The effects of meiosis activating sterol on in-vitro maturation and fertilization of human oocytes from stimulated and unstimulated ovaries

Abstract

The object of this study was to assess functional maturation in vitro by obtaining data on the fertilization and embryonic competence of human oocytes with or without exposure to meiosis activating sterol (MAS) during maturation in vitro. Immature oocytes were either collected from unstimulated patients with polycystic ovaries (PCO) during gynaecological surgery, or were donated by patients undergoing a cycle of intracytoplasmic sperm injection (ICSI) treatment including ovarian stimulation with gonadotrophins. PCO oocytes had variable cumulus cover, which was retained during culture while those from ICSI patients were cultured without cumulus. The study included 119 oocytes from PCO patients and 72 from ICSI patients. The oocytes were allowed to mature in vitro for up to 46 h in the presence or absence of MAS. Mature oocytes were inseminated by ICSI with fertile donor spermatozoa and embryo development was monitored in vitro. MAS (30 microg/ml) significantly increased the survival of oocytes from PCO patients (P < 0.01) but did not significantly affect the proportion completing maturation in vitro. For the ICSI patients, >90% of oocytes survived in all culture groups, regardless of MAS addition, however MAS (10 or 30 microg/ml) significantly increased the proportion of oocytes maturing in vitro (P < 0.05). The apparent tendency towards improved subsequent development in vitro will require larger numbers of oocytes for evaluation. Oocytes from ICSI patients matured more rapidly in vitro than those from PCO patients. Our results show positive effects of MAS on human oocytes, confirming previous data in mice. This work may have implications for the future clinical application of IVM.

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)

“…Furthermore, FF-MAS mediated matured oocytes were found to have a significantly increased degree of cytoplasmic maturation and increased synchrony between nuclear and cytoplasmic maturation (Gröndahl et al, 1999). It has also been found that MAS had positive effects on immature human oocytes retrieved both from unstimulated PCO patients and from patients undergoing ICSI (Cavilla et al, 2001). A recent parallel study (Loft et al, 2004) with a similar design as the present study investigated the effect of FF-MAS on cumulus enclosed oocytes.…”

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.…”

“…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. However, in a recent similar study by Loft et al (2004), where cumulus-enclosed oocytes were used, it was found that the ethanol control group had a significantly lower number of chromosomally normal blastomeres than the inert control group [19].…”

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

“…Byskov et al ( 12 ) purifi ed and identifi ed the sterols from women's follicle fl uid and cattle's testis and nominated them as follicular fl uid derived-meiosis activating sterol and testis-meiosis activating sterol. Follicular fl uid derived-meiosis activating sterol, a direct product of lanosterol 14 ␣ -demethylase (CYP51) ( 13 ), had a dose-dependent effect on stimulating germinal vesicle breakdown (GVBD) in rodent, bovine, and human meiotically arrested oocytes ( 3,4,(14)(15)(16)(17)(18)(19)(20).To better understand the mechanism by which gonadotrophin employs CYP51-mediated sterol as the downstream signal to induce oocytes meiosis, many chemicals, such as Abstract Meiosis activating sterol, produced directly by lanosterol 14-␣ -demethylase (CYP51) during cholesterol biosynthesis, has been shown to promote the initiation of oocyte meiosis. However, the physiological signifi cance of CYP51 action on oocyte meiosis in response to gonadotrophins' induction remained to be further explored.…”

“…Byskov et al ( 12 ) purifi ed and identifi ed the sterols from women's follicle fl uid and cattle's testis and nominated them as follicular fl uid derived-meiosis activating sterol and testis-meiosis activating sterol. Follicular fl uid derived-meiosis activating sterol, a direct product of lanosterol 14 ␣ -demethylase (CYP51) ( 13 ), had a dose-dependent effect on stimulating germinal vesicle breakdown (GVBD) in rodent, bovine, and human meiotically arrested oocytes ( 3,4,(14)(15)(16)(17)(18)(19)(20).…”