Chromosomal abnormality rate in human pre-embryos derived from in vitro fertilization cycles cultured in the presence of Follicular-Fluid Meiosis Activating Sterol (FF-MAS)

Abstract

BACKGROUND: The objective of the study was to investigate the effect of Follicular-fluid meiosis activating sterol (FF-MAS) when added to the culture media on the incidence of chromosomal abnormalities and pre-embryo development in human pre-embryos. METHODS: 243 women undergoing IVF/ICSI treatment donated 353 oocytes in a multicentre, prospective, randomized, double blind, four-arm, controlled trial performed at Danish and Swedish public and private IVF centers. Metaphase II oocytes were randomly assigned to: FF-MAS 5 mM, FF-MAS 20 mM, ethanol 0.2% (vehicle control) or water for injection (inert control). The exposure regimen of FF-MAS to the human oocytes was 4 h prior to fertilization by ICSI and 20 h exposure post ICSI. The primary endpoint was the incidence of numerical chromosomal abnormalities. Secondary endpoints were cleavage rate and pre-embryo quality. RESULT: On the pre-embryo level, no significant differences in chromosomal abnormality rate were observed among the four groups. However, the percentage of uniformly normal pre-embryos was significantly lower in the pooled FF-MAS group (5 mM: 12% and 20 mM: 17%) than in the pooled control group (inert control 32% and vehicle control 42%). A high level of mosaicism (41 -60%) was found in all groups. At the blastomere level, the percentage of blastomeres categorized as normal was significantly lower in the FF-MAS 5 mM group (41%) and the FF-MAS 20 mM (29%) group versus the inert (52%) and the vehicle (61%) groups. Significantly reduced cleavage and good quality pre-embryo rates were found in both FF-MAS groups. CONCLUSION: FF-MAS increased the rate of aneuploidy and had detrimental effects on cleavage and pre-embryo development, when exposed both before and after fertilization.

Principal findings from a multicenter trial investigating the safety of follicular-fluid meiosis-activating sterol for in vitro maturation of human cumulus-enclosed oocytes

“…It should be stressed that if immature oocytes are found in normal IVFs or ICSIs 36 hours after the use of hCG, it means that they have not reacted normally to the hCG trigger, and are perhaps not normally developed. Previous research on immature oocytes collected during IVF and ICSI treatment, and subjected to IVM, showed that developmental competence is lower than in their sibling in vivo-matured oocytes, with a corresponding increased rate of aneuploidy in the blastomeres of the generated embryos (6,7).…”

“…Reports suggest that this new technique remains challenging, and that in many areas, the standard operating procedures still need to be optimized (9). Among the many unresolved issues are: [1] the necessity to pretreat patients with gonadotropins, [2] the target range of follicle diameters to aspirate, [3] the aspiration pressure for oocyte collection, [4] the maturation medium composition, [5] the optimal time for maturation, [6] the time for insemination or sperm injection, and [7] the steroid substitution regimen to prepare a receptive endometrium in the transfer cycle.…”

Reducing CYP51 inhibits follicle-stimulating hormone induced resumption of mouse oocyte meiosis in vitro

“…Our study showed that LH induced CYP51 expression in follicular cells but might not contribute to oocytes maturation; instead, a delayed expression may be related to the cases that MAS improves oocyte cytoplasmic maturation [mouse ( 53,54 ), calf ( 20 ), human ( 55 )] and protects oo-…”

“…The results showed that both FSH and LH upregulated CYP51 expression cytes from precocious chromatins segregation [mouse ( 56 ); and human ( 55,57 )]. Also, CYP51-mediated MAS production is involved in primary follicle formation in fetal ovary and in sperm meiosis in testis ( 8,13,58 ).…”

Effect of rescuing donated immature human oocytes derived after FSH/hCG stimulation following in vitro culture with or without Follicular Fluid Meiosis Activating Sterol (FF-MAS)—an embryo chromosomal and morphological analysis

“…At the time of this study, FF-MAS was only available in an ethanol-based solution. This had been used in other studies with denuded human oocytes [17][18], without any demonstrated negative effect on embryo development or chromosomal status. In the study by Cavilla et al [17] increased maturation and fertilisation rates of denuded human GV oocytes was shown after supplementation with FF-MAS ( in an 0.5% ethanol formulation) to the culture medium.…”