The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells.

Valentina Notarstefano,Lisa Vaccari,Maurizio Cignitti,Anna Rita Polidori,Elisabetta Giorgini,Andrea Ciavattini,Nina Montik,Oliana Carnevali,Fulvia Antonia Candela,Giorgia Gioacchini

doi:10.3390/ijms21197124

Abstract

Different Follicle Stimulating Hormone (FSH) formulation and Luteinizing Hormone (LH) are used in Assisted Reproductive Technology (ART) to induce follicles development and oocytes maturation, but it is still under debate which protocol is to be preferred. In the present study, the different effects on cumulus cells (CCs) of three controlled ovarian stimulation (COS) protocols, based on urinary FSH, recombinant FSH, or human Menopausal Gonadotropin (hMG) administration, were assessed. CCs were obtained from 42 normal-responders women undergoing COS, randomly divided into three groups according to the used gonadotropin formulation. Differences were found in the expression of genes belonging to the endocannabinoid system (the receptors CNR1, CNR2 and TRPV1, and the enzymes involved in the metabolisms of anandamide, NAPE-PLD and FAAH, and 2-acylglycerol, DAGL and MAGL); consistently, changes in lipid (PPARα, and FASN) and carbohydrate (GLUT1 and GLUT9) metabolisms, in CCs’ macromolecules composition (highlighted by Fourier Transform Infrared Microspectroscopy, FTIRM), and in the number of retrieved oocytes were found. For the first time, statistically significant evidence on the differences related to each COS protocol on the endocannabinoid system, metabolism and macromolecular composition of CCs was found, representing a proof of concept to be further confirmed in a larger cohort of patients.

Highlights

According to the European Society of Human Reproduction and Embryology (ESHRE), Assisted Reproductive Technology (ART) allowed the conception and birth of more than 7 million babies since the first in vitro fertilization (IVF) baby was born in 1978 [1]
Data did not highlight statistically significant differences related to age, BMI, Follicle Stimulating Hormone (FSH) and AMH serum levels; significant differences were found in the number of retrieved oocytes, which was significantly higher in the urinary FSH (uFSH) experimental group, with respect to recombinant FSH (rFSH) and human Menopausal Gonadotropin (hMG)
We focused on the modulation of the endocannabinoid system and on lipid and glucose metabolism, coupled with vibrational information related to the biochemical profile of cumulus cells

Summary

Introduction

According to the European Society of Human Reproduction and Embryology (ESHRE), Assisted Reproductive Technology (ART) allowed the conception and birth of more than 7 million babies since the first in vitro fertilization (IVF) baby was born in 1978 [1]. ART success rates are still unsatisfactory: in 2013, mean European pregnancy rates per aspiration were 29.6% for IVF and 27.8% per ICSI (intra-cytoplasmic sperm injection) [2]. The reasons for these low percentages are ascribable to several factors, such as male and female infertility aetiology [3,4,5], parental reproductive aging [6,7], exposure to xenobiotics [8,9], and the choice of ART treatments [10]. Among the several ovarian stimulation regimens, gonadotropin preparations represent the main formulation for COS protocols in IVF [11]. Since the number of high-quality oocytes to be fertilized is one of the key factors for the success of IVF, several efforts have been made to compare the effects of the different available drugs on IVF outcomes [11]

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