Abstract
Purpose
To assess whether GnRH agonist trigger impacts the implantation potential of euploid embryos.
Methods
Retrospective cohort study done at an academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single-euploid blastocysts were transferred between 2014 and 2019. All embryos were generated in an IVF cycle which used GnRHa or hCG trigger and then were transferred in a programmed or natural FET cycle. Only the first FET cycle was included for each patient. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR), and multiple pregnancy rate (MPR). Logistic regression was performed to control for confounding variables. A p value of < 0.05 was considered statistically significant.
Results
Two hundred sixty-three FET cycles were included for analysis (GnRHa = 145; hCG = 118). The GnRHa group was significantly younger (35.2 vs. 37.5 years) and had higher AMH values (4.50 ng/ml vs. 2.03 ng/ml) than the hCG group, respectively (p < 0.05). There was no significant difference in OPR/LBR (64.1% (93/145) vs. 65.3% (77/118); p = 0.90) between the GnRHa and hCG groups, respectively. There was also no significant difference in IR, CPR, CLR, or MPR between groups. After controlling for confounding variables, the adjusted odds ratio for OPR/LBR was 0.941 (95% CI, 0.534–1.658); p = 0.83) comparing GnRHa to hCG. Pregnancy outcomes did not significantly differ when groups were stratified by age (< 35 vs. > 35 years old).
Conclusions
Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.
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References
Alyasin A, Mehdinejadiani S. GnRH Agonist Trigger versus HCG Trigger in GnRH Antagonist in IVF/ICSI Cycles: A Review Article. Int J Reprod BioMed. 2016;14:557–66.
Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The Use of Gonadotropin-Releasing Hormone (GnRH) Agonist to Induce Oocyte Maturation after Cotreatment with GnRH Antagonist in High-Risk Patients Undergoing in Vitro Fertilization Prevents the Risk of Ovarian Hyperstimulation Syndrome: A Prospective Randomized Controlled Trial. Fertil Steril. 2008;89:84–91.
Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, et al. GnRH Agonist (Buserelin) or HCG for Ovulation Induction in GnRH Antagonist IVF / ICSI Cycles : A Prospective Randomized Study. Hum Reprod. 2005;20:1213–20.
Youssef, M., Van der Veen, F., Al-Inany, H., Griesinger, G., Mochtar, M., Aboulfoutouh, I., Khattab, S., Van Wely, M. Gonadotropin-Releasing Hormone Agonist versus HCG for Oocyte Triggering in Antagonist Assisted Reproductive Technology Cycles. Cochrane Database of Syst Rev 2009; 4.
Engmann L, Benadiva C, Humaidan P. GnRH Agonist Trigger for the Induction of Oocyte Maturation in GnRH Antagonist IVF Cycles: A SWOT Analysis. Reprod BioMed Online. 2016;32:274–85.
Haahr T, Roque M, Esteves S, Humaidan P. GnRH Agonist Trigger and LH Activity Luteal Phase Support versus Hcg Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-a Systematic PRISMA Review and Meta-Analysis. Front Endocrinol. 2017;8:1–10.
Humaidan P, Ejdrup-Bredkjaer H, Westergaard LG, Yding Anderson C. 1,500 IU Human Chorionic Gonadotropin Administered at Oocyte Retrieval Rescues the Luteal Phase When Gonadotropin-Releasing Hormone Agonist Is Used for Ovulation Induction: A Prospective, Randomized, Controlled Study. Fertil Steril. 2010;93:847–54.
Iliodromiti S, Blockeel C, Tremellen KP, Fleming R, Torunaye H, Humaidan P, et al. Consistent High Clinical Pregnancy Rates and Low Ovarian Hyperstimulation Syndrome Rates in High-Risk Patients after GnRH Agonist Triggering and Modified Luteal Support: A Retrospective Multicentre Study. Hum Reprod. 2013;28:2529–36.
Radesic B, Tremellen K. Oocyte Maturation Employing a GnRH Agonist in Combination with Low-Dose HCG Luteal Rescue Minimizes the Severity of Ovarian Hyperstimulation Syndrome While Maintaining Excellent Pregnancy Rates. Hum Reprod. 2011;26:3437–42.
Shapiro B, Said T, Garner F, Aguirre M, Hudson S. Comparison of "triggers" using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. Fertil Steril. 2011;95:2715–7.
Galindo A, Bodri D, Guillen JJ, Colodron M, Vernaeve VS, Coll O. Triggering with HCG or GnRH Agonist in GnRH Antagonist Treated Oocyte Donation Cycles : A Randomised Clinical Trial. Gynecol Endocrinol. 2009;25:60–6.
Eldar-geva T, Zylber-Haran E, Babayof R, Halevy-Shalem T, Ben-Chetrit A, Tsafrir A, et al. Similar Outcome for Cryopreserved Embryo Transfer Following GnRH-Antagonist / GnRH- Agonist , GnRH-Antagonist/HCG or Long Protocol Ovarian Stimulation. Reprod BioMed Online. 2007;14:148–54.
Griesinger G, Kolibianakis EM, Papanikolaou EG, Diedrich K, Van Steirteghem A, Devroey P, et al. Triggering of Final Oocyte Maturation with Gonadotropin-Releasing Hormone Agonist or Human Chorionic Gonadotropin. Live Birth after Frozen-Thawed Embryo Replacement Cycles. Fertil Steril. 2007;88:616–21.
Griesinger G, Berndt H, Schultz L, Depenbusch M, Schultze-Mosgau A. Cumulative Live Birth Rates after GnRH-Agonist Triggering of Final Oocyte Maturation in Patients at Risk of OHSS : A Prospective , Clinical Cohort Study. Eur J Obstet Gynecol. 2010;149:190–4.
Melo M, Busso CE, Beliver J, Alama P, Garrido N, Meseguer M, et al. GnRH Agonist versus Recombinant HCG in an Oocyte Donation Programme: A Randomized, Prospective, Controlled, Assessor-Blind Study. Reprod BioMed Online. 2009;19:486–92.
Sismanoglu A, Tekin H, Erden HF, Ciray NH, Ulug U, Bahceci M. Ovulation Triggering with GnRH Agonist vs. HCG in the Same Egg Donor Population Undergoing Donor Oocyte Cycles with GnRH Antagonist: A Prospective Randomized Cross-over Trial. J Assist Reprod Genet. 2009;26:251–6.
Society for Assisted Reproductive Technology. SART National Summary Report. 2015.
Shapiro B, Daneshmand S, Garner F, Aguirre M, Hudson C. Freeze-all can be a suoerior therapy to fresh cycle in patients with prior fresh blastocyst implantation failure. Reprod Biomed Online. 2014;29:286–90.
Thorne J, Loza A, Kaye L, Nulsen J, Benadiva C, Grow D, et al. Euploidy rates between cycles triggered with gonadotropin-releasing hormone agonist and human chorionic gonadotropin. Fertil Steril. 2019;112:258–65.
Friedenthal J, Maxwell S, Munne S, Kramer Y, McCulloh D, McCaffrey C, et al. Next generation sequencing for preimplantation genetic screening improves pregnancy outcomes compared with array comparitive genomic hybridization in single thawed euploid embryo transfer cycles. Fertil Steril. 2018;104:627–32.
Fragouli E, McCaffrey C, Ravichandran K, Spath K, Grifo JA, Munne S, et al. Clinical implications of mitrochondrial DNA quantification on pregnancy outcomes: a blinded prospective non-selection study. Hum Reprod. 2017;32:2340–7.
Rosenbluth E, Shelton D, Wells L, Sparks A, Van Voorhis B. Human embryos secrete microRNAs into culture media--a potential biomarker for implantation. Fertil Steril. 2014;101:1493–500.
Capalbo A, Ubaldi F, Cimadomo D, Noli L, Khalaf Y, Farcomeni A, et al. MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment. Fertil Steril. 2016;105:225–35.
Krisher R, Schoolcraft W, Katz-Jaffe M. Omics as a window to view embryo viability. Fertil Steril. 2015;103:333–41.
Borgbo T, Povlsen B, Andersen C, Borup R, Humaidan P, Grondalh M. Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2013;100:994–1001.
Diluigi AJ, Engmann L, Schmidt DW, Benadiva CA, Nulsen JC. A Randomized Trial of Microdose Leuprolide Acetate Protocol versus Luteal Phase Ganirelix Protocol in Predicted Poor Responders. Fertil Steril. 2011;95:2531–3.
Johnston-MacAnanny EB, DiLuigi A, Engmann L, Maier D, Benadiva C, Nulsen J. Selection of first in vitro fertilization (IVF) cycle stimulation protocol for good prognosis patients: GnRH Antagonist vs. Agonist Protocols. J Reprod Med. 2011;56:12–6.
Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11:307–11.
Kaye L, Marsidi A, Rai P, Thorne J, Nulsen J, Engmann L, et al. Frozen Blastocyst Transfer Outcomes in Immediate versus Delayed Subsequent Cycles Following GnRH Agonist or HCG Triggers. J Assist Reprod Genet. 2018;35:669–75.
Irani M, O'Neill C, Palermo G, Xu K, Zhang C, Qin X, et al. Blastocyst development rate influences implantation and live birth rates of similarly graded euploid blastocysts. Fertil Steril. 2018;110:95–102.
Harton GL, Munné S, Surrey M, Grifo J, Kaplan B, McCulloh DH, et al. Diminished Effect of Maternal Age on Implantation after Preimplantation Genetic Diagnosis with Array Comparative Genomic Hybridization. Fertil Steril. 2013;100:1695–703.
Lee HL, McCulloh DH, Hodes-Wertz B, Adler A, McCaffrey C, Grifo JA. In Vitro Fertilization with Preimplantation Genetic Screening Improves Implantation and Live Birth in Women Age 40 through 43. J Assist Reprod Genet. 2015;32:435–44.
Kang HJ, Melnick AP, Stewart JD, Xu K, Rosenwaks Z. Preimplantation genetic screening: who benefits? Fertil Steril. 2016;106:597–602.
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Makhijani, R., Thorne, J., Bartels, C. et al. Pregnancy outcomes after frozen-thawed single euploid blastocyst transfer following IVF cycles using GNRH agonist or HCG trigger for final oocyte maturation. J Assist Reprod Genet 37, 611–617 (2020). https://doi.org/10.1007/s10815-019-01646-z
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DOI: https://doi.org/10.1007/s10815-019-01646-z