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Fruit of the Womb
Fruit of the Womb

Multiple Gestations - An Introduction

Not long ago I was attending at a twin delivery – one boy and one girl. The mother knew from about 16 weeks into the pregnancy that she had one of each gender. Yet, at the time of the delivery, despite the fact that there really was one of each, her first question to me was “Are they identical twins?” My simple response was to remind her that she had one boy and one girl. “No. she said, I know that but I just want to know if they are identical – do we need to do a blood test to find that out?” At that point my doctorly sense of humor (or consummate lack of professionalism) took over and I told her that “Well, they could be, but then one of them was going to have some gender identification issues throughout his or her’s lifetime depending on which one is phenotypically different than their chromosomal complement.” Despite being a highly educated individual, she looked at me quizzically, clearly not understanding the joke or comprehending the situation. At that point I gently explained they could NOT be identical twins – with one baby being a boy and the other being a girl, they had to have come from separate fertilization events of different eggs. Interestingly, a few weeks later, I got the exact same question from another patient in the same situation who had come to see me for a preconceptional counseling visit. My first thought was that this would be a great introduction to a series on multiple gestations, a topic I have inadvertently overlooked during the last two years of writing this blog…

In reference to my comments above, twins are classified as either ‘monozygotic’ or ‘dizygotic’. Monozygotic twins arise from the same fertilized egg; dizygotic twins result from completely separate fertilization events of separate eggs. Monozygotic twins are then considered to be ‘identical’ and dizygotic twins are ‘fraternal’. The rate for spontaneous monozygotic twinning around the world is relatively constant at 3.5 to 4 per 1000 pregnancies. Rates for dizygotic twinning on the other hand vary widely depending on country location and ethnic origin. Recent U.S. statistics indicate an extraordinarily high overall rate of twinning at 3.3%, or one in every 30 pregnancies and about one-third of all twins in the U.S. are monozygotic! Our rates are probably skewed because of the widespread access to and the success of assisted reproductive technology (ART) programs around the country.

A variety of factors have been correlated with dizygotic twinning over the years. Rates of “double ovulation” that result in dizygotic twins increase with age to about age 35 (and then decrease), increase with the number of previous pregnancies (parity), occur at higher rates in couples during the first 3 months of marriage, and increase with frequency of intercourse. On the other hand, dizygotic twinning rates decrease during times of stress and malnutrition such as the Second World War. Increased rates have been correlated with elevated gonadotropin levels and specific chromosomal mutations. There are clearly higher rates in certain families and a suggestion that the tendency toward ‘double ovulation’ can be heritable by male transmission to his daughters. Due to the variability of genetic material and the random events that separate sister chromosomes into different eggs and sperm, it is almost impossible for dizygotic twins to be ‘identical’, especially if they are different genders!

The etiology of monozygotic twinning is a bit more enigmatic. There appears to be a slight increase with maternal age but this is by no means as significant as with dizygotic twins. Interestingly, rates of monozygotic twinning are increased in ART pregnancies and this has led to a belief that manipulation of the early embryo can lead to perturbations in adhesion between the cells that can then result in the division of the embryo giving rise to monozygotic twins. This concept is supported by observational studies in animals of exposure of early embryos to teratogens resulting in higher rates of monozygotic twinning as well. Although monozygotic twins are usually viewed as genetically ‘identical’, depending on the time of division and subsequent aberrations in mitotic events a well as disparate inactivation of certain chromosomes, they may actually express different genetic makeups. Furthermore, they can be discordant for malformations (for which they are at greater risk than dizygotic twins) and also for growth while in utero as the consequence of various events – a discordance that may carry over into the final growth and development of the ‘identical’ siblings...
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