Metabolic mechanisms underlying the association between the pro-fertility diet and in vitro fertilization endpoints.

Background: The pro-fertility diet is a dietary pattern composed of nutrients and foods most consistently associated with in vitro fertilization (IVF) endpoints in women.

Objective: We examined the potential biological mechanisms underlying the association between adherence to a pro-fertility diet and IVF endpoints using high-resolution metabolomics.

Methods: Among 120 women undergoing 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 pro-fertility diet pattern. Liquid chromatography with high-resolution mass spectrometry was used for untargeted metabolomics analysis of biospecimens. We identified metabolic features (and enriched biological pathways) associated with the pro-fertility diet and two IVF endpoints, live birth and clinical pregnancy, via a meet-in-the-middle approach.

Results: In the follicular fluid metabolome, vitamin D3 metabolism was associated with adherence to the pro-fertility diet pattern and live birth. Additionally, vitamin D3 metabolism, vitamin B6 metabolism, and bile acid biosynthesis, were associated with both adherence to the pro-fertility diet pattern and clinical pregnancy. In the serum metabolome, only tryptophan metabolism was associated with adherence to the pro-fertility diet pattern and live birth. We confirmed the chemical identity of one metabolite with Level-1 evidence, 4-pyridoxate, which was higher in the serum and follicular fluid among women with stronger adherence to the pro-fertility diet pattern and among women with a live birth.

Conclusions: The beneficial association between adherence to the pro-fertility diet and IVF outcomes may be mediated through vitamin D3 metabolism, vitamin B6 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.