A Shift in Glycerolipid Metabolism Defines the Follicular Fluid of IVF Patients with Unexplained Infertility.

Albert Batushansky,Anish Zacharia,Natalya M Kogan,Alaa Shehadeh,Assaf Ben-Meir,Arieh Moussaieff,Shmuel Herzberg,Daniel Saidemberg,Reut Bruck-Haimson,Chanchal Thomas Mannully

doi:10.3390/biom10081135

Abstract

Follicular fluid (FF) constitutes the microenvironment of the developing oocyte. We recently characterized its lipid composition and found lipid signatures of positive pregnancy outcome after in vitro fertilization (IVF). In the current study, we aimed to test the hypothesis that unexplained female infertility is related to lipid metabolism, given the lipid signature of positive-outcome IVF patients we previously found. Assuming that FF samples from IVF patients with male factor infertility can represent a non-hindered metabolic microenvironment, we compared them to FF taken from women with unexplained infertility. FF from patients undergoing IVF was examined for its lipid composition. We found highly increased triacylglycerol levels, with a lower abundance of monoacylglycerols, phospholipids and sphingolipids in the FF of patients with unexplained infertility. The alterations in the lipid class accumulation were independent of the body mass index (BMI) and were altogether kept across the age groups. Potential lipid biomarkers for pregnancy outcomes showed a highly discriminative abundance in the FF of unexplained infertility patients. Lipid abundance distinguished IVF patients with unrecognized infertility and provided a potential means for the evaluation of female fertility.

Highlights

Infertility occurs in a 9% to 18% prevalence in the general population [1]
Following our previous work that demonstrated a differential lipid composition of Follicular fluid (FF) from in vitro fertilization (IVF) patients with positive pregnancy outcomes, we reasoned that currently unexplained infertility may be related to femalelipid metabolism
For a detailed understanding of the differences in the FF lipid composition of IVF patients of different backgrounds, we studied the relative abundance of different lipid classes

Summary

Introduction

Infertility occurs in a 9% to 18% prevalence in the general population [1]. Infertility etiology includes ovulation dysfunction, mechanical factor (uterine cavity or blocked fallopian tubes) and male infertility (mainly abnormal semen analysis). In cases of infertility investigation without any abnormal result, an “unexplained infertility” is diagnosed in ~20–30% of infertile couples. In most cases, the “unexplained” etiology for infertility remains obscure [2,3,4,5]. The oocyte microenvironment provides the necessary requirements for oocyte developmental competence, which is defined as the ability of the oocyte to complete meiosis and undergo fertilization, cleavage and fetal development to a healthy baby. These concerted processes require coordinated cellular metabolism with changing energy requirements [3]

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