What is Recurrent Implantation Failure?
Recurrent Implantation Failure (RIF) is defined as the :
- Failure to get pregnant after > 3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers
- Failure to achieve a clinical pregnancy following the transfer of at least four good-quality embryos in a minimum of 3 three fresh or frozen cycles in a woman under the age of 40 years
What causes Recurrent Implantation Failure?
The reasons for RIF may be due to:
- An embryonic problem due to an abnormality in the number of chromosomes of the embryo. Pre-implantation genetic testing (PGT-A) screens embryos to select normal ones transfer and may be recommended in selected cases.
- Structural problems with the uterine cavity, endometrial thickness issues, suboptimal progesterone levels, endocrine imbalances including thyroid dysfunction, immunological problems etc.
- A displaced window of implantation. The endometrium is normally receptive to receive an embryo for 3-5 days after ovulation or after a certain period of time after exposure to progesterone. At this time there are certain genes expressed in the endometrium that can be identified and this defines the window of implantation.
How do we test for the displaced window of implantation?
ERA (Endometrial Receptivity Array)
This involves taking a biopsy from the endometrium-uterine lining usually 168 hours after an LH surge in a natural cycle or 120 hours after progesterone exposure in a medicated FET cycle. It is performed in out-patients, takes a few minutes and can be painful. An embryo transfer is not carried out in the same cycle as the test results are first awaited. The biopsy sample is analysed by genetic testing using next generation sequencing (NGS) to assess the genes expressed in the endometrium. About 248 genes are analysed.
Following years of research on over 10,000 patients, a group in Spain have used computer algorithms to identify the endometrium expression profiles that are receptive and non-receptive. About a third of cases may be non-receptive.
The embryo transfer is subsequently planned at an earlier or later time in the cycle based on the test results and improved implantation rates have been reported in several studies.
By identifying the displaced Window of Implantation and doing a personalised embryo transfer (pET) embryo implantation rates may be improved.
What other tests for Endometrial causes of RIF are there?
EMMA (Endometrial Microbiome Metagenomic Analysis)
This test evaluates the endometrial flora and recommends if vaginal probiotic treatment is required to balance the endometrial flora, with the intention to improve implantation.
ALICE test (Analysis of Infectious Chronic Endometritis)
This test aims to detect bacteria causing chronic endometritis (infection of the uterine lining) and recommends adequate treatment if required (usually a course of antibiotics).
The EMMA and ALICE tests have been more recently researched and advocated by the same team in Spain. The three tests together ERA, EMMA, ALICE are called the ENDOMETRIO test. They can all be carried out on the same endometrial biopsy sample used for ERA at an additional cost.
While there are many studies showing that ERA may be beneficial, the research in relation to EMMA and ALICE is still in its early stages
Thank you to Dr Sapna Ahuja (Deputy Medical Director) at The Assisted Reproduction & Gynaecology Centre
