**2. Importance**

The number of twins has doubled and the rate of twin births has risen from 18.9 to 33.2 per 1, 000 births in the United States. Recent data brief from the National Center for Health Statistics states that one in every 30 infants born in 2009 was a twin. Twin birth rates increased in all US states from 1980 to 2009, mainly among non-Hispanic white mothers and women aged 40 and over, which demonstrated the largest increase by more than 200 percent as shown in Figure 1 [6].

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Source: CDC/NCHS, National Vital Statistics System [6]

**Figure 1.** Twin birth rates, by age of mother. United States, 1980 and 2009.

A consistent growth in the number of multiple births in England has also been well docu‐ mented [7]. Analysis from the North of England Multiple Pregnancy Register during 1998 and 2002 showed an increasing twinning rate of 13.6 to 16.6 per 1, 000 maternities [8]. Similarly, secular changes in twinning rates were demonstrated by previous study, in which 15 out of 17 European countries listed significant increasing proportions between 1972 and 1996 [9]. Records from the Danish National Birth Cohort revealed an overall frequency of twin deliv‐ eries of 22 per 1000 [10].

Over the last 20 years in Japan, the incidence of twin births increased until 2003, when it started to decrease reaching similar rates to those registered in the 1990s [11]. The reported Chinese twinning rates range from 2.8 to 15.4 per 1000 births. This wide variation may be explained by the lack of systematic vital records [12]. Historically, the lowest twinning rates are registered in Asian countries (5-6 per 1000 maternities), and the highest rates are seen in Sub-Saharan-Africa (23 per 1000 maternities), notably Nigeria, with rates up to 40 per 1000 births [13].

The average rate of twin births in Brazil is 10 per 1000. Cândido Godói is a modest town in South Brazil universally known as "Twins' Town", considering its twinning rate of 2% and an estimated rate of 10% in the very small district of Linha São Pedro. It was hypothesized that such a high rate of twin births could be due to Nazi's experiments commanded by Joseph Mengele in the 1960s. Recent data suggest that this phenomenon is much better explained by a genetic founder effect [14].

There is a global tendency of an increased number of multiple gestations, with the exception of triplets and higher-order multiple gestations [15]. This fact was largely attributed to an elevated amount of dizygotic pregnancies, without significant variations in monozygotic births over the past few decades [4]. The dizygotic twinning rate is affected by innumerous factors such as race, parental consanguinity, maternal age and parity, lifestyle, season, use of fertility drugs and treatments, genetics and others [4, 5, 12].

Currently, it is very difficult to estimate trends in spontaneous twinning regardless of the use of fertility treatments [4]. Assisted reproductive technology has played a major role in multiple birth rates, especially after the 1980s. Evidences indicate that 30-50% of twins and at least 75% of triplets occur after infertility treatment. Therefore, several physicians and reproductive medicine societies have recommended rigorous strategies for reducing the risk of multiple pregnancies, like single-embryo transfer [16].
