title: Endometrial receptivity defects during IVF cycles with and without letrozole.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology,  University Medical Group, Greenville Hospital System, 890 W. Faris Rd, Ste 470, Greenville, SC 29605,  USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Miller
authors.forename: Brent A
authors.initials: BA
authors.lastname: Parnell
authors.forename: Greta
authors.initials: G
authors.lastname: Bushnell
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tallman
authors.forename: David A
authors.initials: DA
authors.lastname: Forstein
authors.forename: H Lee
authors.initials: HL
authors.lastname: Higdon
authors.forename: Jo
authors.initials: J
authors.lastname: Kitawaki
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000328:Adult; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001723:Birth Rate; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D011247:Pregnancy; D018873:Pregnancy Rate; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D039302:Integrin alphaVbeta3; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole