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The general health of the endometrium (the inner lining of the womb) is sometimes overlooked in everyday practice. Igenomix, the designer of the well-known endometrial receptivity analysis (ERA), developed two new tests for the assessment of the endometrium.

The ERA test: Endometrial Receptivity Analysis

Patented in 2009, the ERA test uses Next Generation Sequencing (NGS) technology to evaluate the expression of the 248 genes most commonly involved in the implantation process and to identify the optimal time for embryo implantation. The clinical applicability of the ERA test for patients with a history of failed implantation was scientifically proven by Ruiz-Alonso et al. in 2013 and 2014.

The indications of the ERA test:

1. Repeated failed implantations
2. Patients with morphological normal endometrium following the surgical treatment of congenital uterine anomalies
3. Patients with atrophied or hypertrophied endometrium

The biopsy for the ERA test is performed on the day when the embryo transfer should theoretically take place. The endometrium can be prepped for embryo transfer according to each clinic’s protocol as long as the embryo is transferred in a cycle identical to that for which the biopsy was performed.

The result of the test will show if the endometrium is in a state that precedes, matches or has exceeded the “implantation window”. Based on this, the treatment with progesterone will be extended or shortened.

The EMMA test: The Endometrial Microbiome Metagenomic Analysis

In 2012, the Human Microbiome Project Consortium concluded that certain microorganisms and their genomes are essential to human health.

Recently, researchers found that the pathological variations of lactobacilli in the endometrium play a role in infertility (Moreno et al., Am J Obstet Gynecol, 2016). The EMMA test checks if the microbiome inside the uterine cavity is optimal for implantation.

Although the EMMA test may be useful in improving the success of embryo transfer procedures in all patients, the test is particularly recommended to patients who have experienced repeated failed implantations. EMMA employs New Generation Sequencing (NGS) technology in order to achieve a complete profiling of the endometrial microbiome. The endometrium biopsy is done between days 15-25 of the menstrual cycle or in the secretion phase of embryo transfer preparation cycles. For patients scheduled to undergo both the EMMA and the ERA tests, a single biopsy is sufficient and it is performed according to the ERA requirements.

The difference between assessing the microbiome via NGS versus microbial culture lies with the fact that about 20-60% of bacteria cannot be grown conventionally. NGS presents the advantage of allowing the identification of both bacteria which respond to ordinary culture media and those which do not.

The results of the test include the following information:

1. The percentage of lactobacilli in the biopsy sample
2. The 10 most common bacteria in the uterine cavity (also in percentages)
3. Whether the endometrial microbiome is normal (elevated level of lactobacilli) or abnormal (low level of lactobacilli and/or presence of pathogenic bacteria)
4. Recommended probiotics/antibiotics if necessary

The ALICE test: The Analysis of Infectious Chronic Endometritis

Chronic endometritis is a chronic inflammation of the endometrium caused by an infection with pathogens.

Chronic endometritis is a chronic inflammation of the endometrium caused by an infection with pathogens.

Chronic endometritis often goes undiagnosed because it is mostly asymptomatic and difficult to detect (it requires hysteroscopy with endometrial biopsy and histology with microbial culture).

The endometrium biopsy is done between days 15-25 of the menstrual cycle or in the secretion phase of embryo transfer preparation cycles. For patients scheduled to undergo both the EMMA and the ERA tests, a single biopsy is sufficient and it is performed according to the ERA requirements.

The results of the test will indicate if the biopsy sample contained any evidence of the following bacteria: Enterococcus spp., Enterobacteriaceae, Streptococcus spp., Staphylococcus spp., Mycoplasma spp, si Ureaplasma spp., Chlamydia, and Neisseria spp. If such bacteria are found, an antibiotic treatment will also be prescribed.