Storage Time of Cryopreserved Embryos and Pregnancy Outcomes: A Dose-Response Meta-Analysis

Abstract

Purpose Cryopreservation techniques have become an essential part of assisted reproduction technology. Embryos may be cryopreserved for several years before transfer, and the safety of long-term cryopreservation needs to be considered. This dose-response meta-analysis was conducted to evaluate whether there were dose-response relationships between the storage time of cryopreserved embryos and pregnancy outcomes such as survival rate, implantation rate, miscarriage rate, clinical pregnancy rate, and congenital malformation rate.

Methods After searching the databases PubMed, Embase, MEDLINE, CCRT and related reviews up until June 4, 2020, seven studies were included for analysis. Two reviewers extracted the relevant information and independently assessed the study quality using the Newcastle-Ottawa scale. Potential linear or non-linear dose-response relationships were assessed with a random-effect dose-response meta-analysis.

Results No dose-response association was found between duration of embryo cryostorage and survival rate, implantation rate, miscarriage rate, clinical pregnancy rate or congenital malformation rate.

Conclusion The interval between the start of embryo cryopreservation and frozen/thawed embryo transfer does not influence pregnancy outcomes.

Zusammenfassung

Zielsetzung Kryokonservierungstechniken sind inzwischen zu einem wesentlichen Bestandteil der assistierten Reproduktionstechnologie geworden. Embryos können mehrere Jahre lang kryokonserviert werden, bevor sie transferiert werden. Das bedeutet, dass man sich auch wegen der Sicherheit der langfristigen Kryokonservierung Gedanken machen muss. Diese Metaanalyse wurde durchgeführt, um herauszufinden, ob es eine Dosis-Wirkungs-Beziehung zwischen der Lagerdauer von kryokonservierten Embryos und dem Schwangerschaftsausgang gibt, z. B. ob die Kryokonservierung sich auf die Überlebensrate, Implantationsrate, Fehlgeburtsrate, klinische Schwangerschaftsrate und angeborene Fehlbildungsrate auswirkt.

Methoden Es wurde eine Datenbanksuche von PubMed, Embase, MEDLINE und CCRT bis zum 4. Juni 2020 durchgeführt, und verschiedene Überblicksdarstellungen wurden zusätzlich überprüft. Insgesamt wurden 7 Studien in die Analyse aufgenommen. Die Daten wurden von 2 Wissenschaftlern extrahiert, die die Daten unabhängig voneinander unter Zuhilfenahme der Newcastle-Ottawa-Skala auswerteten. Potenzielle lineare bzw. nicht lineare Dosis-Wirkungs-Beziehungen wurden mithilfe einer Zufallseffekt-Metaanalyse überprüft.

Ergebnisse Es gab keine Dosis-Wirkungs-Beziehung zwischen der Lagerdauer kryokonservierter Embryos und der Überlebensrate, Implantationsrate, Fehlgeburtsrate, klinischen Schwangerschaftsrate oder angeborenen Fehlbildungsrate.

Schlussfolgerung Die Zeitspanne zwischen der Kryokonservierung von Embryos und dem Transfer von eingefrorenen/aufgetauten Embryonen hat keine Auswirkung auf den Schwangerschaftsausgang.

Key words

storage time - cryopreservation - embryo transfer - meta-analysis

Schlüsselwörter

Lagerdauer - Kryokonservierung - Embryotransfer - Metaanalyse

Publication History

Received: 24 August 2020

Accepted after revision: 29 November 2020

Article published online:
05 March 2021

• References

• 1 Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature 1983; 305: 707-709
• 2 Kupka MS, DʼHooghe T, Ferraretti AP. et al. Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. Hum Reprod 2016; 31: 233-248
• 3 Yan J, Suzuki J, Yu X. et al. Effects of duration of cryo-storage of mouse oocytes on cryo-survival, fertilization and embryonic development following vitrification. J Assist Reprod Genet 2011; 28: 643-649
• 4 Ueno S, Uchiyama K, Kuroda T. et al. Cryostorage duration does not affect pregnancy and neonatal outcomes: a retrospective single-centre cohort study of vitrified-warmed blastocysts. Reprod Biomed Online 2018; 36: 614-619
• 5 Li W, Zhao W, Xue X. et al. Influence of storage time on vitrified human cleavage-stage embryos froze in open system. Gynecol Endocrinol 2017; 33: 96-99
• 6 Liu Q, Lian Y, Huang J. et al. The safety of long-term cryopreservation on slow-frozen early cleavage human embryos. J Assist Reprod Genet 2014; 31: 471-475
• 7 Wirleitner B, Vanderzwalmen P, Bach M. et al. The time aspect in storing vitrified blastocysts: its impact on survival rate, implantation potential and babies born. Hum Reprod 2013; 28: 2950-2957
• 8 Aflatoonian N, Pourmasumi S, Aflatoonian A. et al. Duration of storage does not influence pregnancy outcome in cryopreserved human embryos. Iran J Reprod Med 2013; 11: 843-846
• 9 Ashrafi M, Jahangiri N, Hassani F. et al. The factors affecting the outcome of frozen-thawed embryo transfer cycle. Taiwan J Obstet Gynecol 2011; 50: 159-164
• 10 Riggs R, Mayer J, Dowling-Lacey D. et al. Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos. Fertil Steril 2010; 93: 109-115
• 11 Yuan Y, Mai Q, Ma J. et al. What was the fate of human embryos following long-term cryopreservation (>/=12 years) and frozen embryo transfer?. Hum Reprod 2019; 34: 52-55
• 12 Dowling-Lacey D, Mayer JF, Jones E. et al. Live birth from a frozen-thawed pronuclear stage embryo almost 20 years after its cryopreservation. Fertil Steril 2011; 95: 1120-1121
• 13 Orsini N, Li R, Wolk A. et al. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 2012; 175: 66-73
• 14 Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 2010; 29: 1037-1057
• 15 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
• 16 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009; 6: e1000100
• 17 Tripepi G, Jager KJ, Stel VS. et al. How to deal with continuous and dichotomic outcomes in epidemiological research: linear and logistic regression analyses. Nephron Clin Pract 2011; 118: c399-c406
• 18 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-748
• 19 Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 1992; 135: 1301-1309
• 20 Pruksananonda K, Rungsiwiwut R, Numchaisrika P. et al. Eighteen-year cryopreservation does not negatively affect the pluripotency of human embryos: evidence from embryonic stem cell derivation. Biores Open Access 2012; 1: 166-173
• 21 Pogozhykh D, Pogozhykh O, Prokopyuk V. et al. Influence of temperature fluctuations during cryopreservation on vital parameters, differentiation potential, and transgene expression of placental multipotent stromal cells. Stem Cell Res Ther 2017; 8: 66
• 22 Glenister PH, Thornton CE. Cryoconservation–archiving for the future. Mamm Genome 2000; 11: 565-571
• 23 Praveen KM, Shyama SK, Kashif S. et al. Effects of gamma radiation on the early developmental stages of Zebrafish (Danio rerio). Ecotoxicol Environ Saf 2017; 142: 95-101
• 24 Li J, Yin M, Wang B. et al. The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles. Hum Reprod 2020; 35: 1675-1684
• 25 Tan TY, Lau SK, Loh SF. et al. Female ageing and reproductive outcome in assisted reproduction cycles. Singapore Med J 2014; 55: 305-309
• 26 Loutradi KE, Kolibianakis EM, Venetis CA. et al. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril 2008; 90: 186-193
• 27 Shaw JM, Jones GM. Terminology associated with vitrification and other cryopreservation procedures for oocytes and embryos. Hum Reprod Update 2003; 9: 583-605
• 28 Richter KS, Ginsburg DK, Shipley SK. et al. Factors associated with birth outcomes from cryopreserved blastocysts: experience from 4,597 autologous transfers of 7,597 cryopreserved blastocysts. Fertil Steril 2016; 106: 354-362
• 29 Rienzi L, Gracia C, Maggiulli R. et al. 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. Hum Reprod Update 2017; 23: 139-155
• 30 Trounson A. Development of in vitro fertilization in Australia. Fertil Steril 2018; 110: 19-24
• 31 Huang C, Lei L, Wu HL. et al. Long-term cryostorage of semen in a human sperm bank does not affect clinical outcomes. Fertil Steril 2019; 112: 663-669
• 32 Tarahomi M, Van Straalen JP, Vaz FM. et al. The composition of human preimplantation embryo culture media and their stability during storage and culture. Hum Reprod 2017; 32: i26-i27
• 33 Hartshorne G, Sheldon S, Sozou P. On consent rules for storing embryos. Mol Hum Reprod 2009; 24: i49
• 34 Bowen-Simpkins P, Wang JJ, Ahuja KK. The UKʼs anomalous 10-year limit on oocyte storage: time to change the law. Reprod Biomed Online 2018; 37: 387-389