Effect of Blastocyst Morphology and Developmental Rate on Euploidy and Live Birth Rates in Preimplantation Genetic Testing for Aneuploidy Cycles With Single-Embryo Transfer

Na Li, Yichun Guan, Bingnan Ren, Yuchao Zhang, Yulin Du, Hongjiao Kong, Yongjie Zhang, Hua Lou, Na Li, Yichun Guan, Bingnan Ren, Yuchao Zhang, Yulin Du, Hongjiao Kong, Yongjie Zhang, Hua Lou

Abstract

Objective: The aim of this study was to investigate whether blastocyst morphology and developmental rate are associated with euploidy and live birth rates (LBRs) in single euploid frozen-thawed embryo transfer (FET) cycles.

Design: Retrospective cohort study.

Methods: This study included 431 preimplantation genetic testing for aneuploidy (PGT-A) cycles followed by 393 FET cycles performed at our center from June 2017 to March 2021. All cycles were analyzed for euploidy based on blastocyst morphology (good, average and poor), developmental stage (day 5 and 6) and maternal age (< 35 and ≥ 35 years old). Multivariate logistic analysis models were used to identify the independent effects of conventional blastocyst morphology, developmental rate and morphological parameters (degree of blastocoele expansion, and grade of inner cell mass and trophectoderm (TE)) on LBRs.

Results: In the group of women aged < 35 years, compared with poor-quality blastocysts, good-quality blastocysts (62.90% vs. 32.46%; odds ratio (OR) 3.163, 95% confidence interval (CI) 2.247-4.451; P < 0.001) and average-quality blastocysts (46.70% vs. 32.46%; OR 1.665, 95% CI 1.287-2.154; P < 0.001) had significantly higher euploidy rates. Additionally, day 5 blastocysts were associated with higher euploidy rates than day 6 blastocysts (49.28% vs. 35.02%; OR 1.506, 95% CI 1.191-1.903; P= 0.001). In the group of women aged ≥ 35 years, euploidy rates were also associated with blastocyst morphology, with 41.86%, 45.65% and 24.39% of good, average and poor-quality embryos, respectively, exhibiting euploidy. However, no relationship was seen between euploidy and blastocyst developmental rate. Multiple logistic regression analysis show that overall blastocyst morphology of euploid embryos was not associated with LBR, only embryos with A-grade TE had significantly higher LBRs than those with C-grade TE (62.71% vs. 45.40%; OR 2.189, 95% CI 1.166-4.109; P=0.015). Similarly, LBRs were significantly higher when day 5 blastocysts were transferred than when day 6 blastocysts were transferred (57.75% vs. 41.67%; OR 2.132, 95% CI 1.370-3.318; P = 0.001).

Conclusion: Poor-quality embryos have reduced rates of euploidy. However, blastocyst developmental rate only significantly associates with euploidy rates in women aged younger than 35. Furthermore, only TE grade and blastocyst developmental rate are significantly associated with LBRs following FET cycles.

Keywords: blastocyst morphology; developmental rate; euploid rates; live birth rates; preimplantation genetic testing for aneuploidy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Li, Guan, Ren, Zhang, Du, Kong, Zhang and Lou.

Figures

Figure 1
Figure 1
Embryo euploidy according to women’s age.
Figure 2
Figure 2
Comparison of euploidy rates by blastocyst morphology and developmental rates in the two age groups. (A) odds ratio was adjusted for blastocyst developmental rate, maternal age, maternal BMI, duration of infertility, type of infertility, infertility diagnosis, number of prior pregnancies, indication for PGT-A and basal FSH; (B) odds ratio was adjusted for blastocyst morphology, maternal age, maternal BMI, duration of infertility, type of infertility, infertility diagnosis, number of prior pregnancies, indication for PGT-A and basal FSH. P values are adjusted p values.

References

    1. Lemos E, Zhang D, Van Voorhis B, Hu X. Healthcare Expenses Associated With Multiple vs Singleton Pregnancies in the United States. Am J Obstet Gynecol (2013) 209(6):586.e1–.e11. doi: 10.1016/j.ajog.2013.10.005
    1. Macklon N, Geraedts J, Fauser B. Conception to Ongoing Pregnancy: The 'Black Box' of Early Pregnancy Loss. Hum Reprod Update (2002) 8(4):333–43. doi: 10.1093/humupd/8.4.333
    1. Steiner AZ, Jukic AM. Impact of Female Age and Nulligravidity on Fecundity in an Older Reproductive Age Cohort. Fertil Steril (2016) 105(6):1584–8 e1. doi: 10.1016/j.fertnstert.2016.02.028
    1. Minasi M, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. . Correlation Between Aneuploidy, Standard Morphology Evaluation and Morphokinetic Development in 1730 Biopsied Blastocysts: A Consecutive Case Series Study. Hum Reprod (Oxf Engl) (2016) 31(10):2245–54. doi: 10.1093/humrep/dew183
    1. Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, et al. . Preimplantation Genetic Testing for Aneuploidy Versus Morphology as Selection Criteria for Single Frozen-Thawed Embryo Transfer in Good-Prognosis Patients: A Multicenter Randomized Clinical Trial. Fertil Steril (2019) 112(6):1071–79. doi: 10.1016/j.fertnstert.2019.07.1346
    1. Rubio C, Bellver J, Rodrigo L, Castillón G, Guillén A, Vidal C, et al. . In Vitro Fertilization With Preimplantation Genetic Diagnosis for Aneuploidies in Advanced Maternal Age: A Randomized, Controlled Study. Fertil Steril (2017) 107(5):1122–9. doi: 10.1016/j.fertnstert.2017.03.011
    1. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, et al. . Live Birth With or Without Preimplantation Genetic Testing for Aneuploidy. N Engl J Med (2021) 385(22):2047–58. doi: 10.1056/NEJMoa2103613
    1. Harper J, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta S, et al. . The ESHRE PGD Consortium: 10 Years of Data Collection. Hum Reprod Update (2012) 18(3):234–47. doi: 10.1093/humupd/dmr052
    1. Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. . Correlation Between Standard Blastocyst Morphology, Euploidy and Implantation: An Observational Study in Two Centers Involving 956 Screened Blastocysts. Hum Reprod (Oxf Engl) (2014) 29(6):1173–81. doi: 10.1093/humrep/deu033
    1. Alfarawati S, Fragouli E, Colls P, Stevens J, Gutiérrez-Mateo C, Schoolcraft W, et al. . The Relationship Between Blastocyst Morphology, Chromosomal Abnormality, and Embryo Gender. Fertil Steril (2011) 95(2):520–4. doi: 10.1016/j.fertnstert.2010.04.003
    1. Majumdar G, Majumdar A, Verma I, Upadhyaya K. Relationship Between Morphology, Euploidy and Implantation Potential of Cleavage and Blastocyst Stage Embryos. J Hum Reprod Sci (2017) 10(1):49–57. doi: 10.4103/0974-1208.204013
    1. Irani M, Reichman D, Robles A, Melnick A, Davis O, Zaninovic N, et al. . Morphologic Grading of Euploid Blastocysts Influences Implantation and Ongoing Pregnancy Rates. Fertil Steril (2017) 107(3):664–70. doi: 10.1016/j.fertnstert.2016.11.012
    1. Irani M, O'Neill C, Palermo G, Xu K, Zhang C, Qin X, et al. . Blastocyst Development Rate Influences Implantation and Live Birth Rates of Similarly Graded Euploid Blastocysts. Fertil Steril (2018) 110(1):95–102.e1. doi: 10.1016/j.fertnstert.2018.03.032
    1. Anderson R, Whitney J, Schiewe M. Clinical Benefits of Preimplantation Genetic Testing for Aneuploidy (PGT-A) for All In Vitro Fertilization Treatment Cycles. Eur J Med Genet (2020) 63(2):1–8. doi: 10.1016/j.ejmg.2019.103731
    1. Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft WB. Single Blastocyst Transfer: A Prospective Randomized Trial. Fertil Steril (2004) 81(3):551–5. doi: 10.1016/j.fertnstert.2003.07.023
    1. Lou H, Li N, Guan Y, Zhang Y, Hao D, Cui S. Association Between Morphologic Grading and Implantation Rate of Euploid Blastocyst. J Ovarian Res (2021) 14(1):18–26. doi: 10.1186/s13048-021-00770-8
    1. Zimmerman R, Tao X, Marin D, Werner M, Hong K, Lonczak A, et al. . Preclinical Validation of a Targeted Next Generation Sequencing-Based Comprehensive Chromosome Screening Methodology in Human Blastocysts. Mol Hum Reprod (2018) 24(1):37–45. doi: 10.1093/molehr/gax060
    1. Kato K, Ueno S, Yabuuchi A, Uchiyama K, Okuno T, Kobayashi T, et al. . Women’s Age and Embryo Developmental Speed Accurately Predict Clinical Pregnancy After Single Vitrified-Warmed Blastocyst Transfer. Reprod BioMed Online (2014) 29:411–6. doi: 10.1016/j.rbmo.2014.06.007
    1. Sunderam S KD, Crawford SB, Folger SG, Jamieson DJ, Warner L. Assisted Reproductive Technology Surveillance - United States, 2012. MMWR Surveill Summ (2015) 64:1–29. doi: 10.15585/mmwr.ss6411a1
    1. Irani M, Zaninovic N, Rosenwaks Z, Xu K. Does Maternal Age at Retrieval Influence the Implantation Potential of Euploid Blastocysts? Am J Obstet Gynecol (2019) 220(4):379.e1–.e7. doi: 10.1016/j.ajog.2018.11.1103
    1. Reig A, Franasiak J, Scott RT, Jr., Seli E. The Impact of Age Beyond Ploidy: Outcome Data From 8175 Euploid Single Embryo Transfers. J Assist Reprod Genet (2020) 37(3):595–602. doi: 10.1007/s10815-020-01739-0
    1. Awadalla MS, Vestal NL, McGinnis LK, Ahmady A, Paulson RJ. Effect of Age and Morphology on Sustained Implantation Rate After Euploid Blastocyst Transfer. Reprod BioMed Online (2021) 43(3):395–403. doi: 10.1016/j.rbmo.2021.06.008
    1. Ferreux L, Bourdon M, Sallem A, Santulli P, Barraud-Lange V, Le Foll N, et al. . Live Birth Rate Following Frozen-Thawed Blastocyst Transfer Is Higher With Blastocysts Expanded on Day 5 Than on Day 6. Hum Reprod (Oxf Engl) (2018) 33(3):390–8. doi: 10.1093/humrep/dey004
    1. Gardner D, Lane M, Stevens J, Schlenker T, Schoolcraft W. Blastocyst Score Affects Implantation and Pregnancy Outcome: Towards a Single Blastocyst Transfer. Fertil Steril (2000) 73(6):1155–8. doi: 10.1016/s0015-0282(00)00518-5
    1. Goto S, Kadowaki T, Tanaka S, Hashimoto H, Kokeguchi S, Shiotani M. Prediction of Pregnancy Rate by Blastocyst Morphological Score and Age, Based on 1,488 Single Frozen-Thawed Blastocyst Transfer Cycles. Fertil Steril (2011) 95(3):948–52. doi: 10.1016/j.fertnstert.2010.06.067
    1. Richter K, Harris D, Daneshmand S, Shapiro B. Quantitative Grading of a Human Blastocyst: Optimal Inner Cell Mass Size and Shape. Fertil Steril (2001) 76(6):1157–67. doi: 10.1016/s0015-0282(01)02870-9
    1. Ahlström A, Westin C, Wikland M, Hardarson T. Prediction of Live Birth in Frozen-Thawed Single Blastocyst Transfer Cycles by Pre-Freeze and Post-Thaw Morphology. Hum Reprod (Oxf Engl) (2013) 28(5):1199–209. doi: 10.1093/humrep/det054
    1. Honnma H, Baba T, Sasaki M, Hashiba Y, Ohno H, Fukunaga T, et al. . Trophectoderm Morphology Significantly Affects the Rates of Ongoing Pregnancy and Miscarriage in Frozen-Thawed Single-Blastocyst Transfer Cycle In Vitro Fertilization. Fertil Steril (2012) 98(2):361–7. doi: 10.1016/j.fertnstert.2012.05.014
    1. Ahlström A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm Morphology: An Important Parameter for Predicting Live Birth After Single Blastocyst Transfer. Hum Reprod (Oxf Engl) (2011) 26(12):3289–96. doi: 10.1093/humrep/der325
    1. Hill M, Richter K, Heitmann R, Graham J, Tucker M, DeCherney A, et al. . Trophectoderm Grade Predicts Outcomes of Single-Blastocyst Transfers. Fertil Steril (2013) 99(5):1283–9.e1. doi: 10.1093/humrep/der325
    1. Tsampalas M, Gridelet V, Berndt S, Foidart J, Geenen V, Perrier d'Hauterive S. Human Chorionic Gonadotropin: A Hormone With Immunological and Angiogenic Properties. J Reprod Immun (2010) 85(1):93–8. doi: 10.1016/j.jri.2009.11.008

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren