Endometrial receptivity defects during IVF cycles with and without letrozole

Hum Reprod. 2012 Mar;27(3):881-8. doi: 10.1093/humrep/der452. Epub 2012 Jan 13.


Background: Our aim was to study ways to improve IVF success rates in women with suspected endometrial receptivity defects.

Methods: We conducted a retrospective cohort study examining the effect of letrozole (aromatase inhibitor) on integrin expression as a marker of endometrial receptivity. We compared IVF outcomes in 97 infertile women who had undergone ανβ3 integrin assessment by immunohistochemistry in mid-luteal endometrial biopsies. Of 79 women undergoing standard IVF, 29 (36.7%) lacked normal integrin expression. Eighteen other women with low integrin were studied after receiving letrozole during early IVF stimulation. An independent set of ανβ3 integrin-negative patients (n = 15) who had undergone repeat endometrial biopsy for integrin testing while taking letrozole were re-evaluated.

Results: Clinical pregnancy and delivery rates were higher in women with normal ανβ3 integrin expression compared with those who were integrin negative [20/50 (40%) versus 4/29 (13.8%); P = 0.02 and 19/50 (38%) versus 2/29 (7%); P < 0.01, respectively]. In 18 women who received letrozole early in IVF, 11 conceived (61.1%; P < 0.001) compared with integrin-negative patients who did not receive letrozole. In integrin-negative women who were rebiopsied on letrozole, 66.7% reverted to normal integrin expression. Positive endometrial aromatase immunostaining using a polyclonal antibody was a common finding in infertile patients compared with controls.

Conclusions: Lack of endometrial ανβ3 integrin expression is associated with a poor prognosis for IVF that might be improved with letrozole co-treatment. Prospective studies are needed to confirm and extend these findings but the data suggest that aromatase expression may contribute to implantation failure in some women.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aromatase Inhibitors / therapeutic use*
  • Birth Rate
  • Embryo Implantation / drug effects*
  • Endometrium / drug effects*
  • Female
  • Fertilization in Vitro*
  • Humans
  • Infertility, Female / drug therapy
  • Integrin alphaVbeta3 / metabolism
  • Letrozole
  • Nitriles / therapeutic use*
  • Pregnancy
  • Pregnancy Rate
  • Retrospective Studies
  • Triazoles / therapeutic use*


  • Aromatase Inhibitors
  • Integrin alphaVbeta3
  • Nitriles
  • Triazoles
  • Letrozole