Thursday, September 21, 2017

Recurrent pregnancy losses/repeated miscarriages - part 1

The treatment of patients with recurrent pregnancy loss is a substantial part of my practice. I would like the spend the next few posts sharing with you my philosophy and approach to the evaluation and treatment of this problem.

Miscarriages are common. In young women (say, about 30 years old), the miscarriage rate is about 20%. For women aged 35, it's about 25%; at age 40, that number rises to 40-50%, and in women 45 or older, about 90% of pregnancies will end in miscarriage. You will see different numbers quoted for these rates, and some of the difference depends on how closely you follow women who are attempting to conceive. If one does sensitive pregnancy tests before the day of expected menstruation, many more pregnancy losses can be identified; I have seen one estimate claiming that in young women about 40% of pregnancies are lost if you include those very early miscarriages. I don't look for pregnancies like that, and I don't recommend that you do it, either. For now, I'm going to use a background miscarriage rate of 20% for most of this discussion. That's the rate you will find among otherwise healthy young women who have a positive home pregnancy test and menstrual delay of a week or two. You might encounter the term "clinical pregnancy" if you read about fertility or miscarriage issues. This term is taken to mean various things, but most commonly refers to a pregnancy that can be seen in the uterus using ultrasound. There are some women who have repeated miscarriages before they even make it that far in pregnancy, and I am going to talk about that group of women later in this discussion.

By the way, the term "miscarriage" can vary a bit with the source. Most experts define a miscarriage as a pregnancy loss before 20 weeks gestation (meaning up to 20 weeks after the first day of the last menses, as pregnancy dates are traditionally given using that reference), but I recently reviewed one publication that included pregnancies lost up to 24 weeks in the definition. The term "pregnancy loss" is sometimes used interchangeably with miscarriage, as most pregnancy losses occur in the first half of pregnancy; however, loss of a pregnancy can occur at any time, even just before birth. I think there is some value to considering losses throughout the entire pregnancy, as there are some problems that can manifest as either a miscarriage or as a loss much later in pregnancy, so maybe "recurrent pregnancy loss" is really a more useful label than "recurrent miscarriages," even though you will see the latter term used more frequently.

Most miscarriages end within the first 12 weeks of pregnancy, and about half of those pregnancy losses are chromosomally abnormal, due to the loss or gain of a chromosome in the egg or sperm, or sometimes due to an extra set of chromosomes in the embryo (triploidy or tetraploidy). These chromosomal errors are usually random, and they generally arise from problems during maturation of the egg, although they can also occur from a random chromosomal error in the sperm, or in the embryo after fertilization occurs. These chromosomal errors are part (but not all) of the reason why older women have more miscarriages, and why they are more likely to have a child with a chromosome disorder like Down syndrome (which is due to having an extra chromosome 21). Most chromosomal errors found in embryos result in miscarriage, or even failure to implant in the uterus.

If you think of a group of women who have a miscarriage, there are probably some who lose the pregnancy due to a non-recurring cause, say a chromosomal error in the embryo, or an embryo that is growing poorly for some other reason. (We see this all the time in women who are undergoing in vitro fertilization (IVF) - not all embryos have the same potential for a continuing pregnancy.) I call this "bad luck", and if those women continue to attempt pregnancy, they are very likely to "get lucky" and have a baby in the next pregnancy. On the other hand, some women in that group may have a problem that increases their miscarriage risk to 40%, 50%, or even 100% in rare cases. Thus, in any group of women attempting pregnancy, the miscarriage rate will tend to rise over time as the women with bad luck leave the group when they get lucky in a subsequent pregnancy, and you are left with more and more women who have some problem. As I noted above, in the first pregnancy the miscarriage rate is about 20%, after one miscarriage it's about 25%, 40% after three miscarriages, and 60% after four miscarriages. In the older medical literature, the miscarriage rates were sometimes quoted as something like 20%/20%/20%/40%, meaning that the miscarriage rate didn't rise until after three miscarriages. Even today you can find weird numbers like that, with the miscarriage rate not being different  between women with two versus three pregnancy losses. I think all those numbers are statistical artifacts, and the majority of the medical literature supports the model I have described above.

So, the prognosis for women with recurrent miscarriages is quite good - even after three miscarriages in a row, about 60% of women will have a baby in pregnancy number 4. I believe the medical term for this is "treatment independent success", and it's important to keep this concept in mind when your neighbor tells you about some crazy treatment she tried that resulted in a baby - it might have happened even if she had done nothing. It's also why your doctor may reassure you after your first miscarriage that your chance of success in a subsequent pregnancy is good, and that you don't need any special testing to look for miscarriage problems. The recommendations for when to start looking for miscarriage problems vary with the source, but most say to start testing after two or three pregnancy losses, or maybe even after one loss if it occurs after 12 weeks of pregnancy.

It is important to keep in mind that those guidelines are meant for women who can achieve pregnancy quickly and easily. For women with a history of infertility, I don't hesitate to offer miscarriage testing after one loss - do you really want to wait for a patient to suffer three miscarriages over several years before you start looking for problems? The down side of that approach is that I am doing miscarriage testing on some women who probably don't need it. This is a price that I (and most patients) gladly accept. When to test and which tests to get is a matter of medical opinion, and this varies among doctors, even within our own clinic. In the next post, I am going to go over my approach to the evaluation of patients with repeated miscarriages, the value of looking at guidelines for medical practice, and why it's important to use guidelines for what they are (recommendations, opinions), rather than to blindly follow them.

New partners!

It's been quite a while since I posted something on this blog, but I haven't forgotten it. There is always something else to do, and since a blog post doesn't really have a deadline, it always gets pushed to the bottom of my to-do list. A lot has happened at Alabama Fertility Specialists since my last post, and the most important event is that I have acquired two new partners! Dr. Janet McLaren Bouknight and Dr. Mamie McLean joined Dr. Beth Malizia and I in September, 2017. Drs. Bouknight and McLean came to join us after a stint at UAB, a path I know well. You can read more about them here: AFS team

Dr. Malizia and I are excited to have these fine physicians be part of our team. Please consider making an appointment with one of them if you need help having a baby.