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Reproductive outcomes with delayed blastocyst development: the clinical value of day 7 euploid blastocysts in frozen embryo transfer cycles
Published online by Cambridge University Press: 13 November 2023
Summary
Embryos of optimal development reach blastocyst stage 116 ± 2 h after insemination. Usable D7 blastocysts represent nearly 5% of embryos in IVF with acceptable pregnancy and live birth rates, however data are still limited. Therefore, this study aimed to analyze the ongoing pregnancy rate (OPR) of D7 blastocysts in single euploid frozen embryo transfer (FET) cycles. An observational study was performed including 1527 FET cycles with blastocysts biopsied on D5 (N = 855), D6 (N = 636) and D7 (N = 36). Blastocysts were classified as good (AA/AB/BA), fair (BB) or poor (AC/BC/CC/CA/CB) (Gardner scoring). FETs were performed in natural cycles (NC) or hormone replacement therapy (HRT) cycles. Patient’s age differed significantly between D5, D6 and D7 blastocysts FET cycles (33.2 ± 5.6, 34.4 ± 5.3 and 35.9 ± 5.2, P < 0.001). OPRs were higher when D5 euploid blastocysts were transferred compared with D6 and D7 (56.0% vs. 45.3% and 11.1%, P < 0.001). Poor quality blastocysts were predominant in D7 blastocyst FET cycles (good quality: 35.4%, 27.2%, 5.6%; fair quality: 52.1%, 38.5%, 11.1%; poor quality: 12.5%, 34.3%, 83.3%, P < 0.001 for D5, D6 and D7 blastocysts; respectively). OPR was significantly reduced by D7 blastocyst FETs (OR = 0.23 [0.08;0.62], P = 0.004), patient’s BMI (OR = 0.96 [0.94;0.98], P < 0.001), HRT cycles (OR = 0.70 [0.56;0.88], P = 0.002) and poor quality blastocysts (OR = 0.33 [0.24;0.45], P < 0.001). OPR is significantly reduced with D7 compared with D5/D6 euploid blastocysts in FET cycles. The older the patient, the more likely they are to have an FET cycle with blastocysts biopsied on D7, therefore culturing embryos until D7 can be a strategy to increase OPR outcomes in patients ≥38 years.
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- © ART FERTILITY CLINICS LLC, 2023. Published by Cambridge University Press
References
Abdala, A., Elkhatib, I., Bayram, A., Arnanz, A., El-Damen, A., Melado, L., Lawrenz, B., Coughlan, C., Garrido, N., Fatemi, H. M. and De Munck, N. (2021). Euploidy rates are not affected when embryos are cultured in a continuous (CCM) or sequential culture medium (SCM): A sibling oocyte study. Journal of Assisted Reproduction and Genetics, 38(8), 2199–2207. doi: 10.1007/s10815-021-02187-0
CrossRefGoogle Scholar
Abdala, A., Elkhatib, I., Bayram, A., Arnanz, A., El-Damen, A., Melado, L., Lawrenz, B., Fatemi, H. M. and De Munck, N. (2022). Day 5 vs day 6 single euploid blastocyst frozen embryo transfers: Which variables do have an impact on the clinical pregnancy rates? Journal of Assisted Reproduction and Genetics, 39(2), 379–388. doi: 10.1007/s10815-021-02380-1
CrossRefGoogle ScholarPubMed
Abdala, A., Elkhatib, I., Bayram, A., El-Damen, A., Melado, L., Lawrenz, B., Fatemi, H. M. and Nogueira, D. (2023). Embryo culture medium has no impact on mosaicism rates: A sibling oocyte study. Reproductive Sciences. doi: 10.1007/s43032-023-01276-y
CrossRefGoogle Scholar
ALPHA Scientists In Reproductive Medicine and ESHRE Special Interest Group Embryology. (2011). Istanbul consensus workshop on embryo assessment: Proceedings of an expert meeting. Reproductive Biomedicine Online, 22(6), 632–646. doi: 10.1016/j.rbmo.2011.02.001
CrossRefGoogle Scholar
Arnanz, A., De Munck, N., Bayram, A., El-Damen, A., Abdalla, A., ElKhatib, I., Melado, L., Lawrenz, B. and Fatemi, H. M. (2020). Blastocyst mitochondrial DNA (mtDNA) is not affected by oocyte vitrification: A sibling oocyte study. Journal of Assisted Reproduction and Genetics, 37(6), 1387–1397. doi: 10.1007/s10815-020-01795-6
CrossRefGoogle Scholar
Brandt, J. S., Cruz Ithier, M. A., Rosen, T. and Ashkinadze, E. (2019). Advanced paternal age, infertility, and reproductive risks: A review of the literature. Prenatal Diagnosis, 39(2), 81–87. doi: 10.1002/pd.5402
CrossRefGoogle ScholarPubMed
Capalbo, A., Rienzi, L., Cimadomo, D., Maggiulli, R., Elliott, T., Wright, G., Nagy, Z. P. and Ubaldi, F. M. (2014). Correlation between standard blastocyst morphology, euploidy and implantation: An observational study in two centers involving 956 screened blastocysts. Human Reproduction, 29(6), 1173–1181. doi: 10.1093/humrep/deu033
CrossRefGoogle ScholarPubMed
Cimadomo, D., Capalbo, A., Levi-Setti, P. E., Soscia, D., Orlando, G., Albani, E., Parini, V., Stoppa, M., Dovere, L., Tacconi, L., Ievoli, E., Maggiulli, R., Ubaldi, F. M. and Rienzi, L. (2018). Associations of blastocyst features, trophectoderm biopsy and other laboratory practice with post-warming behavior and implantation. Human Reproduction, 33(11), 1992–2001. doi: 10.1093/humrep/dey291
CrossRefGoogle ScholarPubMed
Cimadomo, D., Soscia, D., Vaiarelli, A., Maggiulli, R., Capalbo, A., Ubaldi, F. M. and Rienzi, L. (2019). Looking past the appearance: A comprehensive description of the clinical contribution of poor quality blastocysts to increase live birth rates during cycles with aneuploidy testing. Human Reproduction, 34(7), 1206–1214. doi: 10.1093/humrep/dez078
CrossRefGoogle ScholarPubMed
Cimadomo, D., Soscia, D., Casciani, V., Innocenti, F., Trio, S., Chiappetta, V., Albricci, L., Maggiulli, R., Erlich, I., Ben-Meir, A., Har-Vardi, I., Vaiarelli, A., Ubaldi, F. M. and Rienzi, L. (2022). How slow is too slow? A comprehensive portrait of Day 7 blastocysts and their clinical value standardized through artificial intelligence. Human Reproduction, 37(6), 1134–1147. doi: 10.1093/humrep/deac080
CrossRefGoogle ScholarPubMed
Corti, L., Cermisoni, G. C., Alteri, A., Pagliardini, L., Ambrosini, G., Andrisani, A., Papaleo, E., Viganò, P. and Noventa, M. (2022). Clinical outcomes deriving from transfer of blastocysts developed in day 7: a systematic review and meta-analysis of frozen–thawed IVF cycles. Reproductive Sciences, 29(1), 43–53. doi: 10.1007/s43032-020-00424-y
CrossRefGoogle ScholarPubMed
Demko, Z. P., Simon, A. L., McCoy, R. C., Petrov, D. A. and Rabinowitz, M. (2016). Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertility and Sterility, 105(5), 1307–1313. doi: 10.1016/j.fertnstert.2016.01.025.CrossRefGoogle Scholar
Desai, N., Ploskonka, S., Goodman, L., Attaran, M., Goldberg, J. M., Austin, C. and Falcone, T. (2016). Delayed blastulation, multinucleation, and expansion grade are independently associated with live-birth rates in frozen blastocyst transfer cycles. Fertility and Sterility, 106(6), 1370–1378. doi: 10.1016/j.fertnstert.2016.07.1095
CrossRefGoogle ScholarPubMed
De Munck, N., El Khatib, I., Abdala, A., El-Damen, A., Bayram, A., Arnanz, A., Melado, L., Lawrenz, B. and Fatemi, H. M. (2020). Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A). Human Reproduction, 35(2), 317–327. doi: 10.1093/humrep/deaa002
CrossRefGoogle Scholar
Du, T., Wang, Y., Fan, Y., Zhang, S., Yan, Z., Yu, W., Xi, Q., Chen, Q., Mol, B. W., Lyu, Q. and Kuang, Y. (2018). Fertility and neonatal outcomes of embryos achieving blastulation on Day 7: Are they of clinical value? Human Reproduction, 33(6), 1038–1051. doi: 10.1093/humrep/dey092
CrossRefGoogle ScholarPubMed
Duran, H. E., Simsek-Duran, F., Oehninger, S. C., Jones, H. W. Jr. and Castora, F. J. (2011). The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation. Fertility and Sterility, 96(2), 384–388. doi: 10.1016/j.fertnstert.2011.05.056
CrossRefGoogle ScholarPubMed
ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine. (2017). The Vienna consensus: Report of an expert meeting on the development of ART laboratory performance indicators. Reproductive Biomedicine Online, 35(5), 494–510. doi: 10.1016/j.rbmo.2017.06.015
CrossRefGoogle Scholar
Gardner, D. K. and Schoolcraft, W. B. (1999).
In vitro culture of human blastocyst. In Jansen, R. and Mortimer, D. (eds.), Towards Reproductive Certainty: Infertility and Genetics Beyond pp. 378–388. Parthenon Publishing Group Press.Google Scholar
Hammond, E. R., Cree, L. M. and Morbeck, D. E. (2018). Should extended blastocyst culture include Day 7? Human Reproduction, 33(6), 991–997. doi: 10.1093/humrep/dey091
CrossRefGoogle ScholarPubMed
Hernandez-Nieto, C., Lee, J. A., Slifkin, R., Sandler, B., Copperman, A. B. and Flisser, E. (2019). What is the reproductive potential of day 7 euploid embryos? Human Reproduction, 34(9), 1697–1706. doi: 10.1093/humrep/dez129
CrossRefGoogle ScholarPubMed
Johnson, S. L., Dunleavy, J., Gemmell, N. J. and Nakagawa, S. (2015). Consistent age-dependent declines in human semen quality: A systematic review and meta-analysis. Ageing Research Reviews, 19, 22–33. doi: 10.1016/j.arr.2014.10.007
CrossRefGoogle ScholarPubMed
Kaing, A., Kroener, L. L., Tassin, R., Li, M., Liu, L., Buyalos, R., Hubert, G. and Shamonki, M. (2018). Earlier day of blastocyst development is predictive of embryonic euploidy across all ages: Essential data for physician decision-making and counseling patients. Journal of Assisted Reproduction and Genetics, 35(1), 119–125. doi: 10.1007/s10815-017-1038-8
CrossRefGoogle ScholarPubMed
Kovalevsky, G., Carney, S. M., Morrison, L. S., Boylan, C. F., Neithardt, A. B. and Feinberg, R. F. (2013). Should embryos developing to blastocysts on day 7 be cryopreserved and transferred: An analysis of pregnancy and implantation rates. Fertility and Sterility, 100(4), 1008–1012. doi: 10.1016/j.fertnstert.2013.06.021
CrossRefGoogle ScholarPubMed
Kuwayama, M. (2007). Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology, 67(1), 73–80. doi: 10.1016/j.theriogenology.2006.09.014
CrossRefGoogle ScholarPubMed
Lane, S. L., Reed, L., Schoolcraft, W. B. and Katz-Jaffe, M. G. (2022). Euploid day 7 blastocysts of infertility patients with only slow embryo development have reduced implantation potential. Reproductive Biomedicine Online, 44(5), 858–865. doi: 10.1016/j.rbmo.2021.08.027
CrossRefGoogle ScholarPubMed
Martínez-Granados, L., Serrano, M., González-Utor, A., Ortíz, N., Badajoz, V., Olaya, E., Prados, N., Boada, M., Castilla, J. A. and Special Interest Group in Quality of ASEBIR (Spanish Society for the Study of Reproductive Biology). (2017). Inter-laboratory agreement on embryo classification and clinical decision: Conventional morphological assessment vs. time lapse. PLOS ONE, 12(8), e0183328. doi: 10.1371/journal.pone.0183328
CrossRefGoogle ScholarPubMed
May-Panloup, P., Chrétien, M. F., Jacques, C., Vasseur, C., Malthièry, Y. and Reynier, P. (2005). Low oocyte mitochondrial DNA content in ovarian insufficiency. Human Reproduction, 20(3), 593–597. doi: 10.1093/humrep/deh667
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
Niu, X., Wang, C. T., Li, R., Haddad, G. and Wang, W. (2020). Is day 7 culture necessary for in vitro fertilization of cryopreserved/warmed human oocytes? Reproductive Biology and Endocrinology: RB&E, 18(1), 4. doi: 10.1186/s12958-020-0565-9
CrossRefGoogle ScholarPubMed
Su, Y., Li, J. J., Wang, C., Haddad, G. and Wang, W. H. (2016). Aneuploidy analysis in day 7 human blastocysts produced by in vitro fertilization. Reproductive Biology and Endocrinology: RB&E, 14, 20. doi: 10.1186/s12958-016-0157-x
CrossRefGoogle ScholarPubMed
Tiegs, A. W., Sun, L., Patounakis, G. and Scott, R. T. (2019). Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts. Human Reproduction, 34(9), 1632–1639. doi: 10.1093/humrep/dez138. Erratum in: Human Reproduction. (2019), 34(12), 2559–2560. doi: 10.1093/humrep/dez219CrossRefGoogle Scholar
Van Blerkom, J. (2011). Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion, 11(5), 797–813. doi: 10.1016/j.mito.2010.09.012
CrossRefGoogle ScholarPubMed
Whitney, J. B., Balloch, K., Anderson, R. E., Nugent, N. and Schiewe, M. C. (2019). Day 7 blastocyst euploidy supports routine implementation for cycles using preimplantation genetic testing. JBRA Assisted Reproduction, 23(1), 45–50. doi: 10.5935/1518-0557.20180089
Google ScholarPubMed
Xiong, S., Liu, W., Wang, J., Liu, J., Gao, Y., Wu, L., Zhu, J., Hao, X., Li, J., Liu, D., Han, W. and Huang, G. (2021). Trophectoderm biopsy protocols may impact the rate of mosaic blastocysts in cycles with pre-implantation genetic testing for aneuploidy. Journal of Assisted Reproduction and Genetics, 38(5), 1153–1162. doi: 10.1007/s10815-021-02137-w
CrossRefGoogle ScholarPubMed
Zegers-Hochschild, F., Adamson, G. D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., Rienzi, L., Sunde, A., Schmidt, L., Cooke, I. D., Simpson, J. L. and van der Poel, S. (2017). The international glossary on infertility and fertility care, 2017. Fertility and Sterility, 108(3), 393–406. doi: 10.1016/j.fertnstert.2017.06.005
CrossRefGoogle ScholarPubMed
Abdala et al. supplementary material
Abdala et al. supplementary material
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