Markers of Viability

With the routine use of exogenous gonadotropins to stimulate the production of multiple oocytes, clinics are faced with the daily decision of which of the resulting embryos to replace in the mother and which to cryopreserve. There is therefore an obvious clinical need to be able to select those embryos most likely to implant after replacement in the uterus. Methods of predicting and quantifying embryo viability have been discussed extensively (Gardner and Leese, 1999). Parameters for consideration include assessment of morphology, development in culture, production of platelet activating factor, production of human chorionic gonadotropin, enzyme leakage, oxygen uptake measurements, and nutrient uptake measurements. The ability to predict whether an embryo will develop in culture has been associated with rate of cleavage in animal studies (McKiernan and Bavister, 1994). It was observed that the speed at which an embryo developed was related to its ability to form a blastocyst. Furthermore, morulae and blastocysts which developed from slowly dividing embryos gave rise to lower fetal development after transfer than those embryos which developed from more rapidly dividing cleavage stages (McKiernan and Bavister, 1994). Similarly, Shoukir et al., (1998) have observed that those embryos forming blastocyst earlier are the more viable. (Scott and Smith, 1998) have determined that pronuclear embryo morphology can be used to select embryos for transfer. A potential criterion for the quantification of embryo viability is energy metabolism, which can be readily measured non-invasively for individual embryos in culture (Gardner and Leese, 1999). Lane and Gardner (1996) used both glucose uptake and lactate production (to estimate glycolytic activity) to select prospectively individual day-4 mouse blastocysts for transfer. Prior to any transfers the hypothesis developed was that the most viable embryos would be the ones with a glycolytic activity closest to that observed for embryos developed in vivo, around 50%. Therefore those embryos exhibiting excessive lactate production were proposed to be non-viable i.e. they had lost control over their energy metabolism. When morphologically identical blastocysts were selected at random for transfer, resultant fetal development was 20% per blastocyst transferred. However, when blastocysts were prospectively selected with a glycolytic activity similar to in vivo developed blastocysts, the resultant fetal development rate was 80%, a 4-fold increase over random selection. In contrast, those blastocysts with an abnormally elevated glycolytic activity had a fetal development rate of only 6%. Such data therefore supports the hypothesis that it is possible to select embryos for transfer using metabolic criteria. This hypothesis warrants further investigation in clinics performing single blastocyst transfers. Interestingly, the quality of human blastocysts, as assessed using the development of the inner cell mass and trophectoderm, can be used successfully to identify those embryos with an implantation rate of over 65%. Other markers of blastocyst function such as hCG and PAF production prior to transfer also warrant further study. In conclusion, there are several parameters that can be used in order to predict or quantitate embryo viability. It is envisaged that not one but two or more approaches will be most effective in identifying those embryos most likely to give rise to a viable pregnancy, culminating in single embryo transfers.

References:

References

GARDNER DK AND LEESE HJ. Assessment of embryo metabolism and viability. In Handbook of In Vitro Fertilization, Second Edition. Eds. A Trounson and DK Gardner. CRC Press, Boca Raton, pp 347-372, 1999.

LANE M AND GARDNER DK. Selection of viable mouse blastocysts prior to transfer using a metabolic criterion. Hum. Reprod. 11, 1975-1978, 1996.

MCKIERNAN SH AND BAVISTER BD. Timing of development is a critical parameter for predicting successful embryogenesis. Hum. Reprod. 9, 2123-2129, 1994.

SCOTT LA AND SMITH S. The successful use of pronuclear embryo transfers the day following oocyte retrieval. Hum. Reprod. 13, 1003-1013, 1998.

SHOUKIR Y, CHARDONNENS D, CAMPANA A, ET AL. The rate of development and time of transfer play different roles in influencing the viability of human blastocysts. Hum. Reprod. 13, 676-81, 1998.