Recurrent Pregnancy Loss

Recurrent pregnancy loss is defined as 3 or more miscarriages, with or without intervening successful pregnancies.  Although this is the definition, I think it is somewhat cruel to make a woman who is had only 2 miscarriages wait for a third one before offering her any testing or help.   One miscarriage in a woman's reproductive life is quite common and doesn't mean it is likely to happen again, however, and so we do not usually test after just one. We will, therefore, start testing after 2 miscarriages.  The good news is that, even after 3 miscarriages in a row, the vast majority of women will still have a successful pregnancy in the future.

There are many causes of recurrent pregnancy loss.  Some can be treated, and others cannot.  One of the more common causes that I see is problems with the uterus.  A polyp or a fibroid inside the uterine cavity can cause miscarriages.  These tend to be in the first trimester (first 12 week of pregnancy), although they can happen later too.  Some women have an abnormally shaped uterus, and that will lead to miscarriages.  The uterus forms from two separate tubes.  The bottom half of both tubes fuses together.  Then the wall that fuses together is resorbed to form a big opening, which is the uterus.  The second half of the tubes does not fuse together, and that is what forms the fallopian tubes.  Mistakes can happen as the uterus is forming.  The tubes can fail to fuse together at all or only partially fuse together, in which case you end up with 2 small uterine cavities.  Because the space inside each uterus is smaller than it it supposed to be, the woman can go into labor earlier than she should.  Most babies will make it to viability, but occasionally you will see a miscarriage before viability.  More commonly, in women who have had recurrent pregnancy loss, you see that the tubes did fuse together;  but the fused wall did not completely vanish.  The cavity of the uterus can be two separate openings, or it can be heart-shaped, depending on how much of the wall was resorbed.  The wall that is left behind is very fibrous and has a terrible blood supply.  Any embryo implanting on this wall will not be able to get enough of a blood supply to grow and survive, and so a miscarriage happens.  If the embryo implants on a side wall instead, it will survive.  Because the cavity is misshaped, however, there can be preterm deliveries or babies that stay breech with these pregnancies.  This is called a uterine septum.

To diagnose uterine problems, we usually do a special type of ultrasound.  It is called a sonohysterogram or saline-infusion sonohysterogram.  Before the ultrasound is performed, a speculum is placed into the vagina.  The cervix is usually cleansed with an antiseptic like Betadine, and then a small tube is threaded through the cervix and into the uterus.  The speculum is then removed, and an ultrasound is performed.  During the ultrasound, a small amount of saline (usually just a tablespoon or two) is infused through the tube in the uterus to expand the cavity of the uterus.  With the cavity full of saline, it is very easy to see if there are any abnormalities.  When the saline is put in, it can cause mild cramping, and you will get a watery discharge for a little while after the test.  But don't worry, if you are thinking its going to be like an HSG (hysterosalpingogram), it is nowhere near as bad!  Another way to diagnose uterine anomalies is with an HSG.  Please see my previous blog on tubal factor infertility for a full description of the HSG.  I tend not to use the HSG because it is more uncomfortable, requires x-rays and therefore radiation, and can miss some polyps and fibroids.

If your doctor does find something wrong with the uterus, he or she will probably recommend a hysteroscopy.  The is a procedure where a scope is threaded through the cervical canal and into the uterus.  The polyp, fibroid or septum can then be removed from inside the uterus.  You do need some anesthesia for this procedure, but you will probably feel pretty close to back to normal by the next day.  The malformation that results in two separate uteri is not usually surgically corrected.  One would have to cut open both uteri and sew them together, and this tends to cause as many problems as it corrects.

Another condition that can lead to multiple miscarriages is a problem with the blood's ability to keep from clotting.  Our blood contains many factors that either promote or prevent the blood from clotting.  They are all in a very delicate balance that is supposed to prevent your blood from clotting in your blood vessels, and cause it to clot when there is a tear or cut in the blood vessel that needs to be stopped up.  Some people have a defect in one of these factors that either causes blood to not clot when it was supposed to (hemophilia) or clot when it is not supposed to (thrombophilia).  Thrombophilias will lead to miscarriages.  The blood vessels supplying a very early pregnancy are very small.  Even a small blood clot can mean a big loss to the baby.  In the same vein (ouch!  sorry for that very bad pun!), some women will make antibodies that attack their own blood vessels (anti-phospholipid syndrome).  If the blood vessels swell from the attack, the pregnancy's blood supply can also be affected.  Both of these conditions are diagnosed by blood tests to look for the antibodies and clotting factor defects.  The treatment varies, depending on which factor is affected, but it usually involves blood thinners like heparin.

Rearrangements in either partner's chromosomes can also cause miscarriages. Sometime a piece of one chromosome will switch places with a piece of another chromosome.  This is called a translocation.  Usually, the person with the translocation will not even know that there is a problem.  He or she has all the right genes, and they are functioning correctly.  They are just in different places than they are supposed to be.  Most cells in our body have 2 of each chromosome.  Someone with a translocation will have one chromosome where the piece is switched and another that is normal.  When that person makes sperm or eggs, only one of each chromosome is given to the egg or sperm.  So if the sperm, let's say, gets one of the chromosomes that has a piece that is missing and it doesn't get the copy of the other that has that piece, now it is missing a whole bunch of genes.  At this point, any resulting pregnancy is unlikely to survive.  This is diagnosed with a blood test to look at the chromosomes (called a karyotype) and should be done on both partners.  Obviously, we do not have the ability to correct a person's chromosomes, so this is not a treatable condition.  We can however, still help prevent miscarriages caused by the translocation.  IVF (in vitro fertilization or the test-tube baby procedure) can be done.  Before the embryos are chosen for implantation into the uterus, one cell is removed from them and the chromosomes are looked at.  In this way, we can find the embryos that either got both of the normal copies of the chromosomes involved (ideal) or at least have both chromosomes with the switched pieces so there are no genes missing.

There are a few hormonal problems that can lead to miscarriages as well.  Both underactive and overactive thyroids can cause miscarriages.  High levels of a hormone called prolactin can also lead to miscarriages.  Both of these are diagnosed by blood tests and treated with medication to correct the hormonal imbalance.  Progesterone is the hormone most closely linked with miscarriages.  It is the signal that keeps the uterus from starting a period when you are pregnant.  If progesterone levels are low in a pregnancy, it will cause the uterus to start bleeding and even miscarry.  Having said that, however, progesterone is rarely the cause of miscarriages.  The body is very good at keeping a pregnancy going by making progesterone.  When you see low progesterone levels during a miscarriage, which happens a lot, it is because the pregnancy has already stopped growing and the body knows it doesn't need progesterone any more.  In my 20 years of treating recurrent pregnancy loss, and I used to be part of a multi-discipline referral service for pregnancy loss that saw lots of patients, I have only seen 3 patients where a lack of progesterone was actually the cause of the patient's miscarriages.

Another issue that can lead to recurrent miscarriages is diminished ovarian reserve.  The blog previous to this one goes into great detail in describing this condition, but basically it is a low number of and/or poor quality eggs.  As women get older and ovarian reserve goes down, miscarriage rates go up.  A twenty year old has about a 10% chance of miscarrying when she gets pregnant.  A 45 year old will have greater than a 50% chance.  Some women have poorer egg quantity/quality than we would have predicted by their age, however.  These women will have miscarriage rates that are higher than expected too.  This cannot be treated.  We have not found a way to improve the quality or quantity of eggs in a woman's ovaries.  IVF can be helpful, as it let's us pick out the best quality embryos.  Testing the chromosomes during IVF to look for abnormalities in the embryos can also help eliminate embryos that are destined to cause miscarriages.

If you search the internet, you will find sites talking about immune testing for recurrent pregnancy loss.  This is a highly controversial subject.  The data is not at all convincing.  The American Society for Reproductive Medicine has said that such testing should only be done in the context of a research protocol.  It can be expensive as well.  Until we can give better answers as to what, if any, immune factors are important, I would advise against immune testing.

One last word on recurrent miscarriages:  take time grieve the loss of the pregnancies.  Even when the miscarriage happens early in a pregnancy, it is still a loss that you will feel.  You need to take some time to mourn the loss.  If not, those emotions will come out some other way at some other time.  So give yourself permission to be sad for a while.

I hope that gives you more information on recurrent pregnancy loss.  If you are suffering from this condition, talk to a Reproductive Endocrinologist or your Gynecologist.  Many of the causes can be easily treated.  Remember, however, that all women have a chance of miscarrying.  So even after treating the causes of the recurrent loss, there is still a small chance (10% for most women) of another miscarriage.  So don't get discouraged if you do end up with another miscarriage on the treatment.  You still have a 90% chance of being successful next time!