The ERA test was developed to deduce whether the endometrium is receptive to an embryo, and to predict a woman’s personal window of implantation. Over the past few years, the ERA test has become a popular option for those seeking answers on why their embryos have failed to implant, however as you can see in the chart above, the lack of evidence that it improves outcomes has earned the ERA test a “red” rating by the HFEA.

The ERA is a molecular diagnostic test of the endometrium, obtained by biopsy.

In the United States, the biopsy itself averages $200 and the test is approximately $600-$1000. Neither is typically billed to insurance so patients will have to foot the cost themselves. Similarly, in Brazil and Japan, an ERA test will set you back around the equivalent in local currency: approximately R$5,000 and ¥118,000 respectively.

Clinical Data on ERA Effectiveness

As you can see in the chart above, the HFEA gave the ERA a "red" rating. We'll explain the data available below.

Patients Who Have Yet to Have a Failed Transfer

The first adequately powered randomized controlled trial of ERA-guided receptivity-timed transfers was published by Doyle et al. in December 2022 and has poured cold water on the notion that the ERA test is of much value in predicting the window of implantation. The study compared live births from single euploid (genetically normal, as determined by PGT-A screening) frozen embryo transfers in ERA-guided vs. standardized transfers. Participants who did not have euploid blastocysts were excluded. 767 participants were included in the study and the mean age was 35 years. The study was double-blinded meaning that neither the participants nor the investigators knew which treatment the study subjects were receiving and the participants were randomly assigned to their treatment groups.

All control group participants and those intervention group participants with receptive ERA results received frozen embryo transfer at the standard timing of 123 ± 3 hours after the start of progesterone, while the intervention group participants with nonreceptive ERA results underwent frozen embryo transfer based on the recommended timing from the endometrial receptivity results as shown in the table below.

The primary outcome was live birth. Secondary outcomes included clinical pregnancy, biochemical pregnancy, chemical pregnancy, and ongoing pregnancy. The data showed that there were no significant differences between groups for any of the outcomes. The table below shows the results of the primary outcome (live births) and one secondary outcome (clinical pregnancy) for all patients.

Further subgroup analyses showed that there were no statistically significant differences between patients who were deemed nonreceptive by ERA testing across groups as shown in the table below.

Taken together, the data from this double-blind, randomized, controlled trial show that endometrial receptivity testing provided no significant advantage in live birth rates—or any other positive clinical outcome—compared with standard timing for frozen embryo transfer with PGT-A tested euploid embryos.

Patients Who Have Experienced a Previous Failed Transfer

For patients who have had a previous embryo transfer that has failed, the data also indicate that ERA is not helpful in improving outcomes. That said, embryo transfers can fail for a variety of reasons, and despite the conclusions outlined below, proponents of ERA argue it has yet to be proven ineffective for those suffering from recurrent implantation failure (RIF), whereby on multiple occasions transfers failed because embryos did not successfully embed in the endometrium.

Patients experiencing recurrent implantation failure may benefit from considering alternative treatments, which are discussed in more detail in this lesson.

Laws vary region-to-region on whether hopeful parents can use donated eggs, donated sperm, or the help of a gestational surrogate.

As for using donor eggs, we have a detailed course we suggest you consult here, but to oversimplify a few facts:

• Success rates with donor eggs are high compared to using one’s own eggs
• IVF cycles using donated eggs tend to cost substantially more

To elucidate the first point, let’s look at U.K. data comparing IVF success rates using donor eggs versus the success rates for women using their own eggs over age 42, as an example.

In some countries, adding the cost of donor eggs to an IVF cycle can be substantial. In the U.S. context (and with many exceptions), it can be reasonable to assume an additional $15,000 of cost (with ranges from $5,000–$35,000).

Many factors play into the decision to use donor eggs, but on a purely financial basis (and depending upon the circumstances), here’s one way to look at the value.

Below we calculate the costs required to achieve even 50-50 odds of success with IVF for:

• A female patient using donor eggs
• A female patient using their own eggs after age 42

The increased odds of success per cycle (40% vs 2%) more than compensate for the increased cost per cycle ($35,000 - $20,000 = $15,000). Hence, the “cost to target’ (again, 50-50 odds of a live birth) are nearly 80% lower ($42,000 vs $500,000) for the patient who uses donor eggs.

We should point out that this is just an example, and for many patients (e.g. younger women considering donor egg), the cost/benefit analysis may look very different. To learn more, see our lesson on the subject here.

Again, the costs to do IVF with donor eggs can vary dramatically by the region in which you’re treated and even within that region, the type of donor you select and the third parties you work with.

The above analysis assumes an equal chance of success across all donor eggs. In reality, this is not true. Most donor eggs come from egg banks with variations in quality of eggs and costs. When considering egg donation, it's important to recognize that eggs routinely come from banks rather than clinics. Yet, the quality, sources, costs, and guarantees of these banks can vary. Prospective donors and recipients should conduct thorough research to understand these factors before finalizing any egg donation arrangements.

As for using donor sperm or a gestational carrier, both can dramatically improve the odds of a live birth and tend to warrant the costs they drive.

Most fertility treatment drugs involve the use of oral medication (e.g. clomiphene or letrozole) or injectable hormones, known as gonadotropins.

Unlike oral medications which tend to be low-cost in nature, injectable hormones can be incredibly expensive.

Drug Type & Dosing

IUI

In the case of IUI, for many patients, there is a benefit to taking drugs. However, as you can see from the data below, taking oral medications like Clomid (clomiphene) or Femara (letrozole) approach IUI with gonadotropin success rates but with lower costs (in the U.S. context) or risk of delivering twins or triplets (“multiples”).

If your doctor wants to do an IUI cycle with gonadotropin,in addition to discussing the medical risks of a multiple birth, you may want to broach the trade-offs of substituting some or all of the gonadotropin with less expensive oral medication.

IVF

As for IVF, typically the more eggs retrieved, the higher the odds of success, as you can below. However, that’s true only up to a point—after retrieving 15–20 eggs, per-cycle IVF success rates plateau. As a result, for some patients (e.g. “high responders”) prescribing ever higher doses of gonadotropin (to produce more eggs for retrieval) doesn’t improve success rates, but will drive up costs (and medical risk, in the form of hyperstimulation).

As a result, many doctors tend not push the dosing for “high responders” (who are sensitive to gonadotropins and thus will produce a lot of eggs on lower doses) or for “poor responders” who are distinctly less-sensitive to the drugs and for whom more drug does little to improve success rates (see below).

However, as you can see in our course on protocols here, there often is a minimum threshold of gonadotropin that needs to be taken so as not put the patient at a meaningful disadvantage. In the eyes of many, that threshold is around 150 IUs per day.

Ultimately, you may want to discuss with your doctor and clinic the medical and financial implications of adjusting your gonadotropin dosing downwards (or upwards), or substituting some of your more expensive gonadotropin for less expensive oral medication. Doctors are more likely to be open to lower doses of gonadotropin if you’re considered a “poor responder” or “hyper responder.”

Acquiring Medication

As we mentioned, fertility medication can be costly, especially gonadotropins.

It’s not uncommon for patients to discuss the possibility of acquiring medication legally from regions where the products are perceived to be the same but the prices most certainly are not.

Along a similar vein, in some circumstances, clinics themselves have extra doses or “samples” (provided by the drug company) lying around that they can offer to patients.

Rules and regulations around how and from where a patient procures medication are highly country-specific and need to be consulted along with clinical guidance.

In some countries, and at some clinics, the cost to store eggs or embryos can be substantial. For instance, in the United States, storage costs typically equate to $500–$1,000 per year.

Many patients are reluctant to stop paying storage fees given the sizable up-front (emotional, temporal, and financial) costs already laid out. Also, it can be hard to know when you're definitely done building your family and thus no longer need access to those eggs or embryos.

To illustrate, a person who wants three children, each spaced three years apart, might well find themselves paying annual storage fees (e.g. 10 years x $1,000 per year) that begin to rival that initial IVF cycle (e.g. $15,000–$25,000).

In some regions, third party laboratories offer the ability to store eggs and embryos at a discount (often 50% or less) compared to the cost of on-site storage at a clinic.

In regions where frozen donor eggs are shipped between clinics, the logistical cold-storage infrastructure may be in place for transportation to happen more seamlessly.

However, shipping eggs and embryos likely involves an element of hard-to-quantify risk, not to mention a break in accountability if something goes wrong or those embryos don’t work.

For this reason, we suggest closely probing your clinic’s track record shipping eggs and embryos and the results of thawing and using them upon receipt. Likewise, we suggest asking for the third party’s laboratory’s track record in handling eggs and embryos and whether they go on to be of use.

For context, we suggest you consult our course on laboratory quality with an emphasis on “thaw rates” as well as endpoints like implantation rates, pregnancy rates, or live birth rates.