Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Subcutaneous progesterone versus vaginal progesterone for luteal phase support in in vitro fertilization: A retrospective analysis from daily clinical practice

  • Schutt, Marcel (Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital Giessen and Marburg, Philipps University of Marburg) ;
  • Nguyen, The Duy (Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital Giessen and Marburg, Philipps University of Marburg) ;
  • Kalff-Suske, Martha (Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital Giessen and Marburg, Philipps University of Marburg) ;
  • Wagner, Uwe (Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital Giessen and Marburg, Philipps University of Marburg) ;
  • Macharey, Georg (Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki) ;
  • Ziller, Volker (Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital Giessen and Marburg, Philipps University of Marburg)
  • Received : 2020.08.12
  • Accepted : 2021.04.22
  • Published : 2021.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: Progesterone application for luteal phase support is a well-established concept in in vitro fertilization (IVF) treatment. Water-soluble subcutaneous progesterone injections have shown pregnancy rates equivalent to those observed in patients receiving vaginal administration in randomized controlled trials. Our study aimed to investigate whether the results from those pivotal trials could be reproduced in daily clinical practice in an unselected patient population. Methods: In this retrospective cohort study in non-standardized daily clinical practice, we compared 273 IVF cycles from 195 women undergoing IVF at our center for luteal phase support with vaginal administration of 200 mg of micronized progesterone three times daily or subcutaneous injection of 25 mg of progesterone per day. Results: Various patient characteristics including age, weight, height, number of oocytes, and body mass index were similar between both groups. We observed no significant differences in the clinical pregnancy rate (CPR) per treatment cycle between the subcutaneous (39.9%) and vaginal group (36.5%) (p=0.630). Covariate analysis showed significant correlations of the number of transferred embryos and the total dosage of stimulation medication with the CPR. However, after adjustment of the CPR for these covariates using a regression model, no significant difference was observed between the two groups (odds ratio, 0.956; 95% confidence interval, 0.512-1.786; p=0.888). Conclusion: In agreement with randomized controlled trials in study populations with strict selection criteria, our study determined that subcutaneous progesterone was equally effective as vaginally applied progesterone in daily clinical practice in an unselected patient population.

Keywords

Acknowledgement

We thank Dr. Brandon Greene (Institute of Medical Biometry and Epidemiology, Philipps University Marburg, Germany) for his support with the statistical analyses.

References

  1. Fatemi HM. The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online 2009;19 Suppl 4:4331. https://doi.org/10.1016/S1472-6483(10)61065-6
  2. Yanushpolsky EH. Luteal phase support in in vitro fertilization. Semin Reprod Med 2015;33:118-27. https://doi.org/10.1055/s-0035-1545363
  3. van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev 2011;(10):CD009154.
  4. Schwartz E, Bernard L, Ohl J, Bettahar K, Rongieres C, Lichtblau I, et al. Luteal phase progesterone supplementation following induced natural cycle frozen embryo transfer: a retrospective cohort study. J Gynecol Obstet Hum Reprod 2019;48:95-8. https://doi.org/10.1016/j.jogoh.2018.10.011
  5. Doblinger J, Cometti B, Trevisan S, Griesinger G. Subcutaneous progesterone is effective and safe for luteal phase support in IVF: an individual patient data meta-analysis of the phase III trials. PLoS One 2016;11:e0151388. https://doi.org/10.1371/journal.pone.0151388
  6. de Ziegler D, Sator M, Binelli D, Leuratti C, Cometti B, Bourgain C, et al. A randomized trial comparing the endometrial effects of daily subcutaneous administration of 25 mg and 50 mg progesterone in aqueous preparation. Fertil Steril 2013;100:860-6. https://doi.org/10.1016/j.fertnstert.2013.05.029
  7. Venturella R, Vaiarelli A, Buffo L, D'alessandro P, Colamaria S, Pedri S, et al. Progesterone for preparation of the endometrium for frozen-thawed blastocyst transfer in vitro fertilization cycles: a prospective study on patients' opinions on a new subcutaneous formulation. Gynecol Endocrinol 2018;34:766-71. https://doi.org/10.1080/09513590.2018.1451508
  8. Check JH. Luteal phase support in assisted reproductive technology treatment: focus on Endometrin(R) (progesterone) vaginal insert. Ther Clin Risk Manag 2009;5:403-7. https://doi.org/10.2147/TCRM.S4192
  9. Vaisbuch E, Leong M, Shoham Z. Progesterone support in IVF: is evidence-based medicine translated to clinical practice? A worldwide web-based survey. Reprod Biomed Online 2012;25:139-45. https://doi.org/10.1016/j.rbmo.2012.04.005
  10. Penzias AS. Luteal phase support. Fertil Steril 2002;77:318-23. https://doi.org/10.1016/S0015-0282(01)02961-2
  11. Lockwood G, Griesinger G, Cometti B; 13 European Centers. Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study. Fertil Steril 2014;101:112-9.e3. https://doi.org/10.1016/j.fertnstert.2013.09.010
  12. Baker VL, Jones CA, Doody K, Foulk R, Yee B, Adamson GD, et al. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization. Hum Reprod 2014;29:2212-20. https://doi.org/10.1093/humrep/deu194
  13. Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod Biomed Online 2018;36:630-45. https://doi.org/10.1016/j.rbmo.2018.02.001
  14. Supramaniam PR, Mittal M, McVeigh E, Lim LN. The correlation between raised body mass index and assisted reproductive treatment outcomes: a systematic review and meta-analysis of the evidence. Reprod Health 2018;15:34. https://doi.org/10.1186/s12978-018-0481-z
  15. Yavuz A, Demirci O, Sozen H, Uludogan M. Predictive factors influencing pregnancy rates after intrauterine insemination. Iran J Reprod Med 2013;11:227-34.
  16. Gaskins AJ, Toth TL, Chavarro JE. Prepregnancy nutrition and early pregnancy outcomes. Curr Nutr Rep 2015;4:265-72. https://doi.org/10.1007/s13668-015-0127-5
  17. van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev 2015;2015:CD009154.