The More The Merrier: Limiting the Number of Embryo Implantations

Jessica Schmerler
By Jessica Schmerler May 9, 2012 15:19

Sperm are introduced to the harvested eggs in culture and fertilize the eggs to form embryos. Image courtesy of IVF Clinic California.

For the hundreds of thousands of couples facing infertility in the United States, the practice of in vitro fertilization (IVF) provides a promising alternative to have children. The practice common in American medicine to implant multiple embryos all at one time, however, can lead to a long list of complications for both mothers and babies, most of which are related to an increased likelihood of multiple gestations. On the other hand, many other countries have implemented limitations on the number of embryos allowed to be transferred in one IVF cycle, and clear medical evidence supports the implementation of such a policy. Why, then, do we not follow their lead for single-embryo transfer IVF?

What is in vitro fertilization?

Under normal circumstances, an egg is fertilized inside a woman’s body and develops into an embryo, which then implants in the wall of the womb. When a woman cannot conceive naturally, she and her partner can turn to a number of assisted reproductive technologies (ARTs), the most popular of which is in vitro fertilization. IVF involves five steps: (1) ovarian stimulation, in which the woman is given drugs to boost egg production; (2) egg retrieval, in which she undergoes a minor surgery to remove eggs from her ovaries; (3) insemination and fertilization, in which her eggs are exposed to her partner’s sperm in a controlled environment and fertilized; (4) embryo culture, in which the fertilized eggs are grown in petri dishes; and (5) embryo transfer, in which the embryos are transferred to the womb via a catheter, hopefully resulting in implantation of embryo(s), i.e. pregnancy and live birth. Through this process, couples who have been told they cannot have children are provided with hope.

Some clinics choose to culture embryos slightly longer, to the blastocyst stage, before reintroducing them in order to increase likelihood of implantation. Courtesy of nfcares.com

Advantages of Multiple Embryo Transfer

Despite our advances in IVF technology, however, we still cannot gauge the likelihood of a successful embryo transfer. As many as 80 percent of embryos transferred into the uterus fail to implant, mostly due to chromosomal abnormalities, and only about three out of ten IVF procedures lead to a successful live birth. Consequently, doctors frequently opt to transfer multiple embryos in one cycle to increase the chance of pregnancy. For example, a study performed in Québec demonstrated that, following the implementation of a single-embryo transfer (SET) policy in August 2010, the pregnancy success rate decreased from 42 percent to 32 percent. Due to this increased likelihood of pregnancy associated with multiple embryo transfers, transferring more than one embryo per cycle is also much more financially practical. In the United States, insurance companies in only eight states cover IVF; non-insured IVF cycles cost on average $9,500. In other countries, SET policies have been more successful because national health insurance covers IVF, and so there is no penalty for transferring embryos one at a time until pregnancy is achieved. However, in the United States, it is not financially desirable — or possible — for many couples to pay out-of-pocket medical fees multiple times.

Disadvantages of Multiple Embryo Transfer

Although multiple embryo transfers may be easier on the wallet, this practice is certainly not easier on mothers or babies. By transferring more than one embryo at a time, multiple gestation likelihood is greatly increased, and, medically speaking, this in turn increases the medical dangers posed to both mother and baby. In the United States, twins account for 35 percent of IVF pregnancies and triplets account for seven to eight percent; between 1980 and 2009, the twin birth rate has increased by 76 percent. This increase was coupled with the transfer of an average of between two and 3.2 embryos at a time (depending on age, with younger women receiving fewer on average than older women) in 2009.

Multiple pregnancies are associated with increased likelihood of neonatal complications. Nearly all triplets and 70 percent of twins are born prematurely, and these babies are thus at greater risk for low birth weight, mental and physical handicaps, and even death. The mother, meanwhile, is at risk for hypertension, gestational diabetes, heart stress, and placental problems. In Canada, IVF accounts for only one percent of all births but 17 percent of neonatal intensive care unit admissions. Also, the cost of caring for twins, triplets, or higher-order multiples is four, 11, and 18 times higher, respectively, than caring for a single child.

Many women choose to have multiple embryos transferred anyway, as they believe that the importance of getting pregnant outweighs the risk of multiple pregnancies. In the situation of multiple pregnancies, women often choose to terminate one of the pregnancies, creating the risk of unintentional termination of all pregnancies. Anti-abortion ethical arguments also arise when terminating pregnancies.

Multiple embryo transfers during in vitro fertilization can often lead to the undesirable consequence of multiple gestations, as shown in this ultrasound of triplets. Courtesy of Raphael Gonzalez & Richard Woods.

How Could a Single-Embryo Transfer Policy Work?

According to Dr. Pasquale Patrizio, Director of the Yale Fertility Center, a SET policy should be favored, but several obstacles impede the implementation of such an umbrella policy. The first main hurdle is the difficulty in efficiently and safely assessing the developmental competence of embryos. In other words, when it becomes possible to ascertain an embryo’s likelihood of implantation, it will be simpler to implement such a policy. Second, it is important to note that while twin pregnancies may not be a medically favorable outcome, it is the desired outcome for many women, and a SET policy would restrict that freedom of choice. Third, IVF is a costly procedure, involving out-of-pocket expenses, time off from work, and the physical taxation of the procedure itself. To force women to undergo this procedure more than once with a decreasing likelihood of successful pregnancy seems somewhat unethical. Patrizio also points out that although the reduction from three to two embryos transferred has decreased the rate of triplet or higher-order pregnancies without decreasing the pregnancy success rate, an additional reduction of that number to one embryo — in the absence of markers predictive of succesful implantation — would likely decrease the pregnancy success rate as well. Finally, what Patrizio considers the most pressing issue is that of record-keeping. While the number of multiple pregnancies resulting from IVF is well-documented, those from all other forms of ART are not. According to Patrizio, non-IVF forms of ART, such as ovarian stimulation, generate equally high risks for multiple pregnancies, but “unlike IVF,” he notes, “these outcomes are not recorded in a national registry and data on births resulting from its use are not easily available.” A recent survey of women who had multiple pregnancies showed that only 0.7 percent underwent IVF, while four percent used ovarian stimulation drugs, and 12 percent used other ARTs. While a SET policy might have some effect, there are still many other sources of multiple pregnancies.

To address these challenges facing the proposal of a SET policy, Patrizio, his colleagues, and the March of Dimes Foundation have organized a summit to take place this June. The summit will bring together experts in the field of ART, insurance managers, lawyers, patient advocacy representatives, and obstetricians who will “spend two days in June trying to discuss all the possible components that go into the decision of transferring more than one embryo [and] all the possible factors that play a role.”

Often cited as the downside of multiple embryo transfers, Nadya Suleman had twelve embryos transferred and gave birth to octuplets in 2009. Courtesy of news.softpedia.com.

The Current State of the Embryo Transfer Debate

While implementing an umbrella policy regarding the number of embryos transferred per cycle is not currently feasible, much has been proposed in terms of how to maximize pregnancy success rates while minimizing medical complications. In 2011, Congress introduced the Family Act, which proposes to introduce a progressive tax credit on out-of-pocket expenses for IVF, with a 50/50 cost-share and a maximum lifetime credit of $13,360. The American Society for Reproductive Medicine and the Society for Assisted Reproductive Technologies created general guidelines for IVF, recommending a maximum number of embryo transfers dependent on the age and medical condition of women. Many clinics culture embryos for five days instead of only three days in order to maximize the likelihood of only transferring embryos with high potential for implantation, and research is currently being conducted on how to predetermine this potential. Taking all this into consideration, a policy regarding embryo transfers in IVF would need to consider the differing medical, financial, and ethical circumstances of each individual case. IVF is a biomedical engineering feat that has brought much joy to many couples who would previously have suffered under the dark cloud of infertility. In light of this huge contribution, it is our responsibility, as a nation, to find the balance between hope and medical safety.

Jessica Schmerler
By Jessica Schmerler May 9, 2012 15:19