Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-28T02:29:09.790Z Has data issue: false hasContentIssue false
  • English
  • Français

Strategy for embryo transfer to improve pregnancy outcomes in advanced maternal age

Published online by Cambridge University Press:  21 July 2022

Xue Wang Open the ORCID record for Xue Wang [Opens in a new window] ,
Yaling Xiao ,
Zhengyi Sun ,
Jingran Zhen  and
Qi Yu
Xue Wang
Affiliation:
Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yaling Xiao
Affiliation:
Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Zhengyi Sun*
Affiliation:
Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Jingran Zhen
Affiliation:
Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Qi Yu
Affiliation:
Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
*
Author for correspondence: Zhengyi Sun. Department of Gynecology Endocrine and Reproductive Center, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

The purpose of this retrospective study was to optimize the transplantation strategy for women of advanced maternal age to achieve live births within the shortest time. Data were collected from patients older than 40 years who underwent assisted reproductive therapy at our centre from 1 January 2009 to 31 December 2019. In total, 1023 cases of fresh cleavage embryo transfer (CET) cycles, 280 cases of frozen–thawed blastocyst transfer (FBT) cycles, and 26 cases of frozen–thawed CET (FCET) cycles were included. The main outcome was the live birth rate (LBR). The secondary outcomes were the clinical pregnancy rate (CPR) and neonatal outcomes. Multivariable logistic regression was performed to adjust for confounding factors. The blastocyst formation rate of patients older than 40 years was 23.5%, the freezing cycle rate was 19.8%, and the fresh-embryo transfer rate was 83.0%. The implantation rate, CPR, and LBR were significantly different among the CET, FCET, and FBT groups. There were no significant differences in multiple pregnancies and abortion rates among the groups, and neonatal outcomes were similar. Multivariate logistic regression analysis showed that, compared with the CET group, LBR did not increase in the FCET group, whereas LBR increased in the FBT group. For patients older than 40 years when having approximately eight embryos after fertilization, blastocyst transfer can be considered after fully discussing the advantages and disadvantages of blastocyst culture. Alternatively, CET can be performed first, followed by FBT if the cleavage embryo transfer is unsuccessful.

Keywords

Assisted reproductive technologyClinical pregnancyEmbryo transferIn vitro fertilizationLive birth
Type
Research Article
Information
Zygote , Volume 30 , Issue 6 , December 2022 , pp. 781 - 789
Copyright
© The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alfarawati, S., Fragouli, E., Colls, P., Stevens, J., Gutiérrez-Mateo, C., Schoolcraft, W. B., Katz-Jaffe, M. G. and Wells, D. (2011). The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertility and Sterility, 95(2), 520–524. doi: 10.1016/j.fertnstert.2010.04.003 CrossRefGoogle ScholarPubMed
Alhelou, Y., Mat Adenan, N. A. and Ali, J. (2018). Embryo culture conditions are significantly improved during uninterrupted incubation: A randomized controlled trial. Reproductive Biology, 18(1), 40–45. doi: 10.1016/j.repbio.2017.12.003 CrossRefGoogle ScholarPubMed
American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. (2014). Female age-related fertility decline. Committee Opinion No. 589. Fertility and Sterility, 101(3), 633–634. doi: 10.1016/j.fertnstert.2013.12.032 CrossRefGoogle Scholar
Bortoletto, P., Willson, S., Romanski, P. A., Davis, O. K. and Rosenwaks, Z. (2021). Reproductive outcomes of women aged 40 and older undergoing IVF with donor sperm. Human Reproduction, 36(1), 229–235. doi: 10.1093/humrep/deaa286 Google ScholarPubMed
Bosch, E., Bulletti, C., Copperman, A. B., Fanchin, R., Yarali, H., Petta, C. A., Polyzos, N. P., Shapiro, D., Ubaldi, F. M., Garcia Velasco, J. A., Longobardi, S., D’Hooghe, T., Humaidan, P. and Delphi TTP Consensus Group. (2019). How time to healthy singleton delivery could affect decision-making during infertility treatment: A Delphi consensus. Reproductive Biomedicine Online, 38(1), 118–130. doi: 10.1016/j.rbmo.2018.09.019 CrossRefGoogle ScholarPubMed
Bosdou, J. K., Venetis, C. A., Tarlatzis, B. C., Grimbizis, G. F. and Kolibianakis, E. M. (2019). Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: A meta-analysis. Human Reproduction, 34(3), 491–505. doi: 10.1093/humrep/dey388 CrossRefGoogle ScholarPubMed
Broekmans, F. J., Knauff, E. A., te Velde, E. R., Macklon, N. S. and Fauser, B. C. (2007). Female reproductive ageing: Current knowledge and future trends. Trends in Endocrinology and Metabolism, 18(2), 58–65. doi: 10.1016/j.tem.2007.01.004 CrossRefGoogle ScholarPubMed
Coates, A., Kung, A., Mounts, E., Hesla, J., Bankowski, B., Barbieri, E., Ata, B., Cohen, J. and Munné, S. (2017). Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: A randomized controlled trial. Fertility and Sterility, 107(3), 723–730.e3. doi: 10.1016/j.fertnstert.2016.12.022 CrossRefGoogle ScholarPubMed
Coticchio, G., Behr, B., Campbell, A., Meseguer, M., Morbeck, D. E., Pisaturo, V., Plancha, C. E., Sakkas, D., Xu, Y., D’Hooghe, T., Cottell, E. and Lundin, K. (2021). Fertility technologies and how to optimize laboratory performance to support the shortening of time to birth of a healthy singleton: A Delphi consensus. Journal of Assisted Reproduction and Genetics, 38(5), 1021–1043. doi: 10.1007/s10815-021-02077-5 CrossRefGoogle ScholarPubMed
Dar, S., Lazer, T., Shah, P. S. and Librach, C. L. (2014). Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: A systematic review and meta-analysis. Human Reproduction Update, 20(3), 439–448. doi: 10.1093/humupd/dmu001 CrossRefGoogle ScholarPubMed
De Vos, A., Dos Santos-Ribeiro, S., Tournaye, H. and Verheyen, G. (2020). Birthweight of singletons born after blastocyst-stage or cleavage-stage transfer: Analysis of a data set from three randomized controlled trials. Journal of Assisted Reproduction and Genetics, 37(1), 127–132. doi: 10.1007/s10815-019-01641-4 CrossRefGoogle ScholarPubMed
Fang, J., Zhu, L., Li, D., Xu, Z., Yan, G., Sun, H., Zhang, N. and Chen, L. (2018). Effect of embryo and blastocyst transfer on the birthweight of live-born singletons from FET cycles. Journal of Assisted Reproduction and Genetics, 35(10), 1905–1910. doi: 10.1007/s10815-018-1257-7 CrossRefGoogle ScholarPubMed
Gardner, D. K., Lane, M., Stevens, J., Schlenker, T. and Schoolcraft, W. B. (2000). Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertility and Sterility, 73(6), 1155–1158. doi: 10.1016/s0015-0282(00)00518-5 CrossRefGoogle ScholarPubMed
Gleicher, N., Kushnir, V. A. and Barad, D. H. (2015 ). Is it time for a paradigm shift in understanding embryo selection? Reproductive Biology and Endocrinology: RB&E, 13, 3. doi: 10.1186/1477-7827-13-3 CrossRefGoogle ScholarPubMed
Glujovsky, D. and Farquhar, C. (2016). Cleavage-stage or blastocyst transfer: What are the benefits and harms? Fertility and Sterility, 106(2), 244–250. doi: 10.1016/j.fertnstert.2016.06.029 CrossRefGoogle ScholarPubMed
Glujovsky, D., Farquhar, C., Quinteiro Retamar, A. M., Alvarez Sedo, C. R. and Blake, D. (2016). Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database of Systematic Reviews, 6(6), CD002118. doi: 10.1002/14651858.CD002118.pub5 Google Scholar
Kawase, Y., Tachibe, T., Kamada, N., Jishage, K. I., Watanabe, H. and Suzuki, H. (2021). Male advantage observed for in vitro fertilization mouse embryos exhibiting early cleavage. Reproductive Medicine and Biology, 20(1), 83–87. doi: 10.1002/rmb2.12355 CrossRefGoogle ScholarPubMed
Kissin, D. M., Kulkarni, A. D., Mneimneh, A., Warner, L., Boulet, S. L., Crawford, S., Jamieson, D. J. and National ART Surveillance System (NASS) group. (2015). Embryo transfer practices and multiple births resulting from assisted reproductive technology: An opportunity for prevention. Fertility and Sterility, 103(4), 954–961. doi: 10.1016/j.fertnstert.2014.12.127 CrossRefGoogle ScholarPubMed
Levi-Setti, P. E., Cirillo, F., Smeraldi, A., Morenghi, E., Mulazzani, G. E. G. and Albani, E. (2018). No advantage of fresh blastocyst versus cleavage stage embryo transfer in women under the age of 39: A randomized controlled study. Journal of Assisted Reproduction and Genetics, 35(3), 457–465. doi: 10.1007/s10815-017-1092-2 CrossRefGoogle ScholarPubMed
Li, W., Xue, X., Zhao, W., Ren, A., Zhuo, W. and Shi, J. (2017). Blastocyst transfer is not associated with increased unfavorable obstetric and perinatal outcomes compared with cleavage-stage embryo transfer. Gynecological Endocrinology, 33(11), 857–860. doi: 10.1080/09513590.2017.1332175 CrossRefGoogle ScholarPubMed
Liu, J., Zheng, J., Lei, Y. L. and Wen, X. F. (2019). Effects of endometrial preparations and transferred embryo types on pregnancy outcome from patients with advanced maternal age. Systems Biology in Reproductive Medicine, 65(2), 181–186. doi: 10.1080/19396368.2018.1501114 CrossRefGoogle ScholarPubMed
Luna, M., Duke, M., Copperman, A., Grunfeld, L., Sandler, B. and Barritt, J. (2007). Blastocyst embryo transfer is associated with a sex-ratio imbalance in favor of male offspring. Fertility and Sterility, 87(3), 519–523. doi: 10.1016/j.fertnstert.2006.06.058 CrossRefGoogle ScholarPubMed
Maalouf, W. E., Mincheva, M. N., Campbell, B. K. and Hardy, I. C. (2014). Effects of assisted reproductive technologies on human sex ratio at birth. Fertility and Sterility, 101(5), 1321–1325. doi: 10.1016/j.fertnstert.2014.01.041 CrossRefGoogle ScholarPubMed
Maheshwari, A., Kalampokas, T., Davidson, J. and Bhattacharya, S. (2013). Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavage-stage embryos generated through in vitro fertilization treatment: A systematic review and meta-analysis. Fertility and Sterility, 100(6), 1615–21.e1. doi: 10.1016/j.fertnstert.2013.08.044 CrossRefGoogle ScholarPubMed
Marconi, N., Raja, E. A., Bhattacharya, S. and Maheshwari, A. (2019). Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: A retrospective analysis of 67 147 IVF/ICSI cycles. Human Reproduction, 34(9), 1716–1725. doi: 10.1093/humrep/dez133 CrossRefGoogle ScholarPubMed
Minasi, M. G., Colasante, A., Riccio, T., Ruberti, A., Casciani, V., Scarselli, F., Spinella, F., Fiorentino, F., Varricchio, M. T. and Greco, E. (2016). Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: A consecutive case series study. Human Reproduction, 31(10), 2245–2254. doi: 10.1093/humrep/dew183 CrossRefGoogle ScholarPubMed
Murakoshi, Y., Sueoka, K., Takahashi, K., Sato, S., Sakurai, T., Tajima, H. and Yoshimura, Y. (2013). Embryo developmental capability and pregnancy outcome are related to the mitochondrial DNA copy number and ooplasmic volume. Journal of Assisted Reproduction and Genetics, 30(10), 1367–1375. doi: 10.1007/s10815-013-0062-6 CrossRefGoogle Scholar
Papanikolaou, E. G., Camus, M., Kolibianakis, E. M., Van Landuyt, L., Van Steirteghem, A. and Devroey, P. (2006). In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos. New England Journal of Medicine, 354(11), 1139–1146. doi: 10.1056/NEJMoa053524 CrossRefGoogle ScholarPubMed
Papanikolaou, E. G., Kolibianakis, E. M., Tournaye, H., Venetis, C. A., Fatemi, H., Tarlatzis, B. and Devroey, P. (2008). Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis. Human Reproduction, 23(1), 91–99. doi: 10.1093/humrep/dem339 CrossRefGoogle ScholarPubMed
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of Society for Assisted Reproductive Technology. (2013). Criteria for number of embryos to transfer: A committee opinion. Fertility and Sterility, 99(1), 44–46. doi: 10.1016/j.fertnstert.2012.09.038 CrossRefGoogle Scholar
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. (2017). Guidance on the limits to the number of embryos to transfer: A committee opinion. Fertility and Sterility, 107(4), 901–903. doi: 10.1016/j.fertnstert.2017.02.107 CrossRefGoogle Scholar
Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. (2018). Blastocyst culture and transfer in clinically assisted reproduction: A committee opinion. Fertility and Sterility, 110(7), 1246–1252. doi: 10.1016/j.fertnstert.2018.09.011 CrossRefGoogle Scholar
Rienzi, L., Gracia, C., Maggiulli, R., LaBarbera, A. R., Kaser, D. J., Ubaldi, F. M., Vanderpoel, S. and Racowsky, C. (2017). Oocyte, embryo and blastocyst cryopreservation in ART: Systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Human Reproduction Update, 23(2), 139–155. doi: 10.1093/humupd/dmw038 Google ScholarPubMed
Robinson, R. D. (2018). Success rates and pregnancy outcomes in thawed embryos transferred after extended culture: Cryopreserved embryos versus cleavage stage cryopreserved embryos. Fertility and Sterility, 110(1), 59–60. doi: 10.1016/j.fertnstert.2018.04.023 CrossRefGoogle ScholarPubMed
Sfontouris, I. A., Martins, W. P., Nastri, C. O., Viana, I. G., Navarro, P. A., Raine-Fenning, N., van der Poel, S., Rienzi, L. and Racowsky, C. (2016). Blastocyst culture using single versus sequential media in clinical IVF: A systematic review and meta-analysis of randomized controlled trials. Journal of Assisted Reproduction and Genetics, 33(10), 1261–1272. doi: 10.1007/s10815-016-0774-5 CrossRefGoogle ScholarPubMed
Wang, X., Zhen, J., Sun, Z., Yu, Q., Deng, C., Zhou, Y., Wang, H. and He, F. (2016). Effects of fifth day (D5) or sixth day (D6) frozen–thawed blastocysts on neonatal outcomes. Zygote, 24(5), 684–691. doi: 10.1017/S0967199415000696 CrossRefGoogle ScholarPubMed
Wang, X., Du, M., Guan, Y., Wang, B., Zhang, J. and Liu, Z. (2017). Comparative neonatal outcomes in singleton births from blastocyst transfers or cleavage-stage embryo transfers: A systematic review and meta-analysis. Reproductive Biology and Endocrinology: RB&E, 15(1), 36. doi: 10.1186/s12958-017-0255-4 CrossRefGoogle ScholarPubMed
Wei, D., Liu, J. Y., Sun, Y., Shi, Y., Zhang, B., Liu, J. Q., Tan, J., Liang, X., Cao, Y., Wang, Z., Qin, Y., Zhao, H., Zhou, Y., Ren, H., Hao, G., Ling, X., Zhao, J., Zhang, Y., Qi, X., Zhang, L., Deng, X., Chen, X., Zhu, Y., Wang, X., Tian, L-F., Lv, Q., Ma, X., Zhang, H., Legro, R. S. and Chen, Z. J. (2019). Frozen versus fresh single blastocyst transfer in ovulatory women: A multicentre, randomised controlled trial. Lancet, 393(10178), 1310–1318. doi: 10.1016/S0140-6736(18)32843-5 CrossRefGoogle ScholarPubMed
Wong, K. M., Mastenbroek, S. and Repping, S. (2014). Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertility and Sterility, 102(1), 19–26. doi: 10.1016/j.fertnstert.2014.05.027 CrossRefGoogle ScholarPubMed
Zaat, T., Zagers, M., Mol, F., Goddijn, M., van Wely, M. and Mastenbroek, S. (2021). Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database of Systematic Reviews, 2, CD011184. doi: 10.1002/14651858.CD011184.pub3 Google ScholarPubMed
Zhou, Q. W., Jing, S., Xu, L., Guo, H., Lu, C. F., Gong, F., Lu, G. X., Lin, G. and Gu, Y. F. (2018). Clinical and neonatal outcomes of patients of different ages following transfer of thawed cleavage embryos and blastocysts cultured from thawed cleavage-stage embryos. PLOS ONE, 13(11), e0207340. doi: 10.1371/journal.pone.0207340 CrossRefGoogle ScholarPubMed
Zhu, Q., Chen, Q., Wang, L., Lu, X., Lyu, Q., Wang, Y. and Kuang, Y. (2018). Live birth rates in the first complete IVF cycle among 20 687 women using a freeze-all strategy. Human Reproduction, 33(5), 924–929. doi: 10.1093/humrep/dey044 CrossRefGoogle ScholarPubMed