July 5, 2000 -- For couples struggling with fertility problems, there are many important decisions to be made along the road to parenthood. The medications and techniques used by fertility specialists put many women at risk for "high-order multiple pregnancies" -- triplets or more. While these couples can rejoice about becoming pregnant after successful treatment, many problems can lie ahead, because carrying a multiple pregnancy (even twins) places the woman and the babies at a higher risk for complications.
"We want patients to be educated about the risks of multiple gestation. ... We try to caution our membership about their responsibility to patients and the need to serve patients' best interest," Jeffrey Chang, MD, tells WebMD. He is the president of the American Society of Reproductive Medicine (ASRM) and a professor of reproductive medicine at the University of California-San Diego.
Although some of these births make headlines, they don't make for good quality of life. Women carrying such high numbers of fetuses are more likely to have pregnancy-induced hypertension and diabetes, which can compromise both the mother's and the babies' health before and after delivery. High-order multiples are more likely to be born prematurely or smaller than would have been expected for the stage of the pregnancy. Cesarean deliveries are much more likely for twins than for single babies and are almost always performed for three or more babies.
Fertility specialists are well aware of these risks, although it is usually the maternal-fetal medicine specialists and neonatologists who care for the mothers, fetuses, and newborns. After the septuplets born in Des Moines and the octuplets born in Houston, many of these physicians have been working to find ways to help infertile couples become pregnant while lowering their risk of carrying high numbers of fetuses.
Fertility specialists can reduce the risk of such pregnancies if they lower the dose of gonadotropin, the medication used to stimulate ovulation, according to an article published in this week's issue of The New England Journal of Medicine. However, it's not an easy answer, because giving lower doses of gonadotropins is associated with lower overall pregnancy rates.
A treatment that results in a higher number of embryos surviving is a modification of traditional in vitro fertilization (IVF). This procedure involves implantation of more mature embryos, known as blastocysts, which are typically more than 5 days old as opposed to implantation of embryos that are only 3 days old. By inserting into the uterus only two robust embryos, the risk of triplets is virtually eliminated. (It is not totally eliminated because, in rare cases, a developing embryo can split, resulting in a set of twins.)
After reviewing the data of 1,494 women treated at their clinic, the authors suggest that current treatment guidelines still "result in an unacceptably high incidence of high-order multiple pregnancies," write Norbert Gleicher, MD, and colleagues. Gleicher is affiliated with the Center for Human Reproduction in Chicago.
Clinical pregnancies resulted in 441 of these women; a "clinical pregnancy" is defined as a detectable fetal heartbeat. Among them, 314 were carrying only one fetus; there were 88 sets of twins. There were 39 pregnancies with higher orders of multiples, including 22 sets of triplets, 10 sets of quadruplets, five sets of quintuplets, and two sets of sextuplets.
People undergoing infertility treatment need to discuss with their physicians the financial and emotional costs of high-order multiples, Richard A. Levinson, MD, DPA, tells WebMD. "When being treated, a couple should support the therapy least likely to produce multiple births," says Levinson, the associate executive director of the American Public Health Association. He was not involved in the study.
For this to happen, both physicians and patients will have to change their attitudes, write Siladitya Bhattacharya, MD, and Allan Templeton, MD, in an accompanying editorial. "[A] radical change in focus for both providers and consumers of infertility services is required," they write. "The clinical emphasis will need to shift from the rate of pregnancy per cycle to the cumulative rate of live births per woman. ... The safety and well-being of women must not be compromised by competing clinics vying to outperform each other."
"As difficult as infertility is, patients should resist the temptation to 'play the odds,'" Walid Saleh, MD, tells WebMD in an interview seeking an objective assessment of this study. "Even though the rate of high-order multiples is rare, the risks are tremendous: premature birth, low birth weight, and, as a result, lifelong handicaps. We need to redefine success." Saleh is a fertility specialist with the Center for Reproductive Endocrinology in Bedminster, N.J., and he also is an affiliate with the Somerset Medical Center in Somerset, N.J.
The final chapter in reducing the risk of high-order multiples has yet to be written, David Meldrum, MD, tells WebMD. "Gonadotropins are a big cause of high-order multiples, and their results are more difficult to control than is in vitro fertilization in which only two embryos are transferred," he says. His preference is for continued conservative use of this medication, along with transfer of fewer embryos with IVF. Meldrum, scientific director of the Reproductive Partners Medical Group in Redondo Beach, Calif., and a clinical professor of medicine at the University of California at Los Angeles, provided WebMD with an objective analysis of the study.
Although avoiding high-order multiple pregnancies is a goal shared among many fertility specialists, several strategies are being explored, Edward E. Wallach, MD, tells WebMD. "The authors' approach is not very revolutionary, but they touch on a very important subject," says Wallach, who is director of the assisted reproductive technology program at Johns Hopkins University School of Medicine. "In our program, if we are inducing ovulation with gonadotrophins and it appears that there is a risk of a high-order multiple pregnancy, ... we take one of two approaches. We either cancel the cycle, or offer the couple IVF at that point. Both of those actions reduce the chance of high-order multiple pregnancies." Extending the culture of the embryos to the blastocyst stage, and then implanting fewer embryos, also can help reduce the risk, Wallach says.
- Couples who seek medical help to have a baby may discover a complex situation: Depending on the treatment used, a woman often stands a better chance of pregnancy when more than one fertilized egg reaches the uterus at one time. But multiple pregnancies can jeopardize the safety of mother and developing babies.
- A recent review of nearly 1,500 cases showed current treatment practices produced unacceptably high numbers of multiple pregnancies.
- One doctor notes patients and their doctors need to discuss all the complications and concerns that multiple births can create.