# Endometrial Basis for Infertility in Women with Recurrent Implantation Failure and Pregnancy Loss

> **NIH NIH U01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $696,508

## Abstract

ABSTRACT
Pregnancy loss is the most common complication of human gestation, occurring in roughly one-half of
natural conceptions and most frequently in the first two to three weeks of gestation. In recent years it has
become apparent that constitutive endometrial dysfunction represents an important contributor to infertility
in women being treated with assisted reproductive technologies (ART). This application is specifically
focused on the endometrial origins and basis of embryo implantation failure (EIF), early pregnancy failure
(EPF), and recurrent pregnancy loss (RPL) in ART patients. The central hypothesis is that idiopathic
infertility primarily stems from constitutive endometrial dysfunction, attributable to defects in progesterone
responsiveness of the endometrial epithelium and stroma as well as immune cells. The goal of this research
is to begin testing this hypothesis by focusing on infertile women experiencing the continuum of first
trimester pregnancy loss. A team of exceptional extramural and intramural investigators with
complementary and substantial expertise in basic reproductive biology and translational reproductive
sciences will address that hypothesis by conducting a collaborative research project. At the NIH Clinical
Center, the endometrium from cohorts of normal healthy fertile donors and infertile patients with carefully
phenotyped and clinically-defined EIF, EPL or RPL will be biopsied in an outpatient setting (Aim 1).
Advanced single cell technologies will be used to interrogate the endometrium (Aim 1). Organoids will be
used to functionally study progesterone responses of the endometrial epithelium (Aim 2). In vitro
decidualization will be used to functionally interrogate hormone responsiveness and decidualization
capacity of the endometrial stroma and understand the influence of decidual immune cells (Aim 3). Cutting-
edge genomic and transcriptomic technologies and advanced bioinformatics and data integration will be used
to understand cell type heterogeneity, cell-specific differences in gene expression, and discern critical
progesterone-driven biological pathways important for endometrial function that are disrupted in infertile women.
The proposed aims are conceptually and technically innovative and together will have a broad impact on
the field by filling a substantial gap in our fundamental knowledge of uterine biology and infertility. This
application specifically targets NIH funding opportunity announcement PAR-18-951 entitled “Opportunities
for Collaborative Research at the NIH Clinical Center” and focuses on major research priorities of the
Fertility and Infertility Branch of the NICHD. These efforts will contribute to our understanding of the cellular
basis of idiopathic infertility, enable the development of new tests enabling clinicians to diagnose and prescribe
regimens directed at treating specific underlying endometrial dysfunction, and ultimately impact pregnancy
outcomes in assisted and natural concep...

## Key facts

- **NIH application ID:** 10153328
- **Project number:** 1U01HD104482-01
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** ALAN H. DECHERNEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,508
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153328

## Citation

> US National Institutes of Health, RePORTER application 10153328, Endometrial Basis for Infertility in Women with Recurrent Implantation Failure and Pregnancy Loss (1U01HD104482-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153328. Licensed CC0.

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