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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(07): 713-722
DOI: 10.1055/a-0837-3246
GebFra Science
Original Article
Georg Thieme Verlag KG Stuttgart · New York

The Effect of Intrauterine Administration of Human Chorionic Gonadotropin (hCG) Before Embryo Transfer During Assisted Reproductive Cycles: a Meta-Analysis of Randomized Controlled Trials

Auswirkung der intrauterinen Gabe von humanem Choriongonadotropin (hCG) vor dem Embryotransfer in assistierten Reproduktionszyklen: eine Metaanalyse von randomisierten kontrollierten Studien
Huiping Tan
1   Reproductive Medicine Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
,
Shifu Hu
2   Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
,
Qiongyu,
Yuan Chen
3   Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
,
Lei Jin
1   Reproductive Medicine Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
,
Chunlin Wu
4   Center of Reproductive Medicine, The No. 1 Hospital of Wuhan, Wuhan, Hubei, China
› Author Affiliations
Further Information

Publication History

received 01 December 2018
revised 04 January 2019

accepted 19 January 2019

Publication Date:
01 April 2019 (online)

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Abstract

The fertility success rates of clinical and laboratory-assisted reproductive techniques (ART) remain low, despite major advances. The aim of this study was to conduct a systematic literature review and assess whether the intrauterine administration of human chorionic gonadotropin (hCG) before embryo transfer (ET) improved the clinical outcomes of sub-fertile women undergoing assisted reproduction. The electronic databases PUBMED, EMBASE and Web of Science were systematically searched for randomized controlled trials (RCTs) published from inception to June 2018. The trial data were independently extracted and analyzed using risk ratios (RRs) and 95% confidence intervals (CIs) according to a random- or fixed-effect model (as appropriate), and a meta-analysis was conducted using Review Manager 5.2 software. The meta-analysis included 3241 patients from 12 RCTs, and the combined results demonstrated that intrauterine hCG injection significantly improved the rates of clinical (RR = 1.33; 95% CI: 1.12 – 1.58) and ongoing pregnancy (RR = 1.87; 95% CI: 1.54 – 2.27), compared with controls. However, intrauterine hCG injection had no significant effect on the implantation rate (RR = 1.30; 95% CI: 0.89 – 1.90), abortion rate (RR = 1.06; 95% CI: 0.78 – 1.44), ectopic pregnancy rate (RR = 0.77; 95% CI: 0.17 – 3.42) or live birth rate (RR = 0.99; 95% CI: 0.60 – 1.63). In a subgroup analysis, the intrauterine injection of > 500 IU hCG led to a significant increase in the implantation rate (RR = 1.64; 95% CI: 1.04 – 2.61) relative to controls. Furthermore, the subgroup of women with cleavage-stage ETs who received an intracavity injection of hCG (IC-hCG) exhibited increases in the implantation, clinical pregnancy and ongoing pregnancy rates, compared to women with cleavage-stage ETs and no IC-hCG. The current evidence indicates that intrauterine hCG administration before ET provides an advantage in terms of the clinical pregnancy and ongoing pregnancy rates.

Zusammenfassung

Trotz wichtiger Fortschritte bleiben die Erfolgsraten der klinischen und laborassistierten Reproduktionstechniken (ART) niedrig. Ziel dieser Studie war es, eine systematische Analyse der Literatur durchzuführen, um herauszufinden, ob die intrauterine Gabe von humanem Choriongonadotropin (hCG) vor dem Embryotransfer (ET) das klinische Ergebnis bei subfertilen Frauen verbessert, die sich einer assistierten Reproduktion unterziehen. Die elektronischen Datenbanken PUBMED, EMBASE und Web of Science wurden systematisch nach randomisierten, vor Juni 2018 veröffentlichten, kontrollierten Studien durchsucht. Bei der Analyse wurde Modelle mit zufälligen bzw. festen Effekten verwendet. Die Studiendaten wurden individuell analysiert. Das relative Risiko (RR) und das 95%ige Konfidenzintervall (KI) wurden kalkuliert. Die Metaanalyse wurde mithilfe der Review Manager 5.2 Software durchgeführt. Die Metaanalyse umfasste 3241 Patientinnen aus 12 randomisierten kontrollierten Studien. Die kombinierten Ergebnisse zeigen, dass eine intrauterine hCG-Injektion die klinischen Schwangerschaftsrate (RR = 1,33; 95%-KI 1,12 – 1,58) sowie die Rate der weiterführenden Schwangerschaften (RR = 1,87; 95%-KI 1,54 – 2,27) signifikant verbesserte, verglichen mit der Kontrollgruppe. Dagegen hatte eine intrauterine hCG-Injektion keine signifikanten Auswirkungen auf die Implantationsrate (RR = 1,30; 95%-KI: 0,89 – 1,90), die Fehlgeburtenrate (RR = 1,06; 95%-KI 0,78 – 1,44), die Rate ektoper Schwangerschaften (RR = 0,77; 95%-KI 0,17 – 3,42) sowie die Lebendgeburtenrate (RR = 0,99; 95%-KI 0,60 – 1,63). Bei einer Untergruppenanalyse stellte sich heraus, dass eine intrauterine Injektion von > 500 IU hCG zu einer signifikant höheren Implantationsrate führte (RR = 1,64; 95%-KI 1,04 – 2,61), verglichen mit der Kontrollgruppe. Ferner stellte sich heraus, dass die Implantationsrate, die klinische Schwangerschaftsrate und die weiterführende Schwangerschaftsrate höher waren bei einer Untergruppe von Frauen, die ein Embryo in der Teilungsphase transferiert bekamen und eine intrakavitäre hCG-Injektion (IC-hCG) erhielten, verglichen mit Frauen, die ebenfalls ein Embryo in der Teilungsphase transferiert bekamen und keine IC-hCG erhielten. Nach der derzeitigen Beweislage scheint es, dass eine intrauterine hCG-Gabe vor dem ET Vorteile hinsichtlich der klinischen Schwangerschaftsrate und der weiterführenden Schwangerschaftsrate aufweist.

Key words

human chorionic gonadotropin - intrauterine injection - embryo transfer - meta-analysis

Schlüsselwörter

humanes Choriongonadotropin - intrauterine Injektion - Embryotransfer - Metaanalyse
 

  • References

  • 1 te Velde ER, Eijkemans R, Habbema HD. Variation in couple fecundity and time to pregnancy, an essential concept in human reproduction. Lancet 2000; 355: 1928-1929
    CrossrefPubMedGoogle Scholar
  • 2 Skakkebaek NE, Jorgensen N, Main KM. et al. Is human fecundity declining?. Int J Androl 2006; 29: 2-11
    CrossrefPubMedGoogle Scholar
  • 3 Mansour R, Tawab N, Kamal O. et al. 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 2011; 96: 1370-1374.e1
    CrossrefPubMedGoogle Scholar
  • 4 de Mouzon J, Lancaster P, Nygren KG. et al. World collaborative report on Assisted Reproductive Technology, 2002. Hum Reprod 2009; 24: 2310-2320
    CrossrefPubMedGoogle Scholar
  • 5 Kane N, Kelly R, Saunders PT. et al. Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor. Endocrinology 2009; 150: 2882-2888
    CrossrefPubMedGoogle Scholar
  • 6 Wan H, Versnel MA, Cheung WY. et al. Chorionic gonadotropin can enhance innate immunity by stimulating macrophage function. J Leukoc Biol 2007; 82: 926-933
    CrossrefPubMedGoogle Scholar
  • 7 Fritz MA, Speroff L. Clinical gynecologic Endocrinology and Infertility. 8th ed.. USA: Lippincot Williams and Wilkins; 2011
    Google Scholar
  • 8 Wallace LD, Breiner CA, Breiner RA. et al. Administration of human chorionic gonadotropin at embryo transfer induced ovulation of a first wave dominant follicle, and increased progesterone and transfer pregnancy rates. Theriogenology 2011; 75: 1506-1515
    CrossrefPubMedGoogle Scholar
  • 9 Mostajeran F, Godazandeh F, Ahmadi SM. et al. Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on pregnancy rate: A prospective randomized study. J Res Med Sci 2017; 22: 6
    CrossrefPubMedGoogle Scholar
  • 10 Hafezi M, Madani T, Arabipoor A. et al. The effect of intrauterine human chorionic gonadotropin flushing on live birth rate after vitrified-warmed embryo transfer in programmed cycles: a randomized clinical trial. Arch Gynecol Obstet 2018; 297: 1571-1576
    CrossrefPubMedGoogle Scholar
  • 11 Huang P, Wei L, Li X. A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures. Gynecol Endocrinol 2017; 33: 67-69
    CrossrefPubMedGoogle Scholar
  • 12 Hosseini RS, Farzad L, Abdollahi S. et al. Effect of intrauterine injection of human chorionic gonadotropin before frozen-thawed embryo transfer on implantation and clinical pregnancy rate: A randomized controlled trial. International Journal of Womenʼs Health and Reproduction Sciences 2016; 4: 200-203
    PubMedGoogle Scholar
  • 13 Dehghani Firouzabadi R, Janati S, Razi MH. The effect of intrauterine human chorionic gonadotropin injection before embryo transfer on the implantation and pregnancy rate in infertile patients: A randomized clinical trial. Int J Reprod Biomed (Yazd) 2016; 14: 657-664
    PubMedGoogle Scholar
  • 14 Wirleitner B, Schuff M, Vanderzwalmen P. et al. 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 2015; 13: 70
    CrossrefPubMedGoogle Scholar
  • 15 Osman A, Pundir J, Elsherbini M. et al. The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online 2016; 33: 350-359
    CrossrefPubMedGoogle Scholar
  • 16 Higgins JP, Altman DG, Gotzsche PC. et al. The Cochrane Collaborationʼs tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928
    CrossrefPubMedGoogle Scholar
  • 17 Aaleyasin A, Aghahosseini M, Rashidi M. et al. 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 2015; 79: 201-205
    PubMedGoogle Scholar
  • 18 Zarei A, Parsanezhad ME, Younesi M. et al. Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/intracytoplasmic sperm injection: A randomized clinical trial. Iran J Reprod Med 2014; 12: 1-6
    PubMedGoogle Scholar
  • 19 Santibanez A, Garcia J, Pashkova O. et al. 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 2014; 12: 9
    CrossrefPubMedGoogle Scholar
  • 20 Hong KH, Forman EJ, Werner MD. et al. 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 2014; 102: 1591-1595.e2
    CrossrefPubMedGoogle Scholar
  • 21 Navali N, Gassemzadeh A, Farzadi L. et al. Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial. Hum Reprod 2016; 31: 2520-2526
    CrossrefPubMedGoogle Scholar
  • 22 Fluhr H, Krenzer S, Deperschmidt M. et al. Human chorionic gonadotropin inhibits insulin-like growth factor-binding protein-1 and prolactin in decidualized human endometrial stromal cells. Fertil Steril 2006; 86: 236-238
    CrossrefPubMedGoogle Scholar
  • 23 Edwards RG. Chorionic gonadotrophin, genes and embryonic signals regulating the implantation window. Reprod Biomed Online 2007; 14: 538-540
    CrossrefPubMedGoogle Scholar
  • 24 Paiva P, Hannan NJ, Hincks C. et al. Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Hum Reprod 2011; 26: 1153-1162
    CrossrefPubMedGoogle Scholar
  • 25 Srivastava A, Sengupta J, Kriplani A. et al. Profiles of cytokines secreted by isolated human endometrial cells under the influence of chorionic gonadotropin during the window of embryo implantation. Reprod Biol Endocrinol 2013; 11: 116
    CrossrefPubMedGoogle Scholar
  • 26 Sugihara K, Kabir-Salmani M, Byrne J. et al. Induction of trophinin in human endometrial surface epithelia by CGbeta and IL-1beta. FEBS Lett 2008; 582: 197-202
    CrossrefPubMedGoogle Scholar
  • 27 Ye H, Hu J, He W. et al. The efficacy of intrauterine injection of human chorionic gonadotropin before embryo transfer in assisted reproductive cycles: Meta-analysis. J Int Med Res 2015; 43: 738-746
    PubMedGoogle Scholar
  • 28 Wang H, Zhang R, Han D. et al. [Association of human chorionic gonadotropin level in embryo culture media with early embryo development]. Nan Fang Yi Ke Da Xue Xue Bao 2014; 34: 1039-1041 1047
    PubMedGoogle Scholar
  • 29 Lee TK, Kim DI, Song YL. et al. Differential inhibition of Scutellaria barbata D. Don (Lamiaceae) on HCG-promoted proliferation of cultured uterine leiomyomal and myometrial smooth muscle cells. Immunopharmacol Immunotoxicol 2004; 26: 329-342
    CrossrefPubMedGoogle Scholar
  • 30 Schumacher A, Brachwitz N, Sohr S. et al. Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. J Immunol 2009; 182: 5488-5497
    CrossrefPubMedGoogle Scholar
  • 31 Banerjee P, Fazleabas AT. Endometrial responses to embryonic signals in the primate. Int J Dev Biol 2010; 54: 295-302
    CrossrefPubMedGoogle Scholar