Correspondence
Zygotic-Splitting Rates after Single-Embryo Transfers in in Vitro Fertilization
N Engl J Med 2003; 348:2366-2367June 5, 2003
- Article
To the Editor:
The mechanism of spontaneous monozygotic twinning is unknown. However, on the basis of observations first made 15 years ago, it is now generally accepted that all forms of assisted conception increase the rate of zygotic splitting.1-3 The true incidence of zygotic splitting is unknown in a substantial proportion of twins, because same-sex dizygotic twins cannot be differentiated from dichorionic monozygotic twins by either antepartum ultrasonography4 or postpartum clinical examination.
Single-embryo transfers are currently considered to be a means for minimizing the risk of multiple births with in vitro fertilization. In order to assess the risk of zygotic splitting, we analyzed the data for 1991 through 1998 provided by the British Human Fertilization and Embryology Authority, derived from 68 licensed in vitro fertilization clinics and including 15,644 cycles involving single-embryo transfers in 7832 women (Table 1Table 1
Pregnancies and Zygotic-Splitting Rates after Single-Embryo Transfers.). The data include information about cryopreservation and cycle stimulation, but neither the methods used for ovarian stimulation and manipulation of the zona pellucida nor the embryonic stage at transfer is described.Overall, there were 1104 live births (7.1 percent of the cycles, 79.1 percent of the pregnancies), including 22 sets of twins and 3 sets of triplets. The rate of multiple pregnancies after single-embryo transfer represents a 2.3 percent rate of zygotic splitting among in vitro conceptions — a figure that is six times the rate of 0.4 percent quoted in the literature for spontaneous conception. The data indicate that the splitting rates are similar after the transfer of fresh embryos and after the transfer of embryos that have been frozen and thawed and that the rates are also similar after stimulated cycles and unstimulated cycles.
We believe that the difference between the rate we observed and the rate, representing an increase by a factor of 12, that was previously found in a clinic-based population (4.9 percent of 82 pregnancies5) may be explained in part by differences between multiple pregnancies and multiple births; these differences imply that the rates in our series might have been higher if we had counted the embryos and fetuses in multiple gestations that did not survive to delivery. In addition, differences between clinic-based studies and large population-based studies should be considered. On the basis of our study, we would recommend that the risk of iatrogenic zygotic splitting and its potential adverse outcome should be explained to the infertile couple before therapy is initiated, even if a single embryo is transferred in order to minimize the risk of a multiple gestation.
5 ReferencesIsaac Blickstein, M.D.
Kaplan Medical Center, 76100 Rehovot, Israel
blick@netvision.net. il Christopher Jones, M.Sc.
University of Oxford, Oxford OX3 7LF, United KingdomLouis G. Keith, M.D.
Northwestern University, Chicago, IL 606111
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