Department of Obstetrics and Gynecology, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany
1 To whom correspondence should be addressed: Frank.Nawroth{at}medizin.uni-koeln.de
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Abstract |
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Key words: blastocyst culture/ICSI/monozygotic triplets/monozygotic twins/zona pellucida manipulation
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Introduction |
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We report, to our knowledge, on the first published case of monozygotic twins and monozygotic triplets after ICSI and the transfer of two blastocysts. We discuss the literature on the possible connection between monozygotic multiples, ICSI and blastocyst transfer.
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Case report |
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Discussion |
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Recently a discussion started regarding the possible increased risk of monozygotic twinning following IVF (Alikani et al., 2003) especially after prolonged culture and blastocyst transfer in comparison to the transfer of 48 cell stage embryos (Da Costa et al., 2001
). This would be in contrast to one aim of extended culture: the selection of one blastocyst to achieve a single pregnancy. Monozygotic twinning with an estimated incidence of 4.3% after blastocyst transfer (Racowsky et al., 2000
) was first described by Peramo et al. (1999
).
There are also reports of an increased monozygotic twinning rate without prolonged culture (Schachter et al., 2001). It was postulated that culture conditions and not prolonged culture time are responsible for monozygotic twinning (Ménézo et al., 2003
). Belaisch-Allart et al. (1995
) reported on a monozygotic triplet pregnancy following the transfer of frozenthawed embryos. Salat-Baroux et al. (1994
) described trizygotic quintuplets (monoamniotic triplets with two additional fetal sacs) after IVF and the transfer of four embryos without zona pellucida manipulation or extended culture. The patient aborted after fetal reduction. A dichorionicquadriamniotic pregnancy after ICSI, assisted hatching and embryo transfer was recently published (Wehbe et al., 2003
).
While Behr et al. (2000) described an increased incidence of monozygotic twins (5%) after IVF and blastocyst transfer, Abusheika et al. (2000
) and Tarlatzis et al. (2002
) compared IVF and ICSI and found a significantly higher rate only after ICSI and blastocyst transfer (8.9 versus 0%; 5.9 versus 0%). The increased incidence after ICSI and blastocyst transfer could be the result of changes in the zona pellucida during extended culture or of the artificial opening of the zona pellucida during ICSI (Kolibianakis and Devroey, 2002
; Tarlatzis et al., 2002
).
Another form of zona pellucida manipulation which could lead to an increased rate of monozygotic multiples is assisted hatching (Hershlag et al., 1999; Schieve et al., 2000
). In the case of our patient the oocytes were fertilized with ICSI but assisted hatching was not performed.
A single artificial zona pellucida opening (ICSI and/or assisted hatching) may alter the hatching procedure and could cause constriction following bisection of the trophoblast and the inner cell mass, which results in twinning. Repeated manipulation could promote multiple herniation, resulting, for example, in monozygotic triplets due to an unexpected splitting of the inner cell mass (Tarlatzis et al., 2002). It has not been proven that monozygotic twinning is really age-related but zona pellucida changes during ageing (for example, decreased flexibility and/or increased thickness) could influence hatching.
In contradiction to the above-mentioned studies, Sills et al. (2000) did not find a connection between the incidence of monozygotic twinning and assisted hatching, ICSI or the transfer of cryopreserved embryos.
The timing of monozygotic twinning is probably not fixed and the mechanism varies (Scott, 2002). Tarlatzis et al. (2002
) reported only on monochorionicdiamniotic twins. As this type is formed after the splitting of the inner cell mass 48 days after fertilization, they concluded that the embryonic division happens closer to the time of implantation. Our patients pregnancy was also monochorionictriamniotic and monochorionicdiamniotic respectively, which promotes the suggested mechanism. Recently an interesting case was published demonstrating that monochorionic twins can be dizygotic (Souter et al., 2003
). There is only speculation regarding the underlying embryological event. In our case an amniocentesis of the triplets showed three females and the twins were also two female fetuses. The overall micromanipulation data together with the unexpected placentation data suggest that zona-mediated embryo splitting is not the only mechanism of twinning following assisted reproduction (Alikani et al., 2003
).
Familial monozygotic twinning is very rarely seen and can be transmitted by both the father and the mother (Hall, 2003). Steinman (2003
) examined the possible role of inheritance in monozygotic twinning and found an influence of genetics and familial clustering on the monozygotic twinning rate, especially in IVF procedures.
It can be summarized from the literature that prolonged culture as well as manipulations of the zona pellucida (ICSI and/or assisted hatching) could lead to an increased rate of monozygotic multiples. To minimize the resulting risks such as increased abortion rates, increased perinatal morbidity and mortality (Al-Nuaim and Jenkins, 2002), assisted hatching in combination with ICSI and blastocyst culture should be critically performed. The aim of therapy should be the transfer of only one blastocyst in as many patients as possible. In our opinion the incidence of 5.98.9% monozygotic multiples after ICSI and blastocyst transfer reported in the literature requires the prior informing of patients of the uncertainties until this phenomenon and its risk factors are better understood.
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Acknowledgement |
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References |
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Submitted on July 22, 2003; accepted on October 1, 2003.