In couples trying to conceive, 10–15% are affected by subfertility—defined as 1 year of unprotected intercourse without achieving a pregnancy (Evers, 2002). In such cases, subfertility is evaluated by means of a medical workup of both partners, to determine whether couples have an indication for ART. Common causes of subfertility include ovulatory disorders, tubal disease and sperm abnormalities. In nearly one-third of all cases, subfertility remains unexplained after such evaluation (Evers, 2002).
Not all subfertile couples trying to conceive will benefit from an ART treatment. For example, couples with unexplained subfertility may still have a good chance of conceiving spontaneously within the first year after they have been diagnosed (Eijkemans et al., 2008; Steures et al., 2006). To prevent under- and overtreatment, the decision as to whether to wait or to start treatment requires careful consideration.
Various models have been developed for predicting the chances of a spontaneous pregnancy. Hunault et al. (2004) developed a prediction model for the chance of spontaneous pregnancy within the following year for couples with unexplained subfertility, which is integrated in the daily practise of reproductive medicine in the Netherlands. The prediction of Hunault is based on the following predictors: duration of subfertility, the woman’s age, whether the infertility is primary or secondary and the percentage of motile sperm. If the predicted chance of spontaneous pregnancy in the following year is higher than their chance with ART, couples are counselled to postpone ART treatment. If the predicted chance is lower, ART improve the chances of pregnancy (Brosens et al., 2004).
Commonly used ART procedures are IVF and IVF with intracytoplasmic sperm injection (IVF-ICSI). These procedures are invasive, costly and do not guarantee a pregnancy. Only 25–35% of the women become pregnant after the first embryo transfer (ET). If prior to the start of treatment one could predict that the embryo implantation would likely be unsuccessful, then an invasive IVF or IVF-ICSI treatment—with the accompanying physical, emotional and financial burden—could be avoided or postponed.
Over the past decade, research has shown that beside the known factors used in prediction models such as female age, sperm quality and antral follicle count, outcome of assisted reproduction might also be affected by the microorganisms of the urogenital tract (Bracewell-Milnes et al., 2018; Egbase et al., 1996; Fanchin et al., 1998; Moore et al., 2000; Pelzer et al., 2011; Selman et al., 2007). The collection of microorganisms that live on or in the human body constitutes the microbiota, and their complete genetic profile is generally referred to as the microbiome. The microbiota can interact actively, both beneficially as well as detrimentally, with the internal milieu of their host (Cho and Blaser, 2012). The most common bacteria that inhabit the vagina belong to the genus Lactobacillus (Ravel et al., 2011). Studies have shown that the presence of certain Lactobacillus species during ART procedures may have a positive impact on outcome (Eckert et al., 2003; Mangot-Bertrand et al., 2013; Moore et al., 2000), whereas bacterial vaginosis is associated with poorer results (Babu et al., 2017; Haahr et al., 2018).
The use of the composition of the vaginal microbiome as a predictor for ART outcome has not yet been investigated. We aimed to answer the following questions: first, is the presence or absence of certain vaginal bacteria associated with failure or success to become pregnant after an IVF or IVF-ICSI treatment? Second, can the composition of the vaginal microbiome prior to treatment be used as an independent predictor for IVF or IVF-ICSI outcome?
To answer these questions, we prospectively collected vaginal samples from subfertile women prior to their IVF or IVF-ICSI treatment, recorded their IVF or IVF-ICSI outcome and analysed the vaginal microbiome to determine its potential predictive value for IVF or IVF-ICSI outcome after the first fresh ET. A predictive model was built on this data of the prospective exploratory study and externally validated in a clinic outside the Netherlands.
