Techniques to Prevent Multiple Gestations With IVF Treatment

There is no denying that fertility interventions have driven an increased prevalence of multiples. Over the last 40 years in the United States, twin births have doubled and births of triplets and higher-order multiples have quadrupled, according to the Centers for Disease Control and Prevention. Still, multiple gestations are not an unavoidable effect of IVF treatment, nor are they something to strive for intentionally.

Whether they occur naturally or as a result of assisted reproductive technology (ART), multiple births raise the risk of maternal and fetal complications, from preeclampsia and gestational diabetes in mothers, to prematurity, cerebral palsy, developmental delays, chronic lung disease and death in infants. Additionally, medical costs, maternal depression, family financial problems and even divorce rates are higher when multiple births are involved, the American College of Obstetricians and Gynecologists (ACOG) reports.

These and other risks are why ACOG and other health organizations around the world have called for more concerted efforts among reproductive specialists to reduce the rates of multiple pregnancies through prevention and management. The European Society of Human Reproduction and Embryology applauds efforts made in countries such as Sweden and Denmark to reduce rates of multiple births.

Depending on the patient's unique needs and situation, multiple strategies may help reduce the likelihood of twin and triplet births from IVF treatment.

Elective Single Embryo Transfer (eSET)

Notwithstanding the chances of a natural multiple pregnancy, opting for a single embryo transfer — rather than two, three or more embryos — is one of the best methods to ensure a singleton pregnancy.

The notion that transferring more than one embryo is necessary for successful implantation and pregnancy is known to be flawed: Research published in Fertility and Sterility has shown that adopting a single embryo protocol in women younger than 38 can successfully reduce the number of multiple gestations without compromising live birth rates. This research aligns with guidance from the American Society for Reproductive Medicine, which recommends that women under 35 who have a favorable prognosis be encouraged to consider single transfer.

Factors of Feelings, Cost and Global Trends

Even with the noted benefits of single transfer, convincing patients to undergo eSET may be another challenge entirely. Since IVF treatments are rarely covered by U.S. health insurance plans, families often pay out of pocket for fertility care. When faced with spending thousands of dollars on one shot at getting pregnant, some patients may feel a single transfer limits their odds of success — even if the research has shown otherwise.

Emotions may outweigh evidence for infertile patients, especially when money is involved. Conversely, when women have the peace of mind in knowing that future cycles will be covered should an attempt fail, they may be more inclined to select the safer, single embryo option. Global trends reported in an Obstetrics and Gynaecology review show the countries that have successfully adopted single embryo transfer — Belgium, Norway and Denmark — are also the ones that provide the most public funding for IVF treatments.

Similarly, when Quebec launched public funding for IVF treatments, the province saw eSET rates jump from 1.6 percent to 31.6 percent within a year, according to research published in Human Reproduction. The rate of multiple births declined from 29.4 percent to 6.4 percent.

The United Kingdom, which covers IVF for qualifying women, saw its eSET rates increase from less than 5 percent to nearly 30 percent between 2008 and 2014, according to the Obstetrics and Gynaecology review. This jump came with modest increases in pregnancy rates and a roughly 40 percent reduction in multiple births, but it was only possible with national regulation, practitioner involvement, patient education and advances in the lab to improve embryo selection.

Japan, which helps subsidize IVF treatment, also has a history of instituting national frameworks for single transfer protocols. In 2007, the Japan Society for Reproductive Medicine and the Japan Society of Obstetrics published guidelines encouraging single transfer, which paved the way for reductions in twin pregnancies, preterm deliveries and neonatal intensive care unit stays.

The Necessity of Patient Education

In countries such as India and the U.S. where IVF funding and coverage are not so ubiquitous, patient education becomes all the more important. In part, practitioners should share the medical, emotional and financial risks of having multiples. But they should also explore and explain options for future pregnancies, including the opportunity for patients to freeze unused embryos to save on costs down the road and ways to optimize embryo selection.

The quality of any embryos transferred may matter more than the quantity. Transferring multiple embryos will not help a patient's chances of achieving a pregnancy if one or more is of poor quality. Advances such as time-lapse monitoring for embryo selection and embryo selection using AI are also poised to improve outcomes and may factor into IVF treatment conversations.

Basic education on eSET success rates can also have a considerable impact on the decisions patients make regarding ART: In one study reported in The New York Times, researchers found that when IVF patients received proper counseling about the benefits of single gestations, a higher number of women elected for single transfer.

Gonadotropin Cycles Cancellation

In other instances of ART that may involve stimulation rather than IVF, ACOG recommends that providers cancel the gonadotropin cycle if ovarian response on ultrasound provides evidence that the risk of multiple gestations is especially pronounced. The presence of three or more follicles exceeding 15 mm, for example, can inflate the risk for multiples.

Tools such as the SonoAVCfollicle can facilitate those assessments by running automated counts of follicle size and maturity. Practitioners can simply select the ovary, run the scan and within seconds, receive a color-coded map of follicles within specified size ranges.

Multifetal Reduction

If efforts to prevent multiple gestations were not successful, ACOG also provides guidance to practitioners to help them explore the option of multifetal reduction.

This topic is controversial for some patients and practitioners. As such, ACOG recommends that providers work to anticipate questions and prepare responses to common emotional, ethical or religious concerns.

Surrounding patients with as much information and support as possible through multidisciplinary experts such as maternal-fetal medicine specialists, mental health counselors, support groups and others may be beneficial. However, patients deserve autonomy, as ACOG emphasizes: Clinicians are there to give medical guidance as patients explore complicated decisions, but patients' feelings and choices are their own.

The Role of Ultrasound

Regardless of the specifics of a patient's fertility plan, ultrasound plays a vital role in monitoring their health and responses throughout treatment. Whether to assess ovarian reserve, optimize timing for oocyte retrieval, monitor embryo transfer or ultimately confirm and track a pregnancy, providers rely on ultrasound to give patients confidence at every stage of their reproductive journey.

Though clinicians should make efforts to pursue a single, healthy pregnancy when possible, ultrasound is also a useful monitoring tool when multiple gestations occur. Counseling patients about all possible outcomes, including multiple pregnancies, is a critical part of IVF treatment.