You may have learned that the majority of single miscarriages are caused by chromosomal issues and aren’t always preventable. What you may not know is that if you have experienced multiple miscarriages, the likelihood that other causes outside of chromosomal issues may be playing a role increases and many of these causes can be significantly improved upon to lower miscarriage risk!
Many women do not get screened for miscarriage risk factors until they’ve experienced 3 or more recurrent losses which can be a very traumatic experience.
Research shows us that several lab markers are associated with miscarriage risk that can be easily run. I advocate for running these labs much earlier on, absolutely after 2 recurrent losses, and even after 1 loss in some cases. There are 5 tests I run in almost all my patients who have experienced recurrent losses.
Vitamin D
Vitamin D plays an important role in modulating and supporting a balanced immune system1. It’s well established that many immune system cells have Vitamin D receptors including those found in our reproductive tissues.
Recent research points to immune system dysregulation as a likely—and often overlooked—cause in many who are experiencing multiple miscarriages2. An activated immune system can affect healthy implantation and increase the likelihood of a loss2.
A systematic review of the research on this topic to date found that there was a high prevalence of Vitamin D deficiency in women experiencing recurrent miscarriages1. One study found that women with sufficient Vitamin D levels in the pre-conception period were more likely to carry to term than those with Vitamin D deficiency3.
Vitamin D deficiency in pregnancy has also been associated with an increased risk of preeclampsia, gestational diabetes, fetal growth restriction, and pre-term labour1.
All women with a history of miscarriage(s) should have their vitamin D levels screened and should supplement if insufficient.
Important note: Never supplement more than 1,000 IU of Vitamin D without testing blood levels. Vitamin D is a fat-soluble vitamin and taking too much can lead to toxicity.
Thyroid Stimulating Hormone (TSH)
Pregnancy has a profound effect on the thyroid gland and its function. Some studies suggest that the thyroid gland itself can increase up to 10% in size in pregnancy10!
Research suggests that a more narrow thyroid-stimulating hormone (TSH) level should be a target in women with a history of miscarriage(s). Studies have found that miscarriage rates were higher in women who had a TSH value above 2.5 compared to those whose TSH values fell below 2.5 mIU/L9,10. The American Thyroid Association now recommends that the upper acceptable limit for TSH in women in their first trimester is 2.5 mIU/L based on the research to date.
TSH levels should be screened in women with a history of miscarriage to ensure optimal ranges. Most laboratories in Canada consider a normal upper limit of TSH to be 4.0 mIU/L so this means that TSH levels that fall within the reference range may not be optimal when it comes to pregnancy.
If TSH levels are above 2.5 mIU/L, the standard of care treatment is levothyroxine medication which is safe to continue in pregnancy if required10.
Thyroid Peroxidase Antibody (Anti-TPO)
In addition to screening TSH levels, another thyroid marker called Anti-TPO should be tested to look for the presence of thyroid autoimmunity.
Thyroid autoimmunity is the most prevalent autoimmune condition in women of reproductive age4. Women are five times more likely to have thyroid autoimmunity than men4.
Emerging evidence now suggests that we should be looking for the presence of thyroid antibodies known as Anti-TPO, even if the other thyroid markers (such as TSH) are normal. Several studies have found a higher rate of thyroid autoimmunity in women with multiple miscarriages.
The American Journal of Reproductive Immunology published a meta-analysis on this topic this year. It summarized the research to date and concluded that “The presence of serum antithyroid antibodies does harm to women and can even lead to recurrent miscarriages.”4.
Testing thyroid autoimmunity is a simple blood test known as Anti-TPO. There is also another thyroid antibody called Anti-TG that can be screened, however, most research has been done on Anti-TPO.
Fasting Insulin and Fasting Glucose
Insulin’s main job is to regulate blood sugar levels and is therefore essential to our survival. However, too much insulin can cause long or missing cycles making it difficult to conceive, it can impact the implantation of an embryo and even contribute to an increased rate of miscarriages through multiple mechanisms.
Research has found that high insulin can impact the formation of the placenta which allows for a healthy exchange of blood and nutrition to the growing baby7. Other research suggests that elevated insulin can impact the expression of certain proteins that have an important role in the immune response within the endometrial lining which may also be playing a role in the increased miscarriage risk8.
Signs of chronically elevated insulin include long or missing menstrual cycles, weight gain and weight loss resistance, darkening of the colour of skin in skin folds, skin tags, fatigue after meals, and cravings for sugar and carbohydrates.
Insulin should be tested alongside glucose (sugar) to calculate the HOMA-IR which is a measure of insulin resistance. It should always be tested in the morning after a 12 hour overnight fast.
Next Steps
If you have experienced a miscarriage in the past, please know that you are not alone and that you did nothing to cause this loss.
If you’re looking for more support or investigation before trying to conceive again, you can consider running the testing above with the guidance of your health care practitioner.
Please note that these are just some of the testing that I run in practice but depending on your history and symptoms there may be additional labs that would be recommended.
References
- Gonçalves, D., Braga, A., Braga, J., & Marinho, A. (2018). Recurrent pregnancy loss and vitamin D: A review of the literature. American Journal Of Reproductive Immunology, 80(5), e13022. doi: 10.1111/aji.13022
- Schröder-Heurich, B., Springer, C., & von Versen-Höynck, F. (2020). Vitamin D Effects on the Immune System from Periconception through Pregnancy. Nutrients, 12(5), 1432. doi: 10.3390/nu12051432
- Mumford, S., Garbose, R., Kim, K., Kissell, K., Kuhr, D., & Omosigho, U. et al. (2018). Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. The Lancet Diabetes & Endocrinology, 6(9), 725-732. doi: 10.1016/s2213-8587(18)30153-
- Xie, J., Jiang, L., Sadhukhan, A., Yang, S., Yao, Q., & Zhou, P. et al. (2020). Effect of antithyroid antibodies on women with recurrent miscarriage: A meta‐analysis. American Journal Of Reproductive Immunology, 83(6). doi: 10.1111/aji.13238
- Chang, E., Han, J., Seok, H., Lee, D., Yoon, T., & Lee, W. (2013). Insulin resistance does not affect early embryo development but lowers implantation rate inin vitromaturation-in vitrofertilization-embryo transfer cycle. Clinical Endocrinology, 79(1), 93-99. doi: 10.1111/cen.12099
- Ispasoiu, C., Chicea, R., Stamatian, F., & Ispasoiu, F. (2013). High Fasting Insulin Levels and Insulin Resistance May Be Linked to Idiopathic Recurrent Pregnancy Loss: A Case-Control Study. International Journal Of Endocrinology, 2013, 1-4. doi: 10.1155/2013/576926
- Palomba, S., Russo, T., Falbo, A., Di Cello, A., Amendola, G., & Mazza, R. et al. (2012). Decidual Endovascular Trophoblast Invasion in Women With Polycystic Ovary Syndrome. Obstetrical & Gynecological Survey, 67(12), 788-789. doi: 10.1097/01.ogx.0000425651.26360.0c
- Tian, L., Shen, H., Lu, Q., Norman, R., & Wang, J. (2007). Insulin Resistance Increases the Risk of Spontaneous Abortion after Assisted Reproduction Technology Treatment. The Journal Of Clinical Endocrinology & Metabolism, 92(4), 1430-1433. doi: 10.1210/jc.2006-1123
- Kianpour, M., Aminorroaya, A., Amini, M., Feizi, A., Aminorroaya Yamini, S., & Janghorbani, M. (2019). Thyroid‐stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population‐based cohort study. Clinical Endocrinology. doi: 10.1111/cen.13979
- Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., & Negro, R. et al. (2022). Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. Retrieved 23 February 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472679/#B40
