Objective: To investigate factors associated with early in vitro fertilization (IVF) treatment discontinuation. Design: Retrospective cohort study. Setting: High-volume Midwestern academic medical center. Patient(s): Six hundred sixty-nine first-attempt IVF patients who did not have a live birth. Intervention(s): None. Main Outcome Measure(s): Treatment discontinuation and time to return for a second IVF cycle. Result(s):Women without IVF insurance coverage were more likely to discontinue treatment than women with insurance coverage (adjusted odds ratio [aOR] 3.12, 95% confidence interval [CI] 2.22-4.40). African American women were more likely to discontinue treatment (aOR 2.95, 95% CI 1.54-5.66) and returned for treatment more slowly (adjusted hazard ratio [aHR] 0.44, 95% CI 0.28-0.71) than non-Hispanic white women, regardless of IVF insurance coverage or income. Women with a poor prognosis were more likely to discontinue treatment than women with a good

The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young’s modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not.

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Objective The objective of this study was to use high-throughput sequencing to describe the vaginal eukaryotic DNA virome in patients undergoing in vitro fertilisation (IVF) to examine associations between the vaginal virome, antibiotic exposure and IVF outcomes.Design Prospective exploratory study.Setting Single academic fertility centre.Population Subfertile women age 18-43 years undergoing their first IVF cycle with a fresh embryo transfer.Methods The primary exposure was prophylactic azithromycin or no azithromycin before IVF. A mid-vaginal swab was obtained at the time of embryo transfer for virome analysis.Main outcome measures The primary outcomes compared between exposure groups were characteristics of vaginal virome and clinical pregnancy rates. Secondary outcomes were virome associations with number of oocytes retrieved, number of blastocysts and implantation rate.Results Twenty-six women contributed a vaginal swab before embryo transfer. There were no significant differences in IVF outcomes between azithromycin groups. There was no association between viral diversity and clinical pregnancy overall. A higher diversity of herpesviruses and a-papillomaviruses was observed in samples from the azithromycin-treated group compared with the no azithromycin group (P = 0.04). In women that received azithromycin, viral diversity was higher in the group that did not achieve clinical pregnancy compared with those who did (P = 0.06). ConclusionsWe demonstrate that the vaginal eukaryotic virome in women undergoing IVF is associated with antibiotic exposure. Additionally, we demonstrate an inverse trend between viral diversity and pregnancy, with a higher number of viruses detected associated with failure to achieve clinical pregnancy in the azithromycin group.Keywords Embryo transfer, in vitro fertilisation, reproductive tract microbiome, vaginal virus, virome.Tweetable abstract Higher viral diversity is associated with prophylactic antibiotic exposure in subfertile women undergoing IVF. Please cite this paper as: Eskew AM, Stout MJ, Bedrick BS, Riley JK, Omurtag KR, Jimenez PT, Odem RR, Ratts VS, Keller SL, Jungheim ES, Wylie KM. Association of the eukaryotic vaginal virome with prophylactic antibiotic exposure and reproductive outcomes in a subfertile population undergoing in vitro fertilisation: a prospective exploratory study.

To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility. DATA SOURCES: We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov. METHODS: We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscar-riage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I 2 were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs.