COPENHAGEN — The poorer obstetric outcome of singletons conceived through in vitro fertilization, compared with those who are naturally conceived, may be partially explained by the phenomenon of the “vanishing twin”—the disappearance of at least one gestational sac after the documentation of fetal activity, according to Danish researchers.
“One in 10 IVF singletons originates from a twin gestation, and this could be one of the major causes for the higher risk of adverse obstetric outcomes in IVF singletons,” said Anja Pinborg, M.D., who presented her study at the annual meeting of the European Society for Human Reproduction and Embryology.
She speculated the toxic environment created by the demise of one twin could be responsible for compromising the health of the survivor. “This is yet another argument in favor of single embryo transfers.”
There is already strong evidence that, among naturally conceived twins, the death of one twin in utero is associated with as much as a 10-fold increase in the risk of cerebral palsy for the surviving twin, said Dr. Pinborg, of the University of Copenhagen.
In IVF pregnancies, the spontaneous loss of at least one gestational sac has been correlated with a shorter pregnancy and lower birth weight of any surviving fetus (Obstet. Gynecol. Clin. North. Am. 2005;32:17–27).
In another, very recent Danish study, investigators proposed that even the demise of extra embryos after IVF and embryo transfer could pose an obstetric risk. The investigators noted that among more than 9,000 children conceived through IVF, there was an increased incidence of cerebral palsy in pregnancies for which the number of children born was less than the number of embryos originally transferred (Hum. Reprod. 2005;[Epub ahead of print; PMID 15890728]).
In Dr. Pinborg's study, she and her associates retrospectively analyzed 9,557 children conceived through IVF at 11 clinics. The cohort included 5,237 singletons, 3,678 twins, and 642 singleton survivors of a vanishing-twin pregnancy. To be included, the obstetric chart had to document either one or two viable fetuses, or one viable and one nonviable (without heartbeat) fetus.
Among the singleton survivors of vanishing twin pregnancies, 66% were exposed to the loss of the twin early in the pregnancy (before 8 weeks), 29% were exposed to the loss between 8 and 22 weeks' gestation (intermediate), and 5% were exposed to the loss after 22 weeks' gestation (late).
Compared with singletons who did not have a vanishing twin, singleton survivors of vanishing twin pregnancies had significantly lower birth weights and gestational ages, more days in intensive care, and higher neonatal mortality rates. They had a twofold increase in cerebral palsy rates, though this difference was not statistically significant.
In addition, the gestational age of a twin's demise was directly correlated with the severity of adverse events for the surviving twin: Early losses correlated with milder sequelae.
The hypothesis of a toxic environment created by embryonic demise is supported by a separate study presented at the meeting. In that study, Belgian researchers compared data on 251 singleton IVF pregnancies resulting from single embryo transfer (SET) with data on more than 50,000 naturally conceived singleton pregnancies recorded in the Flemish registry of perinatal epidemiology.
With the exception of hypertension, which was significantly more common in SET pregnancies (7.6%), compared with spontaneous singleton pregnancies (4.6%), all other obstetric and neonatal outcomes were similar between the groups, said Diane De Neubourg, M.D., of the Center for Reproductive Medicine in Antwerp, Belgium. This contrasts with what's known about poorer outcomes in IVF singleton pregnancies conceived after multiple embryo transfer, which tend to have about a twofold increase in rates of low birth weight, preterm delivery, small size for gestational age, and neonatal mortality, compared with spontaneously conceived singletons.
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