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.

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 α-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). CONCLUSIONS: We 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. TWEETABLE ABSTRACT: Higher viral diversity is associated with prophylactic antibiotic exposure in subfertile women undergoing IVF.

Ovarian stimulation in the luteal phase: systematic review and meta-analysis.

PURPOSE: The purpose of this study was to evaluate whether outcomes are different if controlled ovarian stimulation (COS) is started in the luteal phase rather than the follicular phase. METHODS: A systematic review and meta-analysis was performed. Sixteen studies were included in the qualitative analysis, and eight studies with a total of 338 women were included in the quantitative analysis. RESULTS: Cycles initiated in the luteal phase were slightly longer (WMD 1.1 days, 95 % CI 0.39-1.9) and utilized more total gonadotropins (WMD 817 IU, 95 % CI 489-1144). However, no differences were noted in peak estradiol levels (WMD -411 pg/ml, 95 % CI -906-84.7) or in the total number of oocytes retrieved (WMD 0.52 oocytes, 95 % CI -0.74-1.7). There were slightly more mature oocytes retrieved in the luteal phase (WMD 0.77 oocytes, 95 % CI 0.21-1.3), and fertilization rates were significantly higher (WMD 10 %, 95 % CI 0.03-0.18). While only three studies reported pregnancy outcomes, no difference was noted in the FET pregnancy rates after COS in the luteal versus follicular phase (RR 0.95, 95 % CI 0.56-1.7). A post hoc power analysis revealed that a sample of this size was sufficient to detect a clinically meaningful difference of 2 oocytes retrieved with 93 % power. CONCLUSION: Although initiating COS in the luteal phase requires a longer stimulation and a higher dose of total gonadotropin, these differences are not clinically significant. Furthermore, COS initiated in the luteal phase does not compromise the quantity or quality of oocytes retrieved compared to outcomes of traditional stimulation in the follicular phase.

IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis.

STUDY QUESTION: Does obesity influence the chance of pregnancy after IVF in donor oocyte recipients? SUMMARY ANSWER: The chance of pregnancy after IVF is no different in obese donor oocyte recipients versus those in the normal BMI range. WHAT IS KNOWN ALREADY: Obesity is associated with decreased chances of pregnancy in women undergoing IVF with autologous oocytes. Prior studies have investigated the impact of obesity on IVF outcomes in donor oocyte recipients, with disparate results. This is the first systematic review and meta-analysis to address this topic. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of published literature identified in Medline, EMBASE and Scopus through December of 2011 were performed to address the association between BMI and outcomes for donor oocyte recipients. The primary outcome of this study was implantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two authors conducted the searches independently, selected the studies and abstracted the data. Studies in English of first donor oocyte cycles with reported recipient BMI were included. Primary data collected from the IVF program at Washington University were also included as one study (n = 123 donor oocyte recipients). Studies limited to frozen embryo transfer were excluded. Data were synthesized using DerSimonian-Laird random effects models for implantation, clinical pregnancy, miscarriage and live birth. MAIN RESULTS AND THE ROLE OF CHANCE: Of 475 screened articles, 7 were reviewed and 5 were included together with primary data from Washington University, giving a total of 4758 women who were included for the assessment of the primary outcome. No associations between obesity (BMI ≥ 30 kg/m(2)) and chance of pregnancy after IVF were noted in women using donor oocytes [risk ratio (RR): 0.98, 95% confidence intervals (CI): 0.83-1.15, I(2): 61.6%]. Additional analyses assessing associations between recipient obesity and embryo implantation (RR: 0.93, 95% CI: 0.80-1.07, I(2): 0%), miscarriage (RR: 1.12, 95% CI: 0.83-1.50, I(2): 0%) and live birth (RR: 0.91, 95% CI: 0.65-1.27, I(2) 47.9%) also failed to show a negative effect. LIMITATIONS, REASONS FOR CAUTION: Included studies were small and they were performed in a variety of locations and practice settings where stimulation and laboratory protocols may differ, and extremes of BMI may also differ. Furthermore, included studies had different inclusion and exclusion criteria. These factors could not be controlled for in this meta-analysis and statistical heterogeneity was noted for some outcomes. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest obesity does not affect IVF outcomes in women using donor oocytes. Oocyte quality rather than endometrial receptivity may be the overriding factor influencing IVF outcomes in obese women using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S): E.S.J. and M.G.T receive support from the Women's Reproductive Health Research Program sponsored by the National Institutes of Health (K12 HD063086). The authors do not have any competing interests. TRIAL REGISTRATION NUMBER: N/A.

Evidence that relaxin's effects on growth and softening of the cervix are not mediated through prostaglandins in the rat.

Relaxin plays a major role in promoting the growth and softening of the cervix that occurs during the second half of pregnancy in the rat. There is limited evidence that prostaglandins play a role in cervical softening in mammalian species. Accordingly, this study was conducted to determine if prostaglandins mediate relaxin's effects on the rat cervix. To attain that objective, indomethacin was used to inhibit cyclooxygenase, the key enzyme in the conversion of arachidonic acid to prostaglandins. Twenty-six nonpregnant female rats were ovariectomized when they were 78 days old (day 1 of treatment). At ovariectomy (O), each rat was fitted with silicon tubing implants containing progesterone (P) and estrogen (E) in doses that provided blood levels similar to those during late pregnancy in rats. Rats were randomly assigned to three treatment groups. Group OPE controls (n = 8 rats) received 2 ml indomethacin vehicle (0.5% methyl cellulose, 0.025 Tween 80 in water) via gavage at 0900 h on days 8 and 9 and 0.5 ml relaxin vehicle (0.9% NaCl) s.c. at 6-h intervals from 1200 h on day 8 through 0600 h on day 10. Group OPER (n = 9 rats) was treated as group OPE except that 20 microg highly purified porcine relaxin was administered. Group OPERI (n = 9 rats) was treated as group OPER except that indomethacin was administered at a dose (20 mg/kg BW) that reduced cervical PGE2 levels by more than 90%. Between 0800 h and 1000 h on day 10, the cervices were removed, trimmed of fat, weighed, and placed in ice-cold Krebs-Ringer bicarbonate buffer, pH 7.5. Cervical extensibility (degree of softening) was determined within 4 h of tissue collection. Both the mean cervical wet weight and the mean cervical extensibility in the relaxin-treated group OPER rats were markedly greater (P < 0.01) than in the group OPE controls. Treatment with indomethacin did not diminish relaxin's effects on either cervical wet weight or cervical extensibility. In conclusion, this study provides evidence that relaxin's effects on cervical growth and softening in the rat are not mediated through prostaglandins.