In Ontario, Canada, the publicly funded fertility program mandated an elective single-embryo transfer (eSET) policy in 2015 for in vitro fertilization (IVF), and this mandate was associated with a decrease in multifetal pregnancy rates, according to a new study.
Multifetal pregnancy rates decreased from 29.4% to 7.1% after IVF and from 12.9% to 9.1% after ovulation induction or intrauterine insemination (OI/IUI).
“The Ontario publicly funded fertility program was implemented to provide equitable access to fertility treatment. Another goal is to decrease multifetal pregnancy rates after IVF by promoting the transfer of a single embryo at a time,” lead author Maria Velez, MD, PhD, associate professor of obstetrics and gynecology and chair of reproductive endocrinology and infertility at Queen’s University in Kingston, Ontario, Canada, told Medscape Medical News.
“Multifetal pregnancy can be associated with maternal health complications and preterm birth and in some cases with associated long-term consequences,” she said. “While most of the epidemiological surveillance about the outcomes of fertility treatments worldwide is focused on IVF, we also wanted to study the impact of IUI on multifetal pregnancy. We are fortunate to have access to such data in Ontario through ICES.”
The study was published online on April 25 in JAMA Network Open.
Analyzing Pregnancies
Velez and colleagues conducted a population-based, retrospective cohort study of Ontario administrative health data to analyze all births and fetal reductions from April 2006 through March 2021, looking at differences between unassisted conception, IVF, and OI/IUI. They compared the time before eSET was promoted (2006-2011) with the time after the 2015 mandate (2016-2021), calculating adjusted relative risks (ARRs), population attributable fractions (PAFs), and absolute rate differences.
Among more than 1.7 million pregnancies, 96.9% were by unassisted conception, 1.7% were by IVF, and 1.4% were by OI/IUI. Those who received IVF or OI/IUI tended to be older, live in a high-income quintile neighborhood, or have preexisting health conditions such as obesity, diabetes, or chronic hypertension.
Overall, multifetal pregnancy rates were 1.4% for unassisted conception, 10.5% after OI/IUI, and 15.5% after IVF. Compared with unassisted conception, the ARR of multifetal pregnancy was 7.0 after OI/IUI and 9.9 after IVF, with PAFs of 7.1% for OI/IUI and 13.4% for IVF.
Multifetal pregnancies declined substantially between 2006 and 2021, particularly for IVF. Comparing 2006-2011 with 2016-2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI and from 29.4% to 7.1% after IVF with eSET.
Twin pregnancy rates were 1.4% for unassisted conception, 9.4% for OI/IUI, and 14.7% for IVF. Compared with unassisted conception, the ARR of twins was 6.4 after OI/IUI and 9.7 after IVF, with PAFs of 6.5% for OI/IUI and 13.1% for IVF. Comparing the pre-eSET and post-eSET eras, twin pregnancy rates dropped from 11% to 8.3% with OI/IUI and from 27.6% to 6.8% with IVF.
Among higher-order multiple pregnancies, 0.03% were by unassisted conception, 1.2% occurred after OI/IUI, and 0.8% occurred after IVF. Compared with unassisted conception, the ARR of higher-order multiple pregnancies was 29.1 after OI/IUI and 19.0 after IVF, with PAFs of 24.6% for OI/IUI and 20.7% for IVF. Comparing the two eras, higher-order multiple pregnancy rates declined from 1.9% to 1% with OI/IUI and 1.8% to 0.3% with IVF.
“We knew that the rates of multifetal pregnancy after IVF had decreased in recent years,” Velez said. “The reduction in multifetal pregnancy after intrauterine insemination has been less pronounced. Although the total numbers are low, this type of treatment is now the main contributor to higher-order multiple pregnancy. More work is needed in this area.”
In Canada and worldwide, one in six reproductive-aged couples experience infertility. Assisted reproductive technologies (ARTs) have been used significantly more often during the past two decades, and public funding has contributed to this growth in Canada, especially in Ontario and Quebec, said Velez. As ART best practices continue to develop, mandating eSET for IVF programs and a parallel policy for OI/IUI could help, she added.
Considering New Policies
Commenting on the findings for Medscape Medical News, Sarka Lisonkova, MD, PhD, associate professor of obstetrics and gynecology at The University of British Columbia in Vancouver, British Columbia, Canada, said, “The rise in IVF with multiple embryo transfer in the past resulted in increased rates of twins and higher-order multiples, which are associated with elevated risks for adverse maternal and infant health outcomes.”
Lisonkova, who wasn’t involved with this study, specializes in maternal-fetal medicine and has researched the increased risks for maternal morbidity and mortality associated with ARTs.
“Publicly funded fertility programs offer more equitable access to IVF, enabling women with infertility to start treatment with single-embryo transfer earlier and thereby enhancing the likelihood of successful pregnancy and childbirth,” she said.
At the same time, researchers, clinicians, and policymakers have noted concerns about multifetal pregnancy rates linked to these programs. The findings suggest that eSET policies contribute to a substantial decrease in multifetal pregnancies, Lisonkova noted.
“This study also demonstrates that under policies promoting single-embryo transfer during the IVF procedure, OI and IUI treatments contribute to an increasing proportion of multifetal pregnancies resulting from assisted reproduction,” she said.
The study was funded by a Canadian Institutes of Health Research grant from the Institute of Human Development, Child and Youth Health for clinician-investigator teams in obstetrics and maternal-fetal medicine. One study author reported receiving grants from PSI during the conduct of the study, and no other disclosures were reported. Lisonkova reported no relevant financial relationships.
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape Medical News, MDedge, and WebMD.
