IVF and the Twin Trend: Educating Patients About the Risks

Don't put all your eggs in one basket.

It's advice that couples tend to ignore when talking to their fertility doctor about the number of embryos to transfer during IVF. Because the cost of fertility treatment is high and is usually not covered by insurance, they hedge their bets and gamble that transferring multiple embryos will increase the chances of getting pregnant. And while stricter guidelines for embryo transfer have been successful at reducing higher order multiples (triplets or more), "the next hurdle is how do we reduce the twin rate while maintaining the same pregnancy rate?" says R. Stan Williams, MD, president of the Society for Assisted Reproductive Technologies (SART), and professor and chair of the Department of OB-GYN at the University of Florida.

Patients, however, tend to not see the risks of being pregnant with two. Michael A. Feinman, MD, Medical Director of HRC Fertility in Southern California, says some couples strongly want to transfer two embryos or actually desire twins. "Some couples think twins are 'cute,' because they do not see the ones who experience the problems of prematurity or see how difficult it is for parents to handle them."

The Risks of Multiples

Fertility doctors and patient advocates are working to educate patients about the serious health risks and high costs of having more than one baby at the same time.

"We have to do a better job educating patients about the health risks - they are not getting these messages," says Barbara Collura, executive director of the infertility patient advocacy group RESOLVE. "They are being told it by their doctor as part of the informed consent process. But reproductive endocrinologists - you can ask any single one of them if they ever get pressure from the patients to transfer more than the required guidelines state, and they will tell you 'yes, every day.'"

Even though there seem to be twins everywhere these days (between 1980 and 2004, the rate of multiple births increased by 70 percent), the risks to the health and well-being of the mother and babies - and the costs to society - are quite high.

"It has been shown that twin pregnancies cost society billions of dollars each year," Dr. Feinman says. "These costs are due to increased maternal hospitalizations to prevent prematurity, increased intensive care for the babies from prematurity, and increased rates of lifelong disabilities like cerebral palsy in twins."

Women who are pregnant with twins are at much higher risk for pregnancy complications, including:

• Premature birth: About 60 percent of twins are born prematurely at an average of 35 weeks.


• Low birthweight: More than half of twins are born at less than 5 翻 pounds. Low birthweight babies, especially those born before 32 weeks and/or weighing less than 3 1/3 pounds, are at increased risk of health problems during the newborn period, as well as lasting disabilities such as mental retardation, cerebral palsy, and vision and hearing loss.


• Cesarean section: Women who carry multiples may be more likely to need Caesarean sections, which may require a longer period of recovery and at times can increase the risk of hemorrhage during and after delivery.


• Twin-Twin Transfusion Syndrome (TTTS): About 10 percent of identical twins who share a placenta develop TTTS, which occurs when a connection between the two babies' blood vessels in the placenta causes one baby to get too much blood flow and the other too little.


• Pre-eclampsia: Women expecting twins are more than twice as likely to develop pre-eclampsia, which is a combination of high blood pressure, protein in the urine and generalized swelling that can be dangerous for mother and baby.


• Gestational diabetes: This pregnancy-related form of diabetes can cause the baby to grow especially large, increasing the risk of injuries to mother and baby during vaginal birth. Babies may also have breathing and other problems during the newborn period.

Single Pregnancy Is Safer

Being pregnant with one child is safer, with the greatest chances for an optimal outcome. A recent study published in BMJ (British Medical Journal) found that women who undergo IVF are almost five times more likely to give birth to a single healthy baby following a single embryo transfer (SET) when compared with women who choose to have two embryos transferred. In addition, the SET appeared to significantly increase the chances of carrying the baby to full term (37 weeks).

With medical advances, assisted reproductive technology (ART) has come a long way from the early days of transferring six embryos in the hopes of getting just one to implant. Newer techniques such as blastocyst stage culture and transfer are maximizing pregnancy rates and minimizing the risk of a multiple pregnancy. By growing embryos for five days in the laboratory and enabling them to reach the blastocyst stage of development, fertility doctors can better determine which embryos have the greatest likelihood of implantation.

Research has shown that success rates for single embryo transfer vs. double embryo transfer are similar in certain circumstances. "In a favorable patient who is having a blastocyst (Day 5 embryo) transfer, one blastocyst is an equivalent pregnancy rate to two," Dr. Williams says.

But some couples have difficulty accepting these studies, according to Dr. Feinman. "They intuitively feel that the second embryo must hedge their bet. Also, input from friends and former patients often affects their feelings."

The most recent 2009 guidelines on embryo transfer from the American Society for Reproductive Medicine (ASRM) and SART are very individualized. For example, for a woman under age 35 who is in the favorable category, the recommendation is to transfer one embryo if it is a Day 5 (blastocyst), and one to two embryos if it is a Day 3.

"The big advantage of the American system is we can look at shades of gray," Dr. Williams explains. "Depending on the patient's age, the prognosis of the patient, and the stage of the embryo development, we can develop guidelines that are more flexible to meet the needs of the patient while trying to reduce the potential for multiples."

Every Fertility Story Is Different

In addition to fertility problems such as blocked tubes, polycystic ovarian syndrome (PCOS) and her husband's low sperm count, Petra, a former fertility patient, now 51 and the mom of 5-year-old twins, had experienced a brain abscess and surgery to repair a congenital heart defect in her early 20s. After trying to get pregnant for 15 years, she and her husband tried in vitro fertilization (IVF).

"Once we got into the surgery room the embryologist told us that we had three blastocysts," she says. "One of them was hatching, which was excellent news. The other one also looked wonderful. However, the last one was fragmented and would not survive the freeze. We had to make the decision to either transfer the last one or discard it. Desperate for a child, we decided to transfer all three."

With her heart problems, however, Petra could not have endured a triplet pregnancy. "In my eighth week, I had a vanishing triplet, but I always wonder: What if that had not been the case? I would have been faced with some terrible decisions that women who undergo fertility treatments do not want to make. If we had to do it again, I would have 'discarded' the third embryo, and I wish I would have been more informed - even fragmented blastocysts can make it."

Dr. Feinman says that when discussing how many embryos to transfer, his fertility clinic usually abides by the ASRM guidelines. However, "personal issues and embryo quality will also affect our advice. For instance, if multi-fetal reduction is not an option, we might transfer one less embryo. Conversely, if embryo quality is poor, we might discuss transferring more than the recommended number. In ideal cases, such as egg donation, single embryo transfer should be strongly considered. Most clinics doing this show very little decrease in pregnancy rates, compared to transferring two embryos. Even a small decrease in success will be balanced by the higher pregnancy loss rates and prematurity associated with twins."

Ultimately, however, the decision-making rests with the fertility patient.

Educating Fertility Patients

The high cost of fertility treatment and the lack of insurance coverage are key reasons why fertility patients tend to turn a deaf ear to the risks involved with having multiples.

According to Petra, she and her husband were advised of the medical risks, but chose to have the three embryos transferred anyway. "I couldn't wrap my head around having one baby... especially since I knew I would not have a chance to do another IVF. I probably would have felt different if we had fertility coverage. I know our decision to transfer more than one embryo was, unfortunately, made with our finances in mind and not based on medical facts and studies."

One of the biggest obstacles in patient care is cost, says Collura. "We also know that patients tend to feel more pressure to transfer more embryos when they have pressures on cost - if somebody does not have insurance, and they only have $15,000, they may say, 'Look, I only have this one shot. Transfer as many as you can.'"

Dr. Feinman has seen this many times. "Some [patients] think [having twins] is cost-effective if they are paying for their care: 'Two for the price of one,'" he explains. "Sometimes it is hard to convince them that this is not true, since twins tend to cost much more than a frozen embryo transfer.

"In Canada and much of Europe, the government will only cover IVF if the clinic performs single embryo transfers," he continues. "In some countries, if a non-identical twin occurs, the clinics have to pay back the government. In the U.S., insurance companies have abdicated their moral right to affect the situation by refusing to cover IVF. Ironically, they spend a lot more money on the multiple births created by IVF than they would if they covered it and helped regulate it. If our government or insurance companies ever wake up and realize this fact, there might be a move toward increased coverage with increased restrictions accompanying this coverage."

Collura says that patients make better health care decisions when the cost pressure recedes. "There's a lot of data out there about insurance coverage in mandated states and the reduction of multiple births in those states."

A new study by Yale School of Medicine researchers and published in Fertility and Sterility has found that the 15 states that provide insurance coverage for infertility saw significantly lower multiple birth rates. In 2005, it was estimated that the economic impact of preterm birth was $26.2 billion nationally.

RESOLVE has worked with Shady Grove Fertility, a Maryland fertility clinic, to produce a patient education video about the risks of multiples. The video is based on a true patient story and a letter the patient wrote to Shady Grove after she had twins born at 25 weeks, specifically asking Shady Grove if they could use her story to help educate others about the risks of premature birth. The video describes how one twin had intestinal surgery and how both spent approximately seven months in a hospital.

"I am hoping that hearing a person's story about her own experience and providing some data is going to be effective," Collura says. "Our idea is for this to be available to any fertility clinic, anywhere in the United States. "Whatever I can do to help that patient know more and be better educated, I'm going to do that."

SART developed a national consent form for fertility clinics to use that gives very detailed risks for pregnancy with multiples. In addition, ASRM is in the early stages of developing a video about the risks of multiples, according to Dr. Williams. "We are very interested in reducing multiple pregnancies."