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

Robert B Hood; Donghai Liang; Yilin Wang; Youran Tan; Irene Souter; Dean P Jones; Russ Hauser; Jorge E Chavarro; Audrey J Gaskins

doi:10.1016/j.tjnut.2024.11.013

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

J Nutr. 2024 Nov 16:S0022-3166(24)01180-5. doi: 10.1016/j.tjnut.2024.11.013. Online ahead of print.

Authors

Robert B Hood¹, Donghai Liang², Yilin Wang³, Youran Tan³, Irene Souter⁴, Dean P Jones⁵, Russ Hauser⁶, Jorge E Chavarro⁷, Audrey J Gaskins⁸

Affiliations

¹ Department of Epidemiology, Emory University, Rollins School of Public Health, Atlanta, GA, United States. Electronic address: robert.baltasar.hood@emory.edu.
² Department of Epidemiology, Emory University, Rollins School of Public Health, Atlanta, GA, United States; Gangarosa Department of Environmental Health, Emory University, Rollins School of Public Health, Atlanta, GA, United States.
³ Gangarosa Department of Environmental Health, Emory University, Rollins School of Public Health, Atlanta, GA, United States.
⁴ Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA, United States.
⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁷ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁸ Department of Epidemiology, Emory University, Rollins School of Public Health, Atlanta, GA, United States.

PMID: 39551358
DOI: 10.1016/j.tjnut.2024.11.013

Abstract

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.

Keywords: bile acid; clinical pregnancy; live birth; metabolomics; profertility diet; tryptophan; vitamin B-6; vitamin D-3.