reprod Biol Endocrinol 13:70CrossRefPubMedPubMedCentral Wirleitner B, Schuff M, Vanderzwalmen P, Stecher A, Okhowat J, Hradecky L et al (2015) Intrauterine administration of human chorionic gonadotropin does not improve pregnancy and life birth rates independently of blastocyst quality: a randomised prospective study. Reprod Biol Endocrinol 13:70CrossRefPubMedPubMedCentral
11.
go back to reference Mansour R, Tawab N, Kamal O, Ei-Faissal Y, Serour A, Aboulghar M et al (2011) Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study. Fertil Steril 96(6):1370–1374CrossRefPubMed Mansour R, Tawab N, Kamal O, Ei-Faissal Y, Serour A, Aboulghar M et al (2011) Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study. Fertil Steril 96(6):1370–1374CrossRefPubMed
12.
go back to reference Santibanez A, Garcia J, Pashkova O, Colin O, Castellanos G, Sanchez AP et al (2014) Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 12:9CrossRefPubMedPubMedCentral Santibanez A, Garcia J, Pashkova O, Colin O, Castellanos G, Sanchez AP et al (2014) Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study. Reprod Biol Endocrinol 12:9CrossRefPubMedPubMedCentral
13.
go back to reference Aaleyasin A, Aghahosseini M, Rashidi M, Safdarian L, Sarvi F, Najmi Z et al (2015) In vitro fertilization outcome following embryo transfer with or without preinstillation of human chorionic gonadotropin into the uterine cavity: a randomized controlled trial. Gynecol Obstet Invest 79(3):201–205CrossRefPubMed Aaleyasin A, Aghahosseini M, Rashidi M, Safdarian L, Sarvi F, Najmi Z et al (2015) In vitro fertilization outcome following embryo transfer with or without preinstillation of human chorionic gonadotropin into the uterine cavity: a randomized controlled trial. Gynecol Obstet Invest 79(3):201–205CrossRefPubMed
14.
go back to reference Craciunas L, Tsampras N, Coomarasamy A, Raine-Fenning N (2016) Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction. Cochrane Database Syst Rev 20(5):CD011537 Craciunas L, Tsampras N, Coomarasamy A, Raine-Fenning N (2016) Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction. Cochrane Database Syst Rev 20(5):CD011537
15.
go back to reference Hong KH, Forman EJ, Werner MD, Upham KM, Gumeny CL, Winslow AD et al (2014) Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized, double-blind, placebo-controlled trial. Fertil Steril 102(6):1591–1595CrossRefPubMed Hong KH, Forman EJ, Werner MD, Upham KM, Gumeny CL, Winslow AD et al (2014) Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized, double-blind, placebo-controlled trial. Fertil Steril 102(6):1591–1595CrossRefPubMed
16.
17.
go back to reference Navali N, Gassemzadeh A, Farzadi L, Abdollahi S, Nouri M, Hamdi K et al (2016) Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial. Hum Reprod 31(11):2520–2526CrossRefPubMed Navali N, Gassemzadeh A, Farzadi L, Abdollahi S, Nouri M, Hamdi K et al (2016) Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial. Hum Reprod 31(11):2520–2526CrossRefPubMed
18.
go back to reference Huang P, Wei L, Li X (2017) A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures. Gynecol Endocrinol 33(1):67–69CrossRefPubMed Huang P, Wei L, Li X (2017) A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures. Gynecol Endocrinol 33(1):67–69CrossRefPubMed
19.
go back to reference Wang JX, Yap YY, Matthews CD (2001) Frozen-thawed embryo transfer: influence of clinical factors on implantation rate and risk of multiple conception. Hum Reprod 16(11):2316–2319CrossRefPubMed Wang JX, Yap YY, Matthews CD (2001) Frozen-thawed embryo transfer: influence of clinical factors on implantation rate and risk of multiple conception. Hum Reprod 16(11):2316–2319CrossRefPubMed
20.
go back to reference Jurisicova A, Antenos M, Kapasi K, Meriano J, Casper RF (1999) Variability in the expression of trophectodermal markers beta-human chorionic gonadotrophin, human leukocyte antigen-G and pregnancy specific beta-1 glycoprotein by the human blastocyst. Hum Reprod 14(7):1852–1858CrossRefPubMed Jurisicova A, Antenos M, Kapasi K, Meriano J, Casper RF (1999) Variability in the expression of trophectodermal markers beta-human chorionic gonadotrophin, human leukocyte antigen-G and pregnancy specific beta-1 glycoprotein by the human blastocyst. Hum Reprod 14(7):1852–1858CrossRefPubMed
21.
go back to reference Leavy O (2012) Tolerance: induced T (Reg) cells evolved to protect the fetus. Nat Rev Immunol 12(8):554–555CrossRefPubMed Leavy O (2012) Tolerance: induced T (Reg) cells evolved to protect the fetus. Nat Rev Immunol 12(8):554–555CrossRefPubMed
22.
go back to reference Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25 + CD4 + regulatory T-cell subset. Immunology 112(1):38–43CrossRefPubMedPubMedCentral Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25 + CD4 + regulatory T-cell subset. Immunology 112(1):38–43CrossRefPubMedPubMedCentral
23.
go back to reference Zhou J, Wang Z, Zhao X, Wang J, Sun H, Hu Y (2012) An increase of Treg cells in the peripheral blood is associated with a better in vitro fertilization treatment outcome. Am J Reprod Immunol 68(2):100–106CrossRefPubMed Zhou J, Wang Z, Zhao X, Wang J, Sun H, Hu Y (2012) An increase of Treg cells in the peripheral blood is associated with a better in vitro fertilization treatment outcome. Am J Reprod Immunol 68(2):100–106CrossRefPubMed
24.
go back to reference Wang WJ, Liu FJ, Zhang X, Liu XM, Qu QL, Li FH et al (2017) Periodic elevation of regulatory T cells on the day of embryo transfer is associated with better in vitro fertilization outcome. J Reprod Immunol 119:49–53CrossRefPubMed Wang WJ, Liu FJ, Zhang X, Liu XM, Qu QL, Li FH et al (2017) Periodic elevation of regulatory T cells on the day of embryo transfer is associated with better in vitro fertilization outcome. J Reprod Immunol 119:49–53CrossRefPubMed
25.
go back to reference Bao SH, Wang XP, De Lin Q, Wang WJ, Yin GJ, Qiu LH (2011) Decidual CD4 + CD25 + CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage. Eur J Obstet Gynecol Reprod Biol 155(1):94–98CrossRefPubMed Bao SH, Wang XP, De Lin Q, Wang WJ, Yin GJ, Qiu LH (2011) Decidual CD4 + CD25 + CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage. Eur J Obstet Gynecol Reprod Biol 155(1):94–98CrossRefPubMed
26.
go back to reference Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M et al (2009) Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol 182(9):5488–5497CrossRefPubMed Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M et al (2009) Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol 182(9):5488–5497CrossRefPubMed
27.
go back to reference Nakayama T, Fujiwara H, Maeda M, Inoue T, Yoshioka S, Mori T, Fujii S (2002) Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC. Hum Reprod 17(1):207–212CrossRefPubMed Nakayama T, Fujiwara H, Maeda M, Inoue T, Yoshioka S, Mori T, Fujii S (2002) Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC. Hum Reprod 17(1):207–212CrossRefPubMed
28.
go back to reference Yoshioka S, Fujiwara H, Nakayama T, Kosaka K, Mori T, Fujii S (2006) Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 21(12):3290–3294CrossRefPubMed Yoshioka S, Fujiwara H, Nakayama T, Kosaka K, Mori T, Fujii S (2006) Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod 21(12):3290–3294CrossRefPubMed
Metadata
Title
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
Authors
Xuemei Liu
Ding Ma
Wenjuan Wang
Qinglan Qu
Ning Zhang
Xinrong Wang
Jianye Fang
Zhi Ma
Cuifang Hao
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 4/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-019-05047-6

Other articles of this Issue 4/2019

Archives of Gynecology and Obstetrics 4/2019 Go to the issue