Recurrent pregnancy loss (RPL) is defined when a woman has two or more consecutive failed pregnancies without a normal pregnancy (for some, it’s defined as three or more). Although more than 50 percent of women will experience sporadic pregnancy loss, only 5 percent of women have RPL.
What Causes Recurrent Pregnancy Loss?
There are many factors to consider when analyzing any pregnancy loss. It is important to determine the gestational age at the time of the loss, as the likelihood of causes differ based on whether it occurred pre-embryonic (“chemical” or anembryonic), embryonic (less than 10 weeks), or fetal (10 weeks or more).
- Genetics and Recurrent Pregnancy Loss
The most common reason for RPL is a genetic abnormality, such as aneuploidy or polyploidy (abnormal chromosomes in the embryo/fetus). These can be found in 50 to 60 percent of pregnancy losses, but the actual rate may be higher, since aneuploidies are sometimes difficult to detect at early gestational ages with the contamination of maternal cells in the miscarriage specimen. Microarray testing is one way to improve detection rates of aneuploidy in miscarriages, as is invasive testing, including CVS.
In vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) is a proposed therapy for recurrent pregnancy loss due to aneuploidy. However, this is a very expensive option, and supportive research of its efficacy are mixed.
There are several known single gene disorders that can cause RPL, and there are likely many more unknown ones. For example, alpha thalassemia can cause second trimester loss from hemoglobin Bart, and multiple pterygium syndrome can cause second trimester loss as well. With further research, there are most likely other single gene mutations that cause pregnancy loss that will be discovered.
- Disorders of Coagulation / Thrombophilias
The association of inherited blood clotting disorders (thrombophilias) with pregnancy loss is controversial. Several authors have reported an association while others have not. The pathophysiologic mechanisms responsible for the association of thrombophilias with early fetal loss are unclear. Maternal thrombophilia could interfere with implantation or development of the uteroplacental circulation, but there are no good data confirming this theory.
However, there is evidence supporting an association between antiphospholipid antibodies and pregnancy loss, particularly fetal losses. Currently, women with three early pregnancy losses who have persistent antiphospholipid antibodies meet criteria for the antiphospholipid antibody syndrome (APAS) and in these women, anticoagulation with low dose aspirin and heparin (or low molecular weight heparin) has been shown to improve outcomes.
- Uterine Anomalies
Early pregnancy loss has been associated with uterine abnormalities, specifically septate uterus and forms of bicornuate uterus with a partial septum. This presumably occurs when implantation at the septum portion provides poor blood flow to the developing pregnancy. The treatment would be removing the septum surgically. Unfortunately, there are no well-designed trials to prove that pregnancy rates improve after surgical correction. However, most authorities recommend surgical correction of a separate uterus in women with RPL.
- Immune Causes
Maternal and paternal immunity have been implicated as causes of RPL, but treatments with immune modulators, such as steroids or intravenous immunoglobulin (IVIG), have not been shown to be effective, except possibly in very select and rare cases. Unfortunately, IVIG therapy is rather expensive and typically not covered by insurance.
- Endocrine Causes
Hypothyroidism, diabetes, luteal phase defects, and polycystic ovary syndrome (PCOS), have been implicated as causes of RPL as well. It is unclear if treatment of euthyroid women found to have thyroid peroxidase antibodies with levothyronxine lowers the risk of pregnancy loss. A Cochrane review in 2010 found a non-significant trend towards fewer pregnancy losses with thyroid replacement therapy.
There have also been studies that progesterone therapy was associated with a significant decrease in the likelihood of pregnancy loss. However, it is not clear if progesterone is effective for women with recurrent pre-embryonic losses.
The connection between PCOS and RPL is unclear, particularly considering that treatment with metformin does not reduce the risk of pregnancy loss. Additionally, obesity is associated with pregnancy loss, and weight loss prior to pregnancy has shown to lower risk of pregnancy loss. Therefore, achieving a normal BMI before getting pregnant is a healthy goal and a possible way to reduce the risk of pregnancy loss.
Fortunately, the vast majority of couples with RPL will have normal testing and will eventually have a successful pregnancy. For more information regarding FPL or any of our women’s healthcare services in New York, visit our blog.
Maternal Fetal Medicine blogs are intended for educational purposes only and do not replace certified professional care. Medical conditions vary and change frequently. Please ask your doctor any questions you may have regarding your condition to receive a proper diagnosis or risk analysis. Thank you!