Repeated Implantation Failure

Successful embryo implantation requires synchronous development and interaction between the embryo and the endometrium.  Recurrent implantation failure causes a lot of mental and financial stress on the infertile couple. It is also very difficult for the treating doctor to explain the reasons for not being successful in spite of everything being right. RIF may be both of embryonic or uterine factors or both.

Repeated Implantation Failure (RIF) may be due to several causes:

• Congenital uterine abnormalities, such as endometrial polyps, uterine fibroids, adhesions, hydrosalpinges, endometriosis, etc.
• Male factors such as severe oligoasthenozoo-spermia with increased sperm DNA fragmentation may also impact on the grading of the embryo.
• Aneuploidy in embryos
• Metabolic disorders like uncontrolled diabetes, impaired thyroid function or prolactin level, etc. in the couple
• Thrombophilias or antiphospholipid syndrome
• Immunological factors
• Impaired endometrium: Impaired endometrium can be a common cause of recurrent  IVF failure.  When morphologically good embryos are transferred, the question arises as to whether the problem is due to incompetent embryo or endometrium or both.
• If the patient is young and there are morphologically good embryos then there is a greater chance that the problem lies with endometrium, either in terms of thickness, character, vascularity or immunology.
• For successful implantation to occur, there are several chemical signals between the embryo and endometrium.
• Any impaired cross-talk between endometrium and embryo leads to unsuccessful attempts after the transfer of good quality embryos in a healthy uterus without any endometrial factor or any medical problem in the couple.

Investigations

Maternal blood tests

• Clotting factors – Small clots in the blood have been identified as a possible cause for pregnancies failing to progress.T hese patients can be treated with aspirin or low dose heparin.
• Immunologic factors – High levels of uterine natural killer cells and auto-antibodies can also be the cause for RIF.

Endometrial tests

Hysteroscopy or endometrial scratching results in decidualization. There is some evidence that these procedures if done in the cycle before ovarian stimulation and IVF/ET increase the pregnancy rate in RIF patients.

Endometrial Receptivity Array – For a short period of time during the menstrual cycle after the embryo reaches the uterus, the receptivity to welcome embryo is called endometrial receptivity. This lasts for a short period and is called window of implantation (WOI). ERA is a reliable test to determine the time of window of implantation for any female and helps in personalized embryo transfer for patients in RIF for increasing the success rate of implantation.

Embryo factors

• Genetic screening– Preimplantation Genetic Screening (PGS) assesses for the presence of all the chromosomes of the embryo (complete chromosomal karyotyping) and can help us to select the most “competent” embryos for transfer.
• Time-lapse imaging– allows assessing subtle changes seen during embryo development and identifying the best embryos for transfer.
• Laser-assisted hatching– is a physical or chemical treatment carried out immediately before embryo transfer. The idea is to weaken an area of the zona pellucida with the aim of improving the chances of implantation.

Therapeutic approaches

The aim of the treatment should be such as to increase the chances of implantation and pregnancy. Effort should be made to increase the receptivity of endometrium and improve the quality of embryos. People have used immunomodulators to increase the receptivity of endometrium, scratching of the endometrium, PRP instillation and autologous stem cells. Intravenous injection of IgG is used to suppress immune responses in order to improve live birth rates.

If nothing works, the couple should be advised to go for Altruistic Surrogacy.

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