Can genetic testing explain the cause of recurrent miscarriages?

Common chromosomal variants of miscarriage

Depending on the specific chromosome, having an extra or a missing copy can make it nearly impossible for an embryo to survive. The most common of these scenarios are:

• Trisomy 16: There are three copies of chromosome 16 instead of the standard two. Research suggests trisomy 16 affects 1% to 1.5% of clinically recognized pregnancies and causes 16% of first-trimester miscarriage.
• Triploidy: There is an extra copy of all chromosomes. It occurs in about 1% of clinically recognized pregnancies.
• Turner syndrome: When only a single sex chromosome (an X chromosome) is present instead of two sex chromosomes (XX or XY). Only 1% of pregnancies in which Turner syndrome is present at conception will result in a live birth.

These chromosomal abnormalities occur at random. They are not hereditary and not passed down from one of the parents. In other words, if it happens, it is not your fault. It’s common after experiencing a miscarriage to worry that it will happen again. However, fewer than 5% of pregnant women will have two miscarriages in a row, and only 1% will experience three or more.

Genetic testing is available after a first-time miscarriage, however it may or may not reveal an explanation for the miscarriage. The genetic testing would be performed on tissue from the miscarriage itself. If a chromosome abnormality like those listed above is identified, it can provide an explanation and reassurance that the recurrence risk is very low.

After two or three miscarriages, the question may arise of whether there is an underlying cause that explains all of the miscarriages. To answer this question, genetic testing of the couple attempting pregnancy as opposed to the miscarriage may provide more useful information.

Related reading: Valor’s story: Love, loss, and legacy with trisomy 18

A potential hereditary factor in recurrent miscarriage

Recurrent miscarriage is defined as two or more consecutive pregnancy losses. The cause can be identified in about half of patients and can be associated with many factors such as maternal medical conditions and problems in the uterus or cervix.

In about 5% of recurrent miscarriages, a genetic variation called a parental balanced chromosome translocation is the culprit. A chromosome translocation occurs when a piece of one chromosome breaks off and switches places with a piece of another chromosome. Chromosome translocations can be classified in two ways:

• Balanced: No genetic material is gained or lost, but chromosomes are rearranged. Individuals with a balanced chromosome translocation are often completely healthy and may never know that they have a balanced translocation unless they are trying for a baby. Men who have a balanced chromosome translocation sometimes can have problems with fertility. Any individual with a balanced chromosome translocation could have a pregnancy or child with normal chromosomes, a balanced chromosome translocation, or an unbalanced chromosome translocation.
• Unbalanced: The change results in extra or missing chromosome material. Unbalanced chromosome translocations can result in a miscarriage or a child born with physical or intellectual disabilities. Couples in which one partner carries a balanced chromosome translocation have approximately 20-30% risk for miscarriage and up to 30% chance to have a child with an unbalanced chromosome translocation.

If you and your partner have had multiple unexplained miscarriages, your health care provider may recommend genetic testing to look for a chromosome translocation. If you have one, you have options. You can continue to try to get pregnant naturally, and if you do, you can use amniocentesis or chorionic villus sampling (CVS) to determine the combination of chromosomes that was passed down to the embryo. Or you can use in vitro fertilization (IVF) with preimplantation genetic testing (PGT) to test embryos for their chromosome status.

What to expect with genetic testing after miscarriage

It may be one of your first instincts when you have a miscarriage to do everything you can to find out why it happened. It’s possible that genetic testing may provide some answers – but it’s not guaranteed. Before you proceed, talk to a genetic counselor about what testing may or may not be able to tell you. You’ll also want to check with your insurance about whether such testing is covered and when.

If you have a miscarriage, your Ob/Gyn may be able to provide you with a kit to collect tissue that can be sent off for testing. In some cases, you may need a procedure such as dilation and curettage (D&C) to remove tissue from inside the uterus. These samples can tell us whether the miscarriage was caused by a chromosomal abnormality.

While genetic testing can provide valuable information, the tests have limitations. For example, a genetic test may prove a miscarriage was caused by trisomy 16 but it can’t tell us definitively that such a problem won’t occur again, although it is unlikely.

Also, not all genetic tests look for the same things. So, if you and your partner have testing done to look for a translocation, it won’t tell you if you are carriers for certain recessive conditions. Carrier screening is a separate test. Our preconception and prenatal genetic counselors are available to meet with you to explain testing options and results.

To discuss genetic testing after a miscarriage, call 214-645-8300 or request an appointment online.