- Email: [email protected]
Reply to the commentary by Professor Gardner on blastocyst culture and transfer
Reproductive BioMedicine Online (2016) 32, 257–258
w w w. s c i e n c e d i r e c t . c o m w w w. r b m o n l i n e . c o m
LETTER Reply to the commentary by Professor Gardner on blastocyst culture and transfer To the Editor We thank Professor Gardner for his commentary “The impact of physiological oxygen during culture and vitrification for cryopreservation on the outcome of extended culture in human IVF” (Gardner, 2015), in response to our article “Should we be promoting embryo transfer at blastocyst stage?” (Maheshwari et al., 2015). We have read the commentary with interest and would like to make the following comments.
Development of the human embryo to the blastocyst stage: all culture systems are not created equal We could not agree more that different centres vary in terms of their culture systems and freezing techniques. However, it is perhaps worth acknowledging that in the context of randomized controlled trials, such variations in practice are expected to be evenly distributed across both arms of the published studies. The data we have presented are based on a contemporary meta-analysis of randomized controlled trials from different parts of the world and therefore likely to be generalizable.
Figure 1
Pregnancy rates and cumulative live birth rates The data quoted in our paper are derived from the published literature. While we appreciate that the use of newer culture systems may lead to better pregnancy rates following blastocyst culture in future randomized trials, such data have yet to be published. Obstetrics and perinatal outcomes Gardner has mentioned the three recent studies (Chambers et al., 2015; Maxwell et al., 2015; Oron et al., 2015) that suggest that there are no differences in obstetric and perinatal outcomes in singleton pregnancies as a result of embryo transfer at cleavage stage when compared with those following blastocyst stage. The studies of Maxwell et al. (2015) and Oron et al. (2015) are based on small numbers (just over 2000 and 3522 singleton pregnancies, respectively) in comparison to those in the published metaanalysis (Maheshwari et al., 2013), which is based on over 75,000 pregnancies. The study of Chambers et al. (2015) was published after our commentary was accepted for publication. We acknowledge that this is based on large numbers from a single continent and shows no difference in the risk of preterm births and small for gestational age babies in singletons, as well as twins from pregnancies as a result of embryo transfer at blastocyst stage compared with
Risk of preterm delivery.
http://dx.doi.org/10.1016/j.rbmo.2015.11.012 1472-6483/© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
258 those at cleavage stage. However, on adding these data to our existing meta-analysis (Maheshwari et al., 2013) the risk of preterm labour is still significantly higher in singleton pregnancies conceived after embryo transfer at blastocyst stage compared with those after cleavage stage, as is shown in Figure 1 (RR 1.18, 95% CI: 1.14–1.21). Role of low oxygen concentration We absolutely take the point that most published data available may have been based on embryo culture not performed in a low oxygen environment. Even in a recent survey (Christianson et al., 2014), less than a quarter of all centres are undertaking the culture of human embryos under physiological conditions. We agree that a high oxygen environment could cause potentially significant levels of oxidative stress to embryos and that we should not be promoting extended culture unless optimal laboratory conditions are available. We look forward to a continued debate on what we believe to be a critical issue in the delivery of safe and effective assisted reproduction. As suggested by ourselves as well as by Chambers et al. (2015), follow-up of offspring of participants in randomized controlled trials will be needed to provide definitive evidence in the years to come.
Letter Christianson, M.S., Zhao, Y., Shoham, G., Granot, I., Safran, A., Khafagy, A., Leong, M., Shoham, Z., 2014. Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey. J. Assist. Reprod. Genet. 31, 1029– 1036. Gardner, D.K., 2015. The impact of physiological oxygen during culture and vitrification for cryopreservation on the outcome of extended culture in human IVF. Reprod. Biomed. Online. doi:10.1016/ j.rbmo.2015.11.008. Maheshwari, A., Kalampokas, T., Davidson, J., Bhattacharya, S., 2013. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavagestage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil. Steril. 100, 1615– 1621, e1–10. Maheshwari, A., Hamilton, M., Bhattacharya, S., 2015. Should we be promoting embryo transfer at blastocyst stage? Reprod. Biomed. Online doi:10.1016/j.rbmo.2015.09.016. Maxwell, S.M., Melzer-Ross, K., McCulloh, D.H., Grifo, J.A., 2015. A comparison of pregnancy outcomes between day 3 and day 5/6 embryo transfers: does day of embryo transfer really make a difference? J. Assist. Reprod. Genet. 32, 249–254. Oron, G., Nayot, D., Son, W.Y., Holzer, H., Buckett, W., Tulandi, T., 2015. Obstetric and perinatal outcome from single cleavage transfer and single blastocyst transfer: a matched case-control study. Gynecol. Endocrinol. 31, 469–472.
References Chambers, G.M., Chughtai, A.A., Farquhar, C.M., Wang, Y.A., 2015. Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand. Fertil. Steril. 104, 997–1003.
b
Abha Maheshwari a, Mark Hamilton a, Siladitya Bhattacharya b a NHS Grampian, Aberdeen, United Kingdom University of Aberdeen, Aberdeen, United Kingdom E-mail address: [email protected]
w w w. s c i e n c e d i r e c t . c o m w w w. r b m o n l i n e . c o m
LETTER Reply to the commentary by Professor Gardner on blastocyst culture and transfer To the Editor We thank Professor Gardner for his commentary “The impact of physiological oxygen during culture and vitrification for cryopreservation on the outcome of extended culture in human IVF” (Gardner, 2015), in response to our article “Should we be promoting embryo transfer at blastocyst stage?” (Maheshwari et al., 2015). We have read the commentary with interest and would like to make the following comments.
Development of the human embryo to the blastocyst stage: all culture systems are not created equal We could not agree more that different centres vary in terms of their culture systems and freezing techniques. However, it is perhaps worth acknowledging that in the context of randomized controlled trials, such variations in practice are expected to be evenly distributed across both arms of the published studies. The data we have presented are based on a contemporary meta-analysis of randomized controlled trials from different parts of the world and therefore likely to be generalizable.
Figure 1
Pregnancy rates and cumulative live birth rates The data quoted in our paper are derived from the published literature. While we appreciate that the use of newer culture systems may lead to better pregnancy rates following blastocyst culture in future randomized trials, such data have yet to be published. Obstetrics and perinatal outcomes Gardner has mentioned the three recent studies (Chambers et al., 2015; Maxwell et al., 2015; Oron et al., 2015) that suggest that there are no differences in obstetric and perinatal outcomes in singleton pregnancies as a result of embryo transfer at cleavage stage when compared with those following blastocyst stage. The studies of Maxwell et al. (2015) and Oron et al. (2015) are based on small numbers (just over 2000 and 3522 singleton pregnancies, respectively) in comparison to those in the published metaanalysis (Maheshwari et al., 2013), which is based on over 75,000 pregnancies. The study of Chambers et al. (2015) was published after our commentary was accepted for publication. We acknowledge that this is based on large numbers from a single continent and shows no difference in the risk of preterm births and small for gestational age babies in singletons, as well as twins from pregnancies as a result of embryo transfer at blastocyst stage compared with
Risk of preterm delivery.
http://dx.doi.org/10.1016/j.rbmo.2015.11.012 1472-6483/© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
258 those at cleavage stage. However, on adding these data to our existing meta-analysis (Maheshwari et al., 2013) the risk of preterm labour is still significantly higher in singleton pregnancies conceived after embryo transfer at blastocyst stage compared with those after cleavage stage, as is shown in Figure 1 (RR 1.18, 95% CI: 1.14–1.21). Role of low oxygen concentration We absolutely take the point that most published data available may have been based on embryo culture not performed in a low oxygen environment. Even in a recent survey (Christianson et al., 2014), less than a quarter of all centres are undertaking the culture of human embryos under physiological conditions. We agree that a high oxygen environment could cause potentially significant levels of oxidative stress to embryos and that we should not be promoting extended culture unless optimal laboratory conditions are available. We look forward to a continued debate on what we believe to be a critical issue in the delivery of safe and effective assisted reproduction. As suggested by ourselves as well as by Chambers et al. (2015), follow-up of offspring of participants in randomized controlled trials will be needed to provide definitive evidence in the years to come.
Letter Christianson, M.S., Zhao, Y., Shoham, G., Granot, I., Safran, A., Khafagy, A., Leong, M., Shoham, Z., 2014. Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey. J. Assist. Reprod. Genet. 31, 1029– 1036. Gardner, D.K., 2015. The impact of physiological oxygen during culture and vitrification for cryopreservation on the outcome of extended culture in human IVF. Reprod. Biomed. Online. doi:10.1016/ j.rbmo.2015.11.008. Maheshwari, A., Kalampokas, T., Davidson, J., Bhattacharya, S., 2013. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavagestage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil. Steril. 100, 1615– 1621, e1–10. Maheshwari, A., Hamilton, M., Bhattacharya, S., 2015. Should we be promoting embryo transfer at blastocyst stage? Reprod. Biomed. Online doi:10.1016/j.rbmo.2015.09.016. Maxwell, S.M., Melzer-Ross, K., McCulloh, D.H., Grifo, J.A., 2015. A comparison of pregnancy outcomes between day 3 and day 5/6 embryo transfers: does day of embryo transfer really make a difference? J. Assist. Reprod. Genet. 32, 249–254. Oron, G., Nayot, D., Son, W.Y., Holzer, H., Buckett, W., Tulandi, T., 2015. Obstetric and perinatal outcome from single cleavage transfer and single blastocyst transfer: a matched case-control study. Gynecol. Endocrinol. 31, 469–472.
References Chambers, G.M., Chughtai, A.A., Farquhar, C.M., Wang, Y.A., 2015. Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand. Fertil. Steril. 104, 997–1003.
b
Abha Maheshwari a, Mark Hamilton a, Siladitya Bhattacharya b a NHS Grampian, Aberdeen, United Kingdom University of Aberdeen, Aberdeen, United Kingdom E-mail address: [email protected]