The control of ovulation in mothers of dizygotic twins.

Abstract

Dizygotic twinning is familial, suggesting that there may be an inherited abnormality of the control of ovulation that predisposes to double ovulation and, therefore, dizygotic twins. The present study examines 17 mothers of dizygotic twins (MODZT) and 8 control mothers of singletons by daily blood sampling throughout an entire menstrual cycle. Blood samples were assayed for LH, FSH, estradiol, progesterone, and inhibin. The process of follicular development was followed by transvaginal ultrasound. The pituitary LH response to iv GnRH was also assessed. Three of the 16 MODZT double ovulated during the study compared to none of the 8 control mothers (P< 0.05). The number of small follicles (<6 mm) declined significantly in control women at midcycle, but not in MODZT. There was no significant difference in serum FSH, LH, estradiol, or inhibin levels between the 2 groups at any stage of the menstrual cycle. During the follicular phase, serum progesterone levels were significantly higher in MODZT. The response to GnRH stimulation was not different between MODZT and controls. In conclusion, this study demonstrates an increased tendency to double ovulate in MODZT that may be due to a reduced rate of atresia in advanced follicles. Furthermore, the elevated progesterone levels in MODZT during the follicular phase suggest altered intrafollicular steroidogenesis that is independent of gonadotropins.

Genome-wide linkage scan for spontaneous DZ twinning

“…With the exception of chorionic gonadotropin alpha chain (FSHA) on chromosome 6, our data were not in favour of linkage of the genes in the FSH pathway, 15 Our results demonstrating DZ twinning is inherited as a dominant model contradicted the sex-limited recessive model with a gene frequency of 0.50 and a penetrance of 0.05 suggested previously. 4,13 We therefore reanalysed our data using this model of inheritance, but could not find any positive 2-point LOD score higher than what was found with the dominant model.…”

“…Mothers of spontaneous DZ twins have a higher incidence of multiple ovulations and several studies report an increased concentration of folliclestimulating hormone (FSH) during their menstrual cycle. 15,16 FSH release is controlled by a complex feedback mechanism from the ovary. Genes in the pathway controlling the synthesis, release and activity of FSH are therefore good candidates for increased DZ twinning frequencies.…”

A Deletion Mutation in GDF9 in Sisters with Spontaneous DZ Twins

“…Women with a history of dizygotic (DZ) twinning have an increased incidence of multiple follicle growth and multiple ovulation (Gilfillan et al, 1996;Martin et al, 1991). Current models suggest multiple ovulation is controlled by both endocrine and paracrine factors (Baird, 1983;Baird & Campbell, 1998;Baker & Spears, 1999;Campbell et al, 1995;Macklon & Fauser, 2000).…”

Ovarian Reserve and Anti-Mullerian Hormone (AMH) in Mothers of Dizygotic Twins

“…In mothers of DZ twins who come from families with multiple twins, elevated FSH in the early follicular phase is also a characteristic feature (Lambalk et al, 1998b;Martin et al, 1991b;Thomas et al, 1998). In general, with familial dizygotic twinning, no clear indication for advanced ovarian aging has been found (Gilfillan et al, 1996), although it has been hypothesized that familial twinning may occur via a hereditary mechanism similar to that of advanced ovarian aging (te Velde et al, 1998), which could imply that DZ twinning is associated with earlier menopause. So advanced biological aging may be responsible for the multiple follicle growth in familial twinning along mechanisms identical to that in normally aging women (Lambalk et al, 2009).…”