Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression

Premature progesterone rise during gonadotrophin-releasing hormone (GnRH) antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. This study evaluated endometrial gene expression on the day of oocyte retrieval according to the concentration of serum progesterone on the day of human chorionic gonadotrophin (HCG) administration in GnRH-antagonist/recombinant FSH IVF cycles with fresh embryo transfer. Endometrial biopsies (n = 14) were analysed with Affymetrix HG U133 Plus 2.0 Arrays. Patients were divided into three groups according to their progesterone serum concentration on the day of HCG administration: ⩽0.9 ng/ml (group A), 1–1.5 ng/ml (group B) and >1.5 ng/ml (group C). Gene expression analysis showed a small number of significantly differentially expressed probe sets between groups A and B (five up/23 down in B) and a large difference between groups B and C (607 up/212 down; P ⩽ 0.05, fold change ⩾1.4). Validation was performed with quantitative real-time PCR on selected genes. As far as is known, this is the first study to demonstrate a distinct difference in endometrial gene expression profile between patients with a progesterone serum concentration above and below the threshold of 1.5 ng/ml on the day of HCG administration.During an IVF treatment in a stimulated cycle, some patients undergo an early elevation of progesterone during the follicular phase of their menstrual cycle. This is associated with lower pregnancy and implantation rates. In this study, we evaluated endometrial gene expression on the day of oocyte retrieval according to the concentration of serum progesterone on the day of human chorionic gonadotrophin (HCG) administration in stimulated IVF cycles with fresh embryo transfer. Fourteen endometrial biopsies were divided into three groups according to their progesterone serum concentration: ⩽0.9 ng/ml (group A), 1–1.5 ng/ml (group B) and >1.5 ng/ml (group C). Microarray gene expression analysis showed a small difference between groups A and B and a large difference between groups B and C. Technical validation with a more quantitative PCR technique was performed on selected genes. As far as is known, this is the first study to demonstrate a distinct difference in endometrial gene expression profile between patients with a progesterone serum concentration above and below the threshold of 1.5 ng/ml on the day of HCG administration, which might reflect an important issue for implantation failure in IVF patients with premature progesterone rise.