Implantation Failure in IVF - Why Does It Happen?

by Chrysa Karakosta, last updated 19 Nov 2021,

5 min read

The first IVF baby was born on the 25th of July 1978 and yet after all these years, scientists are still making huge efforts in order to improve the results of IVF. One of the main issues which still remains a challenge is Recurrent Implantation Failures (RIF).

Repeated failures of IVF treatments have a huge emotional, psychological and financial burden on everyone involved. Failure to achieve a pregnancy that will lead to becoming a parent is a worldwide public health issue and causes anxiety, depression and the feeling of being helpless.

RIF is defined as the failure to achieve a clinical pregnancy after at least three or more IVF treatment cycles in which one or two morphologically high grade embryos are transferred. If a treatment cycle is successful or not mainly depends on the embryo quality (both morphologic and genetic) and to a smaller degree on the endometrial lining receptivity (morphological criteria and timing between the lining and the embryo).

Chromosomal Abnormalities

As women age, the rate of chromosomal abnormalities in the eggs they produce and hence the embryos they create increases. This leads to much lower success rates in older women and higher miscarriage rates. In order to improve success rates, modern laboratories perform all embryo transfers at the blastocyst stage and hence have the knowledge of the final assessment of the embryo. Blastocysts have a lower chance of carrying chromosomal abnormalities, as nature filters some of these, as the embryo develops post fertilisation. In cases where the expected cause of the RIF is suspected to be embryonic, then a Karyotype blood test on both partners is requested, to exclude additional genetic factors that may lead to a higher than expected percentage of abnormalities in the embryos they produce. Preimplantation genetic screening of the embryos at the blastocyst stage may also be recommended depending on the medical history and the expected number of blastocysts.

Structural abnormalities

Structural abnormalities of the uterus may also lead to failed implantations. These may include any pathological alterations in the endometrial cavity such as hyperplasia, the presence of submucous fibroids and polyps. Furthermore, chronic endometritis may affect how the endometrial lining develops and also leads to failed implantations. Moreover, the presence of a hydrosalpinx or endometriosis, may also affect the chances that one has to succeed in an IVF treatment. Structural abnormalities can be detected through non-invasive 3-dimensional ultrasound scans. In certain cases, more invasive procedures like a Hysteroscopy or Laparoscopy may also be required both to investigate but also to treat occurring conditions.

Endometrial Lining

Another aspect that needs to also be investigated when everything else is ruled out is if the endometrial lining is receptive and when. The temporal window of opportunity in which the endometrium becomes receptive to the blastocyst is defined as the ‘implantation window’. As implantation relies on the synchronisation of the embryo and the endometrium, it is essential to make sure that the implantation window is correct. In cases of RIF, there may be a shift in timing of the window which previously was thought to be the same in all women. An investigation that is suggested nowadays, to investigate this, is the ERA test (Endometrial Receptivity Analysis).

The ERA test

The ERA test is used in order to identify the receptivity of the endometrial cavity and diagnose the exact window of implantation. According to the company that carries out the specific analysis, the results are quite accurate and reproducible in the same patient for 29–40 months after the first test. In order to perform an ERA test, a woman needs to follow a specific treatment protocol (endometrial preparation) and then proceed to an endometrial biopsy, at a very specific time. After sequencing the genetic material from the endometrial biopsy, the results will determine if the endometrium is receptive or non-receptive in a specific moment of the endometrial cycle. This result will be coupled to a recommendation for the personalized embryo transfer in each patient according to her specific endometrial profile. The endometrial preparation for the embryo transfer, will then need to follow the exact same steps and the embryo transfer should be timed according to the results.

If implantation fails to occur even if all the above mentioned methods and tests have been completed then, alternative methods should be explored. If the likely source of the problem is embryonic, then the couple in some cases may even need to consider gamete donation. If the problem is caused by uterine factors and the issue may not be resolved then surrogacy should be considered.

In conclusion, there are many factors involved in IVF treatments that may lead to repeated failed implantations. However, there are also many ways to investigate the causes and there are solutions to many of these problems. Individualised treatment protocols and suggestions are required for each patient and depending on the reasons behind the failures they have faced.

The medical and scientific team at Newlife IVF Greece never stop expanding their knowledge and work hard on offering the most up to date treatments and solutions available in the IVF sector. However, apart from offering their experience and guidance medically, they are also here to listen and help you deal with all aspects of your treatment. Visit our website and fill in our contact form so we can offer a free medical consultation in order to discuss your case, answer all your questions and join you in your IVF journey.

Chrysa Karakosta

Chrysa Karakosta, BSc, MSc

Chrysa is the Lab co-Director at Newlife IVF Greece, in Thessaloniki Greece, from the beginning of 2010 and now heads the International Patient Department.

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