Skip to main content
SpringerLink
Log in

Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone: prospective randomized study

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To compare pregnancy rates in GnRH-antagonist cycles triggered with hCG after luteal phase support with intranasal GnRH-agonist as sole luteal phase support versus standard vaginal progesterone preparation.

Methods

Prospective randomized controlled study of patients who underwent antagonist-based IVF cycles triggered with hCG at university-affiliated tertiary medical center between 2020 and 2022. Patients meeting the inclusion criteria were randomly assigned to either intranasal GnRH-agonist or vaginal progesterone for luteal phase support. Pregnancy rates were the main outcome compared between the two study groups.

Results

A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone, respectively, as sole luteal phase support. A significantly higher pregnancy rate was demonstrated in the GnRH-agonist group compared with the progesterone group. After adjustment of several potential confounders such as age, body mass index, past obstetric history, number of IVF cycles, oocyte retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4–8.3). Ovarian hyperstimulation syndrome rates were similar between the groups.

Conclusions

This prospective study suggests that nasal GnRH-agonist for luteal phase support is associated with higher pregnancy rates compared with standard progesterone support in an antagonist-based protocol triggered with hCG, while maintaining a similar safety profile.

Trial registration

Clinicaltrials.gov NCT05484193. Date of registration: August 02 2022. The trial was retrospectively registered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The data that support the findings of this study cannot be shared openly in order to protect study participant privacy. The data are available from the corresponding author upon reasonable request.

References

  1. Beckers NGM, Macklon NS, Eijkemans MJ et al (2003) Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and gnrh antagonist cotreatment. J Clin Endocrinol Metab 88:4186–4192. https://doi.org/10.1210/jc.2002-021953

    Article  CAS  PubMed  Google Scholar 

  2. Pritts EA, Atwood AK (2002) Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod 17(9):2287–2299. https://doi.org/10.1093/humrep/17.9.2287

    Article  CAS  PubMed  Google Scholar 

  3. van der Linden M, Buckingham K, Farquhar C et al (2015) Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev 2015(7):CD009154. https://doi.org/10.1002/14651858.CD009154.pub3

    Article  PubMed  PubMed Central  Google Scholar 

  4. Golan’ A, Ron-El R, Herman A et al (1990) Fetal outcome following inadvertent administration of long-acting DTRP 6 GnRH microcapsules during pregnancy: a case report. Hum Reprod 5(1):123–124. https://doi.org/10.1093/oxfordjournals.humrep.a137031

    Article  PubMed  Google Scholar 

  5. Isherwood PJ, Ibrahim ZHZ, Matson PL et al (1990) Endocrine changes in women conceiving during treatment with an LHRH agonist. Hum Reprod 5(4):409–412. https://doi.org/10.1093/oxfordjournals.humrep.a137112

    Article  CAS  PubMed  Google Scholar 

  6. Jackson AE, Curtis P, Amso N, Shaw RW (1992) Exposure to LHRH agonists in early pregnancy following the commencement of mid-luteal buserelin for IVF stimulation. Human Reprod. https://doi.org/10.1093/oxfordjournals.humrep.a137830

    Article  Google Scholar 

  7. Elefant E, Biour B, Blumberg-Tick J et al (1995) Administration of a gonadotropin-releasing hormone agonist during pregnancy: follow-up of 28 pregnancies exposed to triptoreline. Fertil Steril. https://doi.org/10.1016/S0015-0282(16)57557-8

    Article  PubMed  Google Scholar 

  8. Balasch J, Martinez F, Jove I et al (1993) Inadvertent gonadotrophin-releasing hormone agonist (GiiRHa) administration in the luteal phase may improve fecundity in in-vitro fertilization patients. Human Reprod. https://doi.org/10.1093/oxfordjournals.humrep.a138210

    Article  Google Scholar 

  9. Wilshire GB, Emmi AM, Gagliardi CC, Weiss G (1993) Gonadotropin-releasing hormone agonist administration in early human pregnancy is associated with normal outcomes. Fertil Steril 60:980–983. https://doi.org/10.1016/S0015-0282(16)56396-1

    Article  CAS  PubMed  Google Scholar 

  10. Weissman A, Shoham Z (1993) Favourable pregnancy outcome after administration of a long-acting gonadotrophin-releasing hormone agonist in the mid-luteal phase. Human Reprod. https://doi.org/10.1093/oxfordjournals.humrep.a138079

    Article  Google Scholar 

  11. Young DC, Snabes MC, Poindexter AN (1993) GnRH agonist exposure during the first trimester of pregnancy. Obstet Gynecol 81:587–589

    CAS  PubMed  Google Scholar 

  12. Chardonnens D, Sylvan K, Walker D et al (1998) Triptorelin acetate administration in early pregnancy: case reports and review of the literature. Eur J Obst Gynecol Reprod Biol 80:143–149. https://doi.org/10.1016/S0301-2115(98)00109-2

    Article  CAS  Google Scholar 

  13. Gartner B, Moreno C, Marinaro A et al (1997) Case Report: Accidental exposure to daily long-acting gonadotrophinreleasing hormone analogue administration and pregnancy in an in-vitro fertilization cycle. Hum Reprod 12:2557–2559. https://doi.org/10.1093/HUMREP/12.11.2557

    Article  CAS  PubMed  Google Scholar 

  14. Smitz J, Camus M, Devroey P et al (1991) CLINICAL REPORTThe influence of inadvertent intranasal buserelin administration in early pregnancy. Hum Reprod 6:290–293. https://doi.org/10.1093/OXFORDJOURNALS.HUMREP.A137324

    Article  CAS  PubMed  Google Scholar 

  15. Tesarik J, Hazout A, Mendoza C (2004) Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum Reprod 19:1176–1180. https://doi.org/10.1093/humrep/deh235

    Article  CAS  PubMed  Google Scholar 

  16. Liu Y, Wu Y, Pan Z et al (2022) Single-dose versus multiple-dose gnrh agonist for luteal-phase support in women undergoing IVF/ICSI cycles: a network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 13:1. https://doi.org/10.3389/FENDO.2022.802688

    Article  Google Scholar 

  17. Tesarik J, Hazout A, Mendoza-Tesarik R et al (2006) Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum Reprod 21:2572–2579. https://doi.org/10.1093/humrep/del173

    Article  CAS  PubMed  Google Scholar 

  18. Jam K, van der LindenM MM (2016) Luteal phase support for assisted reproduction cycles (Review) van der Luteal phase support for assisted reproduction cycles (Review). Cochrane Lib Coch Datab Syst Rev. https://doi.org/10.1002/14651858.CD009154.pub3

    Article  Google Scholar 

  19. Oliveira JBA, Baruffi R, Petersen CG et al (2010) Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis. Reprod Biol Endocrinol. https://doi.org/10.1186/1477-7827-8-107

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pirard C, Donnez J, Loumaye E (2005) GnRH agonist as novel luteal support: Results of a randomized, parallel group, feasibility study using intranasal administration of buserelin. Hum Reprod 20:1798–1804. https://doi.org/10.1093/humrep/deh830

    Article  CAS  PubMed  Google Scholar 

  21. Pirard C, Donnez J, Loumaye E (2006) GnRH agonist as luteal phase support in assisted reproduction technique cycles: Results of a pilot study. Hum Reprod 21:1894–1900. https://doi.org/10.1093/humrep/del072

    Article  CAS  PubMed  Google Scholar 

  22. Pirard C, Loumaye E, Laurent P, Wyns C (2015) Contribution to more patient-friendly art treatment: Efficacy of continuous low-dose GnRH agonist as the only luteal support—Results of a prospective, randomized, comparative study. Int J Endocrinol. https://doi.org/10.1155/2015/727569

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bar Hava I, Blueshtein M, Ganer Herman H et al (2017) Gonadotropin-releasing hormone analogue as sole luteal support in antagonist-based assisted reproductive technology cycles. Fertil Steril 107:130-135.e1. https://doi.org/10.1016/J.FERTNSTERT.2016.10.011

    Article  CAS  PubMed  Google Scholar 

  24. Salehpour S, Nazari L, Hosseini S et al (2021) Efficacy of daily GnRH agonist for luteal phase support following GnRH agonist triggered ICSI cycles versus conventional strategy: a randomized controlled trial. JBRA Assist Reprod 25:368–372. https://doi.org/10.5935/1518-0557.20200077

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang R, Lin S, Wang Y et al (2017) Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: a systematic review and meta-analysis. PLoS ONE. https://doi.org/10.1371/JOURNAL.PONE.0175985

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yang J, Zhang X, Ding X et al (2021) Cumulative live birth rates between GnRH-agonist long and GnRH-antagonist protocol in one ART cycle when all embryos transferred: real-word data of 18,853 women from China. Reprod Biol Endocrinol. https://doi.org/10.1186/S12958-021-00814-0

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bhurke AS, Bagchi IC, Bagchi MK (2016) Progesterone-regulated endometrial factors controlling implantation. Am J Reprod Immunol 75:237–245. https://doi.org/10.1111/AJI.12473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bar-Hava I, Mizrachi Y, Karfunkel-Doron D et al (2016) Intranasal gonadotropin-releasing hormone agonist (GnRHa) for luteal-phase support following GnRHa triggering, a novel approach to avoid ovarian hyperstimulation syndrome in high responders. Fertil Steril 106:330–333. https://doi.org/10.1016/J.FERTNSTERT.2016.04.004

    Article  CAS  PubMed  Google Scholar 

  29. Benmachiche A, Benbouhedja S, Zoghmar A et al (2017) Impact of mid-luteal phase GnRH agonist administration on reproductive outcomes in GnRH agonist-triggered cycles: a randomized controlled trial. Front Endocrinol (Lausanne) 8:124. https://doi.org/10.3389/FENDO.2017.00124/BIBTEX

    Article  PubMed  Google Scholar 

  30. Yildiz GA, Şükür YE, Ateş C, Aytaç R (2014) The addition of gonadotrophin releasing hormone agonist to routine luteal phase support in intracytoplasmic sperm injection and embryo transfer cycles: A randomized clinical trial. Eur J Obst Gynecol Reprod Biol 182:66–70. https://doi.org/10.1016/J.EJOGRB.2014.08.026

    Article  CAS  Google Scholar 

  31. Friedler S, Grin L (2019) Luteal phase support with GnRH agonist does not eliminate the risk for ovarian hyperstimulation syndrome. Gynecol Endocrinol 35:368–369. https://doi.org/10.1080/09513590.2018.1548591

    Article  CAS  PubMed  Google Scholar 

  32. Maggi R, Cariboni AM, Marelli MM et al (2020) GnRH and GnRH receptors in the pathophysiology of the human female reproductive system. Hum Reprod Update 22:358–381. https://doi.org/10.1093/HUMUPD/DMV059

    Article  Google Scholar 

  33. Marcus S, Ledger W (2001) Efficacy and safety of long-acting GnRH agonists in in vitro fertilization and embryo transfer. Hum Fertil 4:85–93

    Article  CAS  Google Scholar 

  34. Wilcox AJ, Weinberg CR, O’Connor JF et al (2010) Incidence of early loss of pregnancy. N Engl J Med. https://doi.org/10.1056/NEJM198807283190401

    Article  Google Scholar 

  35. Dolk H, Loane M, Garne E (2010) The prevalence of congenital anomalies in europe. Adv Exp Med Biol 686:349–364. https://doi.org/10.1007/978-90-481-9485-8_20

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Prof. Talia Eldar-Geva for help in designing the study and recruiting patients. We also thank Dr. Michael Gal, Dr. Naama Srebnik, Dr. Karen Kochan, Dr. Jordana Hyman, Dr. Einat Zivi and Dr. Avi Tsafrir for their assistance in patients recruitment. We also thank Tali Bdolah-Abram for assistance with the statistical analysis.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Author notes

  1. Eadit Buhbut and Rinad Nabulsi have contributed equally to this work.

Authors and Affiliations

  1. IVF and Infertility Unit, Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, affiliated with the Faculty of Medicine, Hebrew University of Jerusalem, Shmu’el Bait St 12, 9103102, Jerusalem, Israel

    Eadit Buhbut, Rinad Nabulsi, Gilad Avigdor & Ido Ben-Ami

Authors
  1. Eadit Buhbut
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rinad Nabulsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gilad Avigdor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ido Ben-Ami
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study conception and design was performed by EB, RN, IB-A. Patient recruitment was performed by EB, RN, IB-A. Material preparation, data collection and analysis were performed by all authors. The first draft of the manuscript was written by GA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Eadit Buhbut.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Shaare Zedek Medical Center (Date: May 11, 2020/ number: 0026-20-SZMC).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buhbut, E., Nabulsi, R., Avigdor, G. et al. Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone: prospective randomized study. Arch Gynecol Obstet 308, 255–263 (2023). https://doi.org/10.1007/s00404-023-07017-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-023-07017-5

Keywords

Search

Navigation