Closed vitrification of human oocytes and blastocysts: outcomes from a series of clinical cases

Gook, Debra A.; Choo, Boon S; Bourne, Harold; Lewis, Kelly S.; Edgar, David

doi:10.1007/s10815-016-0748-7

Cited by 23 publications

(9 citation statements)

References 40 publications

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“…Since DMSO is the most commonly used as a cryoprotectant for freezing of oocytes and embryos for storage purposes, we propose that it is imperative to understand its biological effects on the developmental competence of mammalian embryos both in vitro and in vivo ; this remains a major concern in toxicological studies. 17 - 19 Recently, Zhou et al demonstrated that DMSO treatment affected the asymmetric division of mouse oocytes. 20 Detrimental effects of DMSO have also been reported in the development of both rat and zebrafish embryos.…”

Section: Introductionmentioning

confidence: 99%

The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study

et al. 2017

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Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should induce long-term negative effects on both pre- and post-implantation embryo development.Methods: DMSO induced oxidative stress, ER stress, autophagy, mitophagy, signaling responsible genes and proteins were determined by RT-qPCR, Western blotting, immunofluorescence, and confocal microscopy. DMSO induced mitochondrial dysfunction was measured by transmission electron microcopy and JC-1 assay. Apoptosis was estimated using TUNEL and comet assay. Post-implantation embryo developmental capability was estimated by implantation site and fetus numbers.Results: Exposure to DMSO induced an early oxidative stress response within 0.5 to 2 h in 1-cell zygotes by disrupting the balance of pro- and anti-oxidants. Notably, DMSO-treated 2-cell embryos showed increased expression of unfolded protein response genes such as Hspa5, Hsp90b1, Ddit3, Atf4, and Xbp1. As a result, the development of many embryos is arrested at the 2-cell, 4-cell, or morula stages in a dose-dependent manner. Further, DMSO-induced endoplasmic reticulum stress increased mitochondrial Ca2+ levels, induced mitochondrial depolarization/dysfunction, and induced apoptotic cell death via the JNK/ATF2-dependent pathway. Consequently, treatment with DMSO increased the expression of autophagy initiation-, phagophore elongation-, and autophagosome formation-related genes, as well as localization of PINK1/Parkin, which are the main mediators of mitophagy, in mitochondria. Interestingly, DMSO causes cytotoxic effects in preimplantation embryos by inducing extensive mitophagy and autophagy. Especially, DMSO treatment decreased the inner cell mass and trophectoderm cell numbers as well as mRNA expression of B3gnt5 and Wnt3a in developed blastocysts, which decreased the implantation and developmental rates of full-term offspring after being transferred into pseudopregnant mice.Conclusion: These results provide a significant contribution to finding effective protective agents to combat DMSO mediated reproductive toxicity for application in human embryos in the near future.

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Section: Introductionmentioning

confidence: 99%

The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study

et al. 2017

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“…The basic characteristics of the selected literatures are listed on Table 1 . Results of the methodological quality assessment showed that 3 of the prospective studies were of low risk of bias [ 8 , 17 , 22 ], 2 were moderate [ 13 , 16 ] and 3 were of serious risk of bias [ 20 , 21 , 23 ]. The results of the quality assessment of the included retrospective studies were shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Regarding embryo cryopreservation, several studies reported comparable results between open and closed vitrification on survival rates after thawing [ 13 – 18 ]; while others demonstrated that closed vitrification outperformed the open one [ 19 , 20 ]. For oocytes vitrification, some suggested that ‘open’ was better than ‘closed’ in post-thawing survival rates [ 7 , 8 , 21 ]; others found no statistical differences between these two methods [ 22 , 23 ]. In addition, the rest of the embryologic and clinical outcomes differed from each other according to the studies mentioned above.…”

Section: Introductionmentioning

confidence: 99%

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes

Cai

Niringiyumukiza

et al. 2018

Reprod Biol Endocrinol

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BackgroundThe objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos.MethodsAn electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: ‘oocyte’, ‘embryo’, ‘blastocyst’, ‘vitrification’, ‘cryopreservation’, ‘device’, ‘survival rate’, ‘pregnancy rate’, etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results.ResultsTwelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR = 0.91, 95% CI: 0.80–1.03, P = 0.14; n = 2048) or clinical pregnancy rate (RR = 1.29, 95% CI: 0.80–2.06, P = 0.30; n = 150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive βHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P > 0.05). The results of the retrospective studies were similar as the prospective studies.ConclusionsIt is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

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“…One clear advantage that IVF centers have over those only involved in long-term sperm banking is in the continuous demonstration of the effectiveness of their procedures. Vitrification procedures are now providing recovery rates in excess of 85 to 90% for both oocytes and blastocysts, 34,35 which in turn translate into successful pregnancies. Performance testing the process of cryopreservation is therefore relatively straightforward since any significant reduction in recovery or pregnancy rate would prompt investigation of conditions during the addition of cryoprotectants, cooling, and storage.…”

Section: Risk and The Quality Of Frozen-thawed Materialsmentioning

confidence: 99%

Safe Storage of Gametes and Embryos: No Time for Complacency

Tomlinson¹

2018

Semin Reprod Med

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Recent serious untoward incidents in the field of assisted reproduction have once again highlighted the need for vigilance and in particular improved risk management in relation to the cryopreservation of gametes and embryos. Despite increasing levels of regulation and the requirement to adhere to total quality management practices, catastrophic incidents such as the death of an employee or the loss of a freezer full of patient embryos or sperm continue to occur sufficiently frequently for the industry to be concerned and highlight the need to make practices considerably safer. Potential losses through litigation could be considerable if the gamete or embryo bank is found to be negligent and fails to provide the necessary resources and implement recognizable control measures, which may include suitable facilities with adequate ventilation and oxygen monitoring, competent staff, and an appropriate level of well-maintained equipment; round-the-clock emergency procedures, early warning systems to deal with a failing vessel; and contingency to mitigate losses within a failing vessel and validated procedures which are embedded into the organization which lead to a high-quality end product, for example, frozen embryo while permitting a safe system of work. Since cross-contamination incidents have occurred in other disciplines such as blood cryostorage, which have led to the transmission of viral disease, the biological safety of the end product also requires careful consideration despite the fact that no similar incident appears to have come to light in the field of reproductive medicine. Implementation of risk reduction measures may include screening for blood borne viruses and possibly bacterial infection, careful selection of appropriate packaging plastics, and consideration as to whether packaging is suitable for immersion in liquid nitrogen. If not, vapor phase storage may be considered as additional mitigation. In the light of recent events, centers should place risk management of their cryofacilities and service high on the agenda and ensure that it becomes integral to future objective setting and business planning.

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Closed vitrification of human oocytes and blastocysts: outcomes from a series of clinical cases

Cited by 23 publications

References 40 publications

The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study

The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes

Safe Storage of Gametes and Embryos: No Time for Complacency

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