Skip to main content
SpringerLink
Log in

Does the Time of Starting Progesterone Luteal Support Affect Embryo Transfer in Long Agonist Protocol Downregulated ICSI Cycles? A Randomized Controlled Trial

  • Reproductive Endocrinology: Clinical Trials
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The aim of this study was to compare the effects of starting progesterone (P4) luteal support (LS) on day of egg retrieval (ER) or day of embryo transfer (ET) on the ratio of difficult ET and cycle outcome. This was a RCT (ClinicalTrials.gov Identifier: NCT03040830) carried out at Mansoura Integrated Fertility Center (MIFC), Mansoura, Egypt, from November 2015 to January 2017. A total of 171 eligible long agonist ICSI cases were randomly allocated on day of ER into group A (86) starting LS as daily IM 100 mg P4 on day of ER and group B (85) starting P4-LS on day of ET. Difficult ET was defined as blood on ET catheter and/or sounding or dilating the cervix. Primary outcome was the overall ratio of difficult ET and ratios on day 3 and 5 ET. Secondary outcome was the ongoing pregnancy rate (OPR) and implantation rate (IR). The results are presented as % for groups A and B respectively: overall difficult ET (44.1, 24.7) (p = 0.009); day 3 difficult ET (23.2, 24.4) (p = 0.45); day 5 difficult ET (62.7, 25.6) (p = 0.001); overall OPR (38.3, 44.7) (p = 0.43); day 3 ET OPR (41.8, 33.3) (p = 0.51); day 5 ET OPR (34.8, 57.5) (p = 0.048); overall IR (20.0, 22.5) (p = 0.62); day 3 ET IR (17.8, 13.4) (p = 0.44); day 5 ET IR (22, 34.1) (p = 0.09). In conclusion, starting P4 luteal support on egg retrieval day is associated with significantly higher ratio of difficult embryo transfer and lower ongoing pregnancy rate and tendency to lower IR in day 5 ET, so starting P4-LS on day of ET is recommended.

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

References

  1. Sallam HN. Embryo transfer: factors involved in optimizing the success. Curr Opin Obstet Gynecol. 2005;17:289–98.

    Article  Google Scholar 

  2. Mains L, Voorhis BJ. Optimizing the technique of embryo transfer. Fertil Steril. 2010;94:785–90.

    Article  Google Scholar 

  3. Candido T, Kimmo T, Leena T, Juha ST, Hannu M. The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy. Hum Reprod. 2002;17:2632.

    Article  Google Scholar 

  4. Ghanem ME, Ragab AE, Alboghdady LA, Helal AS, Bedairy MH, Bahlol IA, et al. Difficult embryo transfer (ET) components and cycle outcome. Which is more harmful? Middle East Fertil Soc J. 2016;21:114–9.

    Article  Google Scholar 

  5. Beckers NG, Macklon NS, Eijkemans MJ, Ludwig M, Felberbaum RE, Diedrich K, et al. 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. 2003;88:4186–92.

    Article  CAS  Google Scholar 

  6. Hill MJ, Whitcomb BW, Lewis TD, Wu M, Terry N, DeCherney AH, et al. Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis. Fertil Steril. 2013;100:1373–80.

    Article  CAS  Google Scholar 

  7. Van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010;16:577–89.

    Article  Google Scholar 

  8. Senciboy DN, Sharpe-Timms KL. Progesterone affects the cervix prior to embryo transfer. Fertil Steril. 2001;76:S220–1.

    Article  Google Scholar 

  9. Mochtar MH, Van Wely M, Van der Veen F. Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles. Hum Reprod. 2006;21:905–8.

    Article  CAS  Google Scholar 

  10. Connell DO, Jennifer M, Szatkowski BS, Terryb N, DeCherney AH, Propst AM, et al. Timing luteal support in ART: a systematic review F & S 19112 revision non-highlighted. Fertil Steril. 2015;103:939–46.

    Article  Google Scholar 

  11. Tur-Kaspa I, Yuval Y, Bider D, Levron J, Shulman A, Dor J. Difficult or repeated sequential embryo transfers do not adversely affect in-vitro fertilization pregnancy rates or outcome. Hum Reprod. 1998;13(9):2452–5.

    Article  CAS  Google Scholar 

  12. Burke LM, Davenport AT, Russell GB, Deaton JL. Predictors of success after embryo transfer: experience from a single provider. Am J Obstet Gynecol. 2000;82(5):1001–4.

    Article  Google Scholar 

  13. Adrienne B, Neithardt AB, Segars JH, Hennessy S, James AN, Mckeeby JL. Embryo after loading: a refinement in embryo transfer technique that may increase clinical pregnancy. Fertil Steril. 2005;83:710–4.

    Article  Google Scholar 

  14. Ghanem ME, Sadek EE, Elboghdady LA, Helal AS, Gamal A, Eldiasty A, et al. The effect of luteal phase support protocol on cycle outcome and luteal phase hormone profile in long agonist protocol intracytoplasmic sperm injection cycles: a randomized clinical trial. Fertil Steril. 2009;92:486–93.

    Article  CAS  Google Scholar 

  15. Hill GA, Freeman M, Bastias MC, Rogers BJ, Herbert CM, Osteen KG, et al. The influence of oocyte maturity and embryo quality on pregnancy rate in a program for in vitro fertilization-embryo transfer. Fertil Steril. 1989;52:801–6.

    Article  CAS  Google Scholar 

  16. ESHRE Guideline Group on Good Practice in IVF Labs, De los Santos MJ, Apter S, Coticchio G, Debrock S, Lundin K, et al. Hum Reprod. 2016;31(4):685–6.

    Article  Google Scholar 

  17. Practice Committee of the American Society for Reproductive Medicine. Performing the embryo transfer: a guideline. Fertil Steril. 2017;107:882–96.

    Article  Google Scholar 

  18. Bhattacharyya J, Singh S, Das MC, Jayaprakasan K. In: Nagy ZP, Varghese AC, Agarwal A, editors. Embryo transfer: techniques and troubleshooting (in) in vitro fertilization, vol. ch.61: Springer Nature Switzerland AG; 2019. p. 735.

  19. Sohn SH, Penzias AS, Emmi AM, Dubey AK, Layman LC, Reindollar RH, et al. Administration of progesterone before oocyte retrieval negatively affects the implantation rate. Fertil Steril. 1999;71:11–4.

    Article  CAS  Google Scholar 

  20. Williams SC, Oehninger S, Gibbons WE, Van Cleave WC, Muasher SJ. Delaying the initiation of progesterone supplementation results in decreased pregnancy rates after in vitro fertilization: a randomized, prospective study. Fertil Steril. 2001;76:1140–3.

    Article  CAS  Google Scholar 

  21. Baruffi R, Mauri AL, Petersen CG, Felipe V, Franco JG. Effects of vaginal progesterone administration starting on the day of oocyte retrieval on pregnancy rates. J Assist Reprod Genet. 2003;20:517–20.

    Article  Google Scholar 

  22. Gao J, Gu F, Miao B, Chen M, et al. Effect of the initiation of progesterone supplementation in in vitro fertilization–embryo transfer outcomes: a prospective randomized controlled trial. Fertil Steril. 2018;109:97–103.

    Article  CAS  Google Scholar 

  23. Moghissi KS, Syner FN, Evans TN. A composite picture of the menstrual cycle. Am J Obstet Gynecol. 1972;114:405–18.

    Article  CAS  Google Scholar 

  24. Yding Andersen C, Vilbour AK. Improving the luteal phase after ovarian stimulation: reviewing new options. Reprod BioMed Online. 2014;28:552–9.

    Article  CAS  Google Scholar 

  25. Chwalisz K, Shi Shao-Qing Esch A, Elger W Cervical softening in non-pregnant guinea pigs. Acta Endocrinol 1988; [Suppl J: 194–195 (abstract). 117.

  26. Kniss DA, Iams JD. Regulation of parturition update. Endocrine and paracrine effectors of term and preterm labor. Clin Perinatol. 1998;25(4):819–36.

    Article  CAS  Google Scholar 

  27. Chwalisz K, Garfield RE, editors. Basic mechanisms controlling term and preterm birth ©. Berlin: Springer-Verlag; 1994.

    Google Scholar 

  28. Mansour R, Aboulghar M, Serour G. Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate inhuman in vitro fertilization. Fertil Steril. 1990;54:678–81.

    Article  CAS  Google Scholar 

  29. Noyes N, Licciardi F, Grifo J, Krey L, Berkeley A. In vitro fertilization outcome relative to embryo transfer difficulty: a novel approach to the forbidding cervix. Fertil Steril. 1999;72:261–5.

    Article  CAS  Google Scholar 

  30. Spandorfer SD, Goldstein J, Navarro J, Veeck L, Davis OK, Rosenwaks Z. Difficult embryo transfer has a negative impact on the outcome of in vitro fertilization. Fertil Steril. 2003;79:654–5.

    Article  Google Scholar 

  31. Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril. 2012;97:1321–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We are greatly indebted to Professors M. A. Emam, L. A. Al Boghdady, A. S. Helal, and A. Elmetwally and all the staff of Mansoura Integrated Fertility Centre for their valuable contribution in conducting this work.

Author information

Authors and Affiliations

  1. Mansoura Integrated Fertility Centre (MIFC), Mansoura, Egypt

    M. E. Ghanem, M.H. Bedairy & Ibrahim A Albahlol

  2. Department of Obstetrics and Gynecology, College of Medicine, Mansoura University, Mansoura, Egypt

    M.H. Bedairy & Ibrahim A Albahlol

  3. Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    A. Shaaban

  4. Department of Obstetrics and Gynecology, College of Medicine, Jouf University, Sakaka, Saudi Arabia

    Ibrahim A Albahlol

Authors
  1. M. E. Ghanem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M.H. Bedairy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Shaaban
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ibrahim A Albahlol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ibrahim A Albahlol.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Patient Consent

All participants were informed and written consent was taken prior to contribution.

Ethical Approval

The study was supervised and approved by the ethical committee of the Mansoura Integrated Fertility Centre.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghanem, M.E., Bedairy, M., Shaaban, A. et al. Does the Time of Starting Progesterone Luteal Support Affect Embryo Transfer in Long Agonist Protocol Downregulated ICSI Cycles? A Randomized Controlled Trial. Reprod. Sci. 28, 897–903 (2021). https://doi.org/10.1007/s43032-020-00309-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00309-0

Keywords

Search

Navigation