Subscribe to RSS
DOI: 10.1055/s-0038-1676849
Human Reproductive Cell Cryopreservation, Storage, Handling, and Transport: Risks and Risk Management
Publication History
Publication Date:
04 April 2019 (online)
![](https://www.thieme-connect.de/media/srm/201805/lookinside/thumbnails/10-1055-s-0038-1676849_001140-1.jpg)
Abstract
Millions of human oocytes and embryos are stored in thousands of locations across the globe. This inventory continues to grow as cryopreservation becomes more successful and more widely applied. The results of studies assessing pregnancy and neonatal outcomes following frozen embryo transfer (FET) have been encouraging, showing lower incidences of small for gestational age neonates and preterm birth compared with fresh transfers. However, many of these studies have also shown that the odds of large for gestational age births and macrosomia are higher after FET. The origin of these conditions remains unclear. Cryostorage presents many potential risks to the cryopreserved cells/tissues, including loss of viability and contamination, but risks are faced also by care providers—for example, injury and financial liability—and by patients—for example, accidental loss of their reproductive tissues, the burden of embryos they no longer wish to use and failing to meet their contractual obligations. Studies are urgently needed to explore and understand all dimensions of cryostorage to help ART clinics develop effective strategies to manage associated risks. The future of cryostorage, as for many other areas of ART and medicine, is automation.
-
References
- 1 Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature 1983; 305 (5936): 707-709
- 2 Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC. Two pregnancies following transfer of intact frozen-thawed embryos. Fertil Steril 1984; 42 (02) 293-296
- 3 Cohen J, Simons RF, Fehilly CB. , et al. Birth after replacement of hatching blastocyst cryopreserved at expanded blastocyst stage. Lancet 1985; 1 (8429): 647
- 4 Imudia AN, Goldman RH, Awonuga AO, Wright DL, Styer AK, Toth TL. The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles. J Assist Reprod Genet 2014; 31 (01) 65-71
- 5 Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril 2014; 102 (01) 10-18
- 6 Calhaz-Jorge C, De Geyter C, Kupka MS. , et al; European IVF-Monitoring Consortium (EIM); European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum Reprod 2017; 32 (10) 1957-1973
- 7 CDC; American Society for Reproductive Medicine. Society for Assisted Reproductive Technology. 2015 assisted reproductive technology fertility clinic success rates report. Atlanta, GA: US Department of Health and Human Services; 2017
- 8 ANZARD (The Australia and New Zealand Assisted Reproduction Database). 2016 Annual Report, 2018. Available at: https://npesu.unsw.edu.au/sites/default/files/npesu/surveillances/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202016%20Summary.pdf . Accessed December 3, 2018
- 9 Saito H, Jwa SC, Kuwahara A. , et al. Assisted reproductive technology in Japan: a summary report for 2015 by The Ethics Committee of The Japan Society of Obstetrics and Gynecology. Reprod Med Biol 2017; 17 (01) 20-28
- 10 Adamson GD, Zegers-Hochschild F, Dyer S. , et al. ICMART World Report 2014. Abstracts of the 34th Annual Meeting of the ESHRE, Barcelona, 2018. i65
- 11 Lomax GP, Trounson AO. Correcting misperceptions about cryopreserved embryos and stem cell research. Nat Biotechnol 2013; 31 (04) 288-290
- 12 Hoffman DI, Zellman GL, Fair CC. , et al; Society for Assisted Reproduction Technology (SART) and RAND. Cryopreserved embryos in the United States and their availability for research. Fertil Steril 2003; 79 (05) 1063-1069
- 13 Snow D, Cattapan A, Baylis F. Contesting estimates of cryopreserved embryos in the United States. Nat Biotechnol 2015; 33 (09) 909
- 14 Science Daily. July 3, 2018. Available at: https://www.sciencedaily.com/releases/2018/07/180703084127.htm . Accessed December 3, 2018
- 15 Wennerholm UB, Söderström-Anttila V, Bergh C. , et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod 2009; 24 (09) 2158-2172
- 16 Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 2012; 98 (02) 368-77.e1 , 9
- 17 Pinborg A, Loft A, Aaris Henningsen AK, Rasmussen S, Andersen AN. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006. Fertil Steril 2010; 94 (04) 1320-1327
- 18 Pinborg A, Wennerholm UB, Romundstad LB. , et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update 2013; 19 (02) 87-104
- 19 Wennerholm UB, Henningsen AK, Romundstad LB. , et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod 2013; 28 (09) 2545-2553
- 20 Maheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer?. Hum Reprod Update 2018; 24 (01) 35-58
- 21 Berntsen S, Pinborg A. Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART). Birth Defects Res 2018; 110 (08) 630-643
- 22 Mäkinen S, Söderström-Anttila V, Vainio J, Suikkari AM, Tuuri T. Does long in vitro culture promote large for gestational age babies?. Hum Reprod 2013; 28 (03) 828-834
- 23 Ishihara O, Araki R, Kuwahara A, Itakura A, Saito H, Adamson GD. Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. Fertil Steril 2014; 101 (01) 128-133
- 24 Zhang J, Wang Y, Liu H. , et al. Effect of in vitro culture period on birthweight after vitrified-warmed transfer cycles: an analysis of 4201 singleton newborns. Fertil Steril 2019; 111: 97-104
- 25 Nachtigall RD, Mac Dougall K, Harrington J, Duff J, Lee M, Becker G. How couples who have undergone in vitro fertilization decide what to do with surplus frozen embryos. Fertil Steril 2009; 92 (06) 2094-2096
- 26 Sweet CR, Papkov G, Wiedman-Klayum KC. , et al. The number of children living at home and the duration of embryo cryopreservation are significant risk factors for cryopreserved embryo abandonment. Fertil Steril 2016; 106 (03) e71
- 27 Cattapan A, Baylis F. Frozen in perpetuity: ‘abandoned embryos’ in Canada. Reprod Biomed Soc Online 2016; 1 (02) 104-112
- 28 Ethics Committee of the American Society for Reproductive Medicine. Disposition of abandoned embryos: a committee opinion. Fertil Steril 2013; 99 (07) 1848-1849
- 29 Tonkens R. Why should we discard all abandoned human embryos?. Fertil Steril 2013; 100 (04) e28
- 30 Gleicher N, Caplan AL. An alternative proposal to the destruction of abandoned human embryos. Nat Biotechnol 2018; 36 (02) 139-141
- 31 Alikani M. The debate surrounding human embryonic stem cell research in the USA. Reprod Biomed Online 2007; 15 (Suppl. 02) 7-11
- 32 Cohen J, Inge KL, Wiker SR, Wright G, Fehilly CB, Turner Jr TG. Duration of storage of cryopreserved human embryos. J In Vitro Fert Embryo Transf 1988; 5 (05) 301-303
- 33 Glenister PH, Whittingham DG, Lyon MF. Further studies on the effect of radiation during the storage of frozen 8-cell mouse embryos at -196 degrees C. J Reprod Fertil 1984; 70 (01) 229-234
- 34 Riggs R, Mayer J, Dowling-Lacey D, Chi TF, Jones E, Oehninger S. Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos. Fertil Steril 2010; 93 (01) 109-115
- 35 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 (04) 471-475
- 36 Parmegiani L, Garello C, Granella F. , et al. Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles. Reprod Biomed Online 2009; 19 (03) 374-379
- 37 Goldman KN, Kramer Y, Hodes-Wertz B, Noyes N, McCaffrey C, Grifo JA. Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy. Fertil Steril 2015; 103 (03) 662-668
- 38 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 (06) 614-619
- 39 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 (11) 2950-2957
- 40 Sekhon L, Lee JA, Flisser E, Copperman AB, Stein D. Blastocyst vitrification, cryostorage and warming does not affect live birth rate, infant birth weight or timing of delivery. Reprod Biomed Online 2018; 37 (01) 33-42
- 41 Tomlinson M, Morroll D. Risks associated with cryopreservation: a survey of assisted conception units in the UK and Ireland. Hum Fertil (Camb) 2008; 11 (01) 33-42
- 42 Alikani M. Cryostorage of human gametes and embryos: a reckoning. Reprod Biomed Online 2018; 37 (01) 1-3
- 43 McDonald CA, Valluzo L, Chuang L, Poleshchuk F, Copperman AB, Barritt J. Nitrogen vapor shipment of vitrified oocytes: time for caution. Fertil Steril 2011; 95 (08) 2628-2630
- 44 Parmegiani L, Maccarini AM, Rastellini A. , et al. Oocyte vitrification/storage/handling/transportation/warming, effect on survival and clinical results in donation programmes. Curr Trends Clin Embryol 2017; 4: 34-40
- 45 Mazur P. Equilibrium, quasi-equilibrium, and nonequilibrium freezing of mammalian embryos. Cell Biophys 1990; 17 (01) 53-92
- 46 Kushnir VA, Darmon SK, Barad DH, Gleicher N. New national outcome data on fresh versus cryopreserved donor oocytes. J Ovarian Res 2018; 11 (01) 2
- 47 Sansinena M, Santos MV, Chirife J, Zaritzky N. In-vitro development of vitrified-warmed bovine oocytes after activation may be predicted based on mathematical modelling of cooling and warming rates during vitrification, storage and sample removal. Reprod Biomed Online 2018; 36 (05) 500-507
- 48 Bielanski A. A review of the risk of contamination of semen and embryos during cryopreservation and measures to limit cross-contamination during banking to prevent disease transmission in ET practices. Theriogenology 2012; 77 (03) 467-482
- 49 Pomeroy KO, Harris S, Conaghan J. , et al. Storage of cryopreserved reproductive tissues: evidence that cross-contamination of infectious agents is a negligible risk. Fertil Steril 2010; 94 (04) 1181-1188
- 50 Selman H, Mariani M, Barnocchi N. , et al. Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. J Assist Reprod Genet 2007; 24 (09) 395-399
- 51 Criado E, Moalli F, Polentarutti N. , et al. Experimental contamination assessment of a novel closed ultravitrification device. Fertil Steril 2011; 95 (05) 1777-1779
- 52 Parmegiani L, Cognigni GE, Bernardi S. , et al. Efficiency of aseptic open vitrification and hermetical cryostorage of human oocytes. Reprod Biomed Online 2011; 23 (04) 505-512
- 53 Vajta G, Lewis IM, Kuwayama M. , et al. Sterile application of the Open Pulled Straw (OPS) vitrification method. Cryo Lett 1998; 19: 389-392
- 54 Parmegiani L, Accorsi A, Cognigni GE, Bernardi S, Troilo E, Filicori M. Sterilization of liquid nitrogen with ultraviolet irradiation for safe vitrification of human oocytes or embryos. Fertil Steril 2010; 94 (04) 1525-1528
- 55 Parmegiani L, Accorsi A, Bernardi S, Arnone A, Cognigni GE, Filicori M. A reliable procedure for decontamination before thawing of human specimens cryostored in liquid nitrogen: three washes with sterile liquid nitrogen (SLN2). Fertil Steril 2012; 98 (04) 870-875
- 56 Superior Health Council. Preservation of reproductive cells and tissues by vitrification. 2011
- 57 Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Available at: https://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:102:0048:0058:en:PDF . Accessed December 3, 2018
- 58 ASRM Statement on Second Report of Storage Tank Failure. Washington, DC: ASRM Office of Public Affairs; 2018;20(6) 8630