ALICE Analysis of Infectious Chronic Endometritis

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Overview

ALICE
Indications
Benefits

What is ALICE test?

ALICE is a test that detects pathogenic bacteria and recommends adequate treatment.

Pathogenic bacteria cause chronic endometritis, which is linked to implantation failure and recurrent miscarriage.

In cases of repeated implantation failure or recurrent pregnancy loss, chronic endometritis can rise to 66%.

Methodology

ALICE can be performed on a small piece of an endometrial biopsy.

If the patient is undergoing an ERA test, a small portion of the same biopsy can be used, so no additional sample will be required.

How to collect and send the sample

For EMMA, an endometrial biopsy should be taken from day 15 to day 25 of the menstrual cycle. After retrieval, it is important that the sample is briefly shaken vigorously and immediately placed in the refrigerator at 4–8°C for a minimum of 4 hours.

Who should use ALICE?

ALICE may be beneficial for patients with a history of recurrent pregnancy loss or recurrent implantation failure because chronic endometritis has been linked to these events.

Test limitations

Any planned uterine surgical intervention should be performed before sample collection, so that the endometrium is in suitable condition for embryo transfer
Some reports describe a higher prevalence of microbiota alterations in patients with endometriosis
If the patient has fluid in the endometrial lining, the biopsy can be taken. This liquid is most likely caused by an infection of the endometrium
The biopsy could be performed even if the endometrium does not have a trilaminar appearance
If a Dilation and Curettage takes place after EMMA or ALICE test, the results could change. We recommend repeating the test after D&C procedures, ideally in the cycle immediately before the embryo transfer.
We currently have no data about the effect of chemotherapy or radiation on the endometrial microbiome
We currently have no data about the relationship between chronic thyroiditis or polycystic ovary syndrome and the abnormal microbiota
Use of antibiotics can affect EMMA results and should be disclosed when requesting the test
- Inadequate sample or sample preservation:
- Sample not stored at 4–8°C for a minimum of 4 hours.
- Degradation of sample due to displacement of RNAlater stabilization solution from the cryotube by a biopsy that is very large or not fully immersed in preserving agent.
- Insufficient starting material: Not enough tissue sample. (7mm tissue is optimal)
- Excessive blood and mucus in the biopsy sample
- External or residual contamination
- Exposure to excessively high temperatures

Clinical Limitations:

These tests are not able to detect resistance to antibiotics
ALICE only detects the presence of pathogens associated with chronic endometritis. A negative result does not rule out the presence of other endometrial pathogens.
The tests are not 100% accurate at determining the bacterial species.

Why use ALICE?

ALICE is a diagnostic test to detect and quantify the most common pathogenic bacteria causing chronic endometritis, recommending appropriate antibiotic and probiotic treatment
ALICE uses the latest Next Generation Sequencing (NGS) technology to provide microbiome information in endometrial tissue by analysing the abundance of specific bacteria causing chronic endometritis
Using NGS allows the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis
If the ALICE test is positive, the report will focus on the detection of the specific bacteria causing the condition
A list with the recommended antibiotics and probiotics will be provided depending on ALICE results
Microbiology counselling is available

Documentation

Authors: Moreno I, Garcia-Grau I, Perez-Villaroya D, Gonzalez-Monfort M, Bahçeci M, Barrionuevo M. J, Taguchi S, Puente E, Dimattina M, Lim M. W, Meneghini G, Aubuchon M, Leondires M, Izquierdo A, Perez-Olgiati M., Chavez A., Seethram K., Bau D., Gomez C., Valbuena D, Vilella F, Simon C

Publication: Microbiome. 2022 Jan 4;10(1):1. doi: 10.1186/s40168-021-01184-w.

PMID: 34980280

Title: Human Microbiome Project Consortium – Structure, function and diversity of the healthy human microbiome

Authors: Human Microbiome Project Consortium

Publication: Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234.

PMID: 22699609

Title: Evidence that the endometrial microbiota has an effect on implantation success or failure

Authors: Moreno I, Codoñer F, Vilella F, Valbuena D, Martinez-Blanch J F, Jimenez-Almazán J, Alonso R, Alamá P, Remohí J, Pellicer A, Ramon D, Simon C

Publication: Am J Obstet Gynecol. 2016 Dec;215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. Epub 2016 Oct 4.

PMID: 27717732

Title: The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology

Authors: Moreno I, Cicinelli E, Garcia-Grau I, Gonzalez-Monfort M, Bau D, Vilella F, De Ziegler D, Resta L, Valbuena D, Simon C

Publication: Am J Obstet Gynecol. 2018 Jun;218(6):602.e1-602.e16. doi: 10.1016/j.ajog.2018.02.012. Epub 2018 Feb 23.

PMID: 29477653

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