There are several possible causes of recurring early pregnancy loss. Studies indicate that if all of the following testing is completed, approximately 50% of the time a cause for recurrent miscarriage will be found. Please be aware that it takes 3-4 weeks for the blood tests listed below to be completed.
Developmental abnormalities of the uterus
It is possible to have a developmental abnormality (medical term anomaly) of the uterus as a cause of pregnancy loss. The uterus will be evaluated with ultrasound, an x-ray test called a hysterosalpingogram (HSG) and in some cases, a pelvic MRI. Some developmental abnormalities of the uterus that cause recurrent pregnancy loss can be treated surgically with significant improvement in successful pregnancy rate. Other developmental abnormalities of the uterus are not amenable to surgical repair.
Hematologic abnormalities
You will be tested for several hematologic conditions that can cause pregnancy loss. A blood test is performed to see if you have any of the following conditions: Protein C deficiency, Protein S deficiency, anti-thrombin III deficiency, Factor V Leiden Mutation, Factor II mutation, abnormal prothrombin time, or activated partial thromboplastin time. If you have one of these conditions, a Hematology consultation will be requested for recommended treatment which may be as simple as daily aspirin or it may be a daily injection of an anticoagulant (blood thinner) like Lovenox.
You will be tested for elevated blood level of homocysteine. Homocysteine elevation can interfere with blood levels of folate during early pregnancy and lead to pregnancy loss. Treatment is accomplished by giving higher levels of folate supplement during pregnancy. Some recurrent pregnancy loss test panels include testing for the MTHFR gene. We are well aware of MTHFR testing. The point of this testing relates to homocysteine. Some patients with certain MTHFR genes have elevated homocysteine and some do not. Therefore, we do not find testing for MTHFR to be useful. Rather, we test for an elevation of homocysteine which becomes the finding that will require treatment.
Antiphospholipid antibody syndrome
You will be tested for the “antiphospholipid antibody syndrome”. This is an autoimmune disease and is similar to other conditions noted above, in that it is thought to cause clotting between the uterus and placenta as a cause of pregnancy loss. It is treated with an anticoagulant (blood thinner) like Lovenox. Tests that will be performed include: anti-cardiolipin antibody, lupus anticoagulant, and beta 2 glycoprotein antibody.
Genetic abnormalities
Pregnancy losses may be caused by a genetic abnormality of the developing pregnancy which is incompatible with life. There are two very different categories of genetic abnormalities. The first is called a spontaneous genetic abnormality and is linked to maternal age. The risk of this type of pregnancy loss is: age 20yo-10% risk of loss; age 30yo-15% risk of loss; age 40yo-50% risk of loss. This type of age-related pregnancy loss cannot be prevented unless in vitro fertilization (IVF) is performed and embryos are tested to evaluate their chromosomes. There is more to know about this category as it relates to in vitro fertilization technology, to be discussed with your doctor if appropriate.
Some pregnancy losses are caused by an imbalance of chromosome material in one of the parents. This leads to a chromosome imbalance in the early pregnancy which may not be compatible with life. This is called a “balanced translocation.” In this condition, one of the parents carries the balanced translocation and is normal in every way but the risk of pregnancy loss is increased. The degree of increase and the type of abnormality that might affect a newborn vary depending on the type of translocation. Testing for this condition is a blood test called a karyotype (performed on both partners) and if a translocation is diagnosed there will be a consultation with a geneticist for guidance about the degree of risk related to all the above issues. As above, there is more to know about this category related to in vitro fertilization-again, to be discussed with your doctor if appropriate.
Thyroid function
Over-active or under-active thyroid function can increase the risk of pregnancy loss. Several different thyroid function blood tests will be performed. In addition to significant over-activity or under-activity, there is information in the infertility medical literature suggesting that the risk of pregnancy loss is increased if there is only low level under-activity of the thyroid discovered if the hormone thyroid stimulating hormone (TSH) is more than 2.5 units. This TSH level would be considered to be in the normal range for women not attempting pregnancy but is of concern in pregnancy. Management of this finding is simple by treatment with a low dose of thyroid hormone.
Diabetes mellitus
Unrecognized diabetes can cause pregnancy loss. A general screening test for diabetes will be performed with a blood test called hemoglobin A1c.
Progesterone deficiency
During early pregnancy, the ovary produces progesterone and a minimum level is necessary for maintenance of the pregnancy. In a very small percentage of pregnancies, loss occurs because of insufficient progesterone production. Making the diagnosis of pregnancy loss due to progesterone deficiency is difficult. If a pregnancy is failing because of genetic or other factors noted above, the progesterone level tends to be low and therefore it becomes impossible to know whether an early pregnancy failure is due to progesterone deficiency or the pregnancy is failing and that is causing progesterone deficiency. It is our routine to test the progesterone level along with the initial blood test to confirm pregnancy, and if the progesterone is less than normal, to give supplemental progesterone as a treatment until a diagnosis of normally progressive pregnancy or failing pregnancy is established. The medical literature related to progesterone deficiency as an issue does not support testing in non-pregnant cycles, prior to conception, to identify women who will have progesterone deficiency during subsequent conception.
Testing for recessive genes
Testing for recessive genes has not traditionally been part of recurrent pregnancy loss evaluation. There are now powerful test panels which can be performed, by way of a blood test, to look for recessive genes that have the potential to lead to birth of a baby with significant congenital defects or cause early pregnancy loss if both partners have the same gene. These test panels evaluate for presence of hundreds recessive genes. These are genes that do not affect the individual carrying the trait but if both partners are affected by the same gene, the embryo would be affected. We will provide information for you about one of these test panels. In vitro fertilization with specialized embryo testing can be useful in dealing with this situation.
Financial Evaluation for Recurrent Pregnancy Loss (RPL)
Factor II and Factor V as well as Karyotypes (Chromosome Analysis) are genetic test that may not be covered by insurance companies because they consider them experimental and investigational. Your doctor may recommend that you do these tests and if they are not covered by insurance, it is your decision to choose to pay to do or opt not to do the tests. Costs of all the tests vary widely from lab to lab and are also dependent upon whether they are covered or not by your insurance company.