Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle.

Richard J Kordus,Holly A Lavoie

doi:10.1530/rep-16-0500

Abstract

Cumulus and mural granulosa cells of the ovarian follicle surround and interact with the developing oocyte. These follicular cells reflect the oocyte's overall health and may indicate subsequent developmental competence of embryos. Biomarkers of granulosa cells associated with individual oocytes could potentially be used in assisted reproduction to indicate which embryos have the best chance of implanting in the uterus and completing gestation. In this review, we have performed a comprehensive assessment of the recent literature for human cumulus and mural granulosa cell mRNA biomarkers as they relate to pregnancy and live birth. A critical discussion of variables affecting granulosa gene expression profiles for in vitro fertilization patients, including patient demographics and ovarian stimulation regimens, is presented. Although studies with microarray data were evaluated, this synopsis focuses on expressed genes that have been validated by quantitative RT-PCR. Furthermore, we summarize the current published data that support or refute identified granulosa expressed genes as potential biomarkers of embryos that give rise to ongoing pregnancy and live birth. Finally, we review studies that offer predictive models for embryo selection for uterine transfer based on biomarkers that show differential gene expression.

Highlights

Even with improvements in assisted reproductive technologies (ART) over the past couple of decades, the success rates for procedures treating infertility and leading to live births is still less than optimal
By examining the previous published literature, Ekart and coworkers (2013) developed a ranking system for selection of mature oocytes that would theoretically lead to pregnancy based on cumulus cell (CC) gene transcription. They selected an 8 gene panel, hyaluronan synthase 2 (HAS2), follicle=stimulating hormone receptor (FSHR), solute carrier family 2 member 4 (SLC2A4), activated leukocyte cell adhesion molecule (ALCAM), secreted frizzled-related protein 2 (SFRP2), VCAN, neuropilin 1 (NRP1) and progesterone receptor (PGR) based on prior published studies (McKenzie et al 2004, Gebhardt et al 2011, Wathlet et al 2011, Fragouli et al 2012, Iager et al 2013) to predict the mature oocytes that would lead to live birth
CC and mural granulosa cells (MGC) associated with individual oocytes may be a valuable source for identifying biomarkers that result reliably in choosing embryos capable of leading to a live birth

Summary

Introduction

Even with improvements in assisted reproductive technologies (ART) over the past couple of decades, the success rates for procedures treating infertility and leading to live births is still less than optimal. The granulosa gene biomarker studies undertaken have varied among the chosen endpoints that include oocyte nuclear maturation, fertilization, day 2 and day 3 embryo morphologies, day 5 and day 6 blastocyst morphologies, implantation, ongoing pregnancy and live birth.

Results

Conclusion