Carta Revisado por pares

Oocyte vitrification: a watershed in ART

2012; Elsevier BV; Volume: 98; Issue: 3 Linguagem: Inglês

10.1016/j.fertnstert.2012.07.1096

ISSN

1556-5653

Autores

Ana Cobo,

Tópico(s)

Sperm and Testicular Function

Resumo

You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/coboa-oocyte-vitrification-art-aneuploidy-blastocyst/Cryopreservation of the female gamete has represented an important challenge since the beginning of assisted reproduction given its potential for overcoming several of the problems that arise during fertility treatment. The reasons for the lack of success achieved with this technique until now are various and well known. Over the past 5–6 years, with the introduction and refinement of the vitrification process, the situation has changed radically. Thanks to the outcomes rendered by contemporary vitrification methods, oocyte cryopreservation has become a feasible, effective, and consistently used strategy of daily practice. A growing body of literature provides evidence of the consolidation of this technology. The availability of egg banks that allow oocytes to be cryostored affords great benefits to women undergoing IVF cycles with donated or with their own oocytes. This situation has opened a window of hope for the growing population of female cancer survivors and for women whose career choices challenge their biological clocks.Findings reported by Forman et al. (1Forman E.J. Li X. Ferry K.M. Scott K. Treff N.R. Scott Jr., R.T. Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after ICSI: a novel, paired randomized controlled trial using DNA fingerprinting.Fertil Steril. 2012; PubMed Google Scholar) in the current issue of Fertility and Sterility constitute important evidence of the safety of oocyte vitrification. Using a finely tuned study design, the authors conclude that rates of aneuploidy are not increased in embryos developed from vitrified oocytes of patients undergoing cycles with their own eggs. A cohort of oocytes retrieved from infertile patients was divided into two groups. One group of oocytes underwent temporary vitrification while their counterparts remained in culture. Insemination was performed simultaneously in both groups (fresh and warmed). Most intriguingly, the study design allowed the impact of vitrification per se to be evaluated, because blastocysts obtained from vitrified and fresh oocytes were transferred in pairs and embryonic aneuploidy was accurately determined in each one. The authors detected no differences between the two groups. In addition, the ongoing pregnancy rate per transferred embryo was similar for vitrified and fresh control oocytes. This clinical outcome is consistent with findings reported by other authors.In addition to providing evidence that transferable embryos obtained after oocyte vitrification have similar chances of culminating in pregnancy to those derived from fresh oocytes, the truly novel achievement of Forman and coworkers is their objective determination of the chromosomal status of implanted embryos following vitrification. Their results indicate that the machinery responsible for adequate chromosome segregation during anaphase is not impaired by the vitrification process or is restored afterwards.The overall efficiency of the IVF cycle reported by Forman and coworkers deserves special attention. They observed that both fertilization rates and embryo development were significantly lower in vitrified oocytes. However, contradictory evidence can be found in the literature, with other authors reporting similar fertilization rates after oocyte vitrification in ovum donation cycles (2Cobo A. Kuwayama M. Perez S. Ruiz A. Pellicer A. Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method.Fertil Steril. 2008; 89: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar, 3Trokoudes K.M. Pavlides C. Zhang X. Comparison outcome of fresh and vitrified donor oocytes in an egg-sharing donation program.Fertil Steril. 2011; 95: 1996-2000Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar), and one study describing significant differences in favor of vitrified oocytes (4Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar). In a large controlled and randomized clinical trial in which >3,000 vitrified donor oocytes were evaluated, statistically similar rates of fertilization, embryo development until day 3, and ongoing pregnancy were detected in vitrified vs. fresh oocytes (5Cobo A. Meseguer M. Remohi J. Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.Hum Reprod. 2010; 25: 2239-2246Crossref PubMed Scopus (408) Google Scholar). The outcome of that study provided valuable evidence of the safety of the vitrification procedure in terms of preserving the developmental potential of oocytes. Although it is true that blastocyst formation was not evaluated, data are available from studies that have analyzed blastocyst rates in vitrified oocytes. A study conducted with donor oocytes with a very similar design to that of Forman et al. showed highly comparable blastocyst formation rates between vitrified oocytes and fresh controls (48.7% vs. 47.5%) (2Cobo A. Kuwayama M. Perez S. Ruiz A. Pellicer A. Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method.Fertil Steril. 2008; 89: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar). It should be pointed out that only surplus embryos underwent extended culture in the study in question, which means that eligible embryos (those transferred while fresh) were not evaluated to see how they developed to the blastocyst stage. Other authors have addressed blastocyst rates achieved with vitrified oocytes in ovum donation cycles (approximately 60%), though they did not perform comparisons with fresh oocytes (4Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar, 6Schoolcraft W.B. Keller J.L. Schlenker T. Excellent embryo quality obtained from vitrified oocytes.Reprod Biomed Online. 2009; 19: 820-823Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar).It is important to emphasize that the abovementioned studies were performed with oocytes from young fertile donors. This leaves room for us to suggest that oocyte quality plays a key role in the inferior performance of vitrified oocytes observed by Forman and coworkers. Other explanations are possible, such as the timing of intracytoplasmic sperm injection, which may affect vitrified oocytes. However, these hypotheses are somewhat difficult to sustain in light of the positive outcomes Forman et al. achieved with fresh oocytes. Once again, the available evidence is contradictory. A prospective randomized sibling-oocyte study comparing embryo development in fresh vs. vitrified oocytes in patients undergoing cycles with their own oocytes (7Rienzi L. Romano S. Albricci L. Maggiulli R. Capalbo A. Baroni E. et al.Embryo development of fresh “versus” vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study.Human Reprod. 2010; 25: 66-73Crossref PubMed Scopus (359) Google Scholar) found no statistical differences between fertilization rates or embryo development/quality in the two groups. In addition, as pointed out by Forman et al., published data regarding fertilization and blastocyst formation after oocyte vitrification are consistent with those of studies using large series of fresh oocytes.One interesting question that may be posed is whether blastocyst transfer in IVF cycles conducted with vitrified oocytes is a desirable option in all cases. In our opinion, each patient should be considered on an individual basis. We cannot deny the obvious: it is true that cycles conducted with vitrified oocytes are likely to “pay a toll” in terms of survival possibilities, though this “toll” may serve as a selection filter. Accordingly, in our ovum donation program, conducted with cryobanked gametes, more vitrified oocytes are required to achieve equivalent cumulative ongoing pregnancy rates in blastocysts than when early cleavage-stage embryos are transferred (unpublished data).Forman et al. put things in context when interpreting their data; they point out that the lower efficiency of vitrified oocytes is somewhat irrelevant if we consider “the lack of other options for most individuals employing oocyte vitrification.” The evidence that aneuploidy is not increased in vitrified oocytes is a welcome endorsement of the safety of the vitrification technique and constitutes a giant step toward its definitive validation as a strategy for fertility treatment. Indeed, it would seem a watershed has been reached in assisted reproductive technology. You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/coboa-oocyte-vitrification-art-aneuploidy-blastocyst/ You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/coboa-oocyte-vitrification-art-aneuploidy-blastocyst/ You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/coboa-oocyte-vitrification-art-aneuploidy-blastocyst/ Cryopreservation of the female gamete has represented an important challenge since the beginning of assisted reproduction given its potential for overcoming several of the problems that arise during fertility treatment. The reasons for the lack of success achieved with this technique until now are various and well known. Over the past 5–6 years, with the introduction and refinement of the vitrification process, the situation has changed radically. Thanks to the outcomes rendered by contemporary vitrification methods, oocyte cryopreservation has become a feasible, effective, and consistently used strategy of daily practice. A growing body of literature provides evidence of the consolidation of this technology. The availability of egg banks that allow oocytes to be cryostored affords great benefits to women undergoing IVF cycles with donated or with their own oocytes. This situation has opened a window of hope for the growing population of female cancer survivors and for women whose career choices challenge their biological clocks. Findings reported by Forman et al. (1Forman E.J. Li X. Ferry K.M. Scott K. Treff N.R. Scott Jr., R.T. Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after ICSI: a novel, paired randomized controlled trial using DNA fingerprinting.Fertil Steril. 2012; PubMed Google Scholar) in the current issue of Fertility and Sterility constitute important evidence of the safety of oocyte vitrification. Using a finely tuned study design, the authors conclude that rates of aneuploidy are not increased in embryos developed from vitrified oocytes of patients undergoing cycles with their own eggs. A cohort of oocytes retrieved from infertile patients was divided into two groups. One group of oocytes underwent temporary vitrification while their counterparts remained in culture. Insemination was performed simultaneously in both groups (fresh and warmed). Most intriguingly, the study design allowed the impact of vitrification per se to be evaluated, because blastocysts obtained from vitrified and fresh oocytes were transferred in pairs and embryonic aneuploidy was accurately determined in each one. The authors detected no differences between the two groups. In addition, the ongoing pregnancy rate per transferred embryo was similar for vitrified and fresh control oocytes. This clinical outcome is consistent with findings reported by other authors. In addition to providing evidence that transferable embryos obtained after oocyte vitrification have similar chances of culminating in pregnancy to those derived from fresh oocytes, the truly novel achievement of Forman and coworkers is their objective determination of the chromosomal status of implanted embryos following vitrification. Their results indicate that the machinery responsible for adequate chromosome segregation during anaphase is not impaired by the vitrification process or is restored afterwards. The overall efficiency of the IVF cycle reported by Forman and coworkers deserves special attention. They observed that both fertilization rates and embryo development were significantly lower in vitrified oocytes. However, contradictory evidence can be found in the literature, with other authors reporting similar fertilization rates after oocyte vitrification in ovum donation cycles (2Cobo A. Kuwayama M. Perez S. Ruiz A. Pellicer A. Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method.Fertil Steril. 2008; 89: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar, 3Trokoudes K.M. Pavlides C. Zhang X. Comparison outcome of fresh and vitrified donor oocytes in an egg-sharing donation program.Fertil Steril. 2011; 95: 1996-2000Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar), and one study describing significant differences in favor of vitrified oocytes (4Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar). In a large controlled and randomized clinical trial in which >3,000 vitrified donor oocytes were evaluated, statistically similar rates of fertilization, embryo development until day 3, and ongoing pregnancy were detected in vitrified vs. fresh oocytes (5Cobo A. Meseguer M. Remohi J. Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.Hum Reprod. 2010; 25: 2239-2246Crossref PubMed Scopus (408) Google Scholar). The outcome of that study provided valuable evidence of the safety of the vitrification procedure in terms of preserving the developmental potential of oocytes. Although it is true that blastocyst formation was not evaluated, data are available from studies that have analyzed blastocyst rates in vitrified oocytes. A study conducted with donor oocytes with a very similar design to that of Forman et al. showed highly comparable blastocyst formation rates between vitrified oocytes and fresh controls (48.7% vs. 47.5%) (2Cobo A. Kuwayama M. Perez S. Ruiz A. Pellicer A. Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method.Fertil Steril. 2008; 89: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar). It should be pointed out that only surplus embryos underwent extended culture in the study in question, which means that eligible embryos (those transferred while fresh) were not evaluated to see how they developed to the blastocyst stage. Other authors have addressed blastocyst rates achieved with vitrified oocytes in ovum donation cycles (approximately 60%), though they did not perform comparisons with fresh oocytes (4Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar, 6Schoolcraft W.B. Keller J.L. Schlenker T. Excellent embryo quality obtained from vitrified oocytes.Reprod Biomed Online. 2009; 19: 820-823Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). It is important to emphasize that the abovementioned studies were performed with oocytes from young fertile donors. This leaves room for us to suggest that oocyte quality plays a key role in the inferior performance of vitrified oocytes observed by Forman and coworkers. Other explanations are possible, such as the timing of intracytoplasmic sperm injection, which may affect vitrified oocytes. However, these hypotheses are somewhat difficult to sustain in light of the positive outcomes Forman et al. achieved with fresh oocytes. Once again, the available evidence is contradictory. A prospective randomized sibling-oocyte study comparing embryo development in fresh vs. vitrified oocytes in patients undergoing cycles with their own oocytes (7Rienzi L. Romano S. Albricci L. Maggiulli R. Capalbo A. Baroni E. et al.Embryo development of fresh “versus” vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study.Human Reprod. 2010; 25: 66-73Crossref PubMed Scopus (359) Google Scholar) found no statistical differences between fertilization rates or embryo development/quality in the two groups. In addition, as pointed out by Forman et al., published data regarding fertilization and blastocyst formation after oocyte vitrification are consistent with those of studies using large series of fresh oocytes. One interesting question that may be posed is whether blastocyst transfer in IVF cycles conducted with vitrified oocytes is a desirable option in all cases. In our opinion, each patient should be considered on an individual basis. We cannot deny the obvious: it is true that cycles conducted with vitrified oocytes are likely to “pay a toll” in terms of survival possibilities, though this “toll” may serve as a selection filter. Accordingly, in our ovum donation program, conducted with cryobanked gametes, more vitrified oocytes are required to achieve equivalent cumulative ongoing pregnancy rates in blastocysts than when early cleavage-stage embryos are transferred (unpublished data). Forman et al. put things in context when interpreting their data; they point out that the lower efficiency of vitrified oocytes is somewhat irrelevant if we consider “the lack of other options for most individuals employing oocyte vitrification.” The evidence that aneuploidy is not increased in vitrified oocytes is a welcome endorsement of the safety of the vitrification technique and constitutes a giant step toward its definitive validation as a strategy for fertility treatment. Indeed, it would seem a watershed has been reached in assisted reproductive technology. Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after intracytoplasmic sperm injection: a novel, paired randomized controlled trial using DNA fingerprintingFertility and SterilityVol. 98Issue 3PreviewTo assess the impact of oocyte vitrification on aneuploidy and reproductive potential by comparing vitrified and control oocytes from a single patient within a single cycle and a single fresh transfer. Full-Text PDF

Referência(s)