How the Right Diagnosis Can Prevent Miscarriage: The Top 10 Causes

There is so much that we don’t know about what it takes to carry a baby to term. If you’re working with a fertility clinic you’ll notice there’s a lot of observation during the first two weeks of your cycle, and once you’ve ovulated (or post embryo transfer) there’s not much monitoring after that! Rest assured, this article isn’t about what we don’t know but rather what we do! Fifty percent of miscarriages may not have an identifiable cause, but that means 50% of them do. 

Let’s go over the stats here for a moment. 

Recurrent miscarriage is considered two or more consecutive miscarriages, however diagnosis and treatment is often not suggested until three consecutive miscarriages have occurred. Not because you should have to suffer, or because your doctor doesn’t care, but because there’s a 15-25% chance of any pregnancy ending in miscarriage. The most common cause of miscarriage is fetal chromosome abnormality, which is about 60% of the time.

While we’re going over the terminology, a “chemical pregnancy” is considered a miscarriage before 5 weeks, however I still consider it a miscarriage. 

Factors to consider in miscarriage: 

1. Did you have an early loss in the first trimester, or a late loss in the second or even third? Different diagnoses are more likely in late pregnancy versus early pregnancy. 
2. Do you already have a child, and in trying to conceive again have a miscarriage? Having a baby already can rule out some causes of miscarriage. 
3. Do you have a family history of autoimmune, hormonal, or blood disorders? That makes some of the diagnoses more likely. 

Factors NOT to consider in miscarriage: 

1. You haven’t “stressed” yourself to the point of miscarriage. I promise!  
2. Exercise is always healthy! You don’t need to avoid physical activity 
3. Progesterone, in any form, is not always the answer. A 2008 Cochrane review found prophylactic progesterone to have no effect on preventing miscarriage, more on this soon. 

In my practice I don’t wait the “3-loss” rule to begin treatment and diagnosis, if you’ve experienced a loss and you want support, you deserve that support right away. 

Top 10 Most Common Causes of Miscarriage 

The majority of the list can be diagnosed with blood work or imaging. The entirety of the list can be treated! 

1. Anti-phospholipid syndrome (and other causes of poor placental perfusion)
   This is a syndrome where antibodies attack components of your blood vessels. Anti-phospholipid antibodies include: lupus anticoagulant, anticardiolipin antibody, and anti-B2 glycoprotein. These antibodies interfere with uterine blood flow, more specifically the development of the trophoblast, which are the cells that form the placenta.
2. PCOS
   The foundation of PCOS is insulin resistance, which interferes with ovulation, follicle maturation, and maintaining a pregnancy. Insulin resistance, and the corresponding hormonal imbalances, cause poor egg quality, pelvic inflammation, and progesterone deficiency – all which contribute to miscarriage. I will add that metformin has not been found to be beneficial in preventing miscarriage in PCOS, but there are many naturopathic therapies that have!
3. Chromosome translocation (it’s not all about the woman!)
   This genetic condition can occur in men or women. If you have a chromosome translocation you won’t have any signs or symptoms, but some of the gametes you produce (i.e. egg or sperm) will also have the translocation. Unfortunately, if you’re conceiving naturally it’s a game of chance as to whether or not you will produce a viable embryo. IVF with PGS (pre-implantation genetic screening) can determine whether your embryo has a viable number of chromosomes.
4. Hypothyroidism & thyroid antibodies
   TSH greater than 4.0 during pregnancy is associated with miscarriage, preterm birth, premature rupture of membranes, and placental detachment. Thyroid peroxidase antibody, found in Hashimoto’s thyroiditis, causes similar outcomes.
5. Anatomical causes: fibroids, polyps, uterine malformations, cervix incompetence
   Anatomical issues are more commonly at play during second trimester losses, and the outcome depends greatly on the location of the finding. I won’t go into the details here as they are easily diagnosed, and quite obvious, through imaging and pelvic exam.
6. Poor quality sperm (it’s not all about the woman!)
   The best test for measuring sperm quality is called sperm DNA fragmentation. Greater than 25% fragmented DNA indicates poor quality. In my experience, beyond lifestyle factors like diet and recreational drug use, medications are the most common culprit of increased DNA fragmentation. Anti-depressant medication, specifically SSRIs, cause statistically significant increases in DNA fragmentation as well as miscarriage.
7. Poor quality egg
   If only we had a test for egg quality like we do sperm quality! Age is the number one predictor for egg quality, steadily declining after age 35 – lucky us! But don’t worry, there’s lots that can be done!
8. Vitamin D deficiency
   One prospective cohort study identified vitamin D deficiency as a risk factor for miscarriage, preterm birth, and low birth weight. Adequate vitamin D levels, hard to come by in gloomy Canada, are extremely important when it comes to reproductive health. 1 nmol increase in serum vitamin D levels decreases miscarriage rate by 1%. Testing is clearly imperative!
9. Inflammation & oxidative stress
   Conditions like PCOS, listed above, and endometriosis cause increased uterine inflammation and oxidative stress. Inflammation can also be elevated in the presence of other autoimmune diseases during pregnancy. However, there is significant research on specific anti-inflammatories and antioxidants increasing live birth rate and preventing miscarriage in these scenarios!
10. Progesterone deficiency & hyperprolactinemia
    As I’ve already suggested in this article, progesterone supplementation only appears to be helpful when there is a progesterone deficiency. High dose progesterone supplementation is all too common and I often see the extremely uncomfortable side effects in my patients. It may be indicated in cases of recurrent miscarriage. I’ll also mention hyperprolactinemia here as elevated prolactin levels can suppress progesterone production and lead to deficiency. 

Honorable mentions:

1. MTHFR deficiency & elevated homocysteine - MTHFR deficiency refers to a mutation in the gene “MTHFR”, responsible for metabolizing folate (a vitamin found in your prenatal supplement to prevent spina bifida).  When folate is not metabolized properly, a build up of an amino acid called homocysteine results. Elevated homocysteine can cause blood clotting and inhibit uterine and placental blood flow.
2. Immunological cause - I’m going to throw out some pretty fancy terms here: HLA incompatibility, anti-paternal antibodies, and natural killer cells. They’re all terms for potential immunological conditions that cause miscarriage, meaning the woman’s immune system is attacking the embryo. Currently there’s insignificant research to suggest any of the above cause miscarriage, and the treatment is theoretical as well. 
3. Vaginal infection - I’ve noticed many fertility clinics test for ureaplasma and mycoplasma, and treat both partners with antibiotics if present. There is no clear data that these infections cause miscarriage. I have mixed feelings about the results, as there are often comorbidities present in my patients who have been treated for these infections. However, untreated bacterial vaginosis can indeed cause early miscarriage. ​

Have more questions? Meet with us!
For any of the information we have provided, there are ways of diagnosing and treating these issues. You have options! We offer a free 30 minute consultation to all new patients Book yours today and lets get started! 

Written by Dr Caleigh Sumner ND

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 References

Iqbal, S., Ghani, F., & Qureshi, R. (2016). Frequency of Thyroid Peroxidase Antibody and its Association with Miscarriages Among Pregnant Women. Journal of the College of Physicians and Surgeons Pakistan, 26(10), 831-834.

Sundermann, A. C., Edwards, D. R. V., Bray, M. J., Jones, S. H., Latham, S. M., & Hartmann, K. E. (2017). Leiomyomas in pregnancy and spontaneous abortion: A systematic review and meta-analysis. Obstetrics & Gynecology, 130(5), 1065-1072.

Bärebring, L., Bullarbo, M., Glantz, A., Hulthén, L., Ellis, J., Jagner, Å., ... & Augustin, H. (2018). Trajectory of vitamin D status during pregnancy in relation to neonatal birth size and fetal survival: a prospective cohort study. BMC pregnancy and childbirth, 18(1), 51.

Loss, E. P. PRACTICE BULLETIN.

EVALUATE, W. (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and Sterility, 98(5).

El Hachem, H., Crepaux, V., May-Panloup, P., Descamps, P., Legendre, G., & Bouet, P.-E. (2017). Recurrent pregnancy loss: current perspectives. International Journal of Women’s Health, 9, 331–345. http://doi.org/10.2147/IJWH.S100817

No, G. T. G. (2011). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. April 2011.

Haas, D. M., & Ramsey, P. S. (2008). Progestogen for preventing miscarriage. Cochrane Database Syst Rev, 2.