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By Tiffanee Lenzi, MD, PhD, FACOG, FACMG
Tennessee Maternal Fetal Medicine

Miscarriage, defined as the loss of a recognized pregnancy prior to 20 weeks gestation, affects up to 1 in 5 women during their lifetime. When taking into account very early pregnancies (that may be unrecognized by the woman), it has been estimated that 1 in 3 conceptions may not progress to a live birth.

Recurrent pregnancy loss (RPL) which affects 1-2% of  women  has  been  defined  by  the  American College of Obstetrics and Gynecology as the consecutive loss of 3 early pregnancies.  However, many physicians will begin a work-up for women after two pregnancy losses.

The cause of recurrent pregnancy loss is not determined in approximately 50% of cases after work-up, which is often a source of frustration for couples. Fortunately, the majority of couples with unexplained recurrent losses (>75%) will go on to deliver a baby.

Possible causes of recurrent pregnancy loss:
Possible causes of recurrent losses can be divided into categories including Genetic Factors, Anatomic Factors, Hormonal Factors, Blood Clotting Abnormalities and Maternal Medical Disease and Lifestyle Factors.

Genetic Factors
The most common reason for early pregnancy loss is genetic abnormality of the fetus. Over half of miscarriages have an abnormal number of chromosomes. During formation of an egg or sperm cell (called meiosis), an extra copy of a chromosome may be pulled into a daughter cell, or loss of a chromosome may occur. These types of errors are more common in the egg than sperm because the process of egg formation begins before a female is even born. Additionally, 5% of couples with recurrent early pregnancy losses have a rearrangement of their chromosomes called a translocation (compared with 0.5% in the general population).

Anatomic Factors
Women with abnormalities of the shape of the uterine cavity are at increased risk of fetal loss.  Some women are born with an abnormal uterine cavity shape (also called congenital uterine anomalies). Benign uterine tumors called fibroids are common and can also distort the uterine cavity. Scarring of the uterus (or uterine adhesions) from prior infection or surgery may obliterate the uterine cavity. All of the above may affect blood flow to the lining of the uterus and the growth of a placenta.

Hormonal Factors
Low levels of the hormone progesterone have been implicated in early pregnancy losses. This is sometimes referred to as luteal phase defect. Other hormonal factors that may increase the risk of miscarriage include poorly controlled diabetes, autoimmune thyroid disease and benign tumors that produce the hormone prolactin (prolactinomas).

Blood Clotting Abnormalities
Certain disorders that increase the risk of blood forming clots (also called thrombophilias) are associated with recurrent pregnancy loss. This includes the antiphospholipid antibody syndrome (APL syndrome). Diagnosis of this is based on history and laboratory evaluation.

Maternal Medical Disease and Lifestyle Factors
Some maternal medical diseases may increase the risk of fetal loss. This is particularly true for disorders that affect maternal blood vessels including poorly controlled diabetes and severe range hypertension. Untreated maternal Celiac disease (gluten intolerance) may also increase the risk of miscarriage.

Certain lifestyle factors may increase the risk of miscarriage including smoking, illicit drug use and excessive caffeine use. In addition, high doses of medications such as ibuprofen may increase the risk of fetal loss.

Evaluation of RPL
Blood tests include an evaluation for parental chromosome rearrangements such as translocations. Ideally, this test should be performed on both members of the couple. In addition, testing for certain blood clotting disorders including the antiphospholipid antibody syndrome (APL syndrome) is recommended. Other blood tests that some providers may perform include screening for Celiac disease (gluten intolerance), screening for thyroid antibodies or an evaluation of blood sugar control in diabetics.
The uterine cavity is often evaluated with a special ultrasound involving the insertion of fluid in the uterus (called a sonohysterogram), however, other types of radiology studies or office procedures may also be done to evaluate the shape of the uterine cavity.

Management of Future Pregnancies
Specific treatments depend upon the presence of uterine or laboratory abnormalities. Women with uterine abnormalities may benefit from office procedures. Those who meet criteria for antiphospholipid antibody syndrome should be treated with aspirin and injectable blood thinners. Hormonal abnormalities found during laboratory evaluation should be corrected. Treatment of progesterone deficiency or luteal phase defect is controversial, however, some providers supplement progesterone during the first trimester. Low dose aspirin (81 mg) is often prescribed by some providers. Modification of lifestyle factors may also be recommended. This may include quitting smoking, avoidance of excessive alcohol, limiting caffeine intake to less than 200 mg per day, and maintaining a healthy weight.

The risk of miscarriage with subsequent pregnancies is correlated with the number of prior miscarriages. Losses typically occur at a similar gestational age. The chance of miscarriage in subsequent pregnancies has been estimated to be 15% after one prior miscarriage, 15-30% after 2 miscarriages, and 25-50% after 3 prior miscarriages. Visualization of a fetal heart beat is a reassuring sign, however, the risk of miscarriage in couples with RPL may be up to 20% (compared with 5% in the general population) until the gestational age of the prior losses is exceeded. As above, however, over 75% of couples with recurrent miscarriage will go on to deliver a baby.

Providers at Tennessee Maternal Fetal Medicine see patients by referral.

615-284-TMFM (8636)

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