P-334 Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer
Authors: Choo S P , Lee I , Lee J H , Park J H , Cho S , Choi Y S 
Published: June 2023

Abstract

Study question
To evaluate endometrial transcriptomic patterns in early-secretory phase (ESP) and mid-secretory phase (MSP) in a natural menstrual cycle before IVF-ET

Summary answer
Endometial ranscriptomic patterns in ESP and MSP immediately before IVF-ET appear to differ according to IVF-ET outcome, which may be implicated in endometrial receptivity.

What is known already
Biologic processes and molecular participants in the transition from ESP to MSP endometrium underscore the complex events in preparing for embryo implantation. Previously reported genes with altered expression during endometrial transition from the ES phase to the MS phase were frequently involved in ion binding, cell cycle regulation, transport of signaling proteins, or immune modulation.
Although several studies have compared gene expression in the receptive phase and pre-receptive phases in an attempt to identify a molecular signature characteristic of a receptive endometrium, a consensus has not been reached regarding the genes accounting for transcriptomic differences between phases.

Study design, size, duration
Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter data in both the pregnant and non-pregnant groups.

Participants/materials, setting, methods
A total of 30 patients whose endometrial tissues were obtained in a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle day 16 to 18) or MSP (cycle day 19 to 21) according to Noyes criteria. The patients were divided into two groups depending on IVF-ET outcome: pregnant (n = 14; 7 in ESP and 7 in MSP) or non-pregnant (n = 16; 8 in ESP and 8 in MSP).

Main results and the role of chance
A total of 14 DEGs were identified when comparing the ES phase and MS phase endometrium in the pregnant group. A total of 12 DEGs were identified when comparing the ES phase and MS phase endometrium in the non-pregnant group Nine genes were upregulated in the MS phase endometrium, compared to the ES phase endometrium, in both the pregnant and non-pregnant groups: adrenoceptor alpha 2A (ADRA2A), interleukin 1 receptor-associated kinase 2 (IRAK2), a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1 (SERPINE1), integrin subunit beta 3 (ITGB3), transmembrane protein 252 (TMEM252), huntingtin associated protein 1 (HAP1), C2 calcium-dependent domain containing 4A (C2CD4A), and integrin subunit alpha 2 (ITGA2). Four genes were upregulated in the MS phase endometrium, compared to the ES phase endometrium, only in the pregnant group: TMEM37, galactosidase beta 1 like 2 (GLB1L2), Rho family GTPase 3 (RND3), and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). One gene (ADAMTS8) was downregulated and one gene (monoamine oxidase A [MAOA]) was upregulated in the MS phase endometrium, compared to the ES phase endometrium, only in the non-pregnant group.

Limitations, reasons for caution
Firstly, since our sample size was relatively small, our results should be considered preliminary. Secondly, because endometrial tissue samples wee not obtained in IVF-ET cycle, they may not reflect changes in an actual pregnancy cycle.Thirdly, there may have been embryonic effects on implantation that were not accounted for.

Wider implications of the findings
TMEM37, GLB1L2, RND3, and CYP24A1 were upregulated only in the pregnant group; ADAMTS8 was downregulated while MAOA was upregulated only in the non-pregnant group.These novel DEGs, which have not been previously studied, may have functional significance during the WOI and serve as potential biomarkers of endometrial receptivity.

Trial registration number
not applicable