Metabolic Mechanisms Underlying the Association Between the Profertility Diet and In Vitro Fertilization End Points.

Background: The profertility diet is a dietary pattern composed of nutrients and foods most consistently associated with in vitro fertilization (IVF) end points in women.

Objectives: We examined the potential biological mechanisms underlying the association between adherence to a profertility diet and IVF end points using high-resolution metabolomics.

Methods: Among 120 women who underwent an autologous oocyte IVF cycle (2007-2015) in Northeast United States, we collected a serum sample during controlled ovarian stimulation and a follicular fluid sample on the day of oocyte retrieval. Women completed a food frequency questionnaire upon enrollment into the study to examine adherence to the profertility diet pattern. Liquid chromatography with high-resolution mass spectrometry was used for untargeted metabolomic analysis of biospecimens. We identified metabolic features (and enriched biological pathways) associated with the profertility diet and 2 IVF end points, live birth and clinical pregnancy, via a meet-in-the-middle approach.

Results: In the follicular fluid metabolome, vitamin D-3 metabolism was associated with adherence to the profertility diet pattern and live birth. Additionally, vitamin D-3 metabolism, vitamin B-6 metabolism, and bile acid biosynthesis were associated with both adherence to the profertility diet pattern and clinical pregnancy. In the serum metabolome, only tryptophan metabolism was associated with adherence to the profertility diet pattern and live birth. We confirmed the chemical identity of a metabolite with level 1 evidence, 4-pyridoxate, which was higher in the serum and follicular fluid among women with stronger adherence to the profertility diet pattern and among women with a live birth.

Conclusions: The beneficial association between adherence to the profertility diet and IVF outcomes may be mediated through vitamin D-3 metabolism, vitamin B-6 metabolism, and bile acid biosynthesis in the follicular fluid and tryptophan metabolism in the serum. These results provide new insight in the important biological pathways underlying a dietary pattern providing optimal fertility benefits to women.