Multiple Pregnancy Pathogenesis

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A. Monozygotic Multiple Gestation

Monozygotic twins, resulting from the fertilization of a single ovum by a single sperm, are always of the same sex. However, the twins may develop differently depending on the time of preimplantation division. Normally, monozygotic twins share the same physical characteristics (skin, hair and eye color, body build) and the same genetic features (blood characteristics: ABO, M, N, haptoglobin, serum group; histocompatible genes; skin grafting possible), and they are often mirror images of one another (one left-handed, the other right-handed, etc). However, their fingerprints differ.

The paradox of “identical” twins is that they may be the antithesis of identical. The very earliest splits are sometimes accompanied by a simultaneous chromosomal error, resulting in heterokaryotypic monozygotes, one with Down’s syndrome and the other normal.

Monozygotic triplets result from repeated twinning (also called supertwinning) of a single ovum. Trizygotic triplets develop by individual fertilization of 3 simultaneously expelled ova. Triplets may also be produced by the twinning of 2 ova and the elimination of 1 of the 4 resulting embryos. Similarly, quadruplets may be monozygotic, paired dizygotic, or quadrizygotic (ie, they may arise from 1 to 4 ova).

B. Dizygotic Multiple Gestation

Dizygotic twins are the product of 2 ova and 2 sperms. The 2 ova are released from separate follicles (or, very rarely, from the same follicle) at approximately the same time. Dizygotic (fraternal) twins may be of the same or different sexes. They bear only the resemblance of brothers or sisters and may or may not have the same blood type. Significant differences usually can be identified over time.

About 75% of dizygotic twins are the same sex. Both twins are males in about 45% of cases (a lesser preponderance of males in twins than in singletons) and both females in about 30%.

Many factors influence dizygotic twinning. Race is a factor, with multiple pregnancy most common in blacks, least common in Asians, and of intermediate occurrence in whites. The incidence of dizygotic twinning varies from 1.3 in 1000 in Japan to 49 in 1000 in western Nigeria. The rate in the United States is about 12 in 1000.

Dizygotic multiple pregnancy tends to be recurrent. Women who have borne dizygotic twins have a 10-fold increased chance of subsequent multiple pregnancy. Dizygotic twinning probably is inherited via the female descendants of mothers of twins; the father’s genetic contribution plays little or no part. White women who are dizygotic twins or who are siblings of dizygotic twin mothers have a higher twinning rate among their offspring than women in the general population.

Parity does not influence the incidence of dizygotic twinning, but aging does, with the rate of dizygotic twinning peaking between 35 and 40 years of age and then declining sharply. In women who are twins or daughters of twins, the twinning rate peaks at about age 35, at which time it plateaus until almost age 45 and then declines. Black women, whether or not they are twins or siblings of twins, have a prolonged period of dizygotic twinning from 35 to 45 years of age.

Women of increased height and weight have a higher incidence of twinning, but the rate does not vary among social classes. Blood groups O and A are more prevalent in white mothers of twins than in the general population, for unknown reasons.

High fertility (polyovulation) is associated with multiple pregnancy. Excessive production of pituitary gonadotropins, relatively high frequency of coitus, and inability of one graafian follicle to inhibit others have been postulated as reasons for a higher incidence of dizygotic twinning. Undernutrition appears to be a negative factor. Women who conceive late in an ovulatory cycle have a greater chance of multiple pregnancy, perhaps owing to ovular “overripeness.”

Dizygotic twinning is more common among women who become pregnant soon after cessation of long-term oral contraception. This may be a reflection of high “rebound” gonadotropin secretion. Induction of ovulation with human pituitary gonadotropin in previously infertile patients has resulted in many multiple pregnancies - even the gestation of septuplets and octuplets. The estrogen analog clomiphene citrate increases the incidence of dizygotic pregnancy to about 5-10%.

C. Other Forms of Multiple Gestation

Other kinds of twinning are theoretically possible in humans. Dispermic mosaicism may result from fertilization of 2 ova that have not been independently released but have instead developed from the same oocyte. Another possibility is the fertilization of 1 ovum by 2 sperms. Twinning of discordant twins may be explained by meiotic abnormalities, including polar body twinning, delayed implantation of the embryo, retarded or arrested intrauterine development, or superfetation.

Superfecundation is the fertilization of 2 ova, released at about the same time, by sperm released at intercourse on 2 different occasions. The rare cases in which the fetuses are of disparate size or skin color and have blood groups corresponding to those of the mother’s 2 male partners lend credence to (but do not conclusively validate) this possibility.

Superfetation is the fertilization of 2 ova released in different menstrual cycles. This is virtually impossible in humans, because the initial corpus luteum of pregnancy would have to be suppressed to allow for a second ovulation about 1 month later.

RELATED STORIES:
Multiple Pregnancy Prognosis   Pathologic Factors Associated with Twinning   Multiple Pregnancy Clinical Findings   Multiple Pregnancy Differential Diagnosis   Multiple Pregnancy Prevention   Multiple Pregnancy Treatment   Multiple Pregnancy Complications

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