MAR treatments unlikely to be cause of premature or low birth weight babies

Children born through medically assisted reproduction, such as IVF, are at higher risk of being premature and to be born low birth weight, but it’s unlikely to be due to the procedures used, according to a new study published in The Lancet from the London School of Economics and Political Science.

By comparing these “test tube” children with their naturally conceived siblings, researchers discovered similarities in outcomes which counter widespread medical opinion that some negative effects could be attributed to MAR procedures such as the freezing of embryos, the delayed fertilisation of eggs, and hormonal treatments.

A study led by Dr Alice Goisis of LSE’s Department of Social Policy analysed 65,634 children born in Finland between 1995 and 2000. They found that on average those conceived by Medically Assisted Reproduction (MAR) were at higher risk of being premature and low birth weight. But when – using cutting-edge statistical methods - the researchers analyzed the effects of MAR by focussing on a subset of families who had had children conceived both naturally and through medically assisted reproduction this effect disappeared or became negligible, suggesting that factors other than these procedures were responsible. The results suggested that unobserved factors shared by siblings such as parental health, psychological stress associated with sub-fertility and genetic factors could explain the association. The authors also stressed the importance of considering observed factors that vary between siblings such as birth order. Around 60% of MAR children are first-born, which is a risk factor for poorer birth outcomes.

More than five million children have been born through MAR which includes treatments such as ovulation induction, artificial insemination, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh/frozen embryo transfer. It is one of the key achievements of reproductive medicine, but there are widespread medical concerns over the welfare of the children involved.

The paper, Medically assisted reproduction and birth outcomes: a within-family analysis using Finnish Population Registers, published in the latest edition of The Lancet, explains: “This study is the first to analyze the potentially harmful effects of MAR treatment using a sibling-comparison approach, which enables us to account for all observed and unobserved parental characteristics shared by siblings.”

The paper adds: “While previous studies have consistently found that children born after MAR have worse perinatal outcomes than children who were conceived naturally, the mechanisms underlying this well-established association are not fully understood.”

Prior studies have attributed part of the increased risk to the rates of multiple births, which are 10-20 times higher in the MAR subpopulation than in the general population, and are strong predictors of adverse birth outcomes. Part of the increased risk has also been attributed to parental characteristics that predispose the parents to seek MAR treatments and to be at high risk of adverse birth outcomes, such as subfertility, which are known risk factors for adverse birth outcomes. But because these factors are unable to fully explain the differentials, some studies have suggested that some of the effects could be attributed to the MAR procedures themselves, such as the freezing of embryos, the delayed fertilisation of the oocytes, and the hormonal treatments.

The paper concludes: “As a group, children born after MAR are, in absolute terms, at increased risk of adverse birth outcomes. But the results of the current study indicate that this elevated risk is likely attributable to factors other than the treatment itself. Understanding the risks associated with MAR treatment is very important for couples considering using MAR treatment to conceive, physicians advising patients about the risks of MAR, and public health policy-makers.”

Dr Goisis commented: “These findings will reassure prospective parents and medical professionals that the MAR techniques per se appear unlikely to substantially increase the risks of poor birth outcomes.”