Implantation failure investigation

Implantation failure investigation takes place when a woman has experienced 3 or more unsuccessful attempts of In-Vitro Fertilization (IVF) with transfer of more than 8 good-quality embryos.

Implantation Failure

  • What is implantation failure?

    Implantation failure is when an embryo fails to embed itself in the lining of the womb (endometrium) following embryo transfer. It can also happen in natural cycles, when a conception occurs, but a pregnancy does not develop. Implantation failure in these cases can be suspected by a heavy period at the start of the following cycle, but most of the times, it happens without any symptoms at all.

    A negative pregnancy test, after numerous efforts to conceive and acostly in time, emotion and money fertility treatment is a devastating outcome. But, despite all medical and scientific developments in reproductive medicine and Assisted Reproduction Techniques (ARTs), 40-50% of treatment cycles do not lead to a successful pregnancy.

    So, as in natural conception under normal circumstances, whereembryosare not always able to become implanted in the womb,the same happens in IVF. Therefore, we cannot define an IVF attempt as ‘failed’ after only one or two trials. Experience has shown that after three IVF attempts, more than 80% of women under 35 years of age will be pregnant, but that will not be the case foraround 20% of them.In addition, some of these women will experience recurrent implantation failure.

  • What is recurrent implantation failure?

    We consider a recurrent implantation failure when a woman has experienced 3 or more unsuccessful attempts of IVF with transfer of more than 8 good-quality embryos.

    There are many reasons why implantation failure recurs, and in order to find them out and employ / devise treatments, we carry out investigations addressing maternal and paternal factors, as well as embryo investigations.

Investigations, treatments and solutions

  • Maternal Factors

    • Thrombophilia: A group of conditions that affect normal blood thickness leading to increased blood clotting. When these recur in a vascularized area of the lining of the womb, the result is a failed implantation. It can be detected with blood testing or specific genetic analyses and treated / ameliorated with medication. The main factors that we check to detect a thrombophilia include: anti-phospholipid syndrome, lupus anticoagulant, anti-cardiolipin Ab, Protein C and S deficiency, anti-thrombin III deficiency, MTHFR (or homocysteine), prothrombin G2021OA, and factor V Leiden.
    • Endometrial assessment:
      • The thickness of the endometrium is a crucial parameter for the conception of the early embryo. An endometrium thinner than 5 mm can be the reason for recurrent implantation failure. Endometrial receptivity, which is the most optimal timing for the womb to accept the early embryo, can be sometimes influenced by ovarian stimulation during a cycle of IVF. In cases that this effect is strong, the ‘implantation window’ can be completely altered causing implantation failure. Here in AAFC, to overcome this, we freeze the eggs following egg collection and prepare the endometrium with a pharmacological treatment. The IVF cycle can be resumed with thawing the eggs, fertilization and embryo transfer when the endometriumis ready.

      • The endometrial receptivity can also be affected by advanced maternal age, especially in women older than 37 years of age. To check endometrial receptivity for each of the above cases, we use a fully comprehensive genetic test, the Endometrial Receptivity Array (ERA®). Defining the ‘implantation window’ will help us to perform the embryo transfer at the right time for implantation to occur.

      • Other endometrial conditions, such as the presence of polyps or fibroids can also contribute to a failed implantation. These can be detected by hysteroscopy and, in the majority of cases, surgically corrected(surgical hysteroscopy, for instance).

      • In addition, we can employ assisted hatching, a laser-mediated method for weakening the embryo’s protective layer (zona pellucida). With this technique, the early embryo can easily implant itself in the endometrium.

    • Fallopian tube assessment: Anomalies or blockages to the tubes that link the ovaries to the uterus (fallopian tubes) can also lead to recurrent implantation failure. An examination of the fallopian tubes can be done with tubal patency testing, and depending on the condition, surgical correction and / or medication can be employed for treatment. For instance, as inhydrosalpinx(a condition characterized by blocked and filed-with-fluid fallopian tubes), which we usually treat by laparoscopy.
    • Immunology evaluation: It involves increased levels of natural killer cells and auto-antibodies that may be attacking and destroying the early embryo. Immunological causes can be detected with blood testing and treated or ameliorated with medication.
  • Paternal Factors

    • Genetic Integrity of Sperm:  Damage to the genetic material (DNA) of sperm can affect implantation of the early embryo in the womb. Sometimes, although the early embryo reaches the stage of 2-3 days or the blastocyst stage (5-6 days) in culture and has a good-quality appearance, its further development in the womb ceases, and implantation fails. DNA fragmentation testing can help with such diagnosis.
    • Chromosomal Integrity of Sperm: Chromosomal abnormalities due to a neuploidy (loss of one or more chromosomes) can also affect embryo survival and therefore, implantation after embryo transfer. This possibility can be detected with a FISH test on sperm.When chromosomal abnormalities are found in sperm, then it is necessary to test genetically the embryos before the embryo transfer with Preimplantation Genetic Diagnosis (PGD) and / or Preimplanation Genetic Screening (PGS).
  • Embryo Quality

    • Early embryo assessment: Observable subtle changes during embryo development, from the first cell division of the egg-sperm hybrid cell to the 2-3-stage embryo or through to the blastocyst stage(5-6 days), can be recorded and carefully examined with the use of the EmbryoScope® time-lapse imaging.
    • Genetic screening: This is really important for finding hereditary or impossible-to-observe chromosomal abnormalities in prospective embryos. A chromosomally abnormal embryo is less likely to implant. PGD and / or PGS performed by our partner laboratories in Reprogenetics can be used for this purpose.

    Transfer of the best-quality chromosomally normal embryoswill offer the best chances of implantation.

Implantation Failure Investigation Contribution

  • How does implantation failure investigation contribute in the success of ARTs?

    The above comprehensive investigations can lead to answers and reasons behind repeated implantation failure, as well as to effective treatments and / or use of an alternative more suited ART, before another round of assisted reproduction is employed.

    However, independent of the cause(s) found, recurrent implantation failure is still possible and we cannot guarantee success even after the most comprehensive investigation and treatment. Recurrent implantation failure may be happening due to any of the above reasons, a combination of them, or none (unknown factors). If the latter is the case, then offering a solution and / or treatment is not easy. Recurrent implantation failure can be easily faced if the underlying reason is a treatable thrombophilia, for instance, but it can become a real challenge when the reason is not obvious.

    Here in AAFC, we perform all possible investigations in order to solve recurrent implantation failure. Also, as current methods and techniques progress, our understanding improves and more solutions or treatments may become available in the future. Our specialist doctors can provide you with further information, consult you on all applicable options and offer you support when necessary.