Recurrent Miscarriage: Causes & Diagnosis with our Fertility Experts
Recurrent pregnancy loss is defined by the American Society of Reproductive Medicine as two or more pregnancy losses that occur before the 28th week of pregnancy. In the India, approximately 25% of all pregnancies are lost at some point during gestation. Only 5% of women experience two or more pregnancy losses and less than 1% of women experience three or more pregnancy losses. Although this condition can be very frustrating and emotionally challenging, the overwhelming majority of patients with recurrent pregnancy loss eventually will successfully deliver a healthy child.
Causes of Recurrent Pregnancy Loss
1. Anatomic 22%
2. Genetic 3%
3. Infectious 6%
4. Hematologic or immunologic 25%
5. Hormonal 20%
6. Unknown 40%
As you can see from the table, these numbers total more than 100%, indicating that some patients have multiple causes for their miscarriages. Unfortunately, following the completion of a thorough evaluation for recurrent pregnancy loss, 40% of couples with recurrent pregnancy loss will still not have a definitive diagnosis for their problem.
The Effect of Maternal Age on Recurrent Pregnancy Loss
As women age, their risk of spontaneous miscarriage increases. At age 20, the risk ranges from 9 to 17%; it rises to 20% in women by age 35, 40% at age 40, and 80% in women 45 and over. Most specialists believe that this age-related increase is most likely due to chromosomal abnormalities within the egg.
Anatomic Causes of Recurrent Pregnancy Loss
All healthy pregnancies attach to and grow within the uterine cavity. Unfortunately, some women are born with a uterus that not been formed normally. It appears that approximately 5% of fertile women have uterine anomalies. In other words, despite their abnormally shaped uterus, they were still able to successfully conceive and deliver a child. On the other hand, approximately 15% of patients with recurrent pregnancy loss have an abnormal uterus.
Uterine Development, Structural Causes of Recurrent Pregnancy Loss
When a woman is a fetus developing in her mother’s uterus, she initially has two separate uteruses (“uteri”), each originating near the corresponding kidney. As the female fetus develops, these two early uteruses migrate towards each other and eventually fuse. In the normal situation, the wall between the two separate uteruses reabsorbs, resulting in a normal, single, triangular shaped uterine cavity. Anatomical abnormalities result when this sequence of events does not occur or fails to occur completely.
The most common uterine abnormality is the septate uterus. In a large study from Yale, 85% of patients with a septate uterus either failed to conceive or miscarried repeatedly. Following repair of this abnormality, 88% of patients went on to deliver successfully while only 12% continued to have difficulty – either they failed to conceive or they continued to miscarry. Other uterine abnormalities include the bicornuate uterus (2 separate uterine cavities sharing a single cervix), the unicornuate uterus (a situation where only one of the fetal uteri develops), or a complete uterine duplication (2 uterine cavities, each with its own cervix). These are far less common and surgical correction does not appear to improve the prognosis in these patients.
Another uterine abnormality that can interfere with successful conception is the presence of scar tissue within the uterine cavity. This typically results following a D&C if too much uterine lining tissue is removed – the walls of the uterus can subsequently stick together, making the cavity small and irregular. Additional anatomic abnormalities that are associated with recurrent pregnancy loss include uterine fibroids or endometrial polyps. Fibroids are benign tumors caused by an overgrowth of uterine muscular tissue. They can occur inside the uterine cavity, in the muscular wall of the uterus, or on the outside of the uterus. Polyps are an overgrowth of glandular tissue within the uterus. Either of these conditions can cause abnormal uterine bleeding or they may be asymptomatic. Fibroids may also cause a significant increase in menstrual cramps, pelvic pressure, or pelvic pain.
Genetic abnormalities are one of the most common causes of recurrent pregnancy loss. It is thought that the more severe the embryonic genetic abnormality, the earlier the pregnancy is lost. Studies have shown that 60% of normal appearing day three embryos from 35-year-old women are chromosomally abnormal. This percentage rises to 90% in 40-year-old women. These abnormalities usually result from problems within the egg – either the egg’s chromosomes are abnormal or the structure responsible for chromosome separation as each cell divides is abnormal. Research suggests that, although problems in the sperm can lead to chromosomal abnormalities as well, this occurs much less frequently. Typically, if sperm are not chromosomally normal, either they fail to fertilize the egg or the fertilized egg fails to divide, resulting in loss of the pregnancy.
Despite the fact that genetic abnormalities in miscarried embryos are common, genetic abnormalities in parents are very rare. Even when patients have lost several pregnancies that were known to be chromosomally abnormal, only 2% to 3% of patients or their partners turn out to have a genetic abnormality themselves. Genetic translocations (where parts of two different chromosomes change places) represent the most common parental cause of genetic abnormalities.
Infectious Causes Of Recurrent Miscarriage
Although many studies suggest that infections such as gonorrhea, chlamydia, mycoplasma, and ureaplasma are associated with recurrent pregnancy loss, this still remains somewhat controversial. Regardless, a thorough evaluation of recurrent pregnancy loss includes the performance of cervical cultures designed to detect the presence of these conditions. Regardless of the culture results, each member of the couple is subsequently treated with antibiotics for at least 10-14 days, as cervical cultures have been demonstrated to be accurate less than 70% of the time.
Hematologic or Immunologic Causes
When a pregnancy attaches to the uterine wall, it gets nourishment and oxygen from the mother by way of the placenta. This circulatory connection is critical to the survival and growth of the baby. Some miscarriages are caused by blood clots that form in the small vessels of the placenta, as these clots prevent the transfer of either nutrition or oxygen to the fetus. These clots may be caused by abnormalities in the normal blood clotting mechanism.
This category of miscarriage is referred to as “hematologic or immunologic”, and consists of three basic causes. The first is antiphospholipid antibody syndrome (APAS). APAS has been reported to occur in 3%-15% of women with recurrent pregnancy loss. Although many blood tests can detect the presence of APAS, the only test that has been demonstrated to correlate with recurrent pregnancy loss is the anti-cardiolipin antibody test. This simple blood test effectively confirms the presence or absence of APAS.
The second major hematolgic cause of recurrent pregnancy loss is lupus anticoagulant. While this condition unfortunately shares the same name as the chronic disease commonly referred to as “lupus”, the two conditions have little in common with each other. Like APAS, lupus anticoagulant is a disorder in which blood clots occur within the small vessels of the placenta. As with APAS, a simple blood test can detect the presence of lupus anticoagulant.
The final category of hematologic causes of recurrent pregnancy loss is a group of disorders called thrombophilias. This category includes such conditions as deficiencies of factor V Leiden, protein C, protein S, and methyl-tetrahydrofolate reductase (MTHFR). It remains controversial as to whether thrombophilias cause recurrent pregnancy loss and, in fact, the American Society for Reproductive Medicine in their August, 2008 practice committee report, stated that there is no evidence that it is beneficial to either diagnosis or treat these conditions. Therefore, many fertility specialists no longer test patients with recurrent pregnancy loss for thrombophilias.
The evidence supporting a hormonal cause of recurrent pregnancy loss is also somewhat limited. This condition, called “luteal phase inadequacy”, is thought to result from inadequate progesterone production, leading to a disorder in which the development of the uterine lining is not synchronized with the development of the embryo. Therefore when the embryo tries to attach to the uterine wall, an unstable attachment may occur which may lead to miscarriage. This condition is classically diagnosed by performing an endometrial biopsy – a procedure where a small piece of uterine tissue is removed and subsequently evaluated under a microscope. This test is somewhat uncomfortable and, as even normal women can occasionally have an abnormal biopsy, the biopsy should actually be performed twice (preferably in consecutive cycles) in order to confirm the presence of the abnormality. If luteal phase inadequacy is diagnosed, it is treated with either progesterone or Clomid. Due to the discomfort caused by the biopsy, many fertility specialists will initiate treatment without a repeat biopsy. Other hormonal etiologies that have been associated with luteal phase inadequacy include thyroid disease and hyperprolactinemia.