Follicle-Stimulating Hormone Affects Metaphase I Chromosome Alignment and Increases Aneuploidy in Mouse Oocytes Matured in Vitro1

Abstract

Follicle-Stimulating Hormone (FSH) at a wide range of doses is routinely added to culture media during in vitro maturation (IVM) of oocytes, but the effects on oocyte health are unclear. The suggestion that superovulation may cause aneuploidy and fetal abnormalities prompted us to study the potential role of FSH in the genesis of chromosomal abnormalities during meiosis I. Mouse cumulus-oocyte complexes (COCs) isolated from the antral follicles of unprimed, sexually immature B6CBF1 mice were cultured in increasing concentrations of FSH. Following culture, matured oocytes were isolated, spread, stained with DAPI, and the numbers of chromosomes counted. Significantly increased aneuploidy, arising during the first meiotic division, was observed in metaphase II oocytes matured in higher concentrations of FSH (> or =20 ng/ml). The effect of FSH on spindle morphology and chromosome alignment during metaphase I was then explored using immunocytochemistry and three-dimensional reconstruction of confocal sections. High FSH had no effect on gross spindle morphology but did alter chromosome congression during prometaphase and metaphase, with the spread of chromosomes across the spindle at this time being significantly greater in oocytes cultured in 2000 ng/ml compared with 2 ng/ml FSH. Analysis of three-dimensional reconstructions of spindles in oocytes matured in 2000 ng/ml FSH shows that chromosomes are more scattered and farther apart than they are following maturation in 2 ng/ml FSH. These results demonstrate that exposure to high levels of FSH during IVM can accelerate nuclear maturation and induce chromosomal abnormalities and highlights the importance of the judicious use of FSH during IVM.

Patient selection criteria for blastocyst transfers in extended embryo culture programs

“…There is growing evidence in animal studies to support the hypothesis that elevated FSH is an underlying cause of embryo defects [9,10,39]. However, whereas animal studies seem to support an association between FSH exposure and embryonic defects, human studies have been more inconsistent [25,26,31,37,45]. In our study, the FSH dose and the number of retrieved oocytes had a negative impact on the TE quality.…”

Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice

“…In previous studies that reported a low frequency of aneuploidy, one-cell zygotes were obtained from mated females: thus, they underwent meiotic maturation and fertilization in vivo (16,26). However, several studies have shown that when GV-stage oocytes are matured to the MII stage in vitro, aneuploidy is observed in 11-33% of them (27)(28)(29). Moreover, Fraser and Maudlin (16) reported an increased incidence of aneuploidy (Ϸ4.3%) in one-cell zygotes fertilized in vitro compared with those fertilized in vivo (Ϸ1.5%).…”

The impact of ovarian stimulation for IVF on the developing embryo

“…Moreover, when compared to zygotes derived from spontaneous ovulation, mouse zygotes obtained after ovarian stimulation showed an increased rate of chromosomal aberrations in the female pronucleus and compromised embryo development (Vogel & Spielmann 1992). Likewise, in vitro-matured mouse oocytes exposed to high concentrations of FSH showed accelerated nuclear maturation and increased aneuploidy (Roberts et al 2005).…”