A randomized comparison of the efficacy, side effects and patient convenience between vaginal and rectal administration of Cyclogest® when used for luteal phase support in ICSI treatment

Purpose This study compares the efficacy, side effects and patient convenience of vaginal and rectal routes of administration of progesterone suppositories (Cyclogest) when used for luteal phase support during in vitro fertilization cycles, through the use of antagonist protocols.

147 patients who underwent intra-cytoplasmic sperm injection cycle were randomized on the day of the embryo transfer (ET) by a computer-generated randomization program to receive 400 mg of Cyclogest either vaginally or rectally twice daily for up to 8 weeks. A pregnancy test was conducted 2 weeks after embryo transfer. If the pregnancy test was negative, the application was discontinued. On day 14th after embryo transfer, patient’s acceptability and side effects were assessed using a questionnaire which was given to the patients on the day of ET prior to performing the pregnancy test. The clinical pregnancy rate at the 8th week of gestation and the level of luteal progesterone were evaluated.

There were no substantial differences in the demographics or other characteristics between the two groups. There were no significant differences in serum P concentration 6 days after ET, the clinical pregnancy and abortion rates. The difficulty of administration route, the discomforts experienced following administration, and the proportion leaking out on the 14th day were similar between the two groups. Significantly more patients administering the medication per vagina had perineal irritation (21.3 vs. 2.2 %). The prevalence of tenesmus (35.1 vs. 21.1 %) and rectal itching (26.7 vs. 2.8 %) were significantly more in rectal route.

This study demonstrates that the efficacy of Cyclogest is similar when administered via both the vaginal and rectal routes. Although their side effects differ, the ease of administration for patients and their preference are similar. Similar content being viewed by others

Hubayter ZR, Muasher SJ (2008) Luteal supplementation in vitro fertilization: more questions than answers. Fertil Steril 89:749–758 Dal Prato L, Borini A (2005) Use of antagonists in ovarian stimulation protocols. Reprod Biomed Online 10:330–338 Fatemi HM, Popovic-Todorovic B, Papanikolaou E, Donoso P, Devroey P (2007) Update of luteal phase support in stimulated ICSI cycles. Hum Reprod Update 13:581–590 Fatemi HM (2009) The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online 19:4331 Humaidan P, Papanikolaou EG, Kyrou D, Alsbjerg B, Polyzos NP, Devroey P, Fatemi HM (2012) The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod Biomed Online 24:134–141 Albano C, Grimbizis G, Smitz J, Riethmüller-Winzen H, Reissmann T, Van Steirteghem A, Devroey P (1998) The luteal phase of nonsupplemented cycles after ovarian superovulation with human menopausal gonadotropin and the gonadotropin-releasing hormone antagonist Cetrorelix. Fertil Steril 70:357–359 Kolibianakis EM, Devroey P (2002) The luteal phase after ovarian stimulation. Reprod Biomed Online 5 Suppl 1 (3):26–35 Fauser BC, Devroey P (2003) Reproductive biology and ICSI: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab 14:236–242 Bahceci M, Ulug U (2008) Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyper-stimulation for ICSI with ICSI using GnRH antagonist. J Assist Reprod Genet 25:499–502 ASRM Practice Committee (2008) Progesterone supplementation during the luteal phase and in early pregnancy in the treatment of infertility: an educational bulletin. ASRM Practice Committee Position Statement. Fertil Steril 90:S150–S153 Ng EHY, Chan CC, Tang OS, Ho PC (2007) A randomized comparison of side effects and patient convenience between Cyclogest1 suppositories and Endometrin1 tablets used for luteal phase support in ICSI treatment. Eur J Obstet Gynecol Reprod Biol 131:182–188 Daya S, Gunby J (2004) Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev CD004830 Nosarka S, Kruger T, Siebert I, Grove D (2005) Luteal phase support in in vitro fertilization: meta-analysis of randomized trials. Gynecol Obstet Invest 60:67–74 Soliman S, Daya S, Collins J, Hughes EG (1994) The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. Fertil Steril 61:1068–1076 Araujo E, Bernadini L, Frederick JL, Asch RH, Balmaceda JP (1994) Prospective randomized comparison of human chorionic gonadotropin versus intramuscular progesterone for luteal phase support in assisted reproduction. J Assist Reprod Genet 11:74–78 Levine H, Watson N (2000) Comparison of the pharmacokinetics of crinone 8 % administered vaginally versus Prometrium administered orally in postmenopausal women (3). Fertil Steril 73:516–521 Tavaniotou A, Smitz J, Bourgain C, Devroey P (2000) Comparison between different routes of progesterone administration as luteal phase support in infertility treatments. Hum Reprod Update 6:139–148 Penzias AS, Alper MM (2003) Luteal support with vaginal micronized progesterone gel in assisted reproduction. Reprod Biomed Online 6:287–295 Schoolcraft WB, Hesla JS, Gee MJ (2000) Experience with progesterone gel for luteal support in a highly successful ICSI programme. Hum Reprod 15:1284–1288 Chakmakjian ZH, Zachariah NY (1987) Bioavailability of progesterone with different modes of administration. J Reprod Med 32:443–448 Ioannidis G, Sacks G, Reddy N, Seyani L, Margara R, Lavery S, Trew G (2005) Day 14 maternal serum progesterone levels predict pregnancy outcome in ICSI/ICSI treatment cycles: a prospective study. Hum Reprod 20:741–746 Posaci C, Smitz J, Camus M, Osmanagaoglu K, Devroey P (2000) Progesterone for the luteal support of assisted reproductive technologies: clinical options. Hum Reprod 15(Suppl 1):129–148 Moyer DL, de Lignieres B, Driguez P, Pez JP (1993) Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. Fertil Steril 59:992–997 Ganesh A, Chakravorty N, Mukherjee R, Goswami S, Chaudhury K, Chakravarty B (2011) Comparison of oral dydrogesterone with progesterone gel and micronized progesterone for luteal support in 1,373 women undergoing in vitro fertilization: a randomized clinical study. Fertil Steril 95:1961–1965 Kimzey LM, Gumowski J, Merriam GR, Grimes GJ Jr, Nelson LM (1991) Absorption of micronized progesterone from a non-liquefying vaginal cream. Fertil Steril 56:995–996 Archer D, Fahy G, Viniegra-Sibal A, Anderson FD, Snipes W, Foldesy RG (1995) Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone. Am J Obstet Gynecol 173:471–478 Pouly JL, Bassil S, Frydman R et al (1996) Luteal support after in vitro fertilization: crinone 8 %, a sustained release vaginal progesterone gel, vs. utrogestan, an oral micronized progesterone. Hum Reprod 11:2085–2089 Ng EHY, Miao B, Cheung W, Ho PC (2003) A randomized comparison of side effects and patient convenience of two vaginal progesterone formulations used for luteal support in in vitro fertilization cycles. Eur J Obstet Gynecol Reprod Biol 111:50–54 Acknowledgments The authors would like to thank Seyed Muhammed Hussein Mousavinasab for his sincere cooperation in editing this work. Conflict of interest The authors declare no conflict of interests. Author information Authors and Affiliations Corresponding author Additional information Clinical Trail Registration ID: IRCT138807192568N1. Rights and permissions About this article Cite this article Aghsa, MM., Rahmanpour, H., Bagheri, M. et al. A randomized comparison of the efficacy, side effects and patient convenience between vaginal and rectal administration of Cyclogest® when used for luteal phase support in ICSI treatment. Arch Gynecol Obstet 286, 1049–1054 (2012). https://doi.org/10.1007/s00404-012-2410-7 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-012-2410-7