Advertisement

Effect of the co-administration of HCG and GnRH agonist (dual trigger) versus standard HCG trigger on morphokinetic embryo parameters

  • Galia Oron
    Correspondence
    Corresponding author.
    Affiliations
    Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Onit Sapir
    Affiliations
    Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Yoel Shufaro
    Affiliations
    Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally to this work.
    Avital Wertheimer
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally to this work.
    Avi Ben-Haroush
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Infertility and IVF Unit, Helen Schneider Hospital for Women, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally to this work.

      Abstract

      Research question

      Does dual trigger (the co-administration of triptorelin 0.2 mg and recombinant human chorionic gonadotrophin (HCG) [Decapeptyl 0.2 mg + Ovitrelle 250 µg]) versus standard recombinant HCG (Ovitrelle 250 µg) affect embryo quality and morphokinetic parameters?

      Design

      Morphokinetic parameters and embryo quality of embryos derived from the first gonadotrophin-releasing hormone (GnRH) antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles triggered by dual trigger or standard HCG trigger in women ≤42 years. Outcome measures included time to pronucleus fading (tPNf), cleavage timings (t2–t8), synchrony of the second cycle (s2), duration of the second cycle (cc2) and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors.

      Results

      A total of 4859 embryos were analysed: 1803 embryos from 267 cycles in the dual trigger group and 3056 embryos from 463 cycles in the HCG trigger group. The groups were similar in patient and treatment characteristics apart from a higher maternal body mass index and lower maturation rate in the dual trigger group. Time to second polar body extrusion was shorter in the dual trigger group. Cleavage timings from zygote to an 8-cell embryo did not differ between the two groups. There was a higher percentage of embryos with an optimal cc2 duration in the HCG group. In multivariate logistic regression models, the trigger type was not a significant factor for cell cycle division parameters.

      Conclusions

      Overall, there was no significant difference in the morphokinetic parameters or quality of embryos evaluated using a time-lapse monitoring system between embryos derived following dual trigger compared with HCG.

      Keywords

      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:

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

      References

        • Alikani M.
        • Cohen J.
        Patterns of cell fragmentation in the human embryo.
        J. Assist. Reprod. Genet. 1995; 12: 28S
        • ALPHA Scientists in Reproductive Medicine, ESHRE Special Interest Group Embryology
        Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.
        Reprod. Biomed. Online. 2011; 22: 632-646
        • Atef A.
        • Francois P.
        • Christian V.
        • Marc-André S.
        The potential role of gap junction communication between cumulus cells and bovine oocytes during in vitro maturation.
        Mol. Reprod. Dev. 2005; 71: 358-367
        • Baart E.B.
        • Macklon N.S.
        • Fauser B.J.
        Ovarian stimulation and embryo quality.
        Reprod. Biomed. Online. 2009; 18: 45-50
        • Baart E.B.
        • Martini E.
        • Eijkemans M.J.
        • Van Opstal D.
        • Beckers N.G.
        • Verhoeff A.
        • Macklon N.S.
        • Fauser B.C.
        Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.
        Hum. Reprod. 2007; 22: 980-988
        • Balaban B.
        • Urman B.
        Effect of oocyte morphology on embryo development and implantation.
        Reprod. Biomed. Online. 2006; 12: 608-615
        • Ben-Haroush A.
        • Sapir O.
        • Salman L.
        • Altman E.
        • Garor R.
        • Margalit T.
        • Shufaro Y.
        • Oron G.
        Does ‘dual trigger’ increase oocyte maturation rate?.
        J. Obstet. Gynaecol. 2020; 40: 860-862
        • Conaghan J.
        • Chen A.A.
        • Willman S.P.
        • Ivani K.
        • Chenette P.E.
        • Boostanfar R.
        • Baker V.L.
        • Adamson G.D.
        • Abusief M.E.
        • Gvakharia M.
        • Loewke K.E.
        • Shen S.
        Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial.
        Fertil. Steril. 2013; 100: 412-419
        • Decleer W.
        • Osmanagaoglu K.
        • Meganck G.
        • Devroey P.
        A new approach for ovarian stimulation in IVF using corifollitropin alfa in combination with GnRH analogues to trigger final oocyte maturation. A pilot study.
        Facts Views Vis. Obgyn. 2014; 6: 159-165
        • Devroey P.
        • Bourgain C.
        • Macklon N.S.
        • Fauser B.C.
        Reproductive biology and IVF: ovarian stimulation and endometrial receptivity.
        ABBV Trends Endocrinol. Metab. 2004; 15: 84-90
        • Ding N.
        • Liu X.
        • Jian Q.
        • Liang Z.
        • Wang F.
        Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: a systematic review and meta-analysis.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2017; 218: 92-98
        • Downs S.M.
        • Chen J.
        EGF-like peptides mediate FSH-induced maturation of cumulus cell-enclosed mouse oocytes.
        Mol. Reprod. Dev. 2008; 75: 105-114
        • Eftekhar M.
        • Mojtahedi M.F.
        • Miraj S.
        • Omid M.
        Final follicular maturation by administration of GnRH agonist plus hCG versus hCG in normal responders in ART cycles: an RCT.
        Int. J. Reprod. Biomed. 2017; 15: 429-434
        • Fabris A.M.
        • Cruz M.
        • Legidos V.
        • Iglesias C.
        • Muñoz M.
        • García-Velasco J.A.
        Dual triggering with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin in patients with a high immature oocyte rate.
        Reprod. Sci. 2017; 24: 1221-1225
        • Griffin D.
        • Benadiva C.
        • Kummer N.
        • Budinetz T.
        • Nulsen J.
        • Engmann L.
        Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders.
        Fertil. Steril. 2012; 97: 1316-1320
        • Griffin D.
        • Feinn R.
        • Engmann L.
        • Nulsen J.
        • Budinetz T.
        • Benadiva C.
        Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates.
        Fertil. Steril. 2014; 102: 405-409
        • Gurbuz A.S.
        • Gode F.
        • Uzman M.S.
        • Ince B.
        • Kaya M.
        • Ozcimen N.
        • Ozcimen E.E.
        • Acar A.
        GnRH agonist triggering affects the kinetics of embryo development: a comparative study.
        Ovarian Res. 2016; 8: 9-22
        • Kasum M.
        • Kurdija K.
        • Orešković S.
        • Čehić E.
        • Pavičić-Baldani D.
        • Škrgatić L.
        Combined ovulation triggering with GnRH agonist and hCG in IVF patients.
        Gynecol. Endocrinol. 2016; 32: 861-865
        • Kim C.H.
        • Ahn J.W.
        • You R.M.
        • Kim S.H.
        • Chae H.D.
        • Kang B.M.
        Combined administration of gonadotropin-releasing hormone agonist with human chorionic gonadotropin for final oocyte maturation in GnRH antagonist cycles for in vitro fertilization.
        J. Reprod. Med. 2014; 59: 63-68
        • Kirkegaard K.
        • Agerholm I.E.
        • Ingerslev H.J.
        Time-lapse monitoring as a tool for clinical embryo assessment.
        Hum. Reprod. 2012; 27: 1277-1285
        • Lin M.H.
        • Wu F.S.
        • Lee R.K.
        • Li S.H.
        • Lin S.Y.
        • Hwu Y.M.
        Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles.
        Fertil. Steril. 2013; 100: 1296-1302
        • Meseguer M.
        • Herrero J.
        • Tejera A.
        • Hilligsøe K.M.
        • Ramsing N.B.
        • Remohí J.
        The use of morphokinetics as a predictor of embryo implantation.
        Hum. Reprod. 2011; 26: 2658-2671
        • Muñoz M.
        • Cruz M.
        • Humaidan P.
        • Garrido N.
        • Pérez-Cano I.
        • Meseguer M.
        Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics.
        Reprod. Biomed. Online. 2012; 4: 382-389
        • Muñoz M.
        • Cruz M.
        • Humaidan P.
        • Garrido N.
        • Pérez-Cano I.
        • Meseguer M.
        The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 168: 167-172
        • Oron G.
        • Sapir O.
        • Wertheimer A.
        • Shufaro Y.
        • Bar-Gil R.
        • Margalit T.
        • Shlush E.
        • Ben-Haroush A.
        A matched propensity score study of embryo morphokinetics following gonadotropin-releasing hormone agonist versus human chorionic gonadotropin trigger.
        J. Assist. Reprod. Genet. 2020; 37: 2777-2782
        • Pellicer A.
        • Ruiz A.
        • Castellvi R.M.
        • Calatayud C.
        • Ruiz M.
        • Tarin J.J.
        • Miró F.
        • Bonilla-Musoles F.
        Is the retrieval of high numbers of oocytes desirable in patients treated with gonadotrophin-releasing hormone analogues (GnRHa) and gonadotrophins?.
        Hum. Reprod. 1989; 4: 536-540
        • Petersen B.M.
        • Boel M.
        • Montag M.
        • Gardner D.K.
        Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3.
        Hum. Reprod. 2016; 31: 2231-2244
        • Prochazka R.
        • Blaha M.
        • Nemcova L.
        Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig.
        Reproduction. 2012; 144: 535-546
        • Rubio C.
        • Mercader A.
        • Alama P.
        • Lizán C.
        • Rodrigo L.
        • Labarta E.
        • Melo M.
        • Pellicer A.
        • Remohí J.
        Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development.
        Hum. Reprod. 2011; 25: 2290-2297
        • Rubio I.
        • Galan A.
        • Larreategui Z.
        • Ayerdi F.
        • Bellver J.
        • Herrero J.
        • Meseguer M.
        Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope.
        Fertil. Steril. 2014; 102: 1287-1294
        • Schachter M.
        • Friedler S.
        • Ron-El R.
        • Zimmerman A.L.
        • Strassburger D.
        • Bern O.
        • Bern O.
        • Raziel A.
        Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study.
        Fertil. Steril. 2008; 90: 1087-1093
        • Scott L.
        The biological basis of non-invasive strategies for selection of human oocytes and embryos.
        Hum. Reprod. Update. 2003; 9: 237-249
        • Seval M.M.
        • Özmen B.
        • Atabekoğlu C.
        • Şükür Y.E.
        • Şimşir C.
        • Kan Ö.
        • Sönmezer M.
        Dual trigger with gonadotropin-releasing hormone agonist and recombinant human chorionic gonadotropin improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles.
        J. Obstet. Gynaecol. Res. 2016; 42: 1146-1151
        • Shapiro B.S.
        • Daneshmand S.T.
        • Garner F.C.
        • Aguirre M.
        • Thomas S.
        Gonadotropin-releasing hormone agonist combined with a reduced dose of human chorionic gonadotropin for final oocyte maturation in fresh autologous cycles of in vitro fertilization.
        Fertil. Steril. 2008; 90: 231-233
      1. Shymaa S. Ali, Elwany Elsenosy, Gamal H. Sayed, Tarek A. Farghaly, Ahmed A. Youssef, Esraa Badran, Ahmed M. Abbas*, Ahmed A. Abdelaleem Journal of Gynecology Obstetrics and Human Reproduction May;49(5):101728.

        • Bosch E.
        • Broer S.
        • Griesinger G.
        • Grynberg M.
        • Humaidan P.
        • Kolibianakis E.
        • Kunicki M.
        • La Marca A.
        • Lainas G.
        • Le Clef N.
        • Massin N.
        • Mastenbroek S.
        • Polyzos N.
        • Sunkara S.K.
        • Timeva T.
        • Töyli M.
        • Urbancsek J.
        • Vermeulen N.
        • Broekmans F.
        • The Eshre Guideline Group on Ovarian Stimulation
        ESHRE guideline: ovarian stimulation for IVF/ICSI.
        Hum. Reprod. Open. 2020 May 1; 2020: hoaa009
        • Van der Gaast M.H.
        • Eijkemans M.J.
        • van der Net J.B.
        • de Boer E.J.
        • Burger C.W.
        • van Leeuwen F.E.
        • Fauser B.C.
        • Macklon N.S.
        Optimum number of oocytes for a successful first IVF treatment cycle.
        Reprod. Biomed. Online. 2006; 13: 476-480
        • Wang R.
        • Lin S.
        • Wang Y.
        • Qian W.
        • Zhou L.
        Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: a systematic review and meta-analysis.
        PLoS One. 2017; 12e0175985
        • Zhang J.
        • Wang Y.
        • Mao X
        • Chen Q.
        • Hong Q.
        • Cai R.
        • Zhang S.
        • Kuang Y.
        Dual trigger of final oocyte maturation in poor ovarian responders undergoing IVF/ICSI cycles.
        Reprod. Biomed. Online. 2017; 35: 701-707
        • Zhou X.
        • Guo P.
        • Chen X.
        • Ye D.
        • Liu Y.
        • Chen S.
        Comparison of dual trigger with combination GnRH agonist and hCG versus hCG alone trigger of oocyte maturation for normal ovarian responders.
        Int. J. Gynecol. Obstet. 2018; 141: 327-331

      Biography

      Galia Oron MD completed her obstetrics and gynaecology residency in 2010 and postgraduate training in reproductive endocrinology and infertility, with excellence, at McGill University, Canada, in 2014. Her special research interests are the effect of growth differentiation factors on maturation of human ovarian follicles and IVF pregnancy outcomes.
      Key message
      Dual trigger does not appear to be related to embryo quality or morphokinetic parameters. This argues against the routine use of dual trigger in the first IVF/ICSI cycle in order to improve embryo quality.