Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

A Comparative Analysis of Outcomes Between Two Different Intramuscular Progesterone Preparations in Women Undergoing Frozen Embryo Transfer Cycles

Authors
1 The Centre for Reproductive and Genetic Health, London, UK
2 Gilbert and Rose-Marie Chagoury Health Sciences Center, The Lebanese American University, Beirut, Lebanon
Abstract
Background: The purpose of the current study was to assess if luteal support with intramuscular (IM) 17 alpha-hydroxyprogesterone caproate (17-OHPC) (Lentogest, IBSA, Italy) improves the pregnancy outcome in comparison to natural intramuscu-lar progesterone (Prontogest, AMSA, Italy) when administered to recipients in a frozen embryo transfer cycle. Methods: A retrospective comparative study was performed to evaluate outcomes between two different intramuscular regimens used for luteal support in frozen embryo transfer cycles in patients underwent autologous in vitro fertilization (IVF) cycles (896 IVF cycles) and intracytoplasmic sperm injection (ICSI) who had a blastocyst transfer from February 2014 to March 2017 at the Centre for Reproductive and Genetic Health (CRGH) in London. Results: The live birth rates were significantly lower for the IM natural progesterone group when compared to 17-OHPC group (41.8% vs. 50.9%, adjusted OR of 0.63 (0.31-0.91)). The miscarriage rates were significantly lower in the 17-OHPC group compared to the IM natural progesterone group (14.5% vs. 19.2%, OR of 1.5, 95% CI of 1.13-2.11). The gestational age at birth and birth weight were similar in both groups (p=0.297 and p=0.966, respectively). Conclusion: It is known that both intramuscular and vaginal progesterone preparations are the standard of care for luteal phase support in women having frozen embryo transfer cycles. However, there is no clear scientific consensus regarding the optimal luteal support. In this study, it was revealed that live birth rates are significantly higher in women who received artificial progesterone compared to women who received natural progesterone in frozen embryo transfer cycles.
Keywords

  1. Trouson A, Moher L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature. 1983;305(5936):707-9.
  2. Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, et al. Cryopreservation of human embryos by vitrifaication or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008;90(1):186-93.
  3. Roque M, Lattes K, Serra S, Solà I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99(1):156-62.
  4. Li Z, Wang YA, Ledger W, Edgar DH, Sullivan EA. Clinical outcomes following cryopreservation of blastocysts by vitrification or slow freezing: a population-based cohort study. Hum Reprod. 2014;29(12):2794-801.
  5. Özgür K, Berkkanoğlu M, Bulut H, Isikli A, Coetzee K. Higher clinical pregnancy rates from frozen-thawed blastocyst transfers compared to fresh blastocyst transfers: a retrospective matched-cohort study. J Assist Reprod Genet. 2015;32(10):1483-90.
  6. Gerris J, De Neubourg D, De Sutter P, Van Royen E, Mangelschots K, Vercruyssen M. Cryopreservation as a tool to reduce multiple birth. Reprod Biomed Online. 2003;7(3):286-94.
  7. Devine K, Connell MT, Richter KS, Ramirez CI, Levens ED, DeCherney AH, et al. Single vitrified blastocyst transfer maximizes liveborn children per embryo while minimizing preterm birth. Fertil Steril. 2015;103(6):1454-60.e1.
  8. Ishihara O, Araki R, Kuwahara A, Itakura A, Saito H, Adamson GD. Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. Fertil Steril. 2014;101(1):128-33.
  9. Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98(2):368-77.e1-9.
  10. Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Freeze-all policy: fresh vs. frozen-thawed embryo transfer. Fertil Steril. 2015;103(5):1190-3.
  11. Maheshwari A, Bhattacharya S. Elective frozen replacement cycles for all: ready for prime time? Hum Reprod. 2013;28(1):6-9.
  12. Casper RF, Yanushpolsky EH. Optimal endometrial preparation for frozen embryo transfer cycles: window of implantation and progesterone support. Fertil Steril. 2016;105(4):867-72.
  13. DiLuigi AJ, Nulsen JC. Effects of gonadotropin-releasing hormone agonists and antagonists on luteal function. Curr Opin Obstet Gynecol. 2007;19(3):258-65.
  14. Frydman R, Testart J, Giacomini P, Imbert MC, Martin E, Nahoul K. Hormonal and histological study of the luteal phase in women following aspiration of the preovulatory follicle. Fertil Steril. 1982;38(3):312-7.
  15. Boynukalin FK, Gultomruk M, Turgut E, Demir B, Findikli N, Serdarogullari M, et al. Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers. Reprod Biol Endocrinol. 2019;17(1):102.
  16. Beltsos AN, Sanchez MD, Doody KJ, Bush MR, Domar AD, Collins MG. Patients' administration preferences: progesterone vaginal insert (Endometrin®) compared to intramuscular progesterone for Luteal phase support. Reprod Health. 2014;11:78.
  17. Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014;29(8):1706-11.
  18. Leonard PH, Hokenstad AN, Khan Z, Jensen JR, Stewart EA, Coddington CC. Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a cohort. J Reprod Med. 2015;60(3-4):103-8.
  19. Kaser DJ, Ginsburg ES, Missmer SA, Correia KF, Racowsky C. Intramuscular progesterone versus 8% Crinone vaginal gel for luteal phase support for day 3 cryopreserved embryo transfer. Fertil Steril. 2012;98(6):1464-9.
  20. Casper RF. Luteal phase support for frozen embryo transfer cycles: intramuscular or vaginal progesterone. Fertil Steril. 2014;101(3):627-8.
  21. Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012;206(5):376-86.
  22. Costabile L, Gerli S, Manna C, Rossetti D, Di Renzo GC, Unfer V. A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2001;76(2):394-6.
  23. Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril. 1998;69(1):96-101.
  24. Jobanputra K, Toner JP, Denoncourt R, Gibbons WE. Crinone 8% (90 mg) given once daily for progesterone support therapy in donor egg cycles. Fertil Steril. 1999;72(6):980-4.
  25. Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril. 2018;109(2):266-75.
  26. Zaman AY, Coskun S, Alsanie AA, Awartani KA. Intramuscular progesterone (Gestone) versus vaginal progesterone suppository (Cyclogest) for luteal phase support in cycles of in vitro fertilization–embryo transfer: patient preference and drug efficacy. Fertil Res Pract. 2017;3:17.
  27. Travanty MN, Calawa B, Shalaby WS, Jozwiakowski MJ, Haraldsen KB. Development and usability of a new subcutaneous auto-injector device to administer hydroxyprogesterone caproate to reduce the risk of recurrent preterm birth. Med Devices (Auckl). 2018;11:241-52.
  28. Northen AT, Norman GS, Anderson K, Moseley L, DiVito M, Cotroneo M, et al. Follow-up of children exposed in utero to 17 α-hydroxyprogesterone caproate compared with placebo. Obstet Gynecol. 2007;110(4):865-72.
  29. Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN, et al. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins. Am J Obstet Gynecol. 2007;197(6):599.e1-7.
  30. Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013;99(1):174-8.e1.