Correspondence
Zygotic Splitting after Assisted Reproduction
N Engl J Med 1999; 340:738-739March 4, 1999
- Article
To the Editor:
It is unknown why monozygotic twins are more frequent in conceptions brought about by assisted-reproduction techniques.1-4 One hypothesis is that the exposure of the zona pellucida to biochemical or mechanical trauma leads to herniation of the blastocyst and cleavage of the zygote. This possibility is not only of biologic importance in understanding spontaneous monozygotic twinning but is a major area of clinical concern, primarily because of the confirmed increase in morbidity and mortality associated with monozygotic twinning.
A zygote may split anytime during the first 14 days after fertilization, resulting in the various forms of monozygotic twins. With assisted-reproduction techniques, splitting is customarily inferred when the number of fetuses exceeds the number of embryos transferred or in cases of monoamniotic twins.2 However, such an inference may underestimate in several ways the incidence of zygotic splitting. First, when one of two transferred embryos is lost and the other splits into dichorionic monozygotic twins, the number of fetuses does not exceed the number of transferred embryos. Second, we are unable to clinically differentiate same-sex dichorionic dizygotic twins from dichorionic monozygotic twins. Third, the incidence of zygotic splitting cannot be estimated by Weinberg's rule5 or by referring to monochorionicity, since the ratios observed in spontaneous conceptions may not be the same as those observed after assisted reproduction. Finally, differences in incidence are expected depending on whether the zona pellucida is manipulated (as with intracytoplasmic sperm injection) or not (as with induction of ovulation and in vitro fertilization).
It follows that only by choosing the correct numerator (twin pregnancies after transfers of single embryos) and the correct denominator (a specific assisted-reproduction technique) can one overcome the flaw in this construct and calculate the true risk of monozygotic twinning when counseling patients on the risks of embryo transfers.
Recent articles fail to provide sufficient information by using data related to multiembryo transfers,1 omitting the frequency of the manipulations of the zona pellucida,2 focusing on monoamniotic twins,3 or overlooking the number of embryo transfers per cycle.4 We therefore studied the outcome of single-embryo transfers without assisted hatching from January 1994 to July 1998 at the Center for Reproductive Medicine in Dusseldorf, Germany. About 15 percent of the patients were lost to follow-up. Among 82 pregnancies after 645 single-embryo transfers after in vitro fertilization (pregnancy rate, 12.7 percent) there were 4 monozygotic twins (4.9 percent — 12 times the expected spontaneous rate of monozygotic twins). In contrast, no twins were observed among 94 pregnancies after 920 single-embryo transfers after intracytoplasmic sperm injection (pregnancy rate, 10.2 percent), a procedure expected to result in a higher rate of monozygotic twins. Since both groups followed similar protocols, this difference may be attributed to differences in the treatments of the gametes rather than to puncturing the zona pellucida in vitro.
5 ReferencesIsaac Blickstein, M.D.
Kaplan Medical Center, Rehovot 76100, IsraelHugo C. Verhoeven, M.D.
Center for Reproductive Medicine, 40219 Dusseldorf, GermanyLouis G. Keith, M.D.
Prentice Women's Hospital, Chicago, IL 606111
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- Citing Articles (29)
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Gerardo Vela, Martha Luna, Jason Barritt, Benjamin Sandler, Alan B. Copperman. (2011) Monozygotic pregnancies conceived by in vitro fertilization: understanding their prognosis. Fertility and Sterility 95:2, 606-610
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Carrie Williams, Alastair Sutcliffe. (2009) Infant outcomes of assisted reproduction. Early Human Development 85:11, 673-677
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W. Verpoest, L. Van Landuyt, S. Desmyttere, A. Cremers, P. Devroey, I. Liebaers. (2009) The incidence of monozygotic twinning following PGD is not increased. Human Reproduction 24:11, 2945-2950
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Deborah M. Taylor, Meen-Yau Thum, Hossam Abdalla. (2008) Dichorionic triamniotic triplet pregnancy with monozygotic twins discordant for trisomy 13 after preimplantation genetic screening: case report. Fertility and Sterility 90:5, 2017.e5-2017.e9
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Y. Ville. (2006) Chorionicity and mode of fertilization: a long-standing misconception. Ultrasound in Obstetrics and Gynecology 28:5, 635-636
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S. A. Shalev, E. Shalev, E. Pras, Y. Shneor, E. Gazit, Y. Yaron, R. Loewenthal. (2006) Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for Down syndrome. Prenatal Diagnosis 26:9, 782-784
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Isaac Blickstein. (2005) Estimation of iatrogenic monozygotic twinning rate following assisted reproduction: Pitfalls and caveats. American Journal of Obstetrics and Gynecology 192:2, 365-368
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Laura A. Schieve, Sonja A. Rasmussen, Germaine M. Buck, Diana E. Schendel, Meredith A. Reynolds, Victoria C. Wright. (2004) Are Children Born After Assisted Reproductive Technology at Increased Risk for Adverse Health Outcomes?. Obstetrics & Gynecology 103:6, 1154-1163
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GEORGE GRAHAM, LYNN L. SIMPSON. (2004) Diagnosis and Management of Obstetrical Complications Unique to Multiple Gestations. Clinical Obstetrics and Gynecology 47:1, 163-180
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Souter, Vivienne L., Kapur, Raj P., Nyholt, Dale R., Skogerboe, Kristen, Myerson, David, Ton, Carl C., Opheim, Kent E., Easterling, Thomas R., Shields, Laurence E., Montgomery, Grant W., Glass, Ian A., . (2003) A Report of Dizygous Monochorionic Twins. New England Journal of Medicine 349:2, 154-158
Full Text23
Blickstein, Isaac, , Jones, Christopher, , Keith, Louis G., . (2003) Zygotic-Splitting Rates after Single-Embryo Transfers in in Vitro Fertilization. New England Journal of Medicine 348:23, 2366-2367
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Amin A Milki, Sunny H Jun, Mary D Hinckley, Barry Behr, Linda C Giudice, Lynn M Westphal. (2003) Incidence of monozygotic twinning with blastocyst transfer compared to cleavage-stage transfer. Fertility and Sterility 79:3, 503-506
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Ashley E.R Merién, Jim van Eyck, Birgit Arabin. (2001) Two Cases With Dichorionic Diamniotic Triplet Pregnancy and Early Cord Entanglement. Twin Research and Human Genetics 4:4, 219-222
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Annika K Schröder, Klaus Diedrich, Michael Ludwig. (2001) Fertilization rate and preimplantation development after intracytoplasmic sperm injection. Reproductive BioMedicine Online 3:3, 241-249
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Gareth Weston, Fleur Cattrall, Alan O. Trounson, David L. Healy. (2000) Cloning: its relevance to monozygotic twins. The Australian and New Zealand Journal of Obstetrics and Gynaecology 40:3, 317-325
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