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Assisted reproductive technology (ART) use likely mediates about one quarter of the association between twin births and a pre-pregnancy body mass index (BMI) of 30-40, new research suggests.

In a cohort study that included more than half a million deliveries, the proportion of women who conceived by ART increased with increasing BMI. ART was associated with nearly a 12-fold higher rate of twin delivery. 

ART was the explanation for 23% of the association between obesity class I (BMI, 30-34.9) and class II (BMI, 35-39.9) and twin delivery. However, ART did not mediate the association among patients with class III obesity (BMI ≥ 40).

"We were surprised to find that ART use did not explain any of the association between the high rates of twins in women with a BMI > 40," study author Jeffrey N. Bone, a graduate student and statistician at the University of British Columbia and BC Children's and Women's Hospital and Health Centre in Vancouver, British Columbia, Canada, told Medscape Medical News. "We assessed several different types of epidemiological explanations and types of bias for our findings, but these did not meaningfully alter our primary findings."

The study was published online January 9 in JAMA Network Open.

Twin Deliveries

The investigators examined the association between BMI and twin birth and the role of ART as a potential mediator in this association. They included in their retrospective cohort study all live births and stillbirths in British Columbia with a gestational age of 20 weeks or longer from 2008 to 2020. 

A total of 524,845 eligible deliveries occurred during the study period, and 392,046 women had complete data on pre-pregnancy BMI. Participants' median age was 31.4 years, about half were nulliparous, and less than 10% smoked during pregnancy. 

In all, 8295 women had a twin delivery (15.8 per 1000 deliveries). The researchers found "a relatively small excess" of twin deliveries among women with overweight and obesity before pregnancy compared with women with normal BMIs. Specifically, 4% of twin deliveries in the overweight and obesity group were attributable to elevated BMI. 

The rates of twin deliveries per 1000 deliveries were 11.9 in the underweight group, 15.1 in the group with normal BMI, 16.0 in patients with overweight, 16.0 in patients with obesity class I, 16.7 in patients with obesity class II, and 18.9 in patients with obesity class III. 

After adjustment for covariates, women with underweight had 16% fewer twins compared with women with a normal BMI (adjusted risk ratio [aRR], 0.84). In contrast, the aRR of twin delivery was 1.14 among women with overweight, 1.16 among women with class I obesity, 1.17 among women with class II obesity, and 1.41 in women with class III obesity.

The proportion of women who conceived by ART increased with increasing BMI, and ART was associated with a nearly 12-fold higher rate of twin delivery (aRR, 11.80). About one quarter of the association between obesity class I and II and twin delivery was explained by ART. None of this association was mediated by ART in women with class III obesity, however.

The study's limitations included a large proportion of missing data, a lack of information on chorionicity, and lack of information on race and ethnicity, which is a possible confounder. Furthermore, women with class III obesity may have a higher rate of fertility drug use, which could explain the higher rate of twin births in this group.

Given the findings, clinicians could consider informing patients with higher BMIs that they may have a higher chance of twin pregnancy, said Bone. "However, the absolute rate of twins is still low, and this is by no means any reason for patients with high BMI not to try and conceive."

Twin Pregnancies Confer Risks

Commenting on the study for Medscape Medical News, Janet Stein, MD, director of obstetrics at Maimonides Health in Brooklyn, New York, noted that "The study did not address decisions during the in vitro fertilization [IVF] process that impact the occurrence of twins, such as the number of embryos transferred, and the use of selective reduction, where a multiple gestation is reduced to a singleton, either for reasons of abnormalities in one twin or by patient choice." Stein did not participate in the study. 

Stein also shared: "Of note, the use of single embryo transfers has increased in recent years, due to risks associated with multiple gestations. Local laws related to abortion also impact patient choices and must be part of counseling when planning IVF pregnancies."

Twin pregnancy confers higher risks to mothers and infants, she said. "Therefore, any factors that impact twinning, especially those that can be controlled or modified, should be discussed when any pregnancy is planned. As conception is timed with IVF, this presents an opportunity to reduce risks."

Like the authors did, Stein noted that although BMI has been used as a proxy for health issues related to obesity, "this has recently been called into question, as BMI may be a proxy for other social determinants of health. Rates of obesity are highest in the Black, Indigenous, and people-of-color communities. Associated factors, rather than BMI, may be the underlying reasons for health outcomes." These factors may be economic, access to healthcare, access to healthy foods, chronic stress, weight-related stigma, and systemic racism. 

"For the individual patient," Stein advised, "the focus should not rely on an arbitrary number such as BMI to address overall health."

This study was supported by a grant from the SickKids Foundation. Bone is supported by a 4-year PhD fellowship from the University of British Columbia. Bone and Stein reported no conflicts of interest.