Given the risks associated with twin/triplet pregnancies, a critical question is: at which developmental stage should we transfer a single embryo to have the best chance of achieving a healthy pregnancy with a single offspring? The best single embryo transfer pregnancy rate will be accomplished when transferring embryos associated with the highest implantation rate. To date, the highest published implantation rates have resulted from transferring blastocysts. Cleavage-stage embryos are essentially a “promise” of an embryo, cleaving under the direction and support of proteins, nutrients and messenger RNA packed into the egg during earlier growth and maturation processes. Experience in the laboratory suggests that due to genetic and metabolic deficiencies, on average, only 20% of IVF embryos will convert to viable implantations. In contrast, a blastocyst with a verifiable inner cell mass (ICM) has demonstrated activation of the embryonic genome and some initial metabolic competency. Therefore, the transfer of one proven blastocyst instead of a single unproven cleavage-stage embryo should be much more likely to result in a healthy baby.
Elective single blastocyst transfer (SBT) mandates a complimentary blastocyst cryopreservation program. Blastocyst culture and subsequent SBT have been discouraged, in part, by less than acceptable blastocyst cryopreservation outcomes. Fortunately, the embryology laboratory of the Frisco Institute for Reproductive Medicine has been able to achieve some of the highest take home baby rates from frozen-thawed blastocysts (consistently >50%).
Excellent live-birth rates can be realized when transferring two blastocysts obtained in an optimized blastocyst culture system. Optimization may include incubation in physiological sequential culture media, culturing at a reduced oxygen concentration using appropriate equipment at all stages of gamete and embryo manipulation and practicing vigorous quality management. In an investigation of more than 1000 patients, the clinical and cryopreservation outcomes were compared for patients with two good quality embryos for transfer on day five and patients not having at least two good quality embryos (Meintjes et al., 2002)(Table 1). Two patient populations were identified as having a high risk for twins: young patients (≤34 years) and patients using donor oocytes. The lowest implantation rate (51.1%) was obtained in young patients not having at least two quality blastocysts for transfer and the highest (75.5%) in patients using donor oocytes with at least two quality blastocysts for transfer. Even though these implantation- and pregnancy rates were considered excellent, the resulting high twin implantation rates between 52% and 77% are to be considered unacceptable.
It has been well established that twin pregnancies are not benign, but that it poses significant risks to the mother and babies; furthermore, multiple births have a significant financial and psychological impact on the prospective parents, their families, the healthcare industry and society in general. With the rate of blastocyst cryopreservation (37% to 67%) observed in this study population, it became clear that the threshold to act should no longer be to contain triplet pregnancies, but rather to reduce twin pregnancies in this high-risk target population by transferring a single blastocyst.
To reduce the risk of twins, SBT was offered to patients ≤37 years of age and to patients using donor oocytes (Meintjes et al., 2004). A SBT was offered only at the time of transfer if at least two quality blastocysts were available for transfer. This resulted in a 100% day-5 cryopreservation rate following the SBT. A total of 103 patients accepted a SBT. 187 refused and insisted on the transfer of two quality blastocysts. Implantation rates were not different for SBT (73.8%) and two-blastocyst transfers (71.2%). The initial live-birth rate for two-blastocyst transfers was higher than that for SBT (79.0% and 70.9%, respectively). However, when accounting for additional frozen-thawed blastocyst transfers, the live birth rate was not different for the two-blastocyst- and SBT transfer group (83.4% and 79.6%, respectively). The twin implantation rate was reduced from 67.8% when transferring two blastocysts to 2.4% (two monozygotic twins) for SBT.It became apparent that the two main reasons for insisting on two blastocysts for transfer were a lack of appreciation for the risk inherent to carrying and delivering twins and an understandable dread of incurring the additional expense related to a subsequent thawed cycle, should the SBT fail to result in a live-born baby. For this reason, the Frisco Institute for Reproductive Medicine offers a financial incentive program to patients wishing to transfer a single blastocyst.