Subcutaneous progesterone versus vaginal progesterone for luteal-phase support in frozen-thawed embryo transfer: A cross-sectional study

Abstract

Background: Luteal-phase support is a complex and controversial issue in the field of reproductive management.


Objective: To compare the safety and efficacy of low-dose subcutaneous progesterone with the vaginal progesterone for luteal-phase support in patients undergoing rozenthawed embryo transfer.


Materials and Methods: In this cross-sectional study, information related to 77 women that had frozen-thawed embryo transfer was reviewed. The patients were divided into two groups based on the route of progesterone administration used as a luteal-phase support. When the endometrial thickness reached ≥ 8 mm, in one group progesterone (Prolutex) 25 mg/ daily subcutaneous and in another group, vaginal progesterone (Cyclogest®) 400 mg twice or (Endometrin®) 100 mg thrice daily, were administrated and continued until menstruation or in case of clinical pregnancy for 8 wk after the embryo transfer when the fetal heart activity was detected by ultrasonography.


Results: The patient’s characteristics were matched and there was no significant difference. The chemical and clinical pregnancy rate was higher in the vaginal progesterone group compared to the prolutex group, but statistically unnoticeable, (40% vs. 29.6%, p = 0.367) and (28% vs. 22.2%, p = 0.581), respectively. C


Conclusion: The findings of this study demonstrate that the new subcutaneous progesterone can be a good alternative for intramuscular progesterone in women that dislike and do not accept vaginal formulations as luteal-phase support in assisted reproductive technology.


Key words: Progesterone, Subcutaneous, Vaginal, Pregnancy.

References
[1] Kalem Z, Kalem MN, Gürgan T. Methods for endometrial preparation in frozen-thawed embryo transfer cycles. J Turk Ger Gynecol Assoc 2016; 17: 168–172.

[2] Jiang L, Luo Zh-Y, Hao G-M, Gao B-L. Effects of intramuscular and vaginal progesterone supplementation on frozen-thawed embryo transfer. Sci Rep 2019; 9: 15264.

[3] 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.

[4] Cometti B. Pharmaceutical and clinical development of a novel progesterone formulation. Acta Obstet Gynecol Scand 2015; 94 (Suppl.): 28–37.

[5] 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: 766–771.

[6] Doblinger J, Cometti B, Trevisan S, Griesinger G. Subcutaneous progesterone is effective and safe for luteal phase support in IVF: An individual patient data metaanalysis of the phase III trials. Plos One 2016; 11: e0151388.

[7] Lockwood G, Griesinger G, Cometti B, De Placido G, Alviggi C, Ranieri A, et al. Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: A noninferiority randomized controlled study. Fertil Steril 2014; 101: 112–119.

[8] Sator M, Radicioni M, Cometti B, Loprete L, Leuratti C, Schmidl D, et al. Pharmacokinetics and safety profile of a novel progesterone aqueous formulation administered by the s.c. route. Gynecol Endocrinol 2013; 29: 205–208.

[9] Aboulghar MA, Amin YM, Al-Inany HG, Aboulghar MM, Mourad LM, Serour GI, et al. Prospective randomized study comparing luteal phase support for ICSI patients up to the first ultrasound compared with an additional three weeks. Hum Reprod 2008; 23: 857–862.

[10] Sharma S, Majumdar A. Determining the optimal duration of progesterone supplementation prior to transfer of cryopreserved embryos and its impact on implantation and pregnancy rates: A pilot study. Int J Reprod Med 2016; 2016: 7128485.

[11] 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: 2212–2220.

[12] Khan N, Richter KS, Newsome TL, Blake EJ, Yankov V. Matched-samples comparison of intramuscular versus vaginal progesterone for luteal phase support after in vitro fertilization and embryo transfer. Fertil Steril 2009; 91: 2445–2450.

[13] Silverberg KM, Vaughn TC, Hansard LJ, Burger NZ, Minter T. Vaginal (Crinone 8%) gel vs. intramuscular progesterone in oil for luteal phase support in in vitro fertilization: A large prospective trial. Fertil Steril 2012; 97: 344-348.

[14] 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.

[15] Cicinelli E, Borraccino V, Petruzzi D, Mazzotta N, Cerundolo ML, Schönauer LM. Pharmacokinetics and endometrial effects of the vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril 1996; 65: 860–862.

[16] Propst AM, Hill JA, Ginsburg ES, Hurwitz S, Politch J, Yanushpolsky EH. A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles. Fertil Steril 2001; 76: 1144–1149.

[17] 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: 860–866.