Dynamics of the urinary microbiome in pregnancy and the coincidental predictive value of the microbiota for IVF/IVF-ICSI outcome.

RESEARCH QUESTION: What is the impact of clinical pregnancy on the composition of the urinary microbiota? DESIGN: Eighty-five women receiving IVF, without or with intracytoplasmic sperm injection (ICSI) treatment were enrolled in a prospective observational study performed in 2008. Approximately 14 weeks before the start of hormonal treatment and embryo transfer, a midstream urine sample was obtained, followed by an additional sample 16 weeks after embryo transfer. The microbial composition was determined by polymerase chain reaction of the V1-V3 regions of the 16S rRNA bacterial gene. Clinical pregnancy data were collected after the first IVF/IVF-ICSI cycle and 1 year later. RESULTS: A significant decrease in the abundance of Lactobacillus species as well as a significant increase in that of Staphylococcus species was observed in women who became pregnant after IVF/IVF-ICSI treatment (both P < 0.0001). In addition, based on the composition of the pretreatment microbiome it was possible to identify women with a lower likelihood of achieving clinical pregnancy after IVF/IVF-ICSI treatment. The resulting prediction model was validated in another 27 women who did not become pregnant during the first cycle and received additional IVF/IVF-ICSI cycle(s) or frozen embryo transfer(s). The model predicted the women with no clinical pregnancy after IVF/IVF-ICSI treatment with a sensitivity of 0.42 and a specificity of 1.00. CONCLUSIONS: The data primarily showed that clinical pregnancy results in significant changes in the abundance and diversity of the urinary microbiota. Coincidentally, it was discovered that the urinary microbiome composition before IVF/IVF-ICSI treatment can potentially be used as a predictor of clinical pregnancy.

Potential benefits of the use of sympathomimetics for asthmatic disease, on semen quality in men of subfertile couples.

RESEARCH QUESTION: Is there an association between the use of sympathomimetics for asthmatic disease and semen quality in humans? DESIGN: Between 2007 and 2012 a prospective cohort study was conducted among couples visiting the preconception counselling clinic at a tertiary hospital in the Netherlands. The study included 882 men of subfertile couples and information on medication use was obtained from self-administered questionnaires. Moreover, data on semen parameters were retrieved from medical records. RESULTS: The study population of men revealed a mean (± SD) age of 34 ± 4 years with a mean body mass index (BMI) of 26.1 ± 2.3 kg/m2, and sympathomimetic use was reported by 3.6%. The use of sympathomimetics was positively associated with a 10% higher sperm motility (beta 10.265; 95% confidence interval [CI] 3.258-17.272) after adjustment for smoking, alcohol use, age, geographic background, BMI, folic acid supplement use, the four astronomical seasons and asthma/bronchitis. Subgroup analysis between men with total motile sperm count (TMSC) < or ≥10 million showed that this association remained (P ≤ 0.001) after adjustment for these confounders. After adjustment for confounders the sperm concentration was also positively associated with the use of sympathomimetics, but only in men with TMSC ≥10 million (beta 0.300; 95% CI 0.032-0.568). CONCLUSIONS: These preliminary data show the potential benefits of the use of sympathomimetics to improve sperm motility in men of subfertile couples, which needs further investigation.

The ReceptIVFity cohort study protocol to validate the urogenital microbiome as predictor for IVF or IVF/ICSI outcome.

BACKGROUND: During the last decade, research has shown that besides the known predictive factors, such as duration of subfertility, a women's age, the body mass index, also the microbiome might affect fertility. Micro-organisms together with their genetic information and the milieu in which they interact are called the microbiome. Studies have shown that the presence of certain microbiota during assisted reproductive technology (ART) has a positive impact on the outcome. However, the potential role of using the microbiome as a predictor for outcome of ART has not yet been investigated. METHODS: In a prospective study, 300 women of reproductive age and with an indication for in-vitro Fertilization (IVF) with or without Intra Cytoplasmic Sperm Injection (ICSI) treatment will be included. Prior to the IVF or IVF-ICSI treatment, these women provided a midstream urine sample and a vaginal swab. The composition of the urinary and vaginal microbiome will be analysed with both Next Generation Sequencing and the IS-pro technique. The endpoints of the study are pregnancy achieved after fresh embryo transfer (ET) and within the subsequent year after inclusion. External validation of the findings will take place in an additional cohort of 50 women with an IVF or IVF-ICSI indication. DISCUSSION: In the proposed study, the predictive accuracy of the composition of the urinary and vaginal microbiome for IVF or IVF-ICSI outcome will be only validated for fresh ET. Follow-up has to show whether the predictive accuracy will be similar during the consecutive frozen ET's as part of the IVF or IVF-ICSI treatment or for subsequent stimulated or natural cycles. In addition, external validation will take place in another cohort and hospital. Predictive knowledge of the microbiome profile may enable couples to make a more substantiated decision on whether to continue treatment or not. Hence, the unnecessary physical and emotional burden of a failed IVF or IVF-ICSI treatment can be avoided. TRIAL REGISTRATION: ISRCTN ISRCTN83157250 . Registered 17 August 2018. Retrospectively registered.

Identification and evaluation of the microbiome in the female and male reproductive tracts.

BACKGROUND: The existence of an extensive microbiome in and on the human body has increasingly dominated the scientific literature during the last decade. A shift from culture-dependent to culture-independent identification of microbes has occurred since the emergence of next-generation sequencing (NGS) techniques, whole genome shotgun and metagenomic sequencing. These sequencing analyses have revealed the presence of a rich diversity of microbes in most exposed surfaces of the human body, such as throughout the reproductive tract. The results of microbiota analyses are influenced by the technical specifications of the applied methods of analyses. Therefore, it is difficult to correctly compare and interpret the results of different studies of the same anatomical niche. OBJECTIVES AND RATIONALE: The aim of this narrative review is to provide an overview of the currently used techniques and the reported microbiota compositions in the different anatomical parts of the female and male reproductive tracts since the introduction of NGS in 2005. This is crucial to understand and determine the interactions and roles of the different microbes necessary for successful reproduction. SEARCH METHODS: A search in Embase, Medline Ovid, Web of science, Cochrane and Google scholar was conducted. The search was limited to English language and studies published between January 2005 and April 2018. Included articles needed to be original microbiome research related to the reproductive tracts. OUTCOMES: The review provides an extensive up-to-date overview of current microbiome research in the field of human reproductive medicine. The possibility of drawing general conclusions is limited due to diversity in the execution of analytical steps in microbiome research, such as local protocols, sampling methods, primers used, sequencing techniques and bioinformatic pipelines, making it difficult to compare and interpret results of the available studies. Although some microbiota are associated with reproductive success and a good pregnancy outcome, it is still unknown whether a causal link exists. More research is needed to further explore the possible clinical implications and therapeutic interventions. WIDER IMPLICATIONS: For the field of reproductive medicine, determination of what is a favourable reproductive tract microbiome will provide insight into the mechanisms of both unsuccessful and successful human reproduction. To increase pregnancy chances with live birth and to reduce reproduction-related health costs, future research could focus on postponing treatment or conception in case of the presence of unfavourable microbiota and on the development of therapeutic interventions, such as microbial therapeutics and lifestyle adaptations.