PROK1 Level in the Follicular Microenvironment: A New Noninvasive Predictive Biomarker of Embryo Implantation

Abstract

Context: Prokineticin 1 (PROK1), also called endocrine gland-derived vascular endothelial growth factor, is a well-established regulator of endometrial receptivity and placental development. However, its clinical usefulness as a noninvasive predictive biomarker of embryo implantation is yet to be validated.

Objective: The main objective of this article was to determine the relationship between PROK1 levels in the follicular fluid (FF) and fertilization culture media (FCM) and the reproductive outcome in patients who received a first conventional in vitro fertilization-embryo transfer. The secondary objective was to characterize the expression of PROK1 and its receptors (PROKRs) in the human follicular microenvironment.

Design and setting: We conducted a prospective study between January 2013 and June 2015 at the University Hospital of Grenoble.

Patients: A total of 135 infertile in vitro fertilization patients and 10 women undergoing ovarian tissue cryopreservation were included.

Interventions: The PROK1 concentration was measured by ELISA in FF and FCM collected on the day of oocyte retrieval and the day of the oocyte denudation step, respectively. Follicular expression of the PROK1/PROKR system was determined by immunohistochemistry, RT-quantitative PCR, and ELISA.

Main outcome measure: Assessment of the clinical pregnancy rates was the main outcome.

Results: FF and FCM PROK1 levels were significantly higher in the embryo implantation group (P < .001) and were predictive of subsequent embryo implantation (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.81-1.00], P = .001; and 0.88 [0.72-1.00], P = .001, respectively). FF and FCM PROK1 levels remain similar irrespective of the embryo morphokinetic parameters (P = .71 and P = .83, respectively). The PROK1/PROKR system is expressed during human folliculogenesis.

Conclusions: PROK1 levels in FF and FCM could constitute new predictive noninvasive markers of successful embryo implantation in conventional in vitro fertilization-embryo transfer.