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The optimal frozen embryo transfer strategy for the recurrent implantation failure patient without blastocyst freezing: thawing day 3 embryos and culturing to day 5 blastocysts

Published online by Cambridge University Press:  16 November 2023

Xiang Li ,
Youman Zeng ,
Juan He ,
Bowen Luo ,
Xiongcai Lu ,
Lingling Zhu ,
Zengyu Yang ,
Fuman Cai ,
Sheng-ao Chen  and
Yudi Luo Open the ORCID record for Yudi Luo [Opens in a new window]
Xiang Li
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Youman Zeng
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Juan He
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Bowen Luo
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Xiongcai Lu
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Lingling Zhu
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Zengyu Yang
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Fuman Cai
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
Sheng-ao Chen
Affiliation:
College of Animal Sciences, Tarim University, Alar, Xinjiang Uygur Autonomous Region 843300, China
Yudi Luo*
Affiliation:
Reproductive Medicine Center, Yulin Maternal and Child Health Care Hospital, Yulin Guangxi 537000, China
*
Corresponding author: Yudi Luo; Email: 506610571@qq.com
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Summary

This study aimed to investigate the optimal frozen embryo transfer (FET) strategy for recurrent implantation failure (RIF) patients with three consecutive failed cleaved embryo implantations and no blastocyst preservation. This retrospective analysis was divided into three groups based on the FET strategy: thawed day 3 embryo transfer (D3 FET group); and extended culture of frozen–thawed day 3 embryos to day 5 blastocysts transfer (D3–D5 FET group); thawed blastocyst transfer (D5 FET group). Transplant cycle data were compared between the three groups. In total, 43.8% of vitrified–thawed cleavage embryos developed into blastocysts. Analysis of the three transplantation strategies showed that, compared with the D3 FET group, D3–D5 had a significantly better hCG-positivity rate and live-birth rate (P < 0.05). Pregnancy outcomes in the D3–D5 FET group and D5 FET group were similar regarding hCG-positivity rate, implantation rate, clinical pregnancy rate, and live-birth rate. Our findings propose two potentially valuable transfer strategies for patients experiencing repeated implantation failures. The D3–D5 FET approach presents a greater potential for selecting promising embryos in cases without blastocyst preservation; however, this strategy does entail the risk of cycle cancellation. Conversely, in instances where blastocyst preservation is an option, prioritizing consideration of the D5 FET strategy is recommended.

Keywords

BlastocystDay 3 embryoFrozen–thawed embryo transferIn vitro embryo cultureRepeated implantation failure
Type
Research Article
Information
Zygote , Volume 31 , Issue 6 , December 2023 , pp. 596 - 604
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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References

Aytac, P. C. and Kilicdag, E. B. (2022). Extended culture of cleavage-stage embryos in vitrified-thawed cycles may be an alternative to frozen and thawed blastocysts during in vitro fertilization. Gynecological Endocrinology, 38(2), 130–134. doi: 10.1080/09513590.2021.1953465 CrossRefGoogle ScholarPubMed
Baltaci, V., Satiroglu, H., Kabukçu, C., Unsal, E., Aydinuraz, B., Uner, O., Aktas, Y., Cetinkaya, E., Turhan, F. and Aktan, A. (2006). Relationship between embryo quality and aneuploidies. Reproductive Biomedicine Online, 12(1), 77–82. doi: 10.1016/s1472-6483(10)60984-4 CrossRefGoogle ScholarPubMed
Benkhalifa, M., Kahraman, S., Biricik, A., Serteyl, S., Domez, E., Kumtepe, Y. and Qumsiyeh, M. B. (2004). Cytogenetic abnormalities and the failure of development after round spermatid injections. Fertility and Sterility, 81(5), 1283–1288. doi: 10.1016/j.fertnstert.2003.09.075 CrossRefGoogle ScholarPubMed
Bosch, E., Labarta, E., Kolibianakis, E., Rosen, M. and Meldrum, D. (2016). Regimen of ovarian stimulation affects oocyte and therefore embryo quality. Fertility and Sterility, 105(3), 560–570. doi: 10.1016/j.fertnstert.2016.01.022 CrossRefGoogle ScholarPubMed
Bosch, E., De Vos, M. and Humaidan, P. (2020). The future of cryopreservation in assisted reproductive technologies. Frontiers in Endocrinology, 11, 67. doi: 10.3389/fendo.2020.00067 CrossRefGoogle ScholarPubMed
Boyard, J., Reignier, A., Chtourou, S., Lefebvre, T., Barrière, P. and Fréour, T. (2022). Should artificial shrinkage be performed prior to blastocyst vitrification? A systematic review of the literature and meta-analysis. Human Fertility, 25(1), 24–32. doi: 10.1080/14647273.2019.1701205 CrossRefGoogle ScholarPubMed
Braude, P., Bolton, V. and Moore, S. (1988). Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature, 332(6163), 459–461. doi: 10.1038/332459a0 CrossRefGoogle ScholarPubMed
Chen, S. L., He, J. X., Song, H. D., Li, S. Z., Liu, X. N., Li, H. and Xing, F. Q. (2007). [Comparison of clinical outcomes of four protocols for frozen–thawed embryo transfer cycle]. Journal of Southern Medical University, 27(3), 303–306.Google ScholarPubMed
Chen, Z. J., Shi, Y., Sun, Y., Zhang, B., Liang, X., Cao, Y., Yang, J., Liu, J., Wei, D., Weng, N., Tian, L., Hao, C., Yang, D., Zhou, F., Shi, J., Xu, Y., Li, J., Yan, J., Qin, Y., et al. (2016). Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 375(6), 523–533. doi: 10.1056/NEJMoa1513873 CrossRefGoogle ScholarPubMed
Chiang, T., Schultz, R. M. and Lampson, M. A. (2012). Meiotic origins of maternal age-related aneuploidy. Biology of Reproduction, 86(1), 1–7. doi: 10.1095/biolreprod.111.094367 CrossRefGoogle ScholarPubMed
Chinese Association of Reproductive Medicine and Professional Committee of Reproductive Medicine, China Medical Women’s Association (2023). Expert consensus on diagnosis and treatment of recurrent implantation failure. Zhonghua Yi Xue Za Zhi, 103(2), 89–100. doi: 10.3760/cma.j.cn112137-20221105-02317 Google Scholar
De Vos, A., Van Landuyt, L., Santos-Ribeiro, S., Camus, M., Van de Velde, H., Tournaye, H. and Verheyen, G. (2016). Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle. Human Reproduction, 31(11), 2442–2449. doi: 10.1093/humrep/dew219 CrossRefGoogle ScholarPubMed
Fauser, B. C. and Devroey, P. (2003). Reproductive biology and IVF: Ovarian stimulation and luteal phase consequences. Trends in Endocrinology and Metabolism, 14(5), 236–242. doi: 10.1016/s1043-2760(03)00075-4 CrossRefGoogle ScholarPubMed
Fragouli, E., Alfarawati, S., Spath, K. and Wells, D. (2014). Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos. Molecular Human Reproduction, 20(2), 117–126. doi: 10.1093/molehr/gat073 CrossRefGoogle ScholarPubMed
Gardner, D. K. and Schoolcraft, W. B. (1999). Culture and transfer of human blastocysts. Current Opinion in Obstetrics and Gynecology, 11(3), 307–311. doi: 10.1097/00001703-199906000-00013 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
Gorrill, M. J., Kaplan, P. F., Patton, P. E. and Burry, K. A. (1999). Initial experience with extended culture and blastocyst transfer of cryopreserved embryos. American Journal of Obstetrics and Gynecology, 180(6 Pt. 1), 1472–1474. doi: 10.1016/s0002-9378(99)70040-2 CrossRefGoogle ScholarPubMed
Hallamaa, M., Seikkula, J., Willman, S., Ollila, H. and Jokimaa, V. (2021). Pregnancy potential and perinatal outcomes of embryos cryopreserved twice: A case-control study. Reproductive Biomedicine Online, 43(4), 607–613. doi: 10.1016/j.rbmo.2021.06.028 CrossRefGoogle ScholarPubMed
Hershko Klement, A., Ovadia, M., Wiser, A., Berkovitz, A., Shavit, T., Nemerovsky, L., Ghetler, Y., Cohen, I. and Shulman, A. (2017). What we learned from extended culture of “rejected” day-3 cleavage stage embryos: A prospective cohort study. Journal of Ovarian Research, 10(1), 35. doi: 10.1186/s13048-017-0332-5 CrossRefGoogle ScholarPubMed
Holden, E. C., Kashani, B. N., Morelli, S. S., Alderson, D., Jindal, S. K., Ohman-Strickland, P. A. and McGovern, P. G. (2018). Improved outcomes after blastocyst-stage frozen-thawed embryo transfers compared with cleavage stage: A society for assisted reproductive technologies clinical outcomes reporting system study. Fertility and Sterility, 110(1), 89–94.e2. doi: 10.1016/j.fertnstert.2018.03.033 CrossRefGoogle Scholar
Kaartinen, N., Das, P., Kananen, K., Huhtala, H. and Tinkanen, H. (2015). Can repeated IVF-ICSI-cycles be avoided by using blastocysts developing from poor-quality cleavage stage embryos? Reproductive Biomedicine Online, 30(3), 241–247. doi: 10.1016/j.rbmo.2014.11.016 CrossRefGoogle ScholarPubMed
Kojima, Y., Tam, O. H. and Tam, P. P. (2014). Timing of developmental events in the early mouse embryo. Seminars in Cell and Developmental Biology, 34, 65–75. doi: 10.1016/j.semcdb.2014.06.010 CrossRefGoogle Scholar
Laverge, H., Van der Elst, J., De Sutter, P., Verschraegen-Spae, M. R., De Paepe, A. and Dhont, M. (1998). Fluorescent in-situ hybridization on human embryos showing cleavage arrest after freezing and thawing. Human Reproduction, 13(2), 425–429. doi: 10.1093/humrep/13.2.425 CrossRefGoogle ScholarPubMed
Le, M. T., Nguyen, T. T. T., Nguyen, T. V., Dang, H. N. T. and Nguyen, Q. H. V. (2021). Blastocyst transfer after extended culture of cryopreserved cleavage embryos improves in vitro fertilization cycle outcomes. Cryobiology, 100, 26–31. doi: 10.1016/j.cryobiol.2021.04.003 CrossRefGoogle ScholarPubMed
Li, B., Huang, J., Li, L., He, X., Wang, M., Zhang, H., He, Y., Kang, B., Shi, Y., Chen, S. and Wang, X. (2021a). Improving the clinical outcomes by extended culture of day 3 embryos with low blastomere number to blastocyst stage following frozen–thawed embryo transfer. Archives of Gynecology and Obstetrics, 303(2), 573–580. doi: 10.1007/s00404-020-05774-1 CrossRefGoogle ScholarPubMed
Li, Y., Liu, S. and Lv, Q. (2021b). Single blastocyst stage versus single cleavage stage embryo transfer following fresh transfer: A systematic review and meta-analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 267, 11–17. doi: 10.1016/j.ejogrb.2021.10.004 CrossRefGoogle ScholarPubMed
Matsumoto, H. (2017). Molecular and cellular events during blastocyst implantation in the receptive uterus: Clues from mouse models. Journal of Reproduction and Development, 63(5), 445–454. doi: 10.1262/jrd.2017-047 CrossRefGoogle ScholarPubMed
Maurer, M., Ebner, T., Puchner, M., Mayer, R. B., Shebl, O., Oppelt, P. and Duba, H. C. (2015). Chromosomal aneuploidies and early embryonic developmental arrest. International Journal of Fertility and Sterility, 9(3), 346–353. doi: 10.22074/ijfs.2015.4550 Google ScholarPubMed
Nothias, J. Y., Majumder, S., Kaneko, K. J. and DePamphilis, M. L. (1995). Regulation of gene expression at the beginning of mammalian development. Journal of Biological Chemistry, 270(38), 22077–22080. doi: 10.1074/jbc.270.38.22077 CrossRefGoogle ScholarPubMed
Ozturk, S. (2023). Genetic variants underlying developmental arrests in human preimplantation embryos. Molecular Human Reproduction, 29(8). doi: 10.1093/molehr/gaad024 CrossRefGoogle ScholarPubMed
Practice Committee of the American Society for Reproductive Medicine. (2017). Performing the embryo transfer: A guideline. Fertility and Sterility, 107(4), 882–896. doi: 10.1016/j.fertnstert.2017.01.025 CrossRefGoogle Scholar
Quinn, P. and Kerin, J. F. (1986). Experience with the cryopreservation of human embryos using the mouse as a model to establish successful techniques. Journal of In Vitro Fertilization and Embryo Transfer, 3(1), 40–45. doi: 10.1007/BF01131379 CrossRefGoogle Scholar
Rahav-Koren, R., Inbar, S., Miller, N., Wiser, A., Yagur, Y., Berkowitz, C., Farladansky-Gershnabel, S., Shulman, A. and Berkowitz, A. (2021). Thawing day 3 embryos and culturing to day 5 may be a better method for frozen embryo transfer. Journal of Assisted Reproduction and Genetics, 38(11), 2941–2946. doi: 10.1007/s10815-021-02321-y CrossRefGoogle ScholarPubMed
Saravelos, S. H. and Li, T. C. (2019). Embryo transfer techniques. Best Practice and Research. Clinical Obstetrics and Gynaecology, 59, 77–88. doi: 10.1016/j.bpobgyn.2019.01.004 CrossRefGoogle ScholarPubMed
Sfakianoudis, K., Maziotis, E., Karantzali, E., Kokkini, G., Grigoriadis, S., Pantou, A., Giannelou, P., Petroutsou, K., Markomichali, C., Fakiridou, M., Koutsilieris, M., Asimakopoulos, B., Pantos, K. and Simopoulou, M. (2021). Molecular drivers of developmental arrest in the human preimplantation embryo: A systematic review and critical analysis leading to mapping future research. International Journal of Molecular Sciences, 22(15). doi: 10.3390/ijms22158353 CrossRefGoogle ScholarPubMed
Sik, A., Oral, S., Aba, Y. A., Ozolcay, O., Koc, M. and Sismanoglu, A. (2020). Pregnancy results after fresh embryo transfer and selective frozen–thawed embryo transfer: Single-center experience. Journal of Gynecology Obstetrics and Human Reproduction, 49(4), 101707. doi: 10.1016/j.jogoh.2020.101707 CrossRefGoogle ScholarPubMed
Sozen, B., Can, A. and Demir, N. (2014). Cell fate regulation during preimplantation development: A view of adhesion-linked molecular interactions. Developmental Biology, 395(1), 73–83. doi: 10.1016/j.ydbio.2014.08.028 CrossRefGoogle ScholarPubMed
Stern, C. and Agresta, F. (2019). Setting up a fertility preservation programme. Best Practice and Research. Clinical Obstetrics and Gynaecology, 55, 67–78. doi: 10.1016/j.bpobgyn.2018.07.007 CrossRefGoogle Scholar
Truong, T. T. and Gardner, D. K. (2020). Antioxidants increase blastocyst cryosurvival and viability post-vitrification. Human Reproduction, 35(1), 12–23. doi: 10.1093/humrep/dez243 CrossRefGoogle ScholarPubMed
Vanneste, E., Voet, T., Le Caignec, C., Ampe, M., Konings, P., Melotte, C., Debrock, S., Amyere, M., Vikkula, M., Schuit, F., Fryns, J. P., Verbeke, G., D’Hooghe, T., Moreau, Y. and Vermeesch, J. R. (2009). Chromosome instability is common in human cleavage-stage embryos. Nature Medicine, 15(5), 577–583. doi: 10.1038/nm.1924 CrossRefGoogle ScholarPubMed
Vinsonneau, L., Labrosse, J., Porcu-Buisson, G., Chevalier, N., Galey, J., Ahdad, N., Ayel, J. P., Rongières, C., Bouet, P. E., Mathieu d’Argent, E., Cédrin-Durnerin, I., Pessione, F. and Massin, N. (2022). Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: A large multicenter cohort study (14 421 frozen cycles). Human Reproduction Open, 2022(2), hoac007. doi: 10.1093/hropen/hoac007 CrossRefGoogle ScholarPubMed
Walsh, A. P., Shkrobot, L. V., Coull, G. D., Peirce, K. L., Walsh, D. J., Salma, U. and Sills, E. S. (2009). Blastocyst transfer for multiple prior IVF failure: A five year descriptive study. Irish Medical Journal, 102(9), 282–285.Google ScholarPubMed
Wang, B., Sun, H. X., Wang, J. X., Zhang, N. Y. and Hu, Y. L. (2010). Pregnancy outcomes of repeated cycles of in vitro fertilization and embryo transfer. Zhonghua Nan Ke Xue, 16(11), 1007–1011.Google ScholarPubMed
Wang, M., Jiang, J., Xi, Q., Li, D., Ren, X., Li, Z., Zhu, L. and Jin, L. (2021a). Repeated cryopreservation process impairs embryo implantation potential but does not affect neonatal outcomes. Reproductive Biomedicine Online, 42(1), 75–82. doi: 10.1016/j.rbmo.2020.11.007 CrossRefGoogle Scholar
Wang, N., Zhao, X., Ma, M., Zhu, Q. and Wang, Y. (2021b). Effect of Day 3 and Day 5/6 embryo quality on the reproductive outcomes in the single vitrified embryo transfer cycles. Frontiers in Endocrinology, 12, 641623. doi: 10.3389/fendo.2021.641623 CrossRefGoogle ScholarPubMed
Wang, Y., Tian, Y., Liu, L., Li, T. C., Tong, X., Zhu, H. and Zhang, S. (2021c). The number of previous failed embryo transfer cycles is an independent factor affecting implantation rate in women undergoing IVF/ICSI treatment: A retrospective cohort study. Medicine (Baltimore), 100(9), e25034. doi: 10.1097/MD.0000000000025034 CrossRefGoogle ScholarPubMed
Yu, X. J., Yi, Z., Gao, Z., Qin, D., Zhai, Y., Chen, X., Ou-Yang, Y., Wang, Z. B., Zheng, P., Zhu, M. S., Wang, H., Sun, Q. Y., Dean, J. and Li, L. (2014). The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics. Nature Communications, 5, 4887. doi: 10.1038/ncomms5887 CrossRefGoogle ScholarPubMed
Zhang, X., Gao, Y., Liu, W., Liu, J., Wu, L., Xiong, S., Zhu, J., Han, W., Wang, J., Hao, X., Han, S. and Huang, G. (2021). Frozen blastocyst embryo transfer vs. frozen cleavage-stage embryo transfer in couples with recurrent implantation failure: A cohort study. Human Fertility, 24(4), 284–289. doi: 10.1080/14647273.2019.1633021 CrossRefGoogle ScholarPubMed