P.B. Miller

Endometrial receptivity defects during IVF cycles with and without letrozole

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.

Luteal phase HCG support for unexplained recurrent pregnancy loss – a low hanging fruit?

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and accounts for only 1-5% of pregnancy failures. Treatment options for unexplained RPL (uRPL) are limited. Previous studies suggest a link between delayed implantation and pregnancy loss. Based on this, a timely signal for rescue of the corpus luteum (CL) using human chorionic gonadotrophin (HCG) could improve outcomes in women with uRPL. This retrospective cohort study included 98 subjects with uRPL: 45 underwent 135 monitored cycles without HCG support; and 53 underwent 142 cycles with a single mid-luteal HCG injection. Based on Log-rank Mantel-Cox survival curves, miscarriage rate and time to pregnancy decreased in the HCG group (P = 0.0005). Women receiving luteal HCG support had an increased chance of an ongoing pregnancy compared with those not receiving it (RR = 2.4; 95% CI 1.4-3.6; number need to treat (NNT) = 7; 95% CI 4-18). Subjects receiving HCG support had a significant absolute risk reduction (ARR) of miscarriage (P < 0.001; ARR = 11.5%; 95% CI 3.6-19.5; NNT = 9(5-27). These data suggest restoration of synchrony and CL support improves outcomes in women with RPL. Further randomized controlled trials of luteal-phase HCG in women with RPL appears warranted.

Coexistence of polycystic ovary syndrome and endometriosis in women with infertility

Purpose The aim of this study was to investigate if there is a higher incidence of endometriosis in patients with polycystic ovary syndrome (PCOS), compared with normal fertile controls. Material and methods Women with PCOS according to Rotterdam criteria, with infertility and/or pelvic pain, were identified (n = 104), and together with fertile women seeking bilateral tubal ligation (n = 111), they were submitted to laparoscopy at the Greenville Hospital System or the University of North Carolina at Chapel Hill. A biopsy was performed in 40 patients with PCOS to confirm or not endometriosis. Results Age was similar in both groups (control: 29.7 ± 0.5 years; PCOS: 29.6 ± 0.4). The incidence of suspected endometriotic lesions in controls and PCOS patients was 12.6% (95% confidence interval [95% CI], 7.6%-20%) and 74% (95% CI, 64.8%-81.5%), respectively; with an odds ratio of 19.7 (95% CI, 9.6-40.2) of finding endometriosis in PCOS (p<0.0001). Our results were similar when endometriosis was confirmed by pathology report. Of the PCOS patients with endometriosis, 76% had endometriosis stage I or II, according to the revised American Society for Reproductive Medicine criteria. Conclusions In this case-control study, a significant association between endometriosis and women with PCOS with pelvic pain and/or infertility was found. The majority of endometriotic lesions (76%) were stage I or II.