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Recurrent Miscarriage

Recurrent miscarriage

Image by Brodie Vissers 

Recurrent miscarriage is defined as having had two or more pregnancies in a row that ends before the 20th week. The condition can be caused by chromosomal problems, which are passed from one or both parents; conditions such as diabetes or fibroids, which are noncancerous growths on the uterus; immune system problems; hormonal imbalances; or congenital abnormalities of the uterus.

About 1 percent of women who experience Recurrent miscarriage have more than one in a row. In 50 to 75 percent of women who have recurrent miscarriages, doctors can’t pinpoint the cause. 

Chromosome aneuploidy is common in human gametes and preimplantation embryos and is a major cause of in vitro fertilization (IVF) failure, miscarriage, and stillbirths, with an incidence at the birth of less than 0.3%. Most aneuploidies originate in the oocyte through errors in maternal meiosis and these increase exponentially in women in their late 30s and early 40s. This is associated with a sharp increase in the incidence of miscarriage and a corresponding decline in live birth rates in these women following IVF.⁠

Blood Clots and Miscarriage

Blood clotting disorders can cause miscarriages. Genetic mutations in the Annexin 5 gene and anti-phospholipid syndrome (autoimmune disease) can cause blood clotting disorders to develop.

Roughly 8-42% of recurrent miscarriages are accounted for by antiphospholipid antibody syndrome. The disorder can lead to an increased risk for thrombosis and loss of placental sufficiency required for pregnancy. Current standard treatment calls for aspirin and heparin to increase the likelihood of live birth. Newer emerging treatment options include TNF (tumor necrosis factor-alpha) inhibitors and granulocyte colony-stimulating factor (G-CSF), although more extensive clinical trials are needed to determine the risks and benefits of these drugs for the treatment of recurrent miscarriage.

Treatment/Management

Treatment for recurrent miscarriage should be targeted towards the underlying cause. Apart from antiphospholipid antibody syndrome, other medical conditions potentially attributing to frequent lost pregnancy include thyroid conditions, diabetes, and obesity. These conditions should be treated by a medical professional as appropriate.

If the issue lies with congenital or acquired uterine abnormalities, surgical intervention may be needed. This can include hysteroscopic septum resection, lysis of adhesions, myomectomy, or repair of a bicornuate uterus. 

Given the wide array of potential contributing factors, a collaborative effort between the entire healthcare team (involving embryologists, geneticists, endocrinologists, mental health specialists…) is key to helping with the management of recurrent miscarriage. 

MTHFR Gene mutation

Currently, no professional medical organization recommends testing for MTHFR or measuring homocysteine levels for recurrent pregnancy loss.


•It is possible that there is a link between neural tube defects and MTHFR for some women with two copies of the C677T polymorphism, but the magnitude of the effect is low and the most important factor is whether there is adequate dietary folic acid. Again, folic acid has you covered.

•The current recommendation is not to order MTHFR testing or to use the results of MTHFR testing to inform for risk related to neural tube defects, but rather to recommend that everyone attempting pregnancy take 400 mcg of folic acid.

•The American College of Obstetrics and Gynecology (ACOG), the Association for Reproductive Medicine (ASRM), the American College for Medical Genetics (ACMG), and the National Society of Genetic Counselors (NSGC)— the medical experts in infertility, pregnancy loss, pregnancy complications, and genetic medicine — all recommend against testing for MTHFR polymorphisms for infertility, recurrent miscarriages, and neural tube defects.

References: 

Pillarisetty, L. S., & Gupta, N. (2021). Recurrent Pregnancy Loss. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK554460/

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