A new study published in the journal Fertility and Sterility in February 2020 reports a higher risk for mortality in children who were conceived by the in vitro fertilization (IVF) technique followed by freezing of the embryos, compared to those naturally conceived, but only in the first few weeks of life.
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Assisted reproductive techniques (ART) have come into vogue in recent years as more women pursue a career for many more years before trying to conceive. IVF is the most efficient form of ART.
IVF refers to a complex multistep method to overcome infertility or to ensure that a defective gene is not passed down to the next generation, by artificially creating conditions for fertilization and the very early growth of the embryo to the stage where it can be inserted into the mother’s womb to hopefully grow into a live full-term baby. The fundamental principle is the retrieval of mature eggs from the ovaries, either those of the mother-to-be or a donor, to be fertilized by sperm from the father or a donor in a laboratory. The conceptus is then allowed to grow for a few days to the stage when it would naturally be implanted in the uterus. At this point, it is reintroduced into the uterus, unless a surrogate mother (“gestational carrier”) is used to bring the baby to maturity and birth the baby, before handing it over to the ‘real’ mother.
In many cases, the pregnancies end well with both mother and baby doing well. However, it is known that the risk of babies being born too small, too early, or with birth defects is higher in babies conceived by IVF. Another factor that probably contributes to the poor outcomes in some cases is the increased chances of multiple pregnancies, usually twins, with IVF.
To avoid the effects of these confounding factors, the researchers looked at only singleton children born after IVF as well as other ARTs. They looked at how these children fared after birth, in comparison to naturally conceived controls.
The study findings
The researchers examined the data on 2.8 million children who were born in Sweden over 3 decades, and among whom were about 43,500 conceived through ART.
Altogether, there were more than 7,200 infant deaths before one year of age. 114 of these had been conceived via ART. The investigators then controlled for factors such as being born to older mothers and earlier infertility. They found that compared to those conceived naturally, IVF babies had a 45% increased risk of dying within their first year of life.
The risk depends on the type of ART and on the current age of the child (within the first year of life). It was highest in the first few weeks and then showed a reduction.
When the pregnancy began with the transfer of a frozen embryo, the risk of the baby dying within a week of birth was twice that of naturally conceived children. The sample on which this was based was, however, very small. If the IVF was performed using a fresh embryo, or if the embryo was the result of the ICSI (intracytoplasmic sperm injection) technique, there was no higher mortality than for naturally conceived children at any point in the first year of life.
The major causes for the increased mortality in this group of infants included respiratory distress, pulmonary immaturity, infections, and neonatal bleeds. One reason for these complications could be the significantly increased rate of preterm birth in IVF children, which is an indicator of a poorer outcome. Again, the reason for underlying infertility, which resulted in the use of ART could be linked to a higher chance of complications.
After the first week, the risk declined until it reached almost the same level as that of the infants conceived by natural means.
Commenting on the findings, researcher Anastasia Nyman Iliadou, says, “Our results indicate that the kind of assisted reproductive technique used may make a difference, and therefore it is important to investigate further what causes or underlying mechanisms are behind the risks.”
Iliadou thinks that children born following IVF must require special care in the first week of life to reduce the additional risk. However, co-researcher Kenny Rodriguez-Wallberg emphasizes that the absolute risk for each child born after IVF is minimal, and most of the deaths are in preterm infants. Moreover, they highlight the decreased risk after the first year of life.
The study thus points out a negative association of IVF on the health of the infants conceived through the use of a frozen embryo, which is small though noticeable when the group is observed carefully.
“Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques (ART) vs naturally conceived singletons in Sweden,” Kenny A. Rodriguez-Wallberg, Frida E. Lundberg, Sara Ekberg, Anna L. V. Johansson, Jonas F. Ludvigsson, Catharina Almqvist, Sven Cnattingius and Anastasia N. Iliadou, Fertility and Sterility, online Feb. 18, 2020.