Twins may arise from one of two mechanisms: division of a single fertilized ovum into two embryos (“identical” or monozygotic twins) or fertilization of two separate ova (“fraternal” or dizygotic twins). Either or both processes may be involved in the generation of higher numbers of fetuses. Triplets could develop from one, two or three ova; quadruplets from one, two, three or four and so on. It is exceedingly rare for a zygote to divide more than once.
The two twinning processes have very distinct origins and implications for pregnancy outcome. While all multiple gestations carry a risk of preterm delivery from early labor, monozygotic twin pregnancies carry an additional risk of placental problems, chromosomal abnormalities and fetal malformations. These can dramatically influence pregnancy outcomes.
Biology of monozygotic twinning
It is not known exactly what causes an embryo to divide to produce monozygotic twins. However, it is clear that division of the fertilized ovum at specific early stages of development is responsible for the spectrum of clinical presentations with monozygotic twinning. These stages are depicted in Fig. 35.1. Basically, the earlier the fertilized ovum divides, the more separate the twins. Cleavage prior to development of an inner cell mass will result in two placentas, two sets of membranes and two fetuses, whereas division after the embryonic disc has formed results in conjoined twins.
The most common type of monozygotic twinning arises from division during days 3–8 after fertilization. As division occurs after inner cell mass development, but before amnion or embryonic disk formation, this produces a pregnancy with two amniotic sacs and a single placenta (diamniotic monochorionic twins). The second most common type of monozygotic twinning results from a division of the embryo within the first 72 h after fertilization and produces a pregnancy with two amniotic sacs and two placentas (diamniotic dichorionic twins). Twins resulting from divisions later than day 8 after fertilization are rare. If the division occurs on or after the amnion forms on day 8 post-fertilization, both fetuses will be in the same amniotic sac (monoamniotic monochorionic twins). Siamese or conjoined twins are the rarest and arise from cleavage of the differentiating embryonic disc 13–16 days post-conception. Fraternal twins are always diamniotic dichorionic. Therefore, it is necessary to perform zygosity testing on twins with separate placentas who are suspected of being monozygous.
Etiology of dizygotic twins
Most of the spontaneously conceived multifetal pregnancies are twin gestations. The incidence of conception of twins is at least twice the rate of liveborn twins. In many cases, one of a pair of diamniotic dichorionic twins just disappears. Less often, the whole pregnancy miscarries. The frequency of monozygotic twinning is about 1 set in every 250 births and is relatively fixed in most populations. In contrast to monozygotic twinning, the incidence of dizygotic twinning varies dramatically among different populations. Dizygotic twinning is highly influenced by race and heredity. Maternal age over 40, increasing parity and infertility treatment are positively linked to dizygotic twinning.
The racial differences in dizygotic twinning are quite marked. Twinning among Asians is least common, with a rate of only 1.3 dizygotic twin births per 1000 total births in Japan. White women in the USA and the UK have rates of about 8 dizygotic twin sets per 1000 births. Black women have the highest rates of all. They range from a rate of 11 per 1000 births in the USA to 49 per 1000 in some tribes in Nigeria, or 1 in every 20 births. The influence of heredity on dizygotic twinning is carried largely through maternal lineages, with about a 2% chance of delivering twins if the mother herself is a dizygotic twin. When the father of the baby is a dizygotic twin, the rate of twinning is only 0.8%.
In developed countries, most multifetal pregnancies result from infertility treatments. Ovulation induction, in vitro fertilization (IVF) and other assisted reproductive techniques dramatically increase the frequency not only of twinning, but also of conceiving higher order multiple gestations (triplets, quadruplets and more); (Fig. 35.2). Table 35.1 lists recent outcome data approximating the frequency of multifetal pregnancies in the USA, dependent on the means of conception. If one uses Hellin’s theorem to calculate the expected frequency of twins in Nigeria, which has the highest spontaneous twinning rate in the world, one can see the impact of infertility treatment on the higher-order multiple gestations. Hellin’s theorem states that if the frequency of twinning is n in a population, then the frequency of triplets is n2, quadruplets n3, and so on. Using n = 0.05 for the Nigerian tribes, one would only expect 0.25% triplet and 0.012% quadruplet gestations. Thus, infertility treatment can increase the risk of triplets 20-fold and quadruplets 80-fold over the world’s most “twinningest” people.
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