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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 anb3 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 anb3 integrin-negative patients (n ¼ 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 anb3 integrin expression compared with those who were integrin negative [20/50 (40%) versus 4/29 (13.8%); P ¼ 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 anb3 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.

Objective To evaluate endometrial BCL6 expression as a prognostic biomarker for In Vitro Fertilization (IVF) outcome in women with unexplained infertility (UI) prior to embryo transfer. Design Prospective cohort study. Setting University associated infertility clinic. Patients Women with UI for greater than 1 year. Interventions We studied women with UI who underwent testing for endometrial BCL6, in an LH-timed mid-luteal phase biopsy and completed an IVF cycle and embryo transfer. Main Outcome Measure(s) Clinical pregnancy rate (CPR) and live birth rate (LBR) per transfer was compared for women positive or negative for BCL6 expression. An abnormal BCL6 result was defined by an HSCORE (> 1.4). Results Women with normal and abnormal BCL6 and those who conceived or not had similar characteristics. Women with low levels of BCL6 expression had a significantly higher CPR (11/17; 64.7%; 95%CI: 41.3 to 82.6), compared to women with abnormal (high) BCL6 expression (9/52; 17.3%; 95%CI: 9.3 to 30.8). These results yield a relative risk (RR) of 0.267 (95%CI: 0.13 to 0.53; p = 0.0004) for those with normal BCL6 expression, an absolute benefit (AB) of 47.4% (95%CI: 22.5 to 72). LBR was also significantly higher in women with low BCL6 expression(10/17; 58.8; 95%CI: 36 to 78.4), compared to women with abnormal BCL6 expression (6/52; 11.5%; 95%CI: 5.4 to 23). The RR was 0.19 (95%CI: 0.08 to 0.45; p = 0.0002), yielding an AB of 47.3% (95%CI: 21.8 to 67.8). Conclusions Aberrant BCL6 expression (> 1.4 HSCORE) was strongly associated with poor reproductive outcomes in IVF cycles in women with UI.

Purpose To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic. Methods All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group. Results Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group. Conclusions Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pretreated with medical and surgical management.

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