Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole

Summary

Aromatase inhibitors such as letrozole are hypothesized to maintain normal hypothalamic/ pituitary feedback mechanisms and in the case of OI (ovulation induction) in women with PCOS, may act to increase follicular sensitivity to FSH by increasing intrafollicular androgen levels. Letrozole also may act to increase midluteal P levels presumably by induction of follicles and corpora lutea. The investigators are asking the question whether P supplementation with Crinone (8%) may have an additive beneficial effect on endometrial development in those women taking letrozole. Progesterone levels in the endometrium (tissue levels) have been documented to be significantly higher than serum levels after vaginal administration which may lead to higher pregnancy rates. In addition P has been shown to decrease LH pulse frequency which is elevated in PCOS and has been shown to down regulate endometrial androgen receptors. There have been retrospective studies showing progesterone supplementation seems to benefit both CC and letrozole treatment groups. In fact, this study showed the only pregnancies in the letrozole group were those in women who took P supplementation. However the number of cycles studied was small. There is a place for a randomized controlled trial (RCT) to determine if luteal phase P supplementation with Crinone should be used in all women using letrozole for Ovulation Induction (OI) in combination with Intrauterine Insemination (IUI) or Timed Intercourse (TI). This is currently not done in all clinical practices.

Timeline

Start

2012-07-06

Primary completion

2016-11-02

Completion

2017-12-30

Publications

• Background Franks S. Assessment and management of anovulatory infertility in polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2003 Sep;32(3):639-51. doi: 10.1016/s0889-8529(03)00044-6.
• Background GOLDZIEHER JW, GREEN JA. The polycystic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab. 1962 Mar;22:325-38. doi: 10.1210/jcem-22-3-325. No abstract available.
• Background Richardson MR. Current perspectives in polycystic ovary syndrome. Am Fam Physician. 2003 Aug 15;68(4):697-704.
• Background Hamilton-Fairley D, Taylor A. Anovulation. BMJ. 2003 Sep 6;327(7414):546-9. doi: 10.1136/bmj.327.7414.546. No abstract available.
• Background Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998 Jun 15;101(12):2622-9. doi: 10.1172/JCI2081.
• Background Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.
• Background Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet. 2009 Jan;26(1):19-24. doi: 10.1007/s10815-008-9284-4. Epub 2009 Jan 7.
• Background Casper RF. Aromatase inhibitors in ovarian stimulation. J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):71-5. doi: 10.1016/j.jsbmb.2007.05.025. Epub 2007 May 24.
• Background Eckmann KR, Kockler DR. Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome. Ann Pharmacother. 2009 Jul;43(7):1338-46. doi: 10.1345/aph.1M096. Epub 2009 Jul 7.
• Background 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 Sep;62(3):485-90. doi: 10.1016/s0015-0282(16)56935-0.
• Background Cortinez A, De Carvalho I, Vantman D, Gabler F, Iniguez G, Vega M. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril. 2005 Jan;83(1):110-5. doi: 10.1016/j.fertnstert.2004.05.099.
• Background Montville CP, Khabbaz M, Aubuchon M, Williams DB, Thomas MA. Luteal support with intravaginal progesterone increases clinical pregnancy rates in women with polycystic ovary syndrome using letrozole for ovulation induction. Fertil Steril. 2010 Jul;94(2):678-83. doi: 10.1016/j.fertnstert.2009.03.088. Epub 2009 Jun 9.

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