Thursday, April 15, 2010

More IVF questions: How many embryos to transfer? The "plus/minus rule"

Q: How many embryos do you transfer?

A: Short answer: "Usually two. Sometimes one or two more if you are an especially difficult patient."

Long answer: This is the second most common question IVF patients ask (#1 is "How much is it going to cost?" I'll answer that one another day). It's a tricky issue - who is really the "decider" in this setting: the couple? After all, it's their embryos; the IVF programs? they're the experts; the insurance company or the government? they may be paying for the cycle, as well as the medical care of any children conceived. In Belgium, for example, it's Hobson's choice if you're less than 35 years old doing your first IVF cycle - only one embryo can be transferred if you want to be reimbursed for the cost of the cycle. (On the other hand, the government will reimburse much of the cost of IVF for up to six cycles if you follow their rules. It's not a bad concept. You can do what you want, but you'll have to pay for the privilege.)

The more embryos you put back, the higher the chance of pregnancy. Don't believe what you may read elsewhere, that pregnancy rates fall when higher numbers of embryos are transferred, or some study somewhere (usually in Europe) showed that pregnancy rates weren't increased when extra embryo was transferred. The conclusion about lower pregnancy rates with higher embryo transfer numbers comes from the naive examination of national data sets like those compiled by SART or the CDC. Of course pregnancy rates are lower in women who are getting more embryos - IVF programs are putting more embryos back in those women because they know the chance of pregnancy is lower (because of advanced patient age, poor embryo quality, or repeated failure in previous IVF cycles), and they are trying to compensate for it. If they didn't do this, the outcomes might even be worse. Every viable embryo has some chance of implanting, and the more you put in, the greater the chance that one will turn into a pregnancy.

But the success rate may not increase all that much with additional embryos, and the more embryos you transfer, the greater the chance of multiple pregnancy. Now, many infertile couples welcome the idea of twins or even triplets ("that way we would be finished with all this" is what I often hear). I have twins myself, and they were healthy and a great joy to raise, but I would never wish twins on someone, as the risks of prematurity and its associated complications are higher with twins; and the risks are astronomically higher with triplets or quadruplets. It's best to bear one child at a time.

Thus, IVF programs and their patients balance the risk of no pregnancy versus the risk of multiple pregnancy when choosing how many embryos to put back. At AFS, we use the SART/ASRM guidelines as the starting point for deciding how many embryos to transfer (you can read these guidelines here: Basically, if you are under 35, it's your first IVF cycle, your embryos look good, and if you have extra embryos good enough to freeze, we recommend two embryos to transfer. If you don't meet one of those criteria, we recommend a third embryo (although if you had two really good looking embryos and the others weren't clearly worth freezing, I would still recommend just two). If you're forty or older, we'll usually recommend four embryos, as we have never had more than twins in that age group using their own eggs.

However, I am personally uncomfortable with this dictatorial approach to determining how many embryos to transfer. In virtually every other aspect of medicine, decisions for medical care are made cooperatively between patient and doctor. If you don't like a doctor's recommendation, you can always go find another doctor for a second opinion, but not when you have embryos sitting in the incubator (yes, you could choose to freeze them and find another program to transfer them, but let's not make this any more complicated than it already is). So I have developed my "plus/minus" rule: when we (meaning me, the IVF program director, with input from my staff) make a recommendation about how many embryos to transfer, the patient has the option to choose one more or one less. If we say "two embryos", you can choose 1, 2, or 3 embryos to have transferred. That way, the patient has a say in the decision, too.

More than 90% of patients go along with our recommended number, but our last frozen embryo pregnancy decided to have only one embryo transferred (she already had twins at home from her previous IVF cycle); our last set of triplets asked for that third embryo, even though she was young, was doing her first IVF cycle, and had good embryo quality. She thought she had a low chance of success because she had been trying to get pregnant for such a long time (this is not a prognostic factor for IVF success, but sometimes you just can't talk people out of a concept).

The system isn't perfect, but it works for us. We haven't had triplets in anyone who has followed our advice in quite a while. There are plenty of twins, though - 7 out of the last 29 births (24%) in the under-35 group were twins. Maybe when that good Belgian insurance coverage becomes available in Alabama, more patients will elect to transfer just one embryo.