Comparison of Oral Micronized Progesterone and Dydrogesterone as a Luteal Support in Intrauterine Insemination Cycle

자궁강내인공수정시 황체기 보강으로서 경구 미분화 프로게스테론과 디드로게스테론의 비교

  • Jang, Eun-Jeong (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Jee, Byung-Chul (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Kim, Sang-Don (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Lee, Jung-Ryeol (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Suh, Chang-Suk (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital)
  • 장은정 (분당서울대학교병원 산부인과) ;
  • 지병철 (분당서울대학교병원 산부인과) ;
  • 김상돈 (분당서울대학교병원 산부인과) ;
  • 이정렬 (분당서울대학교병원 산부인과) ;
  • 서창석 (분당서울대학교병원 산부인과)
  • Received : 2009.12.28
  • Accepted : 2010.02.09
  • Published : 2010.06.30

Abstract

Objective: To compare the clinical outcomes between oral micronized progesterone and dydrogesterone as a luteal phase support in stimulated intrauterine insemination (IUI) cycles. Methods: A retrospective analysis was performed in 183 IUI cycles during January 2007 to August 2009. Superovulation was achieved by using gonadotropins combined with or without clomiphene citrate. The luteal phase was supported by oral micronized progesterone 300 mg/day (n=136 cycles) or dydrogesterone 20 mg/day (n=47 cycles) from day of insemination. Results: There were no significant differences in clinical characteristics such as age of female, infertility factors, number of mature follicles ($\geq$16 mm), total motile sperm counts, and endometrial thickness on triggering day between the two groups. The clinical pregnancy rates per cycle were similar between the two groups (21.3% in the micronized progesterone group vs. 19.1% in the dydrogesterone group, p=0.92). The clinical miscarriage rate tended to be 3-fold higher in the micronized progesterone group (34.5% vs. 11.1%, p=0.36). Conclusion: Supplementation of oral dydrogesterone as a luteal support has similar clinical outcomes compared with oral micronized progesterone. Large-scaled randomized study would be required to confirm our findings.

목 적: 과배란유도 후 자궁강내 인공수정 시술시 황체기 보강으로서 경구 미분화 프로게스테론 투여법과 경구 디드로게스테론 투여법의 임상적 효용성을 비교하고자 하였다. 연구방법: 2007년 1월부터 2009년 8월까지 시행된 과배란유도 후 자궁강내 인공수정 시술 183주기를 후향적으로 분석하였다. 과배란유도는 성선자극호르몬 단독 또는 클로미펜과 성선자극호르몬의 병합요법을 사용하였다. 136주기에서는 황체기 보강으로서 경구 미분화 프로게스테론을 하루 300 mg으로 투여하였고 47주기에서는 디드로게스테론을 일일 20 mg으로 투여하였다. 결 과: 여성의 연령, 불임 인자, 성숙난포수 ($\geq$16 mm), 총운동성정자수, triggering 날의 자궁내막 두께는 두 군간 유의한 차이가 없었다. 자궁내 태낭이 확인되는 임상적 임신율은 미분화 프로게스테론 투여군에서 21.3%, 디드로게 스테론 투여군에서 19.1%로 차이가 없었다 (p=0.92). 유산율은 미분화 프로게스테론 투여군에서 다소 높은 경향을 보였으나 통계학적인 차이는 없었다 (34.5% vs. 11.1%, p=0.36). 결 론: 황체기 보강으로서 경구 디드로게스테론 투여법은 경구 미분화 프로게스테론 투여에 비하여 비슷한 임신율과 유산율을 보였다. 그러나 상대적으로 디드로게스테론 투여군의 수가 적어 좀더 많은 환자를 대상으로 한 전향적 연구가 필요하다.

Keywords

References

  1. ESHRE Capri Workshop Group. Intrauterine insemination. Hum Reprod Update 2009; 15: 265-77. https://doi.org/10.1093/humupd/dmp003
  2. Kolibianakis EM, Devroey P. The luteal phase after ovarian stimulation. Reprod Biomed Online 2002; 5(Suppl 1): 26-35.
  3. Pabuccu R, Akar ME. Luteal phase support in assisted reproductive technology. Curr Opin Obstet Gynecol 2005; 17: 277-81. https://doi.org/10.1097/01.gco.0000169105.62257.e3
  4. Practice Committee of the American Society for Reproductive Medicine. Progesterone supplementation during the luteal phase and in early pregnancy in the treatment of infertility: an educational bulletin. Fertil Steril 2008; 89: 789-92. https://doi.org/10.1016/j.fertnstert.2008.02.012
  5. Erdem A, Erdem M, Atmaca S, Guler I. Impact of luteal phase support on pregnancy rates in intrauterine insemination cycles: a prospective randomized study. Fertil Steril 2009; 91: 2508-13. https://doi.org/10.1016/j.fertnstert.2008.04.029
  6. Hubayter ZR, Muasher SJ. Luteal supplementation in in vitro fertilization: more questions than answers. Fertil Steril 2008; 89: 749-58. https://doi.org/10.1016/j.fertnstert.2008.02.095
  7. Pouly JL, Bassil S, Frydman R, Hedon B, Nicollet B, Prada Y, et al. Luteal support after in-vitro fertilization: crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone. Hum Reprod 1996; 11: 2085-9. https://doi.org/10.1093/oxfordjournals.humrep.a019054
  8. Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R. Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod 1999; 14: 1944-8. https://doi.org/10.1093/humrep/14.8.1944
  9. Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA. Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril 1999; 71: 614-8. https://doi.org/10.1016/S0015-0282(98)00515-9
  10. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, et al. Classification and pharmacology of progestins. Maturitas 2003; 46(Suppl 1): S7-16.
  11. Gruber CJ, Huber JC. The role of dydrogesterone in recurrent (habitual) abortion. J Steroid Biochem Mol Biol 2005; 97: 426-30. https://doi.org/10.1016/j.jsbmb.2005.08.009
  12. Szekeres-Bartho J, Balasch J. Progestagen therapy for recurrent miscarriage. Hum Reprod Update 2008; 14: 27-35.
  13. Queisser-Luft A. Dydrogesterone use during pregnancy: overview of birth defects reported since 1977. Early Hum Dev 2009; 85: 375-7. https://doi.org/10.1016/j.earlhumdev.2008.12.016
  14. Patki A, Pawar VC. Modulating fertility outcome in assisted reproductive technologies by the use of dydrogesterone. Gynecol Endocrinol 2007; 23(Suppl 1): 68-72. https://doi.org/10.1080/09513590701584857
  15. Chakravarty BN, Shirazee HH, Dam P, Goswami SK, Chatterjee R, Ghosh S. Oral dydrogesterone versus intravaginal micronised progesterone as luteal phase support in assisted reproductive technology (ART) cycles: results of a randomised study. J Steroid Biochem Mol Biol 2005; 97: 416-20. https://doi.org/10.1016/j.jsbmb.2005.08.012
  16. Jee BC, Ku SY, Suh CS, Kim KC, Lee WD, Kim SH. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril 2006; 85: 1774-7. https://doi.org/10.1016/j.fertnstert.2006.02.070
  17. Penzias AS. Luteal phase support. Fertil Steril 2002; 77: 318-23. https://doi.org/10.1016/S0015-0282(01)02961-2
  18. Domitrz J, Wolczynski S, Syrewicz M, Szamatowicz J, Kuczynski W, Grochowski D, et al. The comparison of efficiency of supplement of the second phase in the program IVF-ET by dydrogesterone and progesterone. Ginekol Pol 1999; 70: 8-12.
  19. Tavaniotou A, Smitz J, Bourgain C, Devroey P. Comparison between different routes of progesterone administration as luteal phase support in infertility treatments. Hum Reprod Update 2000; 6: 139-48. https://doi.org/10.1093/humupd/6.2.139