Men's Dietary Patterns in Relation to Treatment Outcomes among Couples Undergoing Infertility Treatment with Assisted Reproductive Technology

Abstract

OVERVIEW: Infertility is a major health concern worldwide, especially in societies where delayed childbearing is becoming more common. While much of the focus on understanding the causes of infertility focuses on women, male factors account for approximately half of the infertility burden. Standard semen analysis is not only an important biomarker of spermatogenesis and testicular function but is also the cornerstone for clinical diagnosis of male factor infertility. However, it is known that semen analysis is not a perfect predictor of a couple's fertility, both in couples attempting conception on their own and in couples attempting conception with medical assistance. Men's diet has been reported as a potentially modifiable factor influencing semen quality. However, there is little data evaluating the impact of men's diet on a couple's fertility. There is a particularly important knowledge gap as some data suggests that associations between diet and semen quality do not necessarily translate into associations with couple-based outcomes, such as fertility. Traditionally, research aimed at understanding the role of nutrition on health has focused on trying to identify the impact of individual foods or nutrients. However, this approach has important shortcomings as it fails to account for known and unknown complex interactions between different nutrients, foods, and non-nutritive components of food. Moreover, results from research focused on individual foods or nutrients are not always easy to translate into clinical or public health recommendations as foods and nutrients are not eaten in isolation but are rather part of dietary patterns. Acknowledging this reality, in this thesis, I have decided to focus on understanding the role of men's dietary patterns on semen quality and infertility treatment outcomes. In general terms, diet patterns can be defined by either an a priori (hypothesis-oriented) approach which generally involves the calculation of diet scores based on a fixed set of external criteria or an a posteriori (data-driven) whereby patterns are identified based on correlation patterns between individual foods/nutrients, correlation patterns between diet and intermediate biomarkers, correlation patterns between different individuals, or a combination thereof. While these different approaches have strengths and limitations, a strength of data-driven approaches is that these can generally account for the totality of diet (rather than specific aspects of diet) and by relying solely on data, any resulting diet pattern is not influenced by pre-existing knowledge or beliefs of what the relation between diet and health outcomes should be. Therefore, we investigated the impact of men's diet on couple's infertility treatment outcomes using prospective observational study data using two different data-driven to identify dietary patterns. Paper 1: We identified underlying dietary patterns among men using principal component analysis (PCA) and then investigated the association between adherence to the resulting dietary patterns and outcomes of infertility treatment with assisted reproductive technology (ART). This analysis provides insights into how the impact that actual dietary behavior observed in men presenting to fertility centers may affect ART outcomes, regardless of the underlying biological mechanisms linking these. Paper 2: We empirically derived a dietary score capturing the overall association of diet with semen quality using reduced rank regression (RRR) and then examined this score in relation to outcomes of infertility treatment with ART. This analysis provides insights into how dietary factors influencing semen quality parameters may in turn impact ART outcomes.