Journal of the Chinese Medical Association
Volume 71, Issue 8 , Pages 386-391, August 2008

Luteal Support for IVF/ICSI Cycles with Crinone 8% (90 mg) Twice Daily Results in Higher Pregnancy Rates Than with Intramuscular Progesterone

  • Chi-Hong Ho

      Affiliations

    • Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Shee-Uan Chen

      Affiliations

    • Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr Shee-Uan Chen, Department of Obstetrics and Gynecology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 100, Taiwan, R.O.C.
    • ,
  • Fu-Shiang Peng

      Affiliations

    • Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Chih-Yuan Chang

      Affiliations

    • Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Yu-Shih Yang

      Affiliations

    • Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, R.O.C.

Received 23 January 2008; accepted 27 June 2008.

Article Outline

Background

The use of progesterone for luteal support has been demonstrated to be beneficial in assisted reproductive cycles, yet the optimal route of progesterone administration has still not been established. This article is a retrospective study in a tertiary reproductive medical unit to compare luteal progesterone supplementation with vaginal gel or intra-muscular progesterone.

Methods

A total of 144 in vitro fertilization or intracytoplasmic sperm injection cycles were analyzed, 67 cycles using vaginal gel 90 mg twice daily and 77 cycles using intramuscular progesterone 50 mg daily as luteal support.

Results

Both groups had similar mean age, cause of infertility, baseline hormone levels, dosage of recombinant follicle-stimulating hormone, number of retrieved and fertilized oocytes, and number of transferred embryos. The vaginal gel group had significantly lower mid-luteal serum progesterone levels but higher implantation rate (32.5% vs. 18.5%, p = 0.001) and ongoing pregnancy rate (55.2% vs. 32.5%, p = 0.006). Within each group, mid-luteal serum progesterone levels between pregnant or non-pregnant patients were comparable. For patients with serum estradiol levels on day of human chorionic gonadotropin greater than 5,000 pg/mL, vaginal gel still resulted in better ongoing pregnancy and implantation rates.

Conclusion

The use of vaginal progesterone gel twice daily for luteal support results in better pregnancy outcomes than intramuscular progesterone. A high local progesterone effect from vaginal gel might improve endometrial receptivity under extraordinarily high serum estradiol levels.

Key Words:  assisted reproductive technology , Crinone , luteal phase , pregnancy rate

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References 

  1. Soliman S , Daya S , Collins J , Hughes EG . The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials . Fertil Steril . 1994;61:1068–1076
  2. Daya S , Gunby J . Luteal phase support in assisted reproduction cycles . Cochrane Database Syst Rev . 2004; CD004830
  3. Levine H . Luteal support in IVF using the novel vaginal progesterone gel Crinone 8%: results of an open-label trial in 1184 women from 16 US centers . Fertil Steril . 2000;74:836–837
  4. Penzias AS , Alper MM . Luteal support with vaginal micronized progesterone gel in assisted reproduction . Reprod Biomed Online . 2003;6:287–295
  5. Pritts EA , Atwood AK . Luteal phase support in infertility treatment: a meta-analysis of the randomized trials . Hum Reprod . 2002;17:2287–2299
  6. Penzias AS . Luteal phase support . Fertil Steril . 2002;77:318–323
  7. Arslan M , Bocca S , Arslan EO , Duran HE , Stadtmauer L , Oehninger S . Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation . J Assist Reprod Genet . 2007;24:111–117
  8. Choi BC , Polgar K , Xiao L , Hill JA . Progesterone inhibits in vitro embryotoxic Th1 cytokine production to trophoblast in women with recurrent pregnancy loss . Hum Reprod . 2000;15(Suppl):46–59
  9. Chen CD , Wu MY , Chao KH , Chen SU , Ho HN , Yang YS . Serum estradiol level and oocyte number in predicting severe ovarian hyperstimulation syndrome . J Formos Med Assoc . 1997;96:829–834
  10. Bulletti C , De ZD , Flamigni C , Giacomucci E , Polli V , Bolelli G , et al.   Targeted drug delivery in gynaecology: the first uterine pass effect . Hum Reprod . 1997;12:1073–1079
  11. Cicinelli E , De ZD , Bulletti C , Matteo MG , Schonauer LM , Galantino P . Direct transport of progesterone from vagina to uterus . Obstet Gynecol . 2000;95:403–406
  12. Miles RA , Paulson RJ , Lobo RA , Press MF , Dahmoush L , Sauer MV . Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study . Fertil Steril . 1994;62:485–490
  13. Fanchin R , De ZD , Bergeron C , Righini C , Torrisi C , Frydman R . Transvaginal administration of progesterone . Obstet Gynecol . 1997;90:396–401
  14. Chantilis SJ , Zeitoun KM , Patel SI , Johns DA , Madziar VA , McIntire DD . Use of Crinone vaginal progesterone gel for luteal support in in vitro fertilization cycles . Fertil Steril . 1999;72:823–829
  15. 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
  16. Damario MA , Goudas VT , Session DR , Hammitt DG , Dumesic DA . Crinone 8% vaginal progesterone gel results in lower embryonic implantation efficiency after in vitro fertilization-embryo transfer . Fertil Steril . 1999;72:830–836
  17. Perino M , Brigandi FG , Abate FG , Costabile L , Balzano E , Abate A . Intramuscular versus vaginal progesterone in assisted reproduction: a comparative study . Clin Exp Obstet Gynecol . 1997;24:228–231
  18. Abate A , Perino M , Abate FG , Brigandi A , Costabile L , Manti F . Intramuscular versus vaginal administration of progesterone for luteal phase support after in vitro fertilization and embryo transfer. A comparative randomized study . Clin Exp Obstet Gynecol . 1999;26:203–206
  19. Pellicer A , Valbuena D , Cano F , Remohi J , Simon C . Lower implantation rates in high responders: evidence for an altered endocrine milieu during the preimplantation period . Fertil Steril . 1996;65:1190–1195
  20. Gibbons WE , Toner JP , Hamacher P , Kolm P . Experience with a novel vaginal progesterone preparation in a donor oocyte program . Fertil Steril . 1998;69:96–101
  21. Paulson RJ , Sauer MV , Lobo RA . Embryo implantation after human in vitro fertilization: importance of endometrial receptivity . Fertil Steril . 1990;53:870–874
  22. Simon C , Cano F , Valbuena D , Remohi J , Pellicer A . Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients . Hum Reprod . 1995;10:2432–2437
  23. Chen QJ, Sun XX, Li L, Gao XH, Wu Y, Gemzell-Danielsson K, et al. Effects of ovarian high response on implantation and pregnancy outcome during controlled ovarian hyperstimulation (with GnRH agonist and rFSH) . Acta Obstet Gynecol Scand . 2007;86:849–854
  24. Toner JP , Hassiakos DK , Muasher SJ , Hsiu JG , Jones HW . Endometrial receptivities after leuprolide suppression and gonadotropin stimulation: histology, steroid receptor concentrations, and implantation rates . Ann NY Acad Sci . 1991;622:220–229
  25. Basir GS , Ws O , Ng EH , Ho PC . Morphometric analysis of peri-implantation endometrium in patients having excessively Comparing vaginal gel and intramuscular progesterone as luteal phase support in IVF/ICSI treatment high oestradiol concentrations after ovarian stimulation . Hum Reprod . 2001;16:435–440
  26. Ng EH , Chan CC , Tang OS , Yeung WS , Ho PC . Endometrial and subendometrial blood flow measured during early luteal phase by three-dimensional power Doppler ultrasound in excessive ovarian responders . Hum Reprod . 2004;19:924–931
  27. Makkar G , Ng EH , Yeung WS , Ho PC . Reduced expression of interleukin-11 and interleukin-6 in the periimplantation endometrium of excessive ovarian responders during in vitro fertilization treatment . J Clin Endocrinol Metab . 2006;91:3181–3188
  28. Wegmann TG , Lin H , Guilbert L , Mosmann TR . Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? . Immunol Today . 1993;14:353–356
  29. Hutchinson-Williams KA , DeCherney AH , Lavy G , Diamond MP , Naftolin F , Lunenfeld B . Luteal rescue in in vitro fertilizationembryo transfer . Fertil Steril . 1990;53:495–501
  30. de Ziegler D , Bouchard P . Understanding endometrial physiology and menstrual disorders in the 1990s . Curr Opin Obstet Gynecol . 1993;5:378–388
  31. Farhi J , Weissman A , Steinfeld Z , Shorer M , Nahum H , Levran D . Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilizationembryo transfer cycles . Fertil Steril . 2000;73:761–766
  32. Gorkemli H , Ak D , Akyurek C , Aktan M , Duman S . Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles . Gynecol Obstet Invest . 2004;58:140–144

PII: S1726-4901(08)70088-1

doi:10.1016/S1726-4901(08)70088-1

Journal of the Chinese Medical Association
Volume 71, Issue 8 , Pages 386-391, August 2008

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