What you need to know about chromosome issues

Why should you get chromosome counts in a pregnancy loss?

by Carolyn Salafia, MD, Ph.D.

If you're on any kind of treatment to prevent pregnancy loss and you lose your pregnancy, you should have that tissue chromosome counted. That's because even though you're being treated, nature can still throw you a nasty curveball and your pregnancy may be chromosomally abnormal. If you never know that your pregnancy failed because of a wrong chromosome number, you'll be considered a treatment failure and may be put on more serious, more costly drugs with greater side effects for no reason. Knowing exactly why your pregnancy failed will give you the level of certainty to make an informed decision as to whether you stick with your treatment or move on to something else.

If you're not on treatment your doctor will most likely assume your loss was due to a chromosonal error when it may have been caused by some other, possibly preventable, reason that a reproductive pathologist could identify. (See "EARLY" for more information.) Also having you and your husband tested for chromosome issues is twice as costly (because two counts are done, one on each of you), and far less useful. In most studies at least 95% + of the types of wrong chromosome number accidents found in failed pregnancies will NOT be detected by studying mom's or dad's chromosomes. That is because most of the time, the wrong chromosome number problem is an extra chromosome (a division by two mistake) or a second sperm getting into the egg (an extra 23 chromosomes!). The ONLY problem of wrong chromosome number picked up by studying mom and dad is something called a translocation. A translocation is a different way of packaging chromosome information, so that a part of the information normally attached to or carried on (for example) chromosome 21 is attached instead to (for example) chromosome 8. If you have a translocation, you have a normal developmental program yourself (and are healthy), but when you try to divide your genetic information to make an egg of a sperm, the genetic information becomes unbalanced and eggs or sperm can end up with extra or missing copies of the genetic information that has been rearranged on your own chromosomes.

We commonly hear patients tell us their chromosomes were normal so they could not have had a wrong chromosome number cause for their loss. This is WRONG. You need to understand that testing you and your husband only checks for the rare condition known as translocation, and misses the overwhelming majority of chromosomal causes for loss. These types of chromosome issues can ONLY be found by counting the chromosomes of the pregnancy itself.

Why doesn't a normal female karyotype mean that the pregnancy was necessarily normal?

Fifty percent of early losses are random wrong chromosome number accidents. Therefore, 50 percent are the correct chromomse number. Of the 50 percent that are correct, half are girls, half are boys. So your doctor's lab should tell patients they were carrying a normal female only about 25 percent of the time. If the lab says it more often, then that lab is not expert in sorting your tissues out from your pregnancy's tissues and the count may not be reliable. In short, the lab may be testing your own tissues and believing it's counting the pregnancy's chromosome numbers.

If you lose a pregnancy with a correct chromosome number, then you are more likely to have lost it because of a reason that has a chance of recurring. It is important to identify that reason so that you can have further testing that can help your doctor choose a treatment, and a means of watching you in your next pregnancy, that may reduce the chances that you suffer another pregnancy loss.

What is a chromosonal error?

About half of the miscarriages before 14 weeks are random wrong chromosone number accidents. That means half are not. However, almost all doctors will assume the cause of your first miscarriage was a chromosomal error and won't do any testing for other possible causes. In fact, most doctors won't do any testing at all until a woman has miscarried three times. Only then will they begin to feel that some other problem may be causing the pregnancy losses. This medical position is based on cost benefit analysis in large groups of women but doesn't consider each woman's individual circumstances. Understandably, many women are frustrated by this medical position and want testing to be done sooner.

If you had a D&C for your earlier miscarriages, chances are your hospital has the slides from that procedure and those can be reviewed for other possible causes. If no slides are available, there are still some ways to tell if your earlier losses were most likely chromosomal errors, or whether other factors contributed to them. A loss was most likely a chromosomal error if...

  • The fetus failed very early. For example, blighted ovums are pregnancy failures in which the fetus never develops. These occur before six-and-a-half weeks and about 90 percent of them are chromosomal errors.
  • A long time goes by between the failure of the fetus and the failure of the pregnancy. For example, let's say you had a blighted ovum but your pregnancy was perceived to be clinically normal at twelve weeks. (The placenta can continue to grow and support itself without a baby for up to two months and, therefore, pregnancy hormone levels will continue to rise.) The fact that your placenta was chugging along without a baby on board speaks for adequacy of the uterine environment and adequacy of placental growth and development.

However, if a heartbeat was documented for your baby at seven weeks and you lose your pregnancy at seven weeks and two days, that starts making it less likely that it's a random wrong chromosome number accident. The shorter the death to loss interval, the more likely it is that other factors contributed to the pregnancy loss. Some of the things I always ask patients are: You saw a heartbeat? When? How long after you saw the heartbeat was it before you had any symptoms? What size did the baby measure at death? Did you have any symptoms at a time when you knew the baby was still alive because there was an ultrasound heartbeat?

If you are cramping and bleeding and the baby is alive that obviously has to raise the suspicion that some malfunction in the uterine environment or placenta is causing the baby's death. Your cramping and bleeding means that your tissues are breaking down. The baby is still functioning fine within its little shell but the shell is actually cracking.

You may wonder why your doctor isn't aware of the classic signs of a chromosonal error and I can't answer that question. I do know that doctors play the numbers/statistics because around 50 percent of all first trimester losses are chromosonal errors and therefore not treatable. There is correctly a fear that if something goes wrong early on and you save the pregnancy, you can end up with cascading problems later on. I hate to intervene to save a pregnancy because when intervention took place women have delivered babies that were badly damaged. But as far as knowing when to test so that your next pregnancy can be saved, there are definite clues that many doctors don't look for. These clues were documented by the epidimeology people at Columbia University. I published on the tissue characteristics that differentiate chromosomally wrong number from chromosomally right number pregnancies in 1992. The fact that there are clinical and tissue clues that can allow you to project likely chromosome cariotype as wrong number vs. right number has been known for a long time. It's important that women become aware of this fact. (It's important that doctors become aware of this fact too!)

However, it's important that you don't start second guessing any of your earlier losses. Often, when women realize their earlier losses may not have been chromosonal errors they start believing they could have rescued those pregnancies if only they'd known what was really wrong. But "if only" doesn't bring you anything except more grief. You don't know if those pregnancies could have been rescued. Rescuing pregnancies scares me because you don't know at what point you've corrected a problem and, even if you do "rescue" a pregnancy, there's still a possibility that those babies can be born preterm with all sorts of problems.

It's better, instead, to take this information and look ahead to your next pregnancy. If you've had one or two losses that seem like they aren't chromosonal errors it's important that you have slides from your earlier losses screened for other possible problems.

Carolyn Salafia, M.D., Ph.D., is board certified in Anatomic and Clinical Pathology and in Pediatric Pathology. She is a world-reknown expert on pregnancy loss and is one of a small handful of pathologists in this country who specialize in reproductive pathology. For more information, see her website, www.earlypath.com. To set up a consultation or have your slides reviewed by Dr. Salafia, you can call her office at 914-834-2598.
Note: This communication is for educational purposes only and should not be used as a substitute for a consultation with your physician.