Endometrial Receptivity Testing

Course / Endometrial Receptivity Testing

Endometrial Receptivity Testing

Course Overview

A successful embryo transfer depends not only on embryo quality but also on the uterine environment at the time of implantation. While many IVF and surrogacy programs focus on embryo grading or genetic testing, the timing of transfer relative to endometrial receptivity is equally critical.

This lesson, presented by fertility specialists at Surrogacy4All, explains how clinicians evaluate and optimize the endometrium — the inner lining of the uterus — to improve implantation rates and live birth outcomes.

The Basics of Implantation

Implantation is a highly coordinated biological process that occurs when a viable embryo attaches to a receptive endometrium. Three key elements must align:

Embryo Competence – A healthy, genetically normal blastocyst ready for implantation.
Endometrial Receptivity – A synchronized uterine lining capable of supporting embryo attachment.
Communication Signals – Molecular interactions between embryo and endometrial cells that allow adhesion and invasion.

This alignment happens during a limited timeframe known as the “window of implantation” (WOI) — typically between days 19–23 of a natural 28-day menstrual cycle or 4.5–6.5 days after progesterone exposure in a controlled cycle.

Even minor misalignment between the embryo’s readiness and endometrial receptivity — as little as 12–24 hours — can prevent implantation, emphasizing the importance of precise timing.

Role of the Endometrium in Implantation

The endometrium plays a dynamic and essential role in early pregnancy establishment.

1. Cyclic Transformation

During the follicular phase, rising estrogen levels promote endometrial thickening and glandular proliferation.
In the luteal phase, progesterone converts this lining into a secretory state, rich in nutrients, growth factors, and cytokines essential for embryo attachment.

2. Molecular Signaling

The endometrium expresses specific markers of receptivity during the WOI, including:

Integrins (αvβ3, α4β1) – adhesion molecules aiding embryo attachment.
Leukemia Inhibitory Factor (LIF) and HOXA10 – key modulators of uterine receptivity.
Pinopodes – microscopic cellular structures appearing at peak receptivity.

3. Structural and Immune Readiness

A receptive endometrium exhibits:

Optimal thickness (≥7mm and trilaminar appearance on ultrasound).
Balanced immune profile, allowing tolerance for the semi-allogenic embryo.
Adequate blood flow to deliver oxygen and nutrients.

When these physiological and molecular cues align, implantation can proceed successfully.

Assessment of Endometrial Receptivity

Clinicians assess endometrial readiness using both imaging and molecular testing techniques.

1. Ultrasound Evaluation

A transvaginal ultrasound assesses:

Thickness (ideally 7–12 mm).
Pattern (trilaminar/“triple-line” appearance before ovulation).
Blood flow, measured by Doppler studies.

While useful, ultrasound cannot determine the exact molecular timing of receptivity — hence the development of advanced diagnostic tools like the Endometrial Receptivity Array (ERA).

2. Endometrial Biopsy and Molecular Profiling

In cases of repeated implantation failure or inconclusive ultrasound findings, an endometrial biopsy may be performed.
Tissue samples are analyzed to identify the gene expression profile associated with a receptive endometrium.

This molecular analysis forms the foundation of ERA testing.

Endometrial Receptivity Array (ERA)

The Endometrial Receptivity Array (ERA) is a genomic test designed to determine the precise timing of a woman’s “window of implantation.”

How It Works

The patient undergoes a mock embryo transfer cycle, identical to a real transfer cycle.
On the day when the embryo would typically be transferred, a small biopsy of the endometrial tissue is taken.
The sample is analyzed for expression of over 200 genes related to endometrial receptivity.
The test classifies the endometrium as:
- Receptive – optimal timing for embryo transfer.
- Pre-receptive or Post-receptive – suggesting that the ideal transfer window occurs earlier or later than expected.

Based on this data, clinicians can personalize the progesterone exposure duration before transfer, ensuring precise synchronization between the embryo and endometrium.

Clinical Use

ERA is especially valuable for:

Patients with repeated implantation failure (RIF).
Surrogates undergoing programmed cycles where timing control is essential.
Cycles using frozen embryos or donor eggs, where hormonal regulation differs from natural cycles.

Cost of the ERA Test

In the United States, the ERA test typically costs between $800–$1,500, excluding the cost of medications or mock cycle monitoring.
While this represents an additional investment, it can reduce the emotional and financial burden of repeated failed transfers by optimizing timing for subsequent attempts.

At Surrogacy4All’s partner clinics, the ERA test is recommended selectively, based on clinical history and previous cycle outcomes. It is not routinely required for first-time IVF or surrogacy transfers unless there are implantation concerns.

Clinical Data on ERA Effectiveness

1. Early Findings

Initial studies suggested that approximately 25% of women may have a displaced window of implantation.
In these cases, personalized embryo transfer timing after ERA testing reportedly improved pregnancy rates.

2. Recent Meta-Analyses

However, more recent large-scale studies have shown mixed results:

In patients without implantation issues, ERA testing did not significantly improve overall pregnancy rates.
For patients with repeated implantation failure, some benefit has been observed — especially when ERA revealed a non-receptive endometrium.

3. Clinical Perspective

The ERA test is best used as a diagnostic adjunct, not a universal solution.
It provides valuable insight for specific patient populations but should be interpreted alongside:

Endometrial morphology
Hormone timing
Embryo quality
Lab performance

At Surrogacy4All, our fertility experts recommend ERA testing as part of a targeted approach, focusing on evidence, prior outcomes, and individualized care rather than routine use.

Endometrial Receptivity Testing