Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial


      Research question

      Does intrauterine administration of HCG before embryo transfer improve live birth rate during IVF cycles?


      A parallel, randomized controlled trial conducted between July 2018 and February 2020. Infertile women (n = 181) scheduled for fresh or vitrified–warmed embryo transfer after IVF carried out for any indication were randomized in a 1:1 ratio to receive either HCG (500 IU in 0.1 ml of tissue culture media) or culture media (0.1 ml of tissue culture media) via intrauterine injection 4 min before embryo transfer. In both groups, an intrauterine insemination catheter was used for administering the medication. Primary outcome was live birth, with ongoing pregnancy and clinical pregnancy as secondary outcomes. Analysis was based on intention-to-treat principle.


      Baseline and cycle characteristics were comparable between the two groups. In the control group, one woman with a confirmed clinical pregnancy was lost to follow-up. Live birth rates were 24% (22/90) in the HCG group versus 19% (17/90) in the control group (RR 1.29, 95% CI 0.74 to 2.27). Clinical pregnancy and ongoing pregnancy rates were 34% versus 26% (RR 1.31, 95% CI 0.84 to 2.04) and 24% versus 19% (RR 1.29, 95% CI 0.74 to 2.27) in the HCG and the control groups, respectively.


      Intrauterine injection of HCG before embryo transfer did not improve live birth rates in women undergoing IVF. As the study was designed to detect a 20% difference between groups, a smaller, clinically important difference could not be ruled out. Treatment outcomes were lower than expected in the control group.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Adamson G.D.
        • de Mouzon J.
        • Chambers G.M.
        • Zegers-Hochschild F.
        • Mansour R.
        • Ishihara O.
        • Banker M.
        • Dyer S.
        International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011.
        Fertil. Steril. 2018; 6: 1067-1080
        • Afshar Y.
        • Stanculescu A.
        • Miele L.
        • Fazleabas A.T.
        The role of chorionic gonadotropin and Notch1 in implantation.
        J. Assist. Reprod. Genet. 2007; 7: 296-302
        • Barnhart K.T.
        Live birth is the correct outcome for clinical trials evaluating therapy for the infertile couple.
        Fertil. Steril. 2014; 5: 1205-1208
        • Craciunas L.
        • Tsampras N.
        • Raine-Fenning N.
        • Coomarasamy A.
        Intrauterine administration of human chorionic gonadotropin (HCG) for subfertile women undergoing assisted reproduction.
        The Cochrane database of systematic reviews. 2018; CD011537
        • Filicori M.
        • Fazleabas A.T.
        • Huhtaniemi I.
        • Licht P.
        • Rao C.V.
        • Tesarik J.
        • Zygmunt M.
        Novel concepts of human chorionic gonadotropin: reproductive system interactions and potential in the management of infertility.
        Fertil. Steril. 2005; 2: 275-284
        • Gleicher N.
        • Orvieto R.
        Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review.
        Journal of ovarian research. 2017; 1: 21
        • Harbin Consensus Conference Workshop Group
        Improving the Reporting of Clinical Trials of Infertility Treatments (IMPRINT): modifying the CONSORT statement.
        Fertil. Steril. 2014; 4 (952-959.e915)
        • Hong K.H.
        • Forman E.J.
        • Werner M.D.
        • Upham K.M.
        • Gumeny C.L.
        • Winslow A.D.
        • Kim T.J.
        • Scott Jr., R.T.
        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; 6 (1591-1595. e1592)
        • Jasinska A.
        • Strakova Z.
        • Szmidt M.
        • Fazleabas A.T.
        Human Chorionic Gonadotropin and Decidualization in Vitro Inhibits Cytochalasin-D-Induced Apoptosis in Cultured Endometrial Stromal Fibroblasts.
        Endocrinology. 2006; 9: 4112-4121
        • Laokirkkiat P.
        • Thanaboonyawat I.
        • Boonsuk S.
        • Petyim S.
        • Prechapanich J.
        • Choavaratana R.
        Increased implantation rate after intrauterine infusion of a small volume of human chorionic gonadotropin at the time of embryo transfer: a randomized, double-blind controlled study.
        Archives of gynecology and obstetrics. 2019; 1: 267-275
        • Lensen S.
        • Shreeve N.
        • Barnhart K.T.
        • Gibreel A.
        • Ng E.H.Y.
        • Moffett A.
        In vitro fertilization add-ons for the endometrium: it doesn't add-up.
        Fertil. Steril. 2019; 6: 987-993
        • Licht P.
        • Fluhr H.
        • Neuwinger J.
        • Wallwiener D.
        • Wildt L.
        Is human chorionic gonadotropin directly involved in the regulation of human implantation?.
        Mol. Cell. Endocrinol. 2007; 1: 85-92
        • Licht P.
        • Lösch A.
        • Dittrich R.
        • Neuwinger J.
        • Siebzehnrübl E.
        • Wildt L.
        Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis.
        Hum. Reprod. Update. 1998; 5: 532-538
        • Licht P.
        • Russu V.
        • Lehmeyer S.
        • Möll J.
        • Siebzehnrübl E.
        • Wildt L.
        Intrauterine microdialysis reveals cycle-dependent regulation of endometrial insulin-like growth factor binding protein-1 secretion by human chorionic gonadotropin.
        Fertil. Steril. 2002; 2: 252-258
        • Licht P.
        • von Wolff M.
        • Berkholz A.
        • Wildt L.
        Evidence for cycle-dependent expression of full-length human chorionic gonadotropin/luteinizing hormone receptor mRNA in human endometrium and decidua.
        Fertil. Steril. 2003; : 718-723
        • Lopata A.
        • Hay D.L.
        The potential of early human embryos to form blastocysts, hatch from their zona and secrete HCG in culture.
        Hum. Reprod. 1989; : 87-94
        • Mansour R.
        • Tawab N.
        • Kamal O.
        • El-Faissal Y.
        • Serour A.
        • Aboulghar M.
        • Serour G.
        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; 6 (1370-1374.e1371)
        • Navali N.
        • Gassemzadeh A.
        • Farzadi L.
        • Abdollahi S.
        • Nouri M.
        • Hamdi K.
        • Mallah F.
        • Jalilvand F.
        Intrauterine administration of HCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial.
        Hum. Reprod. 2016; 11: 2520-2526
        • Oakley L.
        • Doyle P.
        • Maconochie N.
        Lifetime prevalence of infertility and infertility treatment in the UK: results from a population-based survey of reproduction.
        Hum. Reprod. 2008; 2: 447-450
        • Racowsky C.
        • Vernon M.
        • Mayer J.
        • Ball G.D.
        • Behr B.
        • Pomeroy K.O.
        • Wininger D.
        • Gibbons W.
        • Conaghan J.
        • Stern J.E.
        Standardization of grading embryo morphology.
        Fertil. Steril. 2010; 3: 1152-1153
        • Santibañez Á.
        • García J.
        • Pashkova O.
        • Colín O.
        • Castellanos G.
        • Sánchez A.P.
        • De la Jara J.F.
        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; 1: 9
        • Schulz K.F.
        • Grimes D.A.
        Sample size calculations in randomised trials: mandatory and mystical.
        The Lancet. 2005; 9467: 1348-1353
        • Su H.-C.I.
        • Sammel M.D.
        Interim analysis in clinical trials.
        Fertil. Steril. 2012; 3: e9
        • Timeva T.
        • Shterev A.
        • Kyurkchiev S.
        Recurrent implantation failure: the role of the endometrium.
        J. Reprod. Infertil. 2014; 4: 173-183
        • Wirleitner B.
        • Schuff M.
        • Vanderzwalmen P.
        • Stecher A.
        • Okhowat J.
        • Hradecký L.
        • Kohoutek T.
        • Králícková M.
        • Spitzer D.
        • Zech N.H.
        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; 1: 70
        • Zegers-Hochschild F.
        • Adamson G.D.
        • Dyer S.
        • Racowsky C.
        • de Mouzon J.
        • Sokol R.
        • Rienzi L.
        • Sunde A.
        • Schmidt L.
        • Cooke I.D.
        The international glossary on infertility and fertility care, 2017.
        Hum. Reprod. 2017; 9: 1786-1801


      Karim S Abdallah, MSc, is a MD student, Specialist and Assistant Lecturer at the Department of Obstetrics at the Faculty of Medicine at Assiut University, Egypt. He is a Clinical Embryologist at Assiut University IVF unit.
      Key message
      This randomized trial did not show a significant increase in live birth rate with the injection of HCG inside the uterine cavity before embryo transfer; therefore, this treatment is not currently recommended. A large multi-centre study is needed to confirm these results.