Can combining vaginal and rectal progesterone achieve the optimum progesterone range required for implantation in the HRT-FET model?

RESEARCH QUESTION: What is the ongoing pregnancy rate (OPR) in frozen embryo transfer (FET) cycles, using combined rectal and vaginal progesterone in hormonal replacement therapy (HRT)? DESIGN: A prospective cohort study (n = 277) including 239 HRT-FET cycles with serum progesterone measurements studying combined vaginal (90 mg/12 h) and rectal (90 mg/12 h) progesterone administration and single blastocyst transfer on the sixth day of progesterone administration. A total of 134 responses to questionnaires covering convenience and side-effects were collected. RESULTS: The median serum progesterone level was 45 nmol/l (range 2-150 nmol/l). Overall positive HCG rate, OPR at week 12 and pregnancy loss rates were 62%, 44% and 29%, respectively. A non-linear relationship between serum progesterone levels and OPR was found. Crude odds ratio for OPR in the high progesterone group (>45 nmol/l) was 0.56 (95% CI 0.32 to 0.98; P = 0.04) compared with the intermediate progesterone group (28-45 nmol/l). Discomfort after rectal progesterone administration was reported on the embryo transfer day and on the day of pregnancy scan 5 weeks later by a total of 18% (16/87) and 17% (8/47) of patients, respectively. Discomfort related to vaginal administration increased significantly over time and was reported by 18% (16/87) on the day of embryo transfer compared with 45% (21/47) on the day of pregnancy scan (P < 0.002). CONCLUSIONS: Combined rectal and vaginal progesterone in HRT-FET cycles resulted in higher median progesterone levels compared with vaginal administration alone. This study suggests that an upper threshold for serum progesterone exists and that above this concentration serum progesterone levels decrease the OPR. Rectally administered progesterone was well tolerated by patients.

Reproductive outcome of patients undergoing in vitro fertilisation treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta-analysis.

BACKGROUND: Despite recent efforts, the risks associated with bacterial vaginosis (BV) or abnormal vaginal microbiota in IVF patients are not well-established. OBJECTIVES: We aimed to evaluate the risks associated with BV in IVF patients using meta-analysis. SEARCH STRATEGY: Following preliminary searches to find relevant keywords and MeSH terms, a systematic search was performed in PubMed (MEDLINE) in September 2017. SELECTION CRITERIA: The population was infertile women attending IVF treatment. The exposure was BV or abnormal vaginal microbiota. Outcomes included live birth rate, early spontaneous abortion rate and clinical pregnancy rate. DATA COLLECTION AND ANALYSIS: Data were collected for each study and for each outcome using a summary of findings table. If appropriate, data were quantitatively assessed using meta-analysis, sensitivity analysis, funnel plots and GRADE evidence assessment were performed for the above-mentioned outcomes. MAIN RESULTS: A total of 12 studies were eligible, comprising a total of 2980 patients. The prevalence of BV was 16% (95% CI 15-18%) in the general study population and tubal factor infertility was highly prevalent in patients diagnosed with BV compared with normal vaginal microbiota patients (P = 0.001). Despite a significant association with early spontaneous abortion [relative risk (RR) 1.68, 95% CI 1.24-2.27], BV did not significantly impact the live birth rate (RR 1.47, 95% CI 0.96-1.57) or the clinical pregnancy rate (RR 0.93, 95% CI 0.75-1.15). CONCLUSIONS: BV is associated with tubal factor infertility and early spontaneous abortion. However, the quality of evidence was very low and the equivocal results justify the need for further research. TWEETABLE ABSTRACT: Abnormal vaginal microbiota is associated with early spontaneous abortion in IVF patients.

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

STUDY QUESTION: What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? SUMMARY ANSWER: The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. WHAT IS KNOWN ALREADY: Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. STUDY DESIGN, SIZE, DURATION: A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). LIMITATIONS, REASONS FOR CAUTION: Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. STUDY FUNDING/COMPETING INTERESTS: This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. TRIAL REGISTRATION NUMBER: The project was registered at clinicaltrials.gov (file number NCT02042352).