What Is Recurrent Implantation Failure?
IVF is one of the most effective ways to achieve pregnancy for many couples. However, in some patients, even after multiple transfers of high-quality embryos, pregnancy may not occur. This condition is known as Recurrent Implantation Failure (RIF).
Although RIF is defined in various ways in the literature, it is generally considered to be at least three unsuccessful IVF cycles where one or two high-quality embryos were transferred. In such cases, standard protocols may not be sufficient, and more advanced diagnostic methods are needed.
Known Causes of RIF
Most causes of recurrent implantation failure are related to problems within the uterus that prevent embryo attachment. These include:
- Endometrial hyperplasia (thickened uterine lining)
- Submucosal fibroids or polyps
- Chronic endometritis (chronic inflammation or infection of the endometrial lining)
- Intrauterine adhesions
Additional factors such as hydrosalpinx (fluid-filled fallopian tubes), increased chromosomal abnormalities in embryos, and certain clotting disorders (thrombophilia) also contribute to RIF risk.
The Implantation Window and Timing Issues
Scientific studies have shown that the endometrium becomes biologically receptive to embryo implantation during a specific time window. This “implantation window” typically occurs at a standard time following progesterone administration. However, in some patients, the window may open earlier or later than expected.
If the embryo is transferred when the endometrium is not yet receptive—or if that period has already passed—implantation will not occur, regardless of embryo quality. Recognizing this can significantly influence success rates.
What Is the ERA Test and How Is It Performed?
The ERA (Endometrial Receptivity Analysis) test was developed to address this need. It analyzes the genetic activity of the endometrial lining to determine the optimal timing for embryo transfer. The test evaluates the expression of 238 genes involved in receptivity during the implantation window.
At our clinic, the ERA process is as follows:
First, a standard IVF cycle is completed, and the embryos are frozen. Then, a biopsy of the endometrial lining is scheduled. If the patient is being monitored in a natural cycle, LH (luteinizing hormone) levels are tracked, and the biopsy is taken seven days after the LH surge. If the cycle involves hormonal support, the biopsy is done on the fifth day of progesterone administration.
The sample is sent to the lab and analyzed using specialized software. The result indicates whether the endometrial tissue is receptive (ready for implantation) or non-receptive (not ready).
How Are ERA Test Results Interpreted?
If the result is receptive, embryo transfer is scheduled as originally planned. If it is non-receptive, the ideal transfer date is identified and used to schedule the next cycle. The transfer is then personalized to align precisely with the newly identified window of implantation.
Initial studies have shown that, in a significant portion of RIF patients, the implantation window differs from the standard timeline. Aligning the transfer to this personalized window may meaningfully improve pregnancy outcomes.
Contribution of the ERA Test to IVF Success Rates
Studies to date indicate that pregnancy rates can increase by 20–30% in patients who undergo ERA testing. This approach emphasizes that beyond embryo quality, the biological timing of the uterine lining is also critical.
At our clinic, IVF treatment is not only about embryo quality—we also focus on determining the optimal endometrial timing to enable a personalized embryo transfer. This ensures a safer, more informed, and higher-success journey to pregnancy for each couple.
