In the world of REI, we have our own examples of this. The T word is one. (Really, we could have two T words.) We also have two Q words. Who knew we’d have an O word? Together, we can refer to them as the M words, or multiples.
My first experience with a Q word was in residency. I had the great pleasure of taking care of a courageous and committed young lady who was about 26 weeks pregnant (full term is 40 weeks). She was hospitalized, on bed rest, with quadruplets - the lesser Q word.
She was in the hospital in an effort to prevent preterm delivery at home. She had a short cervix and frequently had contractions. Her physicians had placed a cerclage (sewn her cervix shut) to help prevent preterm delivery. She had received steroid injections. Her day consisted of daily heparin injections (blood thinners), twice daily ultrasounds to look for heartbeats, and a laborious trip to the chair next to her bed maybe once or twice a day. She had to sit in the shower and spent most of her time on her computer, watching movies, reading books, but generally feeling miserable.
She had worked so hard to get pregnant and had failed several attempts in the past leading her physicians to get progressively more aggressive with her treatment until she made up for lost time and cycles grouping 4 pregnancies into one. I don’t know who was more worried about her, me or her. I did not help her get pregnant, but felt very obligated to try to keep her pregnant as long as possible. I was usually the first person she saw in the morning and the last doctor to see her at night.
I can’t tell you how many false alarms we had over the next few weeks. We were frequently rushing to her room to check on her or bringing her to labor and delivery to try to stop the contractions. She finally went into labor for real around 32 weeks. It was the fastest Cesarean section I think I ever did. Four babies in under two minutes. Each baby was taken to a different corner of the room and tended to by expert neonatal intensivists and nurses. We filled the nursery quickly that day.
She would be in the hospital for 3 days after her delivery, but her children would remain for up to 8 weeks later, in the intensive care unit.
She had a good outcome. Her babies were born healthy and progressed through infancy without many significant setbacks. The last time I saw her was about 6 months after delivery. She was pushing a ridiculously long stroller that was about 5 feet long and contained four seats, for four babies.
At that point, she was not yet out of the woods. There was still time for lifelong problems to arise, even if she had escaped the immediate complications of preterm delivery.
My next encounter with one of the M words was when I took my first job out of fellowship, in Memphis.
On a hot summer day in 2006, I pulled up to the Memphis Children’s Museum with my wife and child in tow. We were parking when I first saw the sign at a parking spot near the entrance. At first I thought it was just a joke, then I saw the next sign and thought maybe it was an indictment.
The first sign said, Triplet Parking.
The second, Quadruplets Parking.
Since I had just taken the job at Memphis’ only fertility clinic, I worried exactly what in the heck was going on in that city that would prompt a children’s museum to even need such signs.
Did a lot of out-of-towners with triplets and quadruplets travel to Memphis to go to the children’s museum?
Did the clinic where I had just taken a job have so many triplets and quads that it was actually altering parking practices at local businesses?
Or was there a rogue doctor, shooting up fertile women with fertility drugs so that there would be an abundance of children?
I was quickly reassured to learn that triplet pregnancies were very rare at the practice in Memphis and that there weren’t other doctors prescribing fertility shots to women…. So I settled on the idea that the museum was trying to be cute and serve a relatively rare need.
In truth, the triplets and quads parking are sort of like handicapped, expectant mother, or senior citizen parking seen at some businesses and churches. They give assistance to people who might need a little more time, or find it a little more onerous to get from the car to the front door.So where am I going with this? I’m not sure…. I had the pictures and wanted to print them, but I really should talk about the perils of multiple gestation.
I know, I know, most people reading this would never set out to try to have triplets, quadruplets, or octuplets. But the truth is, a high number of fertility patients actually want twins. Most people appreciate a bargain, and when they have to pay out of pocket for fertility treatments, two for the price of one sounds like a good deal.
I have to remind my patients and myself that twins are a high risk pregnancy. With twins, the average duration of a pregnancy is only 36 weeks (four weeks short of term). This means a considerable number will deliver much earlier. The earlier the delivery, the more likely a child will experience life-long complications such as cerebral palsy or chronic lung, eye, or gastrointestinal problems.
The rate of cerebral palsy is 0.1-0.2% in singleton pregnancies, but rises to 1.2-1.3% in twins and up to 4.5% in triplets.
With triplets, average delivery occurs at 32 weeks with approximately 90% being preterm. And preterm delivery is not always the result of preterm labor. Many other complications can arise which might cause a doctor to have to deliver a baby before the baby is ready to be born. Due to competing space within the uterus, some babies may not get the blood flow required for growth and they can be small. If one of the babies becomes ill or if they stop growing in the womb, a woman has to decide if she needs to deliver all the babies to save the sick one.
The higher rates of diabetes (high sugar), preeclampsia (high blood pressure), premature rupture of membranes (water breaks), placental abruption (separation of placenta from uterus) can all lead to the need to deliver these babies early.
Babies born very prematurely frequently are hospitalized for weeks to months in an intensive care unit and face too many perils to be listed here. The earlier the birth, the more likely they are to suffer lifelong consequences. The immediate and long-term medical costs and time required for follow up can put a strain on relationships. Once in a grand rounds lecture, an authority gave the staggering statistic on triplets, saying that more than 80% of parents of triplets ultimately get divorced. I have not been able to find a credible reference with that high a number. Not all data shows that high of a rate, as reported here. While no study to date has looked at this adequately to say with complete authority what affect multiples have marriage, patients should realize that there can be considerable strain on a relationship.
So how do we prevent multiples?
Avoidance is the key.
Many people think IVF (in vitro fertilization) poses the greatest risk for multiples. This is not true. While there are many things which influence the risk of multiples, using injectable gonadotropins can cause a woman to release multiple eggs. The physician may have little control of how many of these eggs fertilize and result in pregnancy.
Very rarely do we get more than twins with IVF. In IVF we can control how many embryos are placed in the uterus. ASRM has published guidelines on the number of embryos to transfer in IVF. Adherence to these guidelines will help practitioners avoid high order multiples (triplets or more) and minimize the risk of twins. To see ASRM guidelines, click here.
One strategy employed to decrease the risk of multiples is to grow embryos out to the blastocyst stage. In the past, physicians routinely transferred embryos at the cleavage stage (three days after fertilization) when embryos are generally made up of around 8 cells. Top quality day 3 embryos have about a 30% chance of resulting in a pregnancy. Some day three embryos will stop growing after day 3. So if we wait two more days, frequently we can see which of the embryos has the greatest potential to make a baby. By waiting until day 5, we can place fewer embryos back into the uterus and theoretically reduce the risk of twins, triplets and more.
At TRM, we encourage women with good quality blastocysts (day 5 embryos) to transfer a single embryo to maximize the chance of a singleton. The down side to blastocyst transfer is that it seems something in the culture system may increase the risk of identical twins! This is a slight increased risk, but not insignificant.
If you want further proof that even elective single embryo (eSET) transfer can’t prevent multiples from occurring, consider the case of an Iowa woman who did IVF, had an eSET and was discovered to have 7 babies implant. Presumably, she conceived 1 through the embryo transfer, but due to the fertility medications and the fact that she had intercourse, she conceived multiple others on her own at the same time. The lessons learned from this case were: 1) don’t have intercourse during IVF if your tubes are open, 2) this lady probably didn’t need IVF in the first place.
The bottom line is that it is very difficult to maximize the pregnancy rate and minimize the multiples rate at the same time. This can be especially true if we rush people into IVF.
Selective reduction, or elimination of embryos within the womb has been used by some patients to decrease the risks associated with high order multiples. Such a procedure requires placing a needle into the uterus and either stopping the fetal heart with potassium, or cutting the umbilical cord.
Many patients would never consider selective reduction under any circumstances. Others thought they would be able to reduce, but after seeing a baby’s heartbeat, the reality of what they are doing sinks in and it is too much for them to do.
It is my opinion, a patient’s stated willingness to undertake selective reduction should never influence the medical decision of how many embryos to place in the uterus or how to proceed with therapy. Because some patients are so desperate to achieve pregnancy, because some just don’t believe it can actually happen, some patients will want more embryos than recommended. If a physician decided to be more aggressive because a woman said she would consider selective reduction, then the patient may wind up in a situation that places her and her babies at risk.
Finally, the nature of health insurance is to blame for some patients wanting to be aggressive and increasing their risks of multiples. Because of the expense of treatments, many patients cannot afford more than 1-2 treatment cycles of any kind. This causes them to want to maximize their chances of pregnancy with each treatment, especially in what they deem as their last treatment. These kinds of pressures can lead to bad decisions and pressures to be more aggressive than recommended.
Concluding Thoughts
Will we ever eliminate the increased risk of multiples in fertility treatment? It’s not likely.
Until insurance pays for fertility care, economic forces will drive couples to aggressively pursue a positive pregnancy test and accept the risk of multiples. In fact, insurance companies should probably pay for IVF (where the number of embryos transferred can be controlled) more readily than they pay for injection-IUI (where the number of eggs released is not always controlled).
Doctors have a fairly equal incentive to maximize their clinics pregnancy rates. Therefore they may risk pushing patients to IVF who don’t need it. They may also have incentives to place more embryos into the uterus to keep those rates high.
Singletons could be maximized by mandating single embryo transfers on day 3 (at the cleavage stage), but we must be willing to accept lower pregnancy rates.
Alternatively, if we are able to improve blastocyst culture to reduce the risk of identical twins, an elective single embryo transfer on that day would increase pregnancy rate without increasing multiples. Embryo biopsy may in the near future maximize the chance of a viable singleton, but this procedure is not quite ready for prime time.
The bottom line is: things need to change. And I think things can and will. Technology needs to change. Patients need to change and doctors need to change. I will do my best to educate patients on the risks and benefits of their choices, and I will still grant patients autonomy in the choices they make. Together, I believe we can minimize the extremes and get the Q words out of our vocabulary, and most of the T words, too.
(Now that I've written this, hopefully, we don't have a patient turn up with high order multiples. I fear writing about this would be similar to working in the Emergency room and saying "everything is so slow tonight" and then the avalanche of patients hits.)
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