IVF and birth defects

The risk of birth defects in the general population is usually cited at 1-3% of all births. The risk is higher with multiple pregnancies. Babies born from in vitro fertilization – IVF may also have birth defects. This may be due in part to the higher rate of multiple births seen in IVF cycles. There have also been studies that suggest that the risk of birth defects may be higher in babies born from IVF even when controlling for the rate of multiple births.

Another confounding factor is that couples who have infertility seem to have a higher rate of birth defects than the general population even if no fertility treatments are used. Thus, any study attempting to look at the birth defect rate in IVF babies must use a carefully chosen comparison or control group. Studies that use birth defect rates from the general population as a comparison to IVF, therefore, are probably overestimating the risk from IVF.

Nonetheless, a recent study from Finland found an increased risk of birth defects in babies conceived from IVF. There were two comparison groups: naturally conceived babies from the general population and babies who were conceived with non-IVF fertility treatments. The rate of birth defects in the IVF babies was 4.3%. The non-IVF fertility treatment rate was 3.7% and the general population rate was 2.9%.

The increased risk due to multiple pregnancies was again confirmed in this study. Even when conceived naturally, the rate of birth defects amongst multiple pregnancy babies was almost twice that of singleton babies (526 birth defects per 10,000 births versus 285 per 10,000).

Statistical analysis showed that the risk was mostly due to singleton boys conceived from IVF. On the other hand, the risk of birth defects in girls from multiple pregnancies was actually decreased.

Another recent study from the University of Iowa also found an increased risk of about 30% in the incidence of birth defects in babies from IVF . This study looked at the birth defect rate in three different groups: IVF babies, babies born after intrauterine insemination, and spontaneously conceived babies from the general population delivering at the University of Iowa.

A higher rate of birth defects was seen in IVF babies compared to the general population but not when compared to babies from insemination. Furthermore, there was no correlation between the invasiveness or complexity of a procedure and the rate of birth defects. For example, embryos that were kept in the laboratory for a longer number of days might be expected to produce babies with a higher rate of birth defect but this did not hold true. Likewise, when fertilization of an egg by ICSI, a more invasive method, was compared to fertilization by placing the sperm and egg together only, there was no difference in the rate of birth defects. Finally, when embryos were frozen and then thawed before transfer were compared to fresh embryos, there was still no difference in the birth defect rate.

In this study, males had a birth defect rate that was double that of females (8.03% vs 4.26%). Further analysis suggested that the increase in birth defects in males was primarily due to an abnormality known as hypospadias. Other studies however, have not shown an increase in the hypospadias incidence in IVF boy babies.

If there is truly a 30% greater chance of birth defects with IVF babies, then the overall rate of birth defects amongst all IVF babies would be from 1.3% to 3.9% of IVF births.

One further study worthy of mention was recently presented at a scientific meeting but has not yet been published. Canadian researchers looked at 2005 birth data from an Ontario database. They identified 870 births including 320 who used fertility medications, 180 who underwent intrauterine insemination and 370 who underwent in vitro fertilization.

The babies born after fertility treatment were compared to deliveries that were not the result of assisted reproductive techniques (ART). The overall incidence of birth defects in the ART population was 2.62% compared with 1.87% in the non-ART population.

When analyzed by the type of treatment, the incidence of birth defects in the IVF group was 2.97% compared to 2.66% for the intrauterine insemination group and 2.19% for ovulation induction with fertility medications.

Gastrointestinal defects were most common followed by cardiovascular defects and then musculoskeletal defects.

Due to the fact that the comparison group was women without infertility, the researchers acknowledged that further studies are needed to clarify the contribution of infertility itself.

On the other hand, a multi-center study funded by the National Institutes of Health was performed in 2005. 36,000 pregnancies were analyzed. 95% were spontaneously conceived, 1222 (3.4%) conceived with ovulation inducing drugs and 554 (1.5%) used IVF. This study found no association between either fertility treatment and the incidence of birth defects.

IVF and Chromosomal abnormalities

Normal human beings have 23 pairs of chromosomes. Embryos commonly have an abnormal number of chromosomes. These are called aneuploidies. As a woman gets older, she produces an increasing number of embryos with chromosome abnormalities.

In 2002, a study published in the New England Journal of Medicine suggested that the rate of chromosome abnormalities in babies may be higher than that seen in the general population. However, a 2005 study in the United States was unable to find an increase in the risk for chromosome abnormalities from IVF.

The use of intracytoplasmic sperm injection (ICSI) to fertilize eggs has been linked with a higher incidence of sex chromosome abnormalities in male offspring. Currently, this is thought to be due to transmission of chromosome abnormalities from the father rather than an effect of the ICSI per se.

Some studies have found that couples with certain types of problems may have a higher rate of chromosome abnormalities than expected. For example, one recent study showed that couples with recurrent miscarriage produce a higher rate of chromosome abnormalities.

IVF and gene imprinting disorders

Genes are the functional part of chromosomes – they are responsible for specific functions in the body. Genes come in pairs with one member of the pair being inherited from the mother and one member from the father. Normally, the genes from both the mother and father function equally. With imprinted genes, however, only one member of the gene pair is functional and this is determined by the parent of origin. For example, maternal imprinting means that for a particular gene only, the copy received from the mother functions.

Imprinted genes have evolved over time in mammals to help fine-tune the growth of a fetus. Paternally expressed genes generally enhance growth, whereas maternally expressed genes appear to suppress growth.

Disruptions in the normal pattern of imprinting may result in human diseases. Recent studies have suggested that babies born from IVF may have a higher rate of certain rare imprinting disorders. Since these disorders are very rare, it has been difficult to determine if there is an association with IVF. Investigators have used rare disease registries to help identify possible risk factors for imprinting disorders.

IVF and Beckwith-Wiedemann Syndrome

Some experts now believe that IVF is associated Beckwith-Wiedemann Syndrome (BWS). BWS is characterized by a triad of pre- and/or post-natal overgrowth, macroglossia (large tongue) and anterior abdominal wall defects. In addition, about 7% of BWS children develop a tumor, most commonly Wilms’ tumor. The incidence of BWS in the general population is estimated at 7.2 cases per 100,000 births. Some estimates suggest that IVF increases the risk 3-4 fold. If true, this would give an incidence of 21.6-28.8 cases per 10,000 births.

This data was based on upon physician’s investigation of patients in the BWS registry. They found that 4.6% of the children in the registry were conceived from IVF whereas, in the United States during that time period IVF made up 0.8% of all births.

Some experts have noted however, that parents who have undergone IVF are more connected to the medical system and are therefore more likely to have their children added to the registry. This may then account for the skewed results.

IVF and Other Imprinting Syndromes

There were a few isolated reports of babies born from IVF having a rare form of Angelman syndrome. However, a 2006 British study was unable to confirm an association. The British study was also unable to find a link to another imprinting disorder known as Prader-Willi Syndrome.

The Danish Study of IVF and Imprinting Syndromes

A 2005 study Danish study examined 442,349 singleton non-IVF and 6052 IVF children. The investigators were unable to find an increase in the incidence of any imprinting disorders.

07/17/2008 IVF Study fails to show any increase in the risk of developmental disorders in babies