ERA, EMMA, and ALICE: Endometrial Testing Explained

After one or more failed embryo transfers, especially with chromosomally tested embryos, the question shifts from egg quality to endometrial receptivity. Three tests developed by Igenomix have become part of the conversation at many IVF clinics: ERA, EMMA, and ALICE. Each addresses a different aspect of endometrial function, and understanding what they actually measure, what the evidence supports, and when they change outcomes is essential before adding them to your protocol.

ERA: Endometrial Receptivity Analysis

The ERA test sequences 238 genes from an endometrial biopsy taken during a mock cycle to determine whether your implantation window aligns with the standard progesterone exposure timing. The result classifies your endometrium as receptive, pre-receptive, or post-receptive at the time of biopsy.

If displaced, the transfer is adjusted. A pre-receptive result means the window opens later than expected, and the transfer is delayed by 12 to 24 hours of additional progesterone exposure. A post-receptive result is rarer and suggests the window has already closed, requiring earlier transfer timing.

What the Evidence Shows

The ERA's clinical utility has been debated since the publication of the largest randomized controlled trial in 2022. That trial, enrolling over 750 patients undergoing their first frozen embryo transfer, found no significant difference in ongoing pregnancy rates between ERA-guided and standard transfer timing.

However, the trial studied unselected patients. The population most likely to benefit, those with repeated implantation failure (RIF) of euploid embryos, was not the primary study group. Smaller retrospective studies in RIF patients have shown a displaced window in 20 to 30% of cases, and personalized timing improved outcomes in that subset.

EMMA: Endometrial Microbiome Analysis

The uterine cavity was long considered sterile. Research over the past decade has shown it hosts a microbiome, and its composition may affect reproductive outcomes. EMMA uses next-generation sequencing to profile the bacterial populations present in an endometrial sample.

A Lactobacillus-dominant endometrium (above 90% Lactobacillus) has been associated with higher implantation rates in some observational studies. Dysbiotic profiles, with high proportions of Gardnerella, Streptococcus, or Enterococcus, have been associated with lower rates, though the studies are mostly observational and the treatment protocols are not standardized.

When dysbiosis is found, treatment typically involves targeted antibiotics or probiotics, followed by a repeat biopsy to confirm resolution before proceeding with transfer. The evidence that this intervention improves pregnancy rates is promising but not yet definitive.

ALICE: Chronic Endometritis Detection

Chronic endometritis (CE) is a persistent, low-grade infection of the uterine lining that often produces no symptoms. It is found in roughly 10 to 15% of infertile women and up to 30% of women with recurrent implantation failure or recurrent pregnancy loss.

ALICE uses molecular detection to identify nine bacterial pathogens most commonly associated with CE, including Enterococcus, E. coli, Streptococcus, Staphylococcus, and Mycoplasma/Ureaplasma species. This approach is more sensitive than traditional histology (looking for plasma cells under a microscope), which misses a meaningful proportion of cases.

Treatment is straightforward: a targeted antibiotic course, typically 14 to 21 days, followed by confirmation that the infection has cleared. Multiple studies have shown that treated CE is associated with improved implantation and pregnancy rates compared to untreated CE.

The Biopsy Procedure

All three tests use the same tissue sample, obtained through an endometrial biopsy. The biopsy is performed during a mock frozen embryo transfer cycle: you take the same progesterone regimen you would before a real transfer, and the biopsy is timed to the day the transfer would normally occur (typically progesterone day 5 for blastocysts).

The procedure takes roughly 30 seconds and is done in the office without anesthesia. Most patients describe it as a sharp cramping sensation that passes quickly. The sample is sent to Igenomix for processing, with results typically available in 2 to 3 weeks.

Because the biopsy requires a dedicated mock cycle, it adds one cycle's worth of time (and medication cost) to your timeline. This is part of the cost-benefit calculation.

Questions to Ask Your Clinic

• How many failed transfers of chromosomally normal embryos justify ERA testing at your clinic?
• Do you treat EMMA dysbiosis findings, and with what protocol?
• How do you diagnose chronic endometritis: histology, ALICE, or both?
• Can all three tests be run from one biopsy, and what is the combined cost?
• If ERA shows a displaced window, how do you adjust transfer timing in practice?