Familial twinning and fertility traits were investigated in Nigerian mothers of dizygotic (DZ) twins (MoDZT; N = 972) and controls (N = 525) who responded to our person-to-person interview, which included questions on pregnancy history and family history of DZ twinning. Controls were defined as women who are not twins themselves and do not have twins in their first-degree relatives. Over 95% of the participants were Yoruba. We found that Nigerian MoDZT had an average of 4.0 (±2.6) pairs of twins among their relatives, and of these, the prevalence of DZ twins was significantly higher than that of monozygotic (MZ) twins (45.9% vs. 25.8%). Controls had an average of 0.5 (±0.4) pairs, and over 95% of the controls had no twins in their relatives. These results suggest genetic influences on DZ twinning in Nigerians. MoDZT were significantly younger in their mean age at first child, and had higher parity than controls, suggesting increased fertility in MoDZT. As compared to mothers with a single set of twins, mothers (N = 130) with multiple sets had significantly more twins among their relatives (5.4 pairs vs. 3.7 pairs) and had their first twins at a younger age (28.4 vs. 30.7 years), indicating that mothers with multiple sets of twins might have higher genetic propensity for twinning associated with earlier age at twin pregnancy. Our findings argue for genomewide association studies for DZ twinning in Nigerians, and may help to develop intervention strategies to overcome infertility/subfertility problems.

Theorems, proofs, laws and rules are commonly named according to the presumed investigator, but often earlier investigators have contributed substantially to the findings. One example of this is Hellin's law, which was named after Hellin, although he was not the first to discover it. In research on twinning and higher multiple maternities, the law has played a central role because it is approximately correct, despite showing discrepancies that are difficult to explain or eliminate. Several improvements to this law have been proposed. In this study, we re-examine some old papers to provide an overview of the scientists who have contributed to the genesis and the improvements of this law. In addition, we consider more recent contributions in which Hellin's law has been discussed and evaluated. It has been mathematically proven that Hellin's law does not hold as a general rule. However, most studies are based on empirical rates of multiple maternities, ignoring random errors. Such studies can never confirm the law, but only serve to identify errors too large to be characterized as random.

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.

It is generally held that there are genetic factors for dizygotic (DZ) twinning, but the pattern of inheritance is far from clear.

We report on a rare pedigree with three sets of spontaneous DZ female twin births in three successive generations. To our knowledge no similar pedigrees have been reported in literature.

Zygosity determination in three pairs of twins was performed with ABO, MN and Rh blood groups from erythrocytes and with STR analysys from samples of saliva.

In our pedigree, the direct trasmission of the DZ twinning through the maternal line seems show an autosomal dominant pattern of inheritance. We believe that the inheritance of DZ twinning appears to be recessive in most case and autosomal dominant only in rare instances. It is plausible with the hypothesis that the expression of the dizygotic twinning trait in a mother shows a genetic heterogeneity.

We wished to establish the frequency, regularity and laterality of multiple ovulation in mothers of dizygotic (DZ) twins and controls. Subjects had regular menses and were not using oral contraceptives. Ovarian ultrasound scans were taken over a number of cycles in 21 mothers of DZ twins and 18 controls (including 13 mothers of monozygotic [MZ] twins). Multiple large follicles (≥ 12 mm diameter) were seen significantly more frequently in mothers of DZ twins (13/21 mothers, 24/77 cycles, average ± SE follicles/cycle 1.34 ± 0.11) than controls (2/18 mothers, 3/31 cycles, average 1.10±0.08). Both ipsilateral and contralateral multiple follicles were observed. In one case a mother of DZ twins showed multiple large follicles in 7 out of 10 cycles in which she was scanned, including both ipsi-and contralateral patterns of occurrence.

Serum gonadotropin, estradiol, prolactin and alpha-1-antitrypsin levels were measured in the first four days of the menstrual cycle in 14 women who were cycling normally. FSH, and to a lesser extent LH levels, were significantly higher in a group of 8 women who had at least one set of DZ twins (6 of whom had 2 sets) than in a control group of 6 women with no DZ twins. Estradiol levels also tended to be higher in mothers of twins but there were no significant differences in prolactin or alpha-1-antitrypsin concentrations. There were no differences between the means of the two groups in age, height, weight or number of pregnancies.

The comparison of 622 twin and 622 singleton births allowed us to confirm the association of dizygotic twinning with maternal age, parity, and maternal weight and height, as well as the occurrence of unlike-sex twins in the mother's family. It was also shown that none of these associations, except for maternal height, can be explained by the others. Dizygotic twinning was also found to be negatively correlated with previous use of oral contraceptives and with irregularity of menstrual cycle. Finally, the relationship between spontaneous abortion in previous pregnancies and maternal exposure to medical irradiation was investigated.

Weinberg's differential method, whereby the frequency of dizygotic twins in a population is obtained by doubling the number of opposite-sexed pairs, might not be valid. Data are presented indicating a higher frequency of same-sexed than opposite-sexed pairs among samples of dizygotic twins ascertained at birth, thus favoring the hypothesis that, contrary to the method's fundamental assumption, the sexes of the two twin zygotes be not independent.