REPEATED IVF/ IMPLANTATION FAILURE (RIF) PART 1

Assisted Reproductive Technology (ART) seem to have the answer to most forms of infertility challenge, it may be however very discouraging to be faced with repeated Invitro Fertilization (IVF) failures which is an indication that the embryos (a baby in the early stage of development) transferred into the womb did not implant and pregnancy has failed for that cycle.

At present, worldwide IVF success rate ranges from 30-35%, with cycle to cycle variation ranges up to 50-60%, a number which has remained static for so many years. IVF has helped many couples across the globe to complete their families and experience the joy of parenthood but the heartbreak and emotional trauma surrounding repeated failed IVF cycles remains. A failed IVF takes an emotional toll on a woman who is attempting pregnancies as well as financial toll on families, with a single IVF cycle costing million of Naira
This week’s discussion would be looking at all the possible causes of repeated implantation failure, resulting in numerous IVF attempts, the evaluation and current trends in the treatment of RIF.

What Is Repeated Implantation Failure? (RIF)

Repeated Implantation Failure is diagnosed when transferred embryos fail to implant following several In-Vitro Fertilization (IVF) treatment cycles. This means that at least three or more consecutive IVF treatment has been carried out with at least 1-2 high grade embryos transferred back to the womb at each attempt without successful pregnancy. The failure may be a consequence of uterine or embryo factors.
What is Implantation?

The process of implantation involves two main components, a healthy embryo that should have the potential to implant and a receptive endometrium (inner layer of the womb where an embryo or embryos are attached). These factors are mandatory for successful implantation and subsequent normal placentation.

These processes are under thorough investigation and seem to involve many mediators originating in the embryos, as well as in the endometrium, and also involve the maternal immunological system. Any abnormality attributed to the embryo, the endometrium or the immune system will result in implantation failure / failed IVF cycles.

Evaluation and Treatment of Repeated Implantation Failure
Causes may be classified as: Maternal Factors or Embryonic Factors.

Maternal Factors.

Assessment of the Uterine Anatomy: The first step in evaluation should be the uterus (womb) and the integrity of the uterine cavity. Anatomical malformations of the uterus, either congenital (septate uterus or bicomuate uterus) or acquired (uterine fibroids especially submucosal fibroids growing into the uterine cavity or endometrium, endometrial polyps, intrauterine adhesion and hydro-salpinx) can interfere with normal implantation. When possible, the intrauterine abnormality should be examined by ultrasonography and hysteroscopy. Hysterosalpinogram or hydro-salpinx, with laparoscopy can be done to confirm or refute diagnosis if necessary.

Thrombophilia: Although the thrombophilic state is either inherited or acquired, it has been mainly associated with repeated pregnancy loss. Several investigations have reported an association between RIF and a tendency for increased ability of blood to form clot (hyper coagulations). It is assumed that the mechanism of implantation failure is similar to that of pregnancy loss, mainly disturbed blood flow to the endometrium and placenta. Disturbed blood flow on one hand can hamper endometrial receptivity and on the other hand cause miscarriage. For patient with RIF, diagnosed with thrombophilia, treatment with medications that thins the blood has been shown to significantly improve implantation, as well as in clinical pregnancy rate in subsequent IVF attempts.

Immunological factors: A number of studies have shown that the immune system plays a major role in the process of implantation and in the subsequent maintenance of pregnancy. A conception must be recognised as non-self in order not to trigger an immunological process that prevents the maternal immune system from rejecting it. The HLA compatibility system evidently plays a vital role in this recognition.
HLA means Human Leucocyte Antigen; they are proteins or makers found on most cells of one’s body. The immune system uses these markers to recognise which cells belong to one’s body and which do not. Couples who share the same HLA alleles may experience recurrent pregnancy loss and repeated implantation failure.

The reason why this is so, is poorly understood. However inadequate response of the maternal immune system to stimulation by the paternal antigen, due to HLA sharing has been implicated, this usually results in imbalance of T-helper cells which basically are immune cells, causing the maternal systems to become intolerant to the fetus.

Management of immunological factors includes carrying out immunological screenings to identify women with immunological problems as well as couple with same HLA allele.

• The use IVIg (Intravenous Immunoglobin) before embryo transfer and a second dose when a fetal heart is noticed has been found to improve implantation and live birth.

• Intralipid(IL) is a fat emulsion that has been reported to suppress the normal activity of NK (natural killer) cells in the body. The infusion of 20% Intralipid solution has also been reported to improve outcome in women with RIF, a 50% pregnancy rate was achieved using Intralipid in women with RIF insome studies with no difference in other studies. IL is normally administered between day 4 and day 9 of the ovarian stimulation and again within 7 days of a positive pregnancy test…TO BE CONTINUED