The immune system plays a critical role in implantation and supporting an ongoing pregnancy. Pregnancy is a really unique situation for the immune system. Normally, the immune system will fight off a foreign body, such as an infection or a transplant. But in pregnancy, the immune system needs to accept and grow an embryo which will have a different immunological system to the mother. This is the basis of lots of interesting theories as to why implantation might not occur.
The whole area of reproductive immunology is controversial. Most specialists and researchers believe that the immune system may be responsible for failed IVF cycles and pregnancy losses in some people at some point. However, we do not know how to identify these couples and do not have any tests which are proven to improve pregnancy outcome.
Research has focused on many different areas in reproductive immunology. I’m going to focus on natural killer cells.
The first problem with natural killer cells is their deceptive name, suggesting that they may be harmful to pregnancy. This is actually wrong, and many studies have shown that helpful in preparing the endometrium, regulating it to improve the chances of implantation occurring.
The second issue is that most research studies into natural killer cells have been badly designed. The studies compare a group of women who have had recurrent implantation, failure and miscarriage, and compare those to women who have had successful pregnancy outcomes.
At face value, this seems a sensible approach. But this is complete nonsense when it comes to research. It’s like trying to compare the size of the womb of someone with miscarriage and implantation failure with someone who’s just had a baby. We all know that the womb of someone who’s just had a baby is much larger than a than one before. But we don’t measure the size of the womb beforehand to try and explain why and pregnancy doesn’t occur.
Only three studies have done things properly where they’ve taken a group of women and checked that natural killer cells and then followed them through to see what the impact is on pregnancy. This is a lot less reliable. The association just isn’t quite there in the same way, and these tests are not always that reliable either.
Testing of natural killer cells is also unreliable. Levels vary between cycles, so taking a sample of a biopsy in one cycle doesn’t mean that that’s going to be the situation in the next cycle.
Given the problems with testing, no reliable treatments have been found to improve outcome. Suppressing the immune system of a pregnant patient also exposes the patient and baby to considerable risks, including life-threatening infections.
The Human Fertilisation and Embryology Authority (HFEA) rate immunological tests and treatments red as part of their guidance on add-on treatments.
The use of immunological tests and treatments as part of fertility treatment in healthy patients is rated red. This is because there is no evidence from randomised controlled trials (RCTs) to show that they are effective at improving the chances of having a baby for most fertility patients.
HFEA
The January 2019 consensus statement between the HFEA and ten other professional and patient bodies agreed that treatments that have no strong evidence of their safety and/or effectiveness should only be allowed in a research setting.
Authors
Matt is an NHS Consultant in Newcastle with over ten years of experience. His PhD research into subfertility and miscarriage involved developing a clinical trial and patient engagement.
