Fertility drug may be a bitter pill

Making babies with the assistance of fertility drugs helps couples create families, but do we really understand all the impacts of these treatments?

Sarka Lisonkova doesn’t think so. A post-doctoral fellow in the Dept. of Obstetrics and Gynecology, she is launching the first population-based study in North America to examine trends in use of the fertility drug clomiphene and its impact on birth outcomes.

“There is extensive research on more invasive assisted-reproductive techniques such as in vitro fertilization, but less is known about the effects of fertility drugs,” she says.  Research results will help prospective parents, health-care providers and health-policy experts with decision-making.

Clomiphene, introduced in 1965, stimulates the ovaries to trigger release of an egg.  It is widely used to treat fertility problems such as those associated with advanced maternal age (older than 35). Evidence from Europe suggests that such fertility drugs may be the most significant contributor to increased rates of multiple pregnancy.

“We don’t really know what’s happening in Canada but we do know the increase in multiple births is being called a perinatal disaster because of the elevated risk of pregnancy complications and problems for newborns,” says Lisonkova, a trainee at Vancouver’s Child & Family Research Institute and a member of the Women’s Health Research Institute.

Fetal, newborn and infant mortality rates are four to 10 times higher among twins and triplets than single births, and cerebral palsy rates are at least eight times higher.  Pregnancy complications of multiple births include higher incidence of pre-eclampsia or toxemia, gestational diabetes, low birth weight and developmental difficulties. In addition, there is higher risk of the mother dying.

There are efforts to regulate techniques such as in vitro fertilization to ensure a singleton pregnancy. However, it is impossible to regulate the number of eggs released during ovulation stimulation, which can result in multiple pregnancy.

Assisted reproductive technologies of all kinds have led to an increase in multiple births in Canada. The rate of twins increased by 50 per cent – from 19 per 1,000 in 1985 to 29 per 1,000 in 2004. The relative increase in triplet and higher order multiple births has been more substantial, with the rate increasing by 175 per cent from 42 per 100,000 births in 1985 to 115 per 100,000 births in 2004.

Lisonkova will use population-based pharmaceutical and health-related data to evaluate clomiphene use among B.C. women from 1996-2006. The research will capture data on approximately 1.1 million women aged 20-55 and a total of 360,000 births.  Pregnancy and birth outcomes of women using fertility drugs will be compared to those who conceive spontaneously, looking at issues such as differences in occurrence of multiple pregnancies, congenital anomalies, preterm births, newborn deaths, and miscarriage.

Although couples bear the costs of assisted reproduction techniques, including fertility drugs, Lisonkova says the impacts of the drugs are a public issue because the consequences of those choices are publicly paid for.  Multiple Births Canada, a national support group, estimates that health-care costs for one set of premature twins is approximately $130,000 from birth to discharge.  Costs include more frequent pre-and post-natal monitoring, specialized birthing procedures such as caesarean delivery and intensive care of newborns.

“We can’t control reproduction entirely and assisted reproduction is not always the easy answer that some might think,” says Lisonkova. “Prospective parents need to carefully evaluate the pros and cons of delayed childbearing and the use of these powerful drugs.”

Research resources include BCPharmanet which collates data on all filled prescriptions; Population Data BC that captures health and demographic data on all residents; and the BC Perinatal Health Program database registry that has information on all births at 20 weeks of gestation or more.

Lisonkova’s research was funded by the Michael Smith Foundation for Health Research. She works with perinatal epidemiologist Dr. K. S. Joseph, UBC professor of obstetrics and gynecology, a scientist at the Child & Family Research Institute and a member of the School of Population and Public Health at UBC.