Abstract
Study question
In men and women undergoing IVF are preconceptual circulating metabolites associated with ongoing pregnancy rates?
Summary answer
Preconceptual serum histidine levels, in both women and men were associated with ongoing pregnancy. Several amino acids and lipoproteins exhibited possible sex-specific associations.
What is known already
Preconceptual maternal health has been associated with pregnancy outcomes after IVF. The extent to which this is because of pre-existing metabolic factors related to infertility and the role of paternal metabolic health is unclear.
Study design, size, duration
Cohort of 398 women and 325 male partners prospectively recruited between 1 April 2017 and 31 March 2019.
Participants/materials, setting, methods
Women and their male partners intending to undergo assisted conception at a University Hospital, had detailed pre-treatment phenotyping including non-fasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis and inflammatory markers) (155 metabolites) quantified by NMR spectroscopy. Multivariable linear and logistic regression were used to examine the associations of pre-treatment serum metabolic profiles, with ongoing pregnancy at 20 weeks gestation with adjustment for confounders.
Main results and the role of chance
392 women and 322 men proceeded to IVF treatment, with an overall ongoing pregnancy rate of 47.2% (95% CI 0.42, 0.52) per cycle started and a multiple pregnancy rate of 1.1% (95%CI 0.0, 0.04). In both females and males in confounder adjusted analyses histidine was associated with the chance of ongoing pregnancy, with similar magnitudes in each parent (OR 1.28 (95% CI 1.03, 1.60) per one standard deviation (SD) increase for males and OR 1.26 (95% CI 0.99, 1.60) per one SD increase for females). In females Alanine (OR = 1.31 (1.05, 1.64)), Isoleucine (OR = 1.28 (1.02, 1.61)) and Leucine (OR = 1.24 (0.99, 1.55)) had a positive association with ongoing pregnancy, while in males, pyruvate (OR = 1.30 (1.02,1.66)) exhibited a positive association with ongoing pregnancy. In both parents, associations of lipids, lipoproteins sub-particles and fatty acids with pregnancy were closer to the null.
Limitations, reasons for caution
Suggestive parental differences could be due to chance. Patients were relatively homogenous undertaking their first IVF cycle and the results may not be generalisable to other clinical populations.
Wider implications of the findings: This study provides data on a range of metabolic pathways and their association with ongoing pregnancy following IVF. The identification of potentially relevant clinical effect sizes in both men and women warrants further exploration.
Trial registration number
Not applicable