A review of the mechanisms and evidence for typical and atypical twinning

doi:10.1016/j.ajog.2015.10.930

American Journal of Obstetrics and Gynecology

Volume 214, Issue 2, February 2016, Pages 172-191

https://doi.org/10.1016/j.ajog.2015.10.930 Get rights and content

The mechanisms responsible for twinning and disorders of twin gestations have been the subject of considerable interest by physicians and scientists, and cases of atypical twinning have called for a reexamination of the fundamental theories invoked to explain twin gestations. This article presents a review of the literature focusing on twinning and atypical twinning with an emphasis on the phenomena of chimeric twins, phenotypically discordant monozygotic twins, mirror-image twins, polar body twins, complete hydatidiform mole with a coexistent twin, vanishing twins, fetus papyraceus, fetus in fetu, superfetation, and superfecundation. The traditional models attributing monozygotic twinning to a fission event, and more recent models describing monozygotic twinning as a fusion event, are critically reviewed. Ethical restrictions on scientific experimentation with human embryos and the rarity of cases of atypical twinning have limited opportunities to elucidate the exact mechanisms by which these phenomena occur. Refinements in the modeling of early embryonic development in twin pregnancies may have significant clinical implications. The article includes a series of figures to illustrate the phenomena described.

Section snippets

Traditional models of twinning

Traditionally it has been thought that dizygotic twins result from fertilization of 2 distinct ova by 2 separate spermatozoa, whereas monozygotic twins are the product of a single ovum and sperm that subsequently divide to form 2 embryos.¹

Widely accepted models of monozygotic twinning are based on the unproven hypothesis of postzygotic division of the conceptus (Figure 1). In this model, the number of fetuses, chorions, and amnions are determined by the timing of the embryo splitting (Table 1).

New models of twinning

In 2013 Herranz⁸ argued that the hitherto-unchallenged hypothesis of postzygotic splitting lacked scientific proof. He argued that factors that initiate cleavage have not been specified, that coexistence of separate embryos within a single zona pellucida is unlikely, that postzygotic splitting becomes more unlikely with the passage of time, and that splitting has never been observed in vitro.

Herranz⁸ offered an alternative theory of twinning based on the following 2 principles: (1) monozygotic

Atypical twinning

A review of the evidence for atypical twinning provides insights into the mechanisms of twinning and challenges aspects of traditional models of twinning.

Conclusion

Twinning is a complex and multifactorial phenomenon and elements of the twinning process remain incompletely understood. A conventional model of monozygotic twinning is based on fission events in the developing embryo. This model lacks definitive evidence and is challenged by cases of atypical twinning.

An alternative model proposes that embryonic fusion events underlie monozygotic twinning. However, supporting evidence is similarly limited. Elucidating the precise mechanisms by which twinning

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: J.M.C. is supported by grants from the Australian National Health and Medical Research Council (grants 1011070 and 1083779), the Financial Markets Foundation for Children (grant 032-2007), and the Murdoch Children’s Research Institute, which is funded by the Victorian Government’s Operational Infrastructure Support Program. S.C.K. is supported by a postgraduate scholarship from the Australian National Health and Medical Research Council.

: The authors report no conflict of interest.

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Expert ReviewsObstetricsA review of the mechanisms and evidence for typical and atypical twinning

Section snippets

Traditional models of twinning

New models of twinning

Atypical twinning

Conclusion

Lancet

Semin Fetal Neonatal Med

Lancet

Hum Immunol

J Pediatr

Fertil Steril

Fertil Steril

Br J Plast Surg

Chest

Brain Dev

Brain Dev

Lancet

Neuropsychologia

Am J Obstet Gynecol

Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Fertil Steril

Am J Obstet Gynecol

Am J Obstet Gynecol

Fertil Steril

Reprod Biomed Online

Consensus views arising from the 50th study group: multiple pregnancy

Monozygotic twinning in the human is associated with the zona pellucida architecture

Hum Reprod

Zygotic splitting after assisted reproduction

N Engl J Med

Chimaeric twins: why monochorionicity does not guarantee monozygosity

Aust N Z J Obstet Gynaecol

The timing of monozygotic twinning: a criticism of the common model

Zygote

Comment on G. Herranz: The timing of monozygotic twinning: a criticism of the common model. Zygote (2013)

Zygote

Blood group chimerism in human multiple births is not rare

Am J Med Genet

A case of twin chimerism

J Med Genet

Chimerism in a fertile woman with 46,XY karyotype and female phenotype

Hum Reprod

Unusual monochorionic placentation with heterosexual twins

Obstet Gynecol

A report of dizygous monochorionic twins

N Engl J Med

Twin-twin transfusion syndrome in a dizygotic monochorionic-diamniotic twin pregnancy

J Matern Fetal Neonatal Med

Blood lymphocyte chimerism associated with IVF and monochorionic dizygous twinning: case report

Hum Reprod

Fusion as the etiology of chimerism in monochorionic dizygotic twins

Fetal Diagn Ther

Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology?

J Hum Genet

Blood chimerism in monochorionic twins conceived by induced ovulation: case report

Hum Reprod

Confined blood chimerism in monochorionic dizygous (MCDZ) twins

Prenat Diagn

Dizygotic monochorionic twin pregnancy conceived following intracytoplasmic sperm injection treatment and complicated by twin-twin transfusion syndrome and blood chimerism

Ultrasound Obstet Gynecol

Monochorionic dizygotic twins in a spontaneous pregnancy: a rare case report

J Matern Fetal Neonatal Med

Discordant blood chimerism in dizygotic monochorionic laser-treated twin–twin transfusion syndrome

Obstet Gynecol

Testicular hypoplasia in monochorionic dizygous twin with confined blood chimerism

J Assist Reprod Genet

Chimerism of buccal membrane cells in a monochorionic dizygotic twin

Pediatrics

The first known case of blood group chimerism in monochorionic dizygotic twins in Korea

Ann Lab Med

Monochorionic dizygotic twins with discordant sex and confined blood chimerism

Eur J Pediatr

The bovine freemartin: a new look at an old problem

Philos Trans R Soc Lond B Biol Sci

Chimerism in monochorionic dizygotic twins: case study and review

Expert Reviews
Obstetrics
A review of the mechanisms and evidence for typical and atypical twinning