Repetitive implantation failures during Assisted Reproductive methods

Close-up of a woman’s stomach at nine months pregnant.

picture courtesy© J.Miller (

Authored by Dr. Rajni Khajuria

A successful embryo implantation depends on manyfactors and the most important factor is the correct “window of implantation (WOI).” Mainly the women who opt forassisted methods like In-Vitro Fertilization (IVF) to achieve successful pregnancy is disappointed when the treatments do not have positive results. One of the major causes of repetitive IVF failures can be due to a weak embryo or because the embryo is implanted when the endometrium is not receptive.

Repetitive implantation failure (RIF) is the inability to achieve an artificial or a clinical pregnancy after the transfer of good quality embryos in 2 or more IVF cycles in a woman under the age of 40 years. One of the causes of RIF is lack of synchronisation between the embryo ready to be implanted and endometrial receptivity.

About 25% of the patients with RIF have a displaced window of implantation (WOI). This means that embryo transfer is performed in a non-receptive endometrium. The WOI is a critical factor in successful conception through IVF. Therefore a displaced WOI has been identified as reason for a failed IVF cycle in RIF patients.

Knowing the right WOI is very crucial to prevent implantation failures. A study by IGENOMIX reveals that 28% of the embryos are transferred in a wrong WOI. IGENOMIX, a pioneer in reproductive genetics has developed and patented a state-of-the-art diagnostic method called Endometrial Receptivity Analysis (ERA)after more than 10 years of research. The ERA test identifies the patient’s personalized WOI estimating the day on which embryo transfer will be successful.

The analysis reveals the timing of the WOI and leads to a personalized embryo transfer (pET) timing based on the individual results obtained. The ERA test shows high sensitivity and specificity for detecting gene expression profiles associated with endometrial receptivity. Globally about 12,500 patients have been investigated, out of which 28.6% were reported Non-receptive on the day of the transfer.

Apart from WOI, fertility clock also plays a vital role in those womenwho opt for pregnancy at later stage.  Female fertility is affected by age. Age is thus a major fertility factor for women. The relationship between age and female fertility is termed as a woman’s “biological clock/fertility clock”.In their late 30s, there is a decline in fertility level and the risk of chromosomal abnormalities also increases with the growing age.Even if the women conceive, there are probabilities of having difficulties in sustaining the pregnancy.

A recent study reveals that in women who are 38 years or more, 79% of embryos have chromosomal abnormalities. The risks of abnormalities grow as the age of the mother increases. Most embryos with an incorrect number of chromosomes fail to implant or miscarry during the first trimester of pregnancy. In late pregnancies, the baby is also prone to developchromosomal abnormalities such as Down syndrome, Edwards syndrome, and Patau syndrome.

Therefore, a woman who tries to opt for a pregnancy in their late 30s should also understand the concept of Fertility Clock.  As soon as a woman attains the age of 25 she is likely to have a successful pregnancy and her chance of not conceiving is as low as 8% while her chances of miscarriage increases to 9%. The ratio of IVF failures in women in the age group of 30-34 years is 12% while the number is 17% for those between the age group of 35 to 39. The failures rates for conceiving in women over the age of 40are as high as 19%.

Therefore, knowing the right WOI and the fertility clock can help in prevention of repetitive failures in IVF treatment leading to a successful pregnancy.





Dr. Rajni Khajuria is Laboratory Director of Igenomix India

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