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William D. Petok, Ph.D.
AFA Mental Health Advisory Council
AFA Education Committee Chair

With the recent birth of octuplets to a California woman the issue of multiple births has been all over the news (http://www.msnbc.msn.com/id/28902137/). After performing an in vitro fertilization (IVF), her doctor transferred 6 embryos; two of which produced twins and an amazing 8 children were born from this single procedure. Aside from the ethical issues raised by this event, more important health related matters are present in stories such as this and it has highlighted a growing trend to perform Single Embryo Transfer (SET) in some countries and under certain circumstances.

Physicians who perform IVF procedures in the United States are typically board certified reproductive endocrinologists, a specialty area within the general practice of obstetrics and gynecology that requires specialized training beyond the basic residency in OB/GYN. In IVF, a woman’s ovaries are stimulated to produce a more than normal amount of eggs (ova). The ova are extracted from her body, fertilized in the laboratory, and when the embryos are matured enough, transferred back into her uterus where they hopefully develop fully, resulting in a live birth. Since the science of IVF is not perfect, it has been standard practice to transfer more than one embryo to improve success rates. 

Current guidelines from the American Society for Reproductive Medicine suggest that reproductive endocrinologists transfer 2 to 3 embryos for women between the ages of 35 and 37. Transfer of 3 to 4 embryos for women 38 to 40 is also noted with these guidelines. However, transfer of a single embryo is the recommendation for women under 35 who have a good chance of achieving a pregnancy.

Multiple births carry a set of risks to both the infants and the mother. The major problem with twin pregnancies is prematurity, where gestation typically is 36 weeks compared to 40 weeks for a singleton. Typically the higher order multiples result in shorter gestation periods.  The more premature the delivery, the greater is the risk of complications.  Less than full term gestation can yield complications for the child. These may include low birth weight, breathing and digestive difficulties, underdeveloped organs, learning disabilities, and developmental problems. A related factor is a longer hospital stay for the children. And of course this will increase the costs for the delivery and subsequent hospital stay. Some estimates for the recent octuplets have placed the hospital costs alone between $1.5 and $3 million.

There are additional risks for mothers of multiples, as well. Mothers of multiples are more likely to develop high blood pressure during pregnancy. When high blood pressure is combined with protein in the urine, the condition is known as preeclampsia. Mothers of multiples are more likely to develop gestational diabetes, a type of diabetes that occurs only during pregnancy. Gestational diabetes may damage the placenta and increase the risk of breathing problems at birth. While it is possible to deliver multiples vaginally, caesarian section deliveries are common for twin pregnancies, especially if the babies aren’t in a head-down position. Sometimes, complications after a vaginal delivery of a first twin may require a C-section for the second twin. C-sections are usually considered the safest option for triplets and higher order multiples.

In addition to the well known medical risks of multiples, there are psychological issues as well. In some cases spontaneous abortion takes place or one or more fetuses may die in utero. In other situations a decision is made to reduce the number of fetuses in order to preserve the life of the mother or improve the chances of survival of the remaining fetuses.  Parents must necessarily cope with the loss associated with either a planned or spontaneous reduction. Grief, depression, guilt feelings and diminished self esteem are not uncommon. Some reports indicate that a mother who loses a fetus of a multiple pregnancy may take as long as 3 years to recover from the depression whereas depression from loss of a singleton can resolve in 1 year.

Even when there is no multifetal reduction, psychological issues can develop with the parent of multiples. Mothers have reported defensive and depressive reactions and a sense of social isolation, presumably because it is difficult for other parents to understand the additional stresses that raising several children of the same exact age can bring.  At the same time some mothers report a sense of gratitude and wonder.

Since the assisted reproductive technologies have matured we tend to forget that in the early days, the late 1970’s and 1980’s, a large number of embryos were transferred with the hope that one would “take” and yield a live birth. Today transferring one embryo instead of two or more to minimize the risk of multiple births is a viable option for some infertile women over 35 undergoing IVF. And with better techniques for growing and selecting the best quality embryos, reproductive endocrinologists have started offering some patients the option of avoiding the complications of multiple births by transferring a single embryo.

As early as 2003 doctors in Australia found that transferring one embryo instead of two during an IVF cycle did not reduce the chances of a woman having a baby, when frozen as well as fresh embryos are taken into account (http://www.eurekalert.org/pub_releases/2003-06/esfh-sas062403.php). In that study, SET had fewer risks for both mothers and fetuses. Dr. Jim Catt, author of this research, noted, “This is the first time that a study of cumulative pregnancy and live birth rates with five-day-old SET embryos has been conducted. Under the conditions of this study, twin pregnancies can be reduced drastically without compromising a patient’s chance of a successful pregnancy. All patients younger than 38 are now offered SET and approximately 70% of them accept, with an acceptable ongoing pregnancy rate of 40%... For this particular study all patients were younger than 38 so as to avoid complicating the analysis with the well known effect of age on pregnancy rates. But transferring two embryos to patients over the age of 38 still carries a substantial risk of twins.”

At the ASRM meeting in November of 2008, additional data was reported that looks favorably at SET. A Center for Disease Control researcher said that although multiple rather than single embryo transfer for in-vitro fertilization is less expensive in the short run, the risk of costly complications is much greater. Universal adoption of single embryo transfer would cost patients an extra $100 million to achieve the same pregnancy rates as multiple embryo transfer, but this approach would save a total of $1 billion in healthcare costs. Maurizio Macaluso, M.D said “In our study, 50% of the infants from multiple gestations had adverse outcomes, and 7% were both premature and very low birth rate. This entails extremely high risk and very high healthcare costs”  (http://www.medpagetoday.com/MeetingCoverage/ASRM/11885).

SET is widely accepted in Europe. For example, in Sweden 70% of IVF cycles are SET. Dr. Barbara Luke of Michigan State University thinks that a similar shift in the United States has been slow because of concerns about lower pregnancy and live birth rates. She, too, has examined existing data and determined that transferring 2 or 3 embryos only improves pregnancy rates slightly and increases multiple rates dramatically. “For women under 40, going from a single to a double embryo transfer increased the pregnancy rate from 40% to 48% (per patient), but increased the multiple birth rate from 2% to 37%,” she says.

It appears that a variety of factors have combined to make SET a viable and reliable option for many women, depending on their age and other fertility related issues. Women/couples who don’t want to risk multiple pregnancies or who have a preexisting medical condition for which a multiple pregnancy would not be safe, should consider single-embryo transfer. The most important factor in the decision to proceed with elective single-embryo transfer may be a “favorable reproductive profile.” Patients are advised to consult with their physician about SET and decide if it makes sense in their particular circumstance.