RIF and RPL risk

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You are at risk for recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). Here is what you need to know.

Implantation failure is the failure of an embryo to implant. Two or more implantation failures of euploid embryos or high-grade non-tested embryos characterize recurrent implantation failure (RIF). Implantation failure is “the ultimate form of placenta failure”. Likewise, two or more miscarriages, constitute recurrent miscarriages.

There are several factors that can lead to RIF/RPL. The implantation process is a highly sophisticated and complicated process with a myriad of bodily functions and factors involved. Imbalances in such factors lead to adverse endometrial environments and implantation failure.

A recent review of the literature is summarized below listing the most important factors responsible for RIF with today’s knowledge; Dr. Kofinas considers all these factors very important for a successful pregnancy and no patient should be diagnosed with unexplained infertility or recurrent miscarriage unless these factors are investigated.

  1. Immune system factors
    1. KIR receptors of NK cells and immune tolerance
    2. HLA-C antigens in fetal trophoblast and KIR interactions
      1. Haplotype A and B and allotype C1 and C2 combinations define risk of failure
  2. Adenomyosis
  3. Endometriosis
  4. Chronic Endometritis
  5. Insulin Resistance, Obesity, and PCOS
  6. Genetic factors (Genetics of Embryo, Maternal Genetics, Paternal genetics)
  7. Genetics of the Endometrium (gene expression during the implantation window and decidualization)
  8. Anatomical abnormalities as in:
    1. Fibroids
    2. Polyps
    3. Uterine Septum
    4. Intrauterine Adhesions
    5. Hydrosalpinx
  9. Hematological Factors
    1. Inherited Thrombophilia (maternal and paternal)
    2. Acquired Thrombophilia (maternal only)
  10. Microbiome in RIF; unhealthy intestinal environment leads to inflammatory conditions
  11. Endometrium
    1. Endocrine Regulation of its cyclical changes (receptivity at time of implantation)
    2. Mechanisms of Endometrial dysregulation (abnormal gene expression, inflammation)

Unless all the above parameters have been evaluated, the causes of your unexplained infertility, implantation failure, and recurrent miscarriage have not been evaluated properly and you need to consider proper testing. Otherwise, it will be unwise to continue with IVF procedures that lead you to more and more failures.

Every time a woman suffers implantation failure or recurrent miscarriage, the odds of this happening again are increased because the immune system gets sensitized from the failed products of conception against the next embryo.

What you should do: Ask your primary care doctor to perform these tests or refer you to a local specialist. You are always welcome to come to one of our New York offices and have all these done in 2-3 visits. We will identify all known issues, create a highly customized protocol of supplements and medications to correct all the imbalances we have identified, and help you realize your dream.  (Franasiak, JM et al. A review of the pathophysiology of recurrent implantation failure, Fertility and Sterility October 2021).