Human Reproduction, Vol. 15, No. 6, 1421,
June 2000
© 2000 European Society of Human Reproduction and Embryology
Letters to the Editor |
Long term follow-up of children born after inadvertent administration of a GnRH-analogue in early pregnancy
Dutch Speaking Brussels Free University, Centre for Reproductive Medicine, Laarbeeklaan 101, 1090 Brussels, Belgium
Dear Sir,
We have read with interest the contribution of Lahat et al. (1999). The authors diagnosed 5 children out of 6 exposed to a long-acting GnRH-analogue, with physical (n = 1) or neurodevelopmental abnormalities (n = 4). The need for long term follow-up possibly sponsored by GnRH-analogue producing pharmaceutical companies echoes the intuition of many clinicians. However, we would like to raise two points of concern.
We were surprised by the statements from the authors that the presence of one major congenital anomaly did not allow them to draw any statistical conclusion because of the small series. Human studies of 284 babies (Chardonnens et al., 1998
) reported a similar rate of major congenital abnormalities as in the general population and this is not surprising as the exposure has encompassed only the first 6 weeks of gestation, before organogenesis. The results of IVF-treatments using long-acting GnRH-analogues are also encouraging. The GnRH-analogue remains in circulation for up to 45 days (Happ et al., 1987) after its initiation, which includes the time of implantation; no reports of neurodevelopmental abnormalities have ever been published in that group of patients.
The authors state that 5 out of the 6 infants were term. From Table II, however, we can read that 50% (n = 3) of the children were preterm and one of the term children was severely growth retarded (2130 g). We wonder what the background incidence is of neurodevelopmental problems in preterm or growth retarded babies?
In view of all these points greater follow-up studies are more than needed before we can draw any conclusions. We think, having a similar study with ICSI-children (Bowen et al., 1998) in mind that we have to be careful not to create any unnecessary fear and confusion amongst patients and clinicians.
Notes
1 To whom correspondence should be addressed 
References
Bowen, J.R., Gibson, F.L., Leslie, G.L. et al. (1998) Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet, 351, 1529–34.[Web of Science][Medline]
Chardonnens, D., Sylvan, K., Walker, D. et al. (1998) Triptorelin acetate administration in early pregnancy: case reports and review of the literature. Eur. J. Obstet. Gynecol. Reprod. Biol., 80, 143–49.[Medline]
Happ, J., Schultheiss, H. and Jacobi, G. (1987) Pharmacodynamics, pharmacokinetics an bioavailibility of prolonged LH-RH agonist Decapeptyl-SR. In Klijn, J. et al (eds), Hormonal manipulation of cancermograph, series of the European organisation for research on treatment of cancer,18, Raven Press, New York, 249.
Lahat, E., Raziel, A., Friedler, S. et al. (1999) Long-term follow-up of children born after inadvertent administration of a gonadotrophin-releasing hormone agonist in early pregnancy. Hum. Reprod., 14, 2656–2660.
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