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What triggers twinning?

Q: In the case of identical twins, what triggers a single zygote to result in two embryos? What is the probability of having identical twins?

A: Your first question has me stumped. I've asked medical experts from various universities and hospitals. The general consensus is: we don't know.

Identical twins do not run in families and, therefore, twinning is not related to genetics. Comparisons among different ethnic groups rule out an ethnic cause-no difference. Only mother's age correlates with twinning: the older the mother, the greater the likelihood.

I can mention how and when two embryos form instead of one even though we don't exactly know what triggers the events. We have some hunches though, which I'll mention as we discuss the timing. Twinning is abnormal in humans. Things can go wrong at different times during the embryo's development.

During the first four days after fertilization, the huge fertilized egg (zygote) splits into many smaller cells suitable for building the eventual baby. Sometime after the fourth day about 30 of these smaller cells are hanging around. The spaces between them have filled with pools of clear fluid and gather together to form a hollow cellular ball, called a blastocyst. An inner cell mass forms inside. This is the stuff that an embryo will develop from.

Now consider the approximate time sequence (from fertilization) of when things can go wrong and what kind of twins result.

  • Day 1: the zygote has only split into two smaller building-block cells. If the 2-cell mass splits into two clumps now, then twins result that are the most identical. These twins always have separate placentas since the split into twins occurs at such an early stage. Doctors often mistakenly identify such twins (with separate placentas) as fraternal twins even though they are the most identical twins that can happen. Ironical.
  • Day 4 to 5: Most twins form at this time. What happens at this time? The blastocyst and its inner cell mass (i.e., the developing embryo) must "hatch out of a shell" says Harvey Kliman, M.D., Ph.D. at the Yale University School of Medicine, much like a chick hatches out of its shell.

Hatching blastocyst photoYou can see this happening in the photograph of Figure 1. Michael Tucker, PhD., F.I. Biology, captured a hatching event with the incredible photograph. The shell (a gelatinous capsule called the zona pallucida) is the fuzzy layer around the blastocyst. The inner cell mass (the proto-embryo) is just starting to hatch through the hole in the shell.

Figure: [Michael Tucker, IVF.com] Hatching blastocyst

When the whole blastocyst passes through its shell, the inner cell mass can fragment into two (or very rarely three) clumps of cells. The two cell clumps form into complete embryos, which become identical fetuses, and eventually twin babies. The twins are mirror images of each other. Dr. Kliman's daughters are mirror-image twins, one having a set of moles on her right side and the other with the same set of moles on her left.

The reason age contributes to the likelihood of a woman having twins is that the enclosing shell (that the blastocyst hatches out of) is harder in older mothers. It's more likely, therefore, that the inner-mass will break into clumps as it hatches out of a tougher shell.

  • Day 9 to 10: After this time, if the inner cell mass divides into two clumps, the twins share the same inner sac. This luckily happens only 1 % of the time because the umbilical cords may twist together then, which can lead to death.
  • Day 13 to 15: If the inner cell mass splits into two masses after Day 13, then the cells forming the two embryos don't totally separate and the twins are born joined together, called conjoined or Siamese twins.

The second part of your question is relatively easy. About three in every 1000 deliveries results in identical twins. This average seems to be the same worldwide and the reasons are uncertain.

(Answered by April Holladay, science correspondent, May 9, 2001)

Further Surfing:

Yale U: Behind every healthy baby is a healthy placenta

U of Pennsylvania: Basics of embryo development

Children's Hospital of Iowa: Twins, a parents' guide

IVF.com: Freezing human eggs

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