Are Blastocysts the Answer?

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The routine transfer of cleavage stage embryos to the patient’s uterus on day 2 or 3 has two inherent drawbacks; firstly the embryo does not reside in the uterus at such time, and secondly, up to the 8-cell stage one is observing a cleaving oocyte, in that the majority of embryonic genes have not been activated. Therefore it is not possible to assess true embryonic developmental potential of the conceptus at this time. Consequently the transfer of cleavage stage embryos has been associated with low implantation rates (10-30%). A further problem associated with the transfer of cleavage stage embryo is that in order to attain acceptable pregnancy rates, multiple embryos are routinely transferred to the patient, which in turn frequently culminates in multiple gestations. In the USA, where the national average for the number of embryos transferred is 4, high order multiple gestations are regularly reported. The issue of high order multiple gestations is of concern to all who practice IVF, and has enormous, medical, social and financial implications (Gardner and Schoolcraft, 1998). 

Increasing embryo implantation rates should not only reduce the need to transfer multiple embryos, but should also increase the overall efficacy of an IVF cycle. Over the past decade a resurgence of interest in embryo physiology has led to the formulation of sequential culture media designed to cater for the changing requirements of the embryo as it develops and differentiates (Gardner and Lane, 1997). Such media were specifically designed based on data regarding the physiology of the maternal reproductive tract and embryo. In a prospective randomized trial a significantly higher implantation rate for blastocysts transferred on day 5 (50%), compared to cleavage stage embryos transferred on day 3 (30%), was confirmed in patients with a good response to gonadotropins (Gardner et al., 1998). Subsequently, it has been determined that the quality of the blastocyst formed has a direct impact on pregnancy outcome (Schoolcraft et al., 1999). When a patient has at least one blastocyst with a well developed inner cell mass and trophectoderm, implantation rates of 65% can be achieved. Therefore it is evident that blastocyst culture and transfer can be used to effectively eliminate high order multiple gestations, and perhaps equally as importantly, will lead to the introduction of single embryo transfer, while establishing pregnancy rates of 50% or greater in certain groups of patients. In a retrospective analysis of blastocyst transfer for all patients entering an IVF program, Marek et al., (1999) determined that for all age groups, extended culture and transfer was associated with an increase in implantation and pregnancy rates, while observing a significant decrease in the number of embryos transferred. An important point about this report is that less than 7% of oocyte retrievals resulted in no embryo transfers, compared to 3% no transfers for day 3. Therefore, concerns regarding no transfer after extended culture appears unjustified. To conclude, blastocyst transfer can be used to effectively eliminate high order multiple gestations. Indeed, single blastocyst transfers should now be considered as a routine procedure. In the general patient population, preliminary results indicate that blastocyst transfer does increase the overall efficacy of IVF.

References:

References

GARDNER DK AND LANE M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum. Reprod. Update 3, 367-382, 1997.

GARDNER DK, SCHOOLCRAFT WB, WAGLEY L, ET AL. A prospective randomized trial of blastocyst culture and transfer in in vitro fertilization. Hum. Reprod.13, 3434-3440, 1998.

GARDNER DK AND SCHOOLCRAFT WB. Elimination of high order multiple gestations by blastocyst culture and transfer. In Female Infertility Therapy: Current Practice. Eds. Z Shoham, C Howles and H Jacobs. Martin Dunnitz, London, pp. 267-74, 1998.

MAREK D, LANGLEY M, GARDNER DK, ET AL. Introduction of blastocyst culture and transfer for all patients in an IVF program. Fertil. Steril. December, 1999.

SCHOOLCRAFT WB, GARDNER DK, LANE M, ET AL. Blastocyst culture and transfer: Analysis of results and parameters affecting outcome in two IVF programs. Fertil. Steril. October, 1999.