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Miscarriage is far more common than most people think. One in every four recognized pregnancies is lost in first trimester miscarriage. The chance of having a miscarriage also increases with maternal age.  For women in their twenties, the risk of miscarriage in each pregnancy is less than 10%. In contrast, women in their early to mid-forties have a rate of miscarriage of about 50% with each conception. This increase in pregnancy loss with age is likely due to higher rates of chromosome abnormalities that naturally occur with increasing maternal age.

Most women who experience a miscarriage go on to have a future healthy pregnancy. However, some women seem to be more prone to miscarriage than others. About five percent of fertile couples will experience two or more miscarriages.

There are many different reasons why miscarriage occurs, the most common being chromosome abnormalities, causing 50% of all first trimester miscarriages. Chromosome abnormalities result from extra or missing whole chromosomes that occur by chance when the egg or sperm is formed. The term used to describe this type of chromosome abnormality is “aneuploidy”.

There are other genetic and chromosome-related abnormalities that can also cause miscarriage, but these types of findings are much less common than aneuploidy.

Chromosome abnormalities are found in more than 50% of first trimester miscarriages, with some studies suggesting that the rate is actually closer to 75% or higher in women aged 35 and over who have had recurrent pregnancy loss². Overall, the rate of chromosome abnormalities increases with age, with a steep increase in women older than 35.

If a chromosome abnormality is identified, you may not need to undergo other extensive testing to determine the cause of the miscarriage.

Although most chromosome abnormalities found in miscarriage studies are not inherited, sometimes a specific finding can alert your doctor to further investigate the possibility of an underlying genetic or chromosome problem in your family that predisposes you to miscarriage (for example, a balanced chromosome rearrangement in one parent).

A chromosomal cause for miscarriage is very common, and women who have had one miscarriage with an identified chromosome abnormality may still have a healthy pregnancy the next time³. In general, if you have had one miscarriage, you are at a slightly elevated risk to have another – about a 25% chance compared to a 15-20% chance if you have not had a previous loss⁵. Women who have had a pregnancy loss with a known chromosome abnormality may actually be at slightly lower risk for a subsequent miscarriage than women who have had a prior miscarriage with unknown cause or normal chromosome results⁵.

If the cause of miscarriage is unknown, your doctor may recommend a full work-up to look for potential causes. This work-up may include some or all of the following tests:

• evaluation of your uterus
• blood tests for hormone levels, infections, certain antibodies, blood clotting factors, and other factors that may contribute to pregnancy loss
• other specific tests on either parent, as indicated by their medical histories

Knowing the reason for a pregnancy loss can help you start the emotional healing process. With so many questions about why the miscarriage occurred, and if it’s likely to happen again, you may find some comfort in being tested to identify what may have happened. If a chromosome abnormality is found, it can eliminate the need for a number of other medical tests, which can reduce stress surrounding medical visits and mounting medical costs.

Testing can also help you to plan your next steps.  If you’ve had multiple miscarriages, and chromosome abnormalities have been identified as a cause, special fertility treatments may be an option that can help to avoid chromosome abnormalities in future pregnancies. The treatment process involves In Vitro Fertilization (IVF) with Preimplantation Genetic Diagnosis (PGD), which can be performed either for routine aneuploidy screening or to detect specific chromosome abnormalities, such as a chromosome translocation.

As with any medical questions or issues, you should talk with your doctor first about what kinds of testing might be right for you.  If your doctor determines that miscarriage testing is appropriate, ask for Natera’s Molecular Karyotyping Analysis with Parental Support.  If you doctor doesn’t currently have a relationship with us, he or she can contact us directly to have a Sample Collection Kit sent.  Your doctor will collect a sample of fetal tissue, as well as a maternal blood sample, and send them to our laboratory for testing.  Results will be returned to your doctor within 2 business days of receipt of the samples.

While Natera's molecular karyotype with Parental Support is sensitive enough to detect a number of chromosomal abnormalities, it cannot detect balanced structural chromosome rearrangements. However, these are not likely to cause a miscarriage. Balanced chromosome rearrangements are seen as normal, and unbalanced chromosome rearrangements are often reported as aneuploidy, deletion, or duplication. The test also cannot detect tetraploidy of 2:2 origin (2 copies from mother, 2 from father), but it will detect all forms of triploidy of 3:1 origin.

If you’re experiencing a miscarriage at home and you are in a situation where you can collect the products that were miscarried, your doctor may want to perform additional tests, including chromosome testing, on this sample.

When you have a miscarriage, the fetus, amniotic sac, and placenta, along with a large amount of blood, will be expelled. If you are less than 8 weeks pregnant when the miscarriage occurs, the expelled tissue will look no different from heavy menstrual bleeding. If you have reached 8 to 10 weeks, more tissue will be expelled which can resemble large blood clots, possibly some pinkish/grayish material, or even a discernable sac.

The sample should be collected in a sterile, or near as clean as can be, container.  This container can be a brand new Ziploc bag, plastic container (like Tupperware) or a specimen cup. It may be helpful to use a medical basin or a colander under the toilet seat to catch the products.  If the tissue falls into the toilet you can remove it and place it into the container.

If you know you are going to have a miscarriage Natera can supply you with a specimen cup in which to place the sample.  You may have already received this kit from your doctor’s office.

If you are unable to bring the miscarriage sample into your doctor’s office immediately, store the sample in the refrigerator (not freezer) to preserve the tissue.

It is important to remember, there is nothing you can do to prevent a miscarriage, and you did not cause this miscarriage to happen.  Chromosome testing after a miscarriage may provide you with more information about the cause of your loss.  Please discuss this option with your physician.

If you wish, Natera will bill your insurance provider directly. All insurance companies are different, but most of them should cover at least part of the cost of testing, if not all. We recommend that you contact your insurance company with specific CPT codes (available through our office) to learn more about the exact coverage prior to testing.

Chromosomes are structures in each cell of the body that carry genetic information, or genes, in the form of DNA. Healthy humans normally have 46 chromosomes arranged in pairs: 22 pairs of ‘autosomes’ and one pair of ‘sex chromosomes’ (XX in females or XY in males) for a total of 24 unique chromosomes (1-22, X, Y).

A chromosome abnormality is defined as too much or too little chromosomal material, or a structural defect in the chromosome itself.

Occasionally, an egg or sperm will form with an abnormal number of chromosomes, a condition called aneuploidy. Having an extra chromosome is called ‘trisomy’; a missing chromosome is called ‘monosomy.’

The vast majority of embryos with aneuploidy do not implant in the uterus or are lost in early miscarriage. In fact, over half of all early miscarriages are due to aneuploidy. In some cases, a baby can be born with an abnormal number of chromosomes, a situation usually associated with mental retardation and birth defects, depending on which chromosome is extra or missing. A common type of aneuploidy is Down syndrome, caused by three copies of chromosome number 21 (Trisomy 21).

A translocation is a chromosome rearrangement in which a small piece of a chromosome breaks off and reattaches in another location.  People who carry balanced translocations are typically healthy – they experience no symptoms from the condition – but they are at a higher risk of infertility, miscarriage, and having a baby with a chromosome abnormality.

An inversion is a chromosome rearrangement in which a portion of the chromosome breaks off, reverses itself end to end, and reattaches to the same chromosome. Inversions generally do not cause any health problems for carriers, as no genetic material is lost, but they may be at a higher risk of infertility, miscarriage, and having a baby with a chromosome abnormality.

A balanced chromosome rearrangement occurs when a piece of a chromosome merely breaks off and attaches to another chromosome, without any loss (or creation) of genetic material. When a balanced translocation carrier’s cells divide to produce egg or sperm cells, those cells may end up with extra or missing genetic material, which can then result in an embryo with extra or missing genetic material.  This condition is known as unbalanced chromosome rearrangement, and often results in miscarriage or a baby born with birth defects.

¹Laurino MY, Bennett RL, Saraiya DS, et al. Genetic evaluation and counseling of couples with recurrent miscarriage: Recommendations of the National Society of Genetic Counselors. J Genet Couns. June 2005;14(3).

²Marquard K, Westphal LM, Milki AA, Lathi RB. Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril, Sept 2010; 94(4): 1473-7.

³Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. Feb 2000; 73(2): 300-304.

⁴Cowchock FS, Zenon G, Jackson LG. Chromosome errors as a cause of spontaneous abortion: the relative importance of maternal age and obstetric history. Fertil Steril, May, 2005;59(5):1011-1014.

⁵Miscarriage (2007). Retrieved September 16, 2010, from www.americanpregnancy.org