Are imprinting disorders more prevalent after human in vitro fertilization or intracytoplasmic sperm injection?

There is solid evidence that Beckwith-Wiedemann syndrome is significantly positively associated with IVF or ICSI. There is no proof for a causal relationship between imprinted diseases and ART.

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Jan P. W. Vermeiden, Ph.D., Rob. E Bernardus, M.D., Ph.D.

Volume 99, Issue 3, Pages 642-651, 1 March 2013



To review the literature and present original data to answer the question whether IVF or ICSI is associated with an increase in imprinted diseases in offspring. If the answer is positive, to investigate whether there is a causal relationship between IVF or ICSI and the imprinted diseases.


Review study.


Eight epidemiological studies were suitable to calculate the weighted relative risk for the birth of a child with Beckwith Wiedemann Syndrome following IVF or ICSI as compared to the risk in the normal population. This relative risk was 5.2 (95% CI 1.6 – 7.4). In one study the relative risk was corrected for parents’ fertility problems and no significant association was found. Data on the Silver Russell Syndrome are too sparse to draw conclusions but a positive association with IVF or ICSI treatment is probable. No significant associations were found between the incidences of the Angelman Syndrome and the Prader Willi Syndrome and IVF or ICSI treatments. Children with Prader Willi Syndrome or Angelman Syndrome are more likely to be born to parents with fertility problems. All retinoblastomas in children born after IVF or ICSI could be explained by de novo mutations in the RB1 gene, and were not associated with imprinted genes. Imprinted diseases result from methylation errors already present in sperms or oocytes. There is no proof of a causal relationship between imprinted diseases and IVF or ICSI treatments.


Imprinting disorders are more prevalent after human IVF or ICSI. Future studies should correct for fertility problems in the affected and comparison groups. It is highly improbable that assisted reproduction technologies cause imprinted diseases in humans.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.