nach oben

Archives of Gynecology and Obstetrics

Erschienen in:

19.01.2019 | 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

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

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

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.

Macklon N (2017) Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertil Steril 108(1):9–14CrossRefPubMed

Simon A, Laufer N (2012) Repeated implantation failure: clinical approach. Fertil Steril 97(5):1039–1043CrossRefPubMed

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

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

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

Diao LH, Li GG, Zhu YC, Tu WW, Huang CY, Lian RC et al (2017) Human chorionic gonadotropin potentially affects pregnancy outcome in women with recurrent implantation failure by regulating the homing preference of regulatory T cells. AM J Reprod Immunol. https://doi.org/10.1111/aji.12618 CrossRefPubMed

17.

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.

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.

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.

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.

Leavy O (2012) Tolerance: induced T (Reg) cells evolved to protect the fetus. Nat Rev Immunol 12(8):554–555CrossRefPubMed

22.

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.

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.

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.

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.

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.

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.

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

Titel: 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
verfasst von: Xuemei Liu
Ding Ma
Wenjuan Wang
Qinglan Qu
Ning Zhang
Xinrong Wang
Jianye Fang
Zhi Ma
Cuifang Hao
Publikationsdatum: 19.01.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 4/2019
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-019-05047-6

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

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