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.
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.
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.
Progesterone is primarily a pregnancy-related hormone, produced in substantial quantities after ovulation and during gestation. Traditionally known to function via nuclear receptors for transcriptional regulation, there is also evidence of nonnuclear action. A previously identified mitochondrial progesterone receptor (PR-M) increases cellular respiration in cell models. In these studies, we demonstrated that expression of PR-M in rat H9c2 cardiomyocytes resulted in a ligand-dependent increase in oxidative cellular respiration and beta-oxidation. Cardiac expression in a TET-On transgenic mouse resulted in gene expression of myofibril proteins for remodeling and proteins involved in oxidative phosphorylation and fatty acid metabolism. In a model of increased afterload from constant transverse aortic constriction, mice expressing PR-M showed a ligand-dependent preservation of cardiac function. From these observations, we propose that PR-M is responsible for progesterone-induced increases in cellular energy production and cardiac remodeling to meet the physiological demands of pregnancy.
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