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Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels

  • Assisted Reproduction Technologies
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Abstract

Purpose

The study was designed to investigate the effect of vitrification and slow freezing for the cryopreservation of human day 3 embryos on serum β-hCG levels in pregnancies established after frozen embryo transfer (FET).

Methods

Of the 1384 FET cycles initiated, 1131 embryo transfers met study criteria and assigned to one of two groups: 797 slow-freezing embryo transfers or 334 vitrified embryo transfers. Median values of β-hCG and outcome of all pregnancies were compared between the two groups. Predictive values of serum β-hCG on day 12 after embryo transfer for establishing ongoing pregnancy and pregnancy failure were determined by receiver operating characteristic (ROC) curve analysis.

Results

In the slow-freezing group, 383 ongoing pregnancies occurred (48.1 %), and transfers of vitrified embryos resulted in 154 pregnancies (46.1 %). Median β-hCG values (279.2 IU/L) for ongoing pregnancies after transfer of vitrified embryos were significantly lower than that of slow frozen embryos (320.5 IU/L). The median values of β-hCG for singleton in the two groups was statistically significant (P <0.05). For slow-freezing embryo transfers, the cut-off value of β-hCG in predicting ongoing pregnancy was 147 IU/L (sensitivity 88.3 %, specificity 80.7 %). For vitrified embryo transfers, the value was 135 IU/L (sensitivity 84.4 %, specificity 76.3 %).

Conclusions

Day 12 β-hCG levels after FET are significantly affected by the methods of embryo cryopreservation for ongoing pregnancies. Furthermore, when using β-hCG cut-off value to assess pregnancy outcome, the cryopreservation methods should be taken into account.

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References

  1. Handschuh K, Guibourdenche J, Tsatsaris V, Guesnon M, Laurendeau I, Evain-Brion D, et al. Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells. Placenta. 2007;28:175–84.

    Article  CAS  PubMed  Google Scholar 

  2. Stone BA, Vargyas JM, Ringler GE, March CM, Marrs RP. The rate at which serum total beta-subunit human chorionic gonadotropin increases after embryo transfer is a predictor of the viability of pregnancy and an identifier of determinants of pregnancy. Fertil Steril. 2006;86:1626–33.

    Article  CAS  PubMed  Google Scholar 

  3. Zegers-Hochschild F, Altieri E, Fabres C, Fernandez E, Mackenna A, Orihuela P. Predictive value of human chorionic gonadotrophin in the outcome of early pregnancy after in-vitro fertilization and spontaneous conception. Hum Reprod. 1994;9:1550–5.

    CAS  PubMed  Google Scholar 

  4. Al-Sebai MA, Diver M, Hipkin LJ. The role of a single free beta-human chorionic gonadotrophin measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability. Hum Reprod. 1996;11:881–8.

    Article  CAS  PubMed  Google Scholar 

  5. Porat S, Savchev S, Bdolah Y, Hurwitz A, Haimov-Kochman R. Early serum beta-human chorionic gonadotropin in pregnancies after in vitro fertilization: contribution of treatment variables and prediction of long-term pregnancy outcome. Fertil Steril. 2007;88:82–9.

    Article  CAS  PubMed  Google Scholar 

  6. Urbancsek J, Hauzman E, Fedorcsák P, Halmos A, Dévényi N, Papp Z. Serum human chorionic gonadotropin measurements may predict pregnancy outcome and multiple gestation after in vitro fertilization. Fertil Steril. 2002;78:540–2.

    Article  PubMed  Google Scholar 

  7. Orasanu B, Jackson KV, Hornstein MD, Racowsky C. Effects of culture medium on HCG concentrations and their value in predicting successful IVF outcome. Reprod Biomed Online. 2006;12:590–8.

    Article  PubMed  Google Scholar 

  8. Rama Raju GA, Haranath GB, Krishna KM, Prakash GJ, Madan K. Vitrification of human 8-cell embryos, a modified protocol for better pregnancy rates. Reprod Biomed Online. 2005;11:434–7.

    Article  PubMed  Google Scholar 

  9. Rezazadeh Valojerdi M, Eftekhari-Yazdi P, Karimian L, Hassani F, Movaghar B. Vitrification versus slow freezing gives excellent survival, post warming embryo morphology and pregnancy outcomes for human cleaved embryos. J Assist Reprod Genet. 2009;26:347–54.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Gvakharia M, Adamson GD. Implementation of an inexpensive method of vitrification and warming of human cleavage-stage embryos using cut standard straws. Fertil Steril. 2011;95:2552–3.

    Article  PubMed  Google Scholar 

  11. Liu SY, Teng B, Fu J, Li X, Zheng Y, Sun XX. Obstetric and neonatal outcomes after transfer of vitrified early cleavage embryos. Hum Reprod. 2013;28:2093–100.

    Article  CAS  PubMed  Google Scholar 

  12. Xue Y, Tong X, Jiang L, Zhu H, Yang L, Zhang S. Effect of cumulus cell removal 4 h post-insemination on fertilization and embryo quality: a prospective randomized sibling-oocyte study. J Assist Reprod Genet. 2013;30(8):1049–53.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Edgar DH, Bourne H, Speirs AL, McBain JC. A quantitative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos. Hum Reprod. 2000;15:175–9.

    Article  CAS  PubMed  Google Scholar 

  14. Kuwayama M, Vajta G, Ieda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod Biomed Online. 2005;11:608–14.

    Article  PubMed  Google Scholar 

  15. Zhou F, Lin XN, Tong XM, Li C, Liu L, Jin XY, et al. A frozen-thawed embryo transfer program improves the embryo utilization rate. Chin Med J (Engl). 2009;122:1974–8.

    PubMed  Google Scholar 

  16. Schmidt LL, Asch RH, Frederick JL, Rojas FJ, Stone SC, Balmaceda JP. The predictive value of a single beta human chorionic gonadotrophin in pregnancies achieved by assisted reproductive technology. Fertil Steril. 1994;62:333–8.

    CAS  PubMed  Google Scholar 

  17. Papageorgiou TC, Leondires MP, Miller BT, Chang AS, Armstrong AB, Scott LA, et al. Human chorionic gonadotropin levels after blastocyst transfer are highly predictive of pregnancy outcome. Fertil Steril. 2001;76:981–7.

    Article  CAS  PubMed  Google Scholar 

  18. Iwatani M, Ikegami K, Kremenska Y, Hattori N, Tanaka S, Yagi S, et al. Dimethyl Sulfoxide Has an Impact on Epigenetic Profile in Mouse Embryoid Body. Stem Cells. 2006;24:2549–56.

    Article  CAS  PubMed  Google Scholar 

  19. Mamo S, Bodo S, Kobolak J, Polgar Z, Tolgyesi G, Dinnyes A. Gene expression profiles of vitrified in vivo derived 8-cell stage mouse embryos detected by high density oligonucleotide microarrays. Mol Reprod Dev. 2006;73:1380–92.

    Article  CAS  PubMed  Google Scholar 

  20. Aye M, Di Giorgio C, De Mo M, Botta A, Perrin J, Courbiere B. Assessment of the genotoxicity of three cryoprotectants used for human oocyte vitrification: Dimethyl sulfoxide, ethylene glycol and propylene glycol. Food Chem Toxicol. 2010;48:1905–12.

    Article  CAS  PubMed  Google Scholar 

  21. Wang Z, Xu L, He F. Embryo vitrification affects the methylation of the H19/Igf2 differentially methylated domain and the expression of H19 and Igf2. Fertil Steril. 2010;93:2729–33.

    Article  CAS  PubMed  Google Scholar 

  22. Dhali A, Anchamparuthy VM, Butler SP, Pearson RE, Mullarky IK, Gwazdauskas FC. Gene expression and development of mouse zygotes following droplet vitrification. Theriogenology. 2007;68:1292–8.

    Article  CAS  PubMed  Google Scholar 

  23. Martino NA, Dell’aquila ME, Cardone RA. Somoskoi B. Cseh S. Vitrification preserves chromatin integrity, bioenergy potential and oxidative parameters in mouse embryos. Reprod Biol Endocrinol: Lacalandra GM; 2013. doi:10.1186/1477-7827-11-27.

    Google Scholar 

  24. Yang HW, Hwang KJ, Kwon HC, Kim HS, Choi K, Oh KS. Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos. Hum Reprod. 1998;13:998–1002.

    Article  CAS  PubMed  Google Scholar 

  25. Ahn HJ, Sohn IP, Kwon HC, Jo DH, Park YD, Min CK. Characteristics of the cell membrane fluidity, actin fibers, and mitochondrial dysfunctions of frozen-thawed two-cell mouse embryos. Mol Reprod Dev. 2002;61:466–76.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao XM, Fu XW, Hou YP, Yan CL, Suo L, Wang YP, et al. Effect of vitrification on mitochondrial distribution and membrane potential in mouse two pronuclear (2-PN) embryos. Mol Reprod Dev. 2009;76:1056–63.

    Article  CAS  PubMed  Google Scholar 

  27. Tatone C, Di Emidio G, Vento M, Ciriminna R, Artini PG. Cryopreservation and oxidative stress in reproductive cells. Gynecol Endocrinol. 2010;26:563–7.

    Article  PubMed  Google Scholar 

  28. Edgar DH, Gook DA. A critical appraisal of cryopreservation (slow cooling versus vitrification) of human oocytes and embryos. Hum Reprod Update. 2012;18:536–54.

    Article  PubMed  Google Scholar 

  29. Kumbak B, Oral E, Karlikaya G, Lacin S, Kahraman S. Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome. Reprod Biomed Online. 2006;13:459–64.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang X, Barnes R, Confino E, Milad M, Puscheck E, Kazer RR. Delay of embryo transfer to day 5 results in decreased initial serum beta-human chorionic gonadotropin levels. Fertil Steril. 2003;80:1359–63.

    Article  PubMed  Google Scholar 

  31. Poikkeus P, Hiilesmaa V, Tiitinen A. Serum HCG 12 days after embryo transfer in predicting pregnancy outcome. Hum Reprod. 2002;17:1901–5.

    Article  CAS  PubMed  Google Scholar 

  32. McCoy TW, Nakajima ST, Bohler Jr HC. Age and a single day-14 beta-HCG can predict ongoing pregnancy following IVF. Reprod Biomed Online. 2009;19:114–20.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81270657), the Natural Science Program of Zhejiang (No. LY13H040005) and Program of Health and Family Planning Commission of Zhejiang (No. 2012RCA036, 2014KYA115).

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Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3, Qingchun Road, Hangzhou, 310016, China

    Yamei Xue, Xiaomei Tong, Lingying Jiang, Haiyan Zhu, Lingyun Yang & Songying Zhang

Authors
  1. Yamei Xue
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  2. Xiaomei Tong
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  3. Lingying Jiang
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  4. Haiyan Zhu
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  5. Lingyun Yang
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  6. Songying Zhang
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Corresponding author

Correspondence to Songying Zhang.

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Capsule This investigation shows that day 12 β-hCG levels after FET are significantly affected by the methods of embryo cryopreservation for ongoing pregnancies.

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Xue, Y., Tong, X., Jiang, L. et al. Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels. J Assist Reprod Genet 31, 1037–1043 (2014). https://doi.org/10.1007/s10815-014-0259-3

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  • DOI: https://doi.org/10.1007/s10815-014-0259-3

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