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Number of twin births
[HIDE]Twins and triplets naturally occur in approximately 1 in 80 and 1 in 8000 pregnancies, respectively, in the United States
Multiple pregnancies comprise an increasing proportion of the total pregnancies in the developed world due to older maternal age at childbirth and the expanded use of fertility treatments. In countries with high rates of multiple births, 30 to 50 percent of twin pregnancies and 75 percent of triplet pregnancies occur after infertility treatment. From the mid-1970s to 1998, the rate of twin pregnancies rose by 50 to 60 percent in England, Wales, France, and the United States. During that period, the rate of triplet or higher order pregnancies rose by 310, 430, and 696 percent in France, England and Wales, and the United States, respectively. In 2000 and 2001, the twin birth rate increased in the United States by 4 and 3 percent, respectively.
Role of maternal age — The rate of multiples increases with increasing maternal age. Although rates of twin births have risen in all maternal age groups in the United States since 1980, the greatest increases occurred in women of advanced maternal age. Between 1990 and 2001, the twin birth rate doubled in 40- to 44-year-old women and increased more than sevenfold in 45- to 49-year-old women. Mechanisms for the increase with maternal age include the greater use of fertility services in this age group and the higher levels of follicle-stimulating hormone with advancing age.
ETIOLOGY OF MULTIPLE BIRTHS — The etiology of MZ twinning is unknown. DZ twinning appears to result from ovulation of multiple follicles.
Elevated follicle-stimulating hormone — The plasma concentration of follicle-stimulating hormone (FSH) is the principal determinant of ovulation and appears to correlate with rates of DZ multiple births.
Plasma concentrations of FSH, luteinizing hormone, and estradiol are higher in women who have had at least one set of DZ twins compared to a control group with no twins. This association also appears to apply to different populations. In two reports, plasma FSH levels were higher in the Nigerian Yorube tribe, which has a high frequency of DZ twins, than in Japanese women who rarely have DZ twins.
Ovarian stimulation — Assisted reproductive technologies stimulate the ovaries with various drugs, such as gonadotropins and clomiphene citrate, to induce ovulation. Depending upon the drug and dose used, the frequency of twins is increased by 5 to 50 percent . In a study from Sweden, for example, ovarian stimulation increased the rates of twins (5.9 versus 1.2 percent) and triplets (0.5 versus 0.02 percent) compared to controls without ovarian stimulation or in vitro fertilization. These increases apply primarily to DZ twins. Some reports also found an increase in MZ twinning, although the mechanism is uncertain.
Clomiphene citrate is the most widely used treatment for fertility enhancement. It exerts its major effects on the hypothalamus, pituitary, ovary, and uterus. Clomiphene citrate binds to hypothalamic estrogen receptors, thereby disrupting the normal feedback inhibition of gonadotropin-releasing hormone (GnRH) and gonadotropin secretion by circulating estrogen. The enhanced gonadotropin secretion stimulates the ovaries, inducing ovulation[/HIDE]