Blastocyst quality and reproductive and perinatal outcomes : a multinational multicentre observational study

Funding H.Z. is supported by a Monash Research Scholarship. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). R.W. is supported by an NHMRC Emerging Leadership Investigator grant (2009767).Peer reviewedPublisher PD

Cdc20 Is Critical for Meiosis I and Fertility of Female Mice

Chromosome missegregation in germ cells is an important cause of unexplained infertility, miscarriages, and congenital birth defects in humans. However, the molecular defects that lead to production of aneuploid gametes are largely unknown. Cdc20, the activating subunit of the anaphase-promoting complex/cyclosome (APC/C), initiates sister-chromatid separation by ordering the destruction of two key anaphase inhibitors, cyclin B1 and securin, at the transition from metaphase to anaphase. The physiological significance and full repertoire of functions of mammalian Cdc20 are unclear at present, mainly because of the essential nature of this protein in cell cycle progression. To bypass this problem we generated hypomorphic mice that express low amounts of Cdc20. These mice are healthy and have a normal lifespan, but females produce either no or very few offspring, despite normal folliculogenesis and fertilization rates. When mated with wild-type males, hypomorphic females yield nearly normal numbers of fertilized eggs, but as these embryos develop, they become malformed and rarely reach the blastocyst stage. In exploring the underlying mechanism, we uncover that the vast majority of these embryos have abnormal chromosome numbers, primarily due to chromosome lagging and chromosome misalignment during meiosis I in the oocyte. Furthermore, cyclin B1, cyclin A2, and securin are inefficiently degraded in metaphase I; and anaphase I onset is markedly delayed. These results demonstrate that the physiologically effective threshold level of Cdc20 is high for female meiosis I and identify Cdc20 hypomorphism as a mechanism for chromosome missegregation and formation of aneuploid gametes

What happens to abnormally fertilized embryos? A scoping review

A dearth of evidence exists on embryos derived from oocytes without two pronuclei (2PN) or ‘normal fertilization’, i.e. embryos arising from non-pronuclear oocytes (0PN), mono-pronuclear oocytes (1PN) and tri-pronuclear oocytes (3PN). We searched the published literature on non-2PN oocytes and their clinical outcomes using a two-part collection strategy of relevant articles. A total of 33 articles were deemed eligible for the scoping review. A significant difference exists between potential development of oocytes with an abnormal number of pronuclei and those with 2PN in most studies; the abnormal pronuclei oocytes occur rarely and significant attrition occurs between day 1 and day 6, with corresponding reduction in chromosome integrity and clinical utility. Most recent studies describe outcomes of blastocysts derived from non-2PN oocytes, rather than cleavage stage embryo transfers. Compared with 2PN oocytes, blastocyst rates are lower in 1PN oocytes (68.3 versus 32.2%), with larger 1PN oocytes having better developmental potential compared with their smaller counterparts. Blastocysts from 1PN oocytes seem to have a slightly reduced implantation potential compared with those from 2PN blastocysts (33.3% versus 35.9%), with a reduced ongoing pregnancy rate (27.3% versus 28.1%). Live birth rates were only reported in 13 of the included studies. The comparators varied between studies, with live birth rates provided ranging from 0–66.7%, with two case reports (100%); this is a clear indication of the variability in practices and the significant heterogeneity of studies. A distinct lack of evidence exists on non-2PN oocytes; however, it seems that most abnormally fertilized oocytes that are non-viable will developmentally arrest in culture, and those that are viable can form viable pregnancies. Concerns remain about the outcome of pregnancies arising from the use of abnormally fertilized oocytes. Coupled with appropriate outcome measures, abnormally fertilized oocytes hold the potential to increase the pool of embryos eligible for transfer