Implantation is a process where the embryo attaches itself to the epithelial lining of the uterus, followed by migration into the deep layer (stratum compactum) of the endometrium of the uterus.

In clinical practice, implantation is often considered to be successful when there is confirmation of an intrauterine gestational sac that can be seen on a vaginal ultrasound and implantation failure is considered when there is no evidence.

In assisted conception treatment like IVF, implantation is considered to be successful when an embryo has produced an intrauterine gestational sac which can be seen on a vaginal ultrasound, usually about six weeks after the oocyte retrieval.

Recurrent Implantation Failure (RIF)

One of the most frustrating group of patients for IVF specialists are those with recurrent implantation failure. Recurrent implantation failure (RIF) refers to failure to achieve a viable pregnancy, following a “greater than 3 embryo transfers with high quality embryos or the transfer of equal or greater than 10 embryos in multiple transfer; exact numbers to be determined by each center”(definition by the 2005 ESHRE PGD Consortium).

Causes of Recurrent Implantation Failure

The Embryo factors

One important variable is clearly the quality of the embryo. If the quality of the embryo is poor, then the possibility of successful implantation is reduced. A good –quality embryo was described as having the correct number of cells corresponding to the day of its development and day-5 embryos (blastocysts) were graded according to expansion and quality of the inner cell mass and trophectoderm (outer layer of the blastocyst).

However, a good quality embryo is not a guaranty of a genetically normal embryo. One of the recommendations in patients with recurrent implantation failure is to perform  genetic screening of the embryos (PGS).

The most common causes for poor-quality embryos is poor-quality sperm and/or compromised quality of oocyte, e.g. in patients with endometriosis or advanced age.

The Endometrium Factors

It is thought that big fibroids, big size endometrial polyp, severe intrauterine adhesions, congenital uterine anomalies, may interfere with implantation and contribute to recurrent implantation failure.

Similarly, the hormones estrogen and progesterone are required for the best preparation of the lining of the uterus. During in Vitro Fertilisation (IVF), these hormones are very carefully controlled and supplied.

Nowadays, there is the latest type of IVF treatment called endometrial scratching, which is a good option for women who have recurrent miscarriages despite having good quality embryos. This technique was used in the previous cycle before the IVF, and various studies have shown improvements in women with a history of repeated failures.

The reason for increased implantation rates after endometrial scratching is unknown. But scientists believe that there may be two reasons for the increased implantation rates:

  • The increase of endometrial white blood cells: It appears that endometrial injury increases the production of white blood cells. These cells control embryo implantation by secreting so-called growth factors.
  • Gene switching within the endometrium: Whether or not the failure to implantation of embryos is due to genetic switching related to endometrial receptivity, is a topic of speculation amongst scientists. There are specific genes that are responsible for implantation of embryos. So if they are not switched on during the time when embryos are supposed to implant, it results in miscarriage due to implantation failure. It is seen that Endometrial scratching may increase expression of genes (switching of genes) which are thought to be responsible for preparing the endometrium for implantation.

This procedure is carried out in the luteal phase of the cycle (i.e. after ovulation) preceding the planned IVF-treatment. Normally this is done around day 21-day of the cycle. Our internationally recognised experts who have published several scientific papers in international journals, also have the possibility to provide you with your individualised treatment to improve the endometrial receptivity.


This Greek word refers to a fallopian tube filled with water or fluid. The fallopian tube is connected with the uterine cavity where the embryo implants, meaning fluid from the hydrosalpinges could flow into the uterine cavity and impair the chance of pregnancy. It might be attributed to a direct embryonic toxic effect of the fluid itself, a mechanical effect whereby the accumulated fluid may flush the embryo out of the uterus as well as a negative effect on endometrial receptivity.

Thrombophilia and Immunological Factors

The immune system is designed to protect against infections and abnormal processes in the body. There is some research and theory to support that uterine natural killer cells is increased in women with recurrent implantation failure, but there is no proven treatment for the condition. Additional the NK cells, which can be found in the blood, don’t represent the presence of the uterine NK cells

Similarly, it has been suggested that thrombophilia could be related not only to recurrent pregnancy loss but also with RIF. Disturbed blood flow to the endometrium and placenta may also inhibit the normal endometrial receptivity.

Possible Treatment Prior to Implantation

In case of low embryo quality achieved after IVF, ICSI could be done in order to improve fertilisation rates and to achieve a greater number of good quality embryos to choose from, indirectly increasing the potential for successful implantation.

Furthermore, treatment of problems within the uterine environment varies with the individual case. Anatomic abnormalities have to be removed surgically, endometrial scratching as described above and/or hysteroscopy could be performed in the preceding cycle.

In selected cases, some therapies that have been shown to be effective in the treatment of recurrent pregnancy loss before implantation can include:

Intravenous Immunoglobulin (IVIg) is a medication that has been shown in randomised placebo-controlled trials to be effective in the treatment of implantation failure for those women experiencing implantation failure after IVF/ET who were good embryo producers and with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells).

Intralipid (IL), helps patients who have an abnormal Natural Killer cell level, and is usually administrated intravenously. It may alsoenhance implantation rate and help in maintenance of pregnancy.

Possible luteal phase Co-treatment in RIF the possible beneficial effects of additional measures like taking Prednisolone, Aspirin or low-dose heparin are still controversial and further research is needed to support the evidence, as every treatment could have side-effects.

Learn More about Implantation

It is important to understand all your options for management of recurrent implantation failure. At IVI Middle East Fertility clinic, our team endeavors to educate our patients on their options before initiating any treatment. Please contact us to schedule a personal consultation with one of our fertility consultant.

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