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  • Writer's pictureDr. H. Singh, ND

Recurrent pregnancy loss may be induced by immune system dysfunction caused by microbiome dysbiosis

I always love sharing the latest research on this topic because even though the cause of recurrent pregnancy loss (RPL) can vary from each individual patient (endocrine, anatomical, epigenetic, immune, etc.) there is one very important point to highlight: the health of the sperm cell is just as important when it comes to supporting a healthy pregnancy as the egg and uterus. Please take a moment to read the previous line one more time.

Yes, I know exactly what you are thinking after reading this. In fact, I will often in my healthcare practice hear it all to often from Patients who have had anywhere from 2-5+ miscarriages, and were screened for 'all possible' causes and the male partner had little to no investigations done to try and understand why there are consecutive miscarriages occurring. A new research paper published in 2022 in the Journal of BMC Immunology observed the importance of how the reproductive microbiome may affect sperm cells and may impact risk of RPL in couples. This contributes more valuable information towards how sperm health may actually affect risk of miscarriages.

The immunogenicity of sperm cells affects risk of miscarriages:

To explain simply, there is a very important immune reaction that needs to occur at the moment of fertilization for pregnancy to progress normally and be healthy. In order for this immune reaction to occur, the immune system of the Patient with the uterus must interact with antigens on the sperm cells (specifically HLA 1 & HLA 2) during insemination. When this normal interaction occurs the Patient with the uterus will produce anti-paternal cytotoxic antibodies (APCAs). APCAs are commonly found in the serum of Patients with previous pregnancies. This process has also been hypothesized to also affect the production of another component of the immune system called T-cells (regulatory and effector T lymphocytes). Conversely, in couples that have a medical history of recurrent miscarriages two important observations may be made: APCAs are absent or very low and the sperm cells of the partner have decreased expression of the HLA 1 and HLA 2 antigens.

So why do sperm cells from couples with RPL have decreased HLA 1 & HLA 2 expression?

This new study published found that the deficiency of APCAs in the patient with the uterus can be caused by a deficiency in the HLA 1 and HLA 2 antigens on the sperm cells. It was observed that a healthy strain of probiotic could reverse this and increase the production of HLA 1 on sperm cells and could increase production of APCAs in couples with a medical history of recurrent miscarriages. It was theorized that the presence of harmful pathogenic bacteria can decrease the expression of HLA-1 and HLA-2 on sperm cells and healthy bacteria may increase their expression (by binding to toll-like receptors/TLRs on sperm cells). Increased expression of these antigens helps to support a normal and healthy immune reaction needed for pregnancy.

Limitations of the study:

The sample size was quite small in this study and further research is needed to help determine if the increase in APCAs in the patient with the uterus and an increase in HLA 1 expression on sperm cells in couples with recurrent pregnancy loss actually translates to an increased likelihood for a live birth.

This article is being shared as educational content and is in no way a replacement for medical advice or medical care, it is advised that anyone concerned about their Health should speak with their Naturopathic Doctor. Please discuss with your healtcare provider and only make changes to your medications regimen if recommended by your doctor and under their guidance and supervision.


  1. Rafiee, M., Sereshki, N., Alipour, R., Ahmadipanah, V., Pashoutan Sarvar, D., & Wilkinson, D. (2022). The effect of probiotics on immunogenicity of spermatozoa in couples suffering from recurrent spontaneous abortion. BMC Immunology, 23(1).

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