One Healthy Baby Part 2: The risks of a multiple pregnancy

Celine Dion at age 42, with the help of IVF, conceived twins, but is a twin pregnancy easy and glamorous?

It is no secret that the rate of mutliple pregnancies has increased over the last 20 years. In developed nations with the highest multiple birth rates, the rapid increase in infertility treatment utilization is the primary driver of this increase. Additionally, there have been links to increasing maternal age as a reason for the rise in multiples particularly in women over the age of 40; however, again, this is likely due to the reliance of infertility treatments among women in this age group to achieve pregnancy.

In part 1 of this series, we reviewed common infertility treatments and the associated risk of the treatment to multiple pregnancy. In the 70s, the rate of twin pregnancies was about 1.25%, while triplets occurred with a frequency of 0.0125%.  In 2008, the rate of twins was about 3.2% and triplets or higher was 0.15% (about a 100x increase!). In 2009, the most recent year of reporting by the CDC the rates remain relatively stable.

OBGYNs understand the risks before, during and after delivery associated with twins or higher order multiples (HOM), but often, infertile patients do not share their physicians' concerns as pointed out by a survey of patients who were treated for infertility at the University of Iowa. One of the main conclusions of the survey was that 20% of infertile women preferred a multiple gestation over a singleton gestation. Not surprisingly, women who had never before been pregnant were more likely to share this desire.

Ultimately, it is important for the physician treating the infertile patient to highlight some of the risks associated with multiple pregnancy. In this part 2, I will describe some of those risks. When I refer to multiple pregnancy, I refer to twins or more. When I use the term higher order multiple (HOM) I am referring to triplets or higher.

The treatments:
It is important to mention the treatments again. In general the rate of HOM has declined since its peak in the late 90's (0.2%). Probably the biggest reason for the decline was an overall awareness of the rising rate in multiples. With more multiple pregnancies comes a higher preterm delivery rate and with a high preterm delivery rate comes more risk of neonatal complications (infection, breathing difficulties, brain bleeding, etc) and more neonatal deaths. As these issues became clear, changes in practice were made.

As IVF techniques have improved and guidelines on what is an acceptable number of embryos to transfer have become more prominent, we have seen the HOM rate drop. Furthermore, the use of COH-IUI, long linked to the rise in multiple pregnancies, particularly HOM, has declined because the risk of HOM is higher with COH-IUI, and IVF is actually more cost effective at achieving pregnancy with a lower risk of HOM. In general, the risk of multiples is inversely proportional to the women's age when it comes to infertility treatments (i.e the older one is, the less likely their treatment is going to result in multiples).

Types of twins

When talking about the risk of multiple pregnancy, it is critical to understand the concept of zygosity. Multiples can arise one of two ways: 1) from one egg being fertilized by sperm and then splitting = monozygote (MZ) or 2) from 2 eggs being realeased, and fertilized by 2 sperm = dizygote (DZ). Most twins (65-70%) are of the dizygotic kind (aka fraternal twins). Anyone you know that has a twin of the opposite sex has the result of a dizygotic twinning event. So called "identical twins" are the result of a monozygotic twinning event. HOM can be a combination of any of these and it is critical to determine zygosity as early as possible when dealing with triplets or greater.

Remember that all twins are considered high risk, however, on the scale of which set of twins are the highest risk, dizygotic twins are on the end of the spectrum that confers "lesser" risk, while monozygotic twins are on the side of "greater" risk. In dizygotic twins, the placenta and the fetus are housed in almost completely separate compartments known as dichorionic diamniotic. In this case the likelihood that one fetus will "steal" nutrition for the other and compromise fetal growth is rare. In monozygotic twins, how the twins are "housed" together in the uterus is a function of when the embryo splits. The later the embryo splits the more likely the twins are to share a common placenta and sac which is called a mono-chorionic monoamniotic gestation.  While this twinning pattern is the rarest, it confers the greatest risk as it is associated with a 20% chance of fetal death/loss. when twins share the same "house" cords can get entangled, and the likeliFurthermore, monozygotic twins are at higher risk for birth defects than dizygotic twins or singleton pregnancies.

So with IVF, most of the time we transfer between 1-3 embryos back inside the uterus, so twinning is typically of the dizygotic kind, however, while the absolute rate remains low, there seems to be a slight bump (0.4 to 1-5%, depending on the study) in the rate of monozyogtic twinning.

The distinction I am trying to make here is that while all twins are high risk, some are much more high risk than others.

Preterm Birth
The biggest concern to fetal well being and ultimately successful pregnancy outcome is the risk of preterm birth associated with twins. The rate of preterm delivery (delivery before 37 weeks) for twins in the US was about 60%. More concerning, however, is that 11.4% are born before 32 weeks! Twins are more likely to result in preterm birth for a variety of reasons, one of which is increased uterine distention. Think about it this way: a women at 40 weeks gestation has a certain uterine size (say "x") and that increase uterine size causes the uterus to contract and helps initiate labor. At 40 weeks this event is appropriate. In a twin pregnancy, uterine size "x" is reached far quicker than 40 weeks since there are two growing fetus's in the uterus and as a result labor may occur much earlier. Therefore it is essential to be vigilant when women with twins have abdominal pain or contractions as it may be preterm labor. As a result, women with twins may have more evaluations in the hospital during the course of their pregnancy, which may lead to alterations in daily activities and perhaps hospitalization in some cases.

Some of the twin pregnancies that are delivered preterm are not all spontaneous deliveries. Many are the result of an induction of labor due to maternal or fetal complications that have arisen likely as a result of the twin pregnancy. Maternal complications that confer a higher risk in twin pregnancies are gestational hypertension and pre-eclampsia, acute fatty liver disease, gestational diabetes, hyperemesis gravidarum, iron deficiency anemia, and formation of blood clot. Gestational hypertension and pre-eclampsia are common causes of inductions.

Another issue to note, is that there is an increased risk of cesarean section associated with twin pregnancy mainly due to malpresentation of the presenting twin. For example if both fetus A (the first or "presenting" twin) and fetus B in a twin pregnancy are head down, then a vaginal delivery is commonly attempted if no other concerns with the fetus arise. If the presenting twin is anything but head down (breech or "butt down" or transvers (back down or up) then a c-section is preferred. Great variability in practice exists in when twin A is head down but twin B is not and I would recommend discussing this scenario with your provider at the first prenatal visit after a twin pregnancy is confirmed.

As the pregnancy progresses, during the third trimester, patients may get frequent ultrasound and fetal heart rate monitoring performed depending in the complexity of the twin pregnancy. Again this means more frequent visits to the physician and a possible likelihood of early induction of fetal well being is compromised.

Infertility treatments and multiple pregnancies have a long history together. While we are better at preventing HOM's, efforts continue to reduce the risk of multiples, particularly twins. One strategy is the use of single embryo transfer in select patients; however concerns still remain about the decrease in pregnancy rate associated with single embryo transfer.

The issues of twinning are extensive, and I have tried to summarize the major issues that I bring up with my patients. There are many other issues that of course are tied to patient specific factors but for more information I recommend checking out the following link from the American College of Obstetricians and Gynecologists (ACOG). In the meantime please feel free to comment as you see fit. In part three of the section we will discuss triplets and higher order multiples, embryos transfer practices and selective reduction. Please stay tuned.