PGS-study

The study


Background PGS


Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) are frequently applied to achieve pregnancy. Despite improving techniques, the rate of success of assisted conception is low: only one in five treatments results in an on-going pregnancy. A possible explanation for this relatively low rate of success is that the quality of the embryos used for IVF have a non-optimal quality. In order to improve embryo quality preimplantation genetic screening (PGS) was developed. In PGS, one or two cells are removed from the embryo; these cells are screened for genetic dysfunctions. Only those embryos without detected genetic dysfunction are used for IVF. Unfortunately, PGS appeared to be less effective than expected: the number of pregnancies resulting in a life born child did not increase. As a consequence, PGS is nowadays less frequently applied.

In the PGS study, we study the development of children that are born following IVF with PGS. We compare their development with that of children who are also born following IVF, but without the application of PGS. In this way we may detect whether PGS is associated with potentially harmful effects on child development. A harmful effect is conceivable as PGS involves more manipulation of the embryo than regular IVF.


Child development


In the PGS study we study a wide array of developmental outcomes. Special attention is paid to neurodevelopmental outcome: neurological, motor, cognitive and behavioural outcome. Neurological condition is evaluated with sensitive, age-specific tools, which include the observation of spontaneous motor behaviour. Cognition is tested with standardized tests and behaviour is evaluated with parental questionnaires.

Next to brain development, general physical development is assessed. This includes the evaluation of blood pressure, height, weight, circumference of specific body parts and skinfold thickness. In addition, we assessed at the age of 2 years the presence of congenital anomalies, such as a cleft palate and an extra finger or toe.


Results


Development up until the age of 9 years

  • At 4 and 9 years cognitive and behavioural development of children born after IVF with PGS was similar to that of children born after IVF without PGS.
  • Neurological development up until the age of 2 years of children born after IVF with PGS was less optimal than that of children born after IVF without PGS. At the age of 4 years this difference had disappeared in singletons, but persisted in twins. This difference had disappeared at 9 years: at that age neurological development of children born after IVF with PGS was similar to that of children born after IVF without PGS.
  • At 2 years, the prevalence of major and minor congenital anomalies of children born after IVF with PGS was similar to that of children born after IVF without PGS.
  • At 4 and 9 years, blood pressure and growth of children born after IVF with PGS was similar to that of children born after IVF without PGS

Collaborators

Mijna Hadders-Algra, MD, PhD        
professor of developmental neurology, UMCG

Maaike L. Haadsma, MD, PhD        
resident clinical genetics, UMCG

Maas Jan Heineman, MD, PhD        
professor of obstetrics & gynaecology, AMC

Joke H. Kok, MD, PhD            
professor of neonatology, AMC

Derk Kuiper, MD/PhD student
Developmental Neurology, UMCG

Sacha la Bastide-van Gemert, Ph.D    
mathematician, UMCG

Tessa J. Rosenboom, PhD        
medical biologist, AMC

Pamela Schendelaar, MD, PhD
  
    
Jorien Seggers, MD, PhD           
general practitioner in training, UMCG

Key publications

  • Middelburg KJ, Heineman MJ, Haadsma ML, Bos AF, Kok JH, Hadders-Algra M. Neurological condition of infants born following preimplantation genetic screening. Pediatr Res 2010; 67: 430-4.
  • Middelburg KJ, Van der Heide M, Houtzager B, Jongbloed-Pereboom M, Fidler V, Bos AF, Kok J, Hadders-Algra M.  Mental, psychomotor, neurological, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial. Fertil Steril 2011; 96: 165-9.
  • Beukers F, Van der Heide M, Middelburg KJ, Cobben JM, Mastenbroek S, Breur R, Van der Lee JH, Hadders-Algra M, Bos AF, Kok JH for the PGS study group. Morphological abnormalities in 2-year-old children born after IVF/ICSI with or without preimplantation genetic screening; follow-up of a randomized controlled trial. Fert Steril, 2013;99:408-413.
  • Schendelaar P, Middelburg KJ, Bos AF, Heineman MJ, Kok JH, La Bastide-van Gemert S, Seggers J, Van den Heuvel ER, Hadders-Algra M. The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT. Hum Reprod 2013; 28:1508-18.
  • Seggers J, Haadsma ML, La Bastide-van Gemert S, Heineman MJ, Kok JH, Middelburg KJ, Roseboom TJ, Schendelaar P, Van den Heuvel ER, Hadders-Algra M. Blood pressure and anthropometrics of 4-year-old children born following preimplantation genetic screening: follow-up of a unique, moderately-sized randomized controlled trial. Pediatr Res, 2013;74:606-14.
  • Kuiper D, Bennema A, La Bastide-van Gemert S, Seggers J, Schendelaar P, Mastenbroek S, Hoek A, Heineman MJ, Roseboom TJ, Kok JH, Hadders-Algra M. Developmental outcome of 9-year-old children born after preimplantation genetic screening: follow-up of a randomized trial. Hum Reprod 2018; 33: 147-155

News letters

in Dutch only

Sponors

  • Behavioural and Cognitive Neurosciences
  • Cornelia stichting
  • Junior Scientific Masterclass
  • Universitair Medisch Centrum Groningen
  • ZonMw

 

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