Correspondence

Estimating the Risk of Cerebral Palsy after Assisted Conceptions

N Engl J Med 1999; 341:1313-1314October 21, 1999

Article

To the Editor:

Multifetal births are a calculated risk of induction of ovulation, because the number of ova that will be fertilized is unknown. By contrast, the number of transferred embryos in in vitro fertilization can be controlled, which is important because the number of embryos influences the pregnancy rate and the outcome of pregnancy.1

The excess risk of cerebral palsy in multifetal pregnancies, which has recently been quantified, is attributed mainly to prematurity and low birth weight.2 Thus, by integrating the risk of multifetal birth with that of neonatal cerebral palsy, it is possible to estimate the risk of this complication after assisted reproduction.

We used population-based British data1 to calculate the number of neonates after spontaneous conception (singletons, 98.7 percent; twins, 1.2 percent; and triplets, 0.1 percent), after the transfer of two embryos (73, 26, and 0.4 percent, respectively), after the transfer of three embryos (65, 29, and 6 percent), and after the transfer of three embryos with all triplets reduced to twins (65, 35, and 0 percent). We integrated these numbers with population-based British data3 on rates of cerebral palsy in singletons, twins, and triplets (2.3, 12.6, and 44.8 cases per 1000 neonates, respectively). In this analysis, we disregarded fetal losses. We assumed that the method of assisted reproduction does not in itself increase the rate of cerebral palsy.

A comparison of the rates of cerebral palsy by the chi-square test (Table 1Table 1Estimated Rates of Cerebral Palsy in Neonates after Spontaneous and Assisted Conception.) shows that the estimated rate is significantly lower after spontaneous conception (2.7 cases per 1000 neonates) than after the transfer of three embryos (16.86 per 1000) or two embryos (8.77 per 1000) or after the transfer of three embryos with a reduction of triplets to twins (10.31 per 1000). In addition, the estimated rate of cerebral palsy is significantly higher after the transfer of three embryos than after the transfer of two or after a reduction of triplets to twins. By contrast, the estimated rates of cerebral palsy are similar after the reduction of triplets to twins and after the transfer of two embryos.

The risk of cerebral palsy appears to depend on the relative proportions of twins and triplets in a given population. Hence, the calculated risks in our model need clinical validation, since actual rates are not available. Nevertheless, the estimated peril of lifelong morbidity should be acknowledged by infertility experts who establish embryo-transfer policies and by patients using assisted-reproduction methods.

Isaac Blickstein, M.D.
Kaplan Medical Center, 76100 Rehovot, Israel

Ariel Weissman, M.D.
Edith Wolfson Medical Center, 58100 Holon, Israel

3 References

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   Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998;339:573-577
   Full Text | Web of Science | Medline

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   Blickstein I. Cerebral palsy in multifetal pregnancies: facts and hypotheses. In: Chervenak FA, Kurjak A, eds. Fetal medicine — the clinical care of the fetus as a patient. Lancaster, England: Parthenon Publishing, 1999:368-73.
   

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   Pharoah PO, Cooke T. Cerebral palsy and multiple births. Arch Dis Child Fetal Neonatal Ed 1996;75:F174-F177
   CrossRef | Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   Ola Didrik Saugstad. (2006) Non-selective fetal reduction is malpractice. Journal of Perinatal Medicine 34:5, 355-358
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2. 2

   A Ito, Y Honma, E Inamori, Y Yada, M Y Momoi, Y Nakamura. (2006) Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques. Journal of Perinatology 26:2, 130-133
   CrossRef

3. 3

   R. Lavery, J. A. Houghton, A. Nolan, M. Glennon, D. Egan, M. Maher. (2005) CAG repeat length in an infertile male population of Irish origin. Genetica 123:3, 295-302
   CrossRef

4. 4

   Isaac Blickstein, Louis G. Keith. (2003) Outcome of triplets and high-order multiple pregnancies. Current Opinion in Obstetrics and Gynecology 15:2, 113-117
   CrossRef

5. 5

   Svetlana V Glinianaia, Judith Rankin, Chris Wright, Stephen N Sturgiss, Marjorie Renwick. (2002) A Multiple Pregnancy Register in the North of England. Twin Research and Human Genetics 5:5, 436-439
   CrossRef

6. 6

   Isaac Blickstein. (2002) Cerebral palsy in multifoetal pregnancies. Developmental Medicine & Child Neurology 44:5, 352-355
   CrossRef

7. 7

   Pier Giorgio Crosignani. (2002) The need for new methods of ovarian stimulation. Reproductive BioMedicine Online 5, 57-60
   CrossRef

8. 8

   Nicholas M Fisk, Geoffrey Trew. (1999) Two's company, three's a crowd for embryo transfer. The Lancet 354:9190, 1572-1573
   CrossRef