Embryo biopsy safe for singleton pregnancies, largest study of PGD children suggests

The Belgian research, which is published online in the January issue of the journal Human Reproduction, is the best answer to date to the question of whether removing a cell or two from an embryo to screen it for inherited conditions or genetic abnormalities can, in itself, put the subsequent foetus and baby at greater risk of other health problems.

Professor Inge Liebaers, head of the Centre for Medical Genetics at the University Hospital Brussels and a member of the Department of Embryology and Genetics at the Vrije Universiteit Brussels (VUB), and colleagues have been collecting data on all pregnancies, deliveries and babies born after preimplantation genetic diagnosis and screening (PGD/PGS) at the VUB since 1992. The current study looks at the health of all the children born between 1992 and 2005; 581 babies were examined at two months old and questionnaires were sent to parents and physicians at the time of conception and delivery.

The same group of researchers has also been following the health of children born with the help of the assisted reproductive technique intracytoplasmic sperm injection (ICSI); in order to determine whether potential differences in outcome were exclusively related to the embryo biopsy in PGD and not to assisted reproduction technology (ART) in general, the PGD/PGS babies were compared with a control group of ICSI children.

There was no statistically significant difference in outcome between the two groups in the gestational ages at delivery, birth weights and major malformations. There was no difference in the numbers of deaths around the time of birth between PGD/PGS and ICSI babies if they were born as a result of singleton pregnancies. However, there were five times more perinatal deaths after multiple pregnancies in the PGD/PGS babies compared to the ICSI babies (11.73% versus 2.54%).

The authors write: "The major finding is that embryo biopsy does not seem to change the risk of major malformations nor does the biopsy seem to add risks to the health of newborn singleton PGD/PGS children." However, they add: "A point of concern in this study was the multiple PGD/PGS children being more often premature and of low birth weight."

Prof Liebaers said: "It is fair to say that from the data of our study and taking into account the limitations of the study (number of children born, time-frame of follow-up) that the health of the singleton children born after embryo biopsy for PGD is similar to the health of singleton children born after IVF/ICSI.

"The perinatal death rate in multiple pregnancies is such that both caution and long-term follow-up are required. At present, we don't have an explanation for why the perinatal death rate should be so much higher in the PGD/PGS children, and we need to be careful about drawing firm conclusions from these observations as they may be biased due to low numbers. In addition, we were comparing them with the best possible group of ICSI children, and the demographic and medical backgrounds of the parents may have been different."

Prof Liebaers and her colleagues are continuing to follow the health of all children born after ICSI and PGD/PGS at their centre, as they believe that this is vital for monitoring the safety of these procedures.

"There is a need for more careful, thorough and long-term follow-up studies after PGD, and the number of cases needs to be expanded. Just as for other forms of ART, not many centres have a well-structured follow-up programme. It is difficult to believe that this is the case since the most important outcome parameter is the health of the children born. The parents-to-be need to be fully informed on the health of offspring. Unfortunately, funding for these kind of studies is hard to find," said Prof Liebaers.

As pioneers in the field, the team at VUB has particular expertise in PGD/PGS and ICSI, and an accompanying editorial stresses the need for such expertise. Prof Liebaers said that to carry out PGD/PGS successfully, a close collaboration was required between a centre for medical genetics and a centre for reproductive medicine. Input was required from clinical geneticists and ART clinicians, embryologists, a genetics laboratory carrying out the diagnosis on a single cell, nurses, counsellors, psychologists and social workers.

"Only a close and smooth collaboration of all involved can provide the conditions for skilful practice of PGD. There are now several PGD centres, but only a few worldwide offering PGD for an ever increasing number of monogenic conditions."

The author of the editorial, Joe Leigh Simpson, Professor of Human and Molecular Genetics and Professor of Obstetrics and Gynecology at the Wertheim College of Medicine, Florida International University, USA, wrote: "PGD is not the purview of amateurs or the inexperienced, nor is any technical procedure. Inferential data suggest that less than fully experienced embryologists or diagnosticians may do more harm than good when performing PGD, especially PGD aneuploidy testing."

He concluded that Prof Liebaers study is "as good as it gets" and shows that: "In experienced hands, removal of one (or more) blastomeres does not result in an increase in birth defects. By extrapolation and analogous data, the same should apply to polar body or blastocyst biopsy. PGD is highly accurate (>99%). Whatever the controversy concerning efficacy of PGD in increasing pregnancy rates, patients may be informed that PGD is safe."