Literature DB >> 34223217

Impending ice age of assisted reproductive technology.

Pietro Bortoletto1.   

Abstract

Entities:  

Year:  2020        PMID: 34223217      PMCID: PMC8244374          DOI: 10.1016/j.xfre.2020.06.001

Source DB:  PubMed          Journal:  F S Rep        ISSN: 2666-3341


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In 1983, a team led by Alan Trounson in Australia reported the first human pregnancy following the transfer of an eight-cell embryo that had been previously cryopreserved for 4 months (1). Although this pregnancy ultimately was terminated at 24 weeks due to preterm premature rupture of membranes leading to a septic chorion amnionitis, the same team would achieve a live birth the very next year, ushering in a new era of assisted reproductive technology (ART) (2). It is impossible to overstate what a monumental leap forward this was for patients who now had the ability to cryopreserve supernumerary embryos, facilitate preimplantation genetic testing, and delay future childbearing. However, this leap became a jog and the jog turned into an outright sprint toward de facto cryopreservation, with multiple intended and unintended consequences. In this edition of F&S Reports, Christianson et al. (3) examine how embryo cryopreservation and use have “snowballed” in the United States during a 10-year period. Using data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, they examined more than 400,000 autologous fresh ART cycles in which at least one embryo was cryopreserved. They found that the percentage of freeze-only cycles in the United States increased from 15.6% in 2010 to greater than 40% in 2013 (test for linear trend, P<.001). During the 10-year period analyzed they calculated that roughly 1,950,000 embryos were cryopreserved–roughly the population of the state of Nebraska–less than 50% of which subsequently were transferred. Although the reasons for this increase are multifactorial, the authors point out that the shift from fresh to frozen cycles extends beyond the traditional ovarian hyperstimulation syndrome prevention. Increasingly, clinics are using a “one-size-fits-all” strategy of blastocyst cryopreservation followed by preimplantation genetic testing for aneuploidies (PGT-A) with subsequent frozen embryo transfer, the merits of which are widely and hotly debated. By design, this strategy necessitates a large number of embryos be available for cryopreservation to then use PGT results to facilitate a transfer order decision. As Christianson et al. (3) pointed out, the mean number of embryos cryopreserved per fresh ART cycle was six, but only a third of patients went on to undergo a frozen embryo transfer cycle using these cryopreserved embryos. Importantly, in this study cohort, 41.5% achieved a live birth with fresh transfer, leaving most cryopreserved embryos awaiting a spring that may never come. This ever-growing number of cryopreserved embryos without a permanent disposition adds a layer of complexity to decisions we ask our patients to make. Up to a third of patients may never return to provide a directive for disposition, and those that do must grapple with personal and religious belief systems that may be ill prepared to deal with the complexity of this uniquely modern decision (3). In 2019, the American Society for Reproductive Medicine Ethics Committee offered compassionate transfer–the transfer of potentially viable embryos in a location or at a time when pregnancy is highly unlikely to occur–as a viable alternative for cryopreserved embryos not intended for reproduction (4). However, this approach is fraught with complex ethical considerations for patients and physicians alike, leading to a glacial pace to determining disposition. As Christianson et al. (3) points out, it is difficult for couples to commit to a disposition decision so decisional regret is avoided by continuing to store embryos. The American Society for Reproductive Medicine suggests using a 5-year cut-off as the time in which an embryo can be considered “abandoned” and discarded after failed, exhaustive efforts to contact the individual or couple regarding disposition (5). With all great leaps forward, there is a point in which stopping and reflecting on the consequences of the innovation are required. Embryo cryopreservation undoubtedly has allowed women to exert greater control over their reproductive timeline, however, the push toward a “one-size-fits-all” in vitro fertilization strategy that demands blastocyst cryopreservation for PGT-A runs the risk of leaving behind patients who may benefit from fresh transfer. The art of ART lies in our ability to customize treatments to patients and their reproductive goals. In our haste to cryopreserve, let us not forget about the utility of the fresh transfer–a bespoke treatment strategy that gives every patient an opportunity to achieve a pregnancy, not just those whose embryos make it blastocysts and can be cryopreserved. After all, our patients will measure the success of treatment not by the number of embryos in a storage tank but by the families we will help them to create.
  4 in total

1.  Disposition of abandoned embryos: a committee opinion.

Authors: 
Journal:  Fertil Steril       Date:  2013-03-05       Impact factor: 7.329

2.  Compassionate transfer: patient requests for embryo transfer for nonreproductive purposes.

Authors: 
Journal:  Fertil Steril       Date:  2020-01       Impact factor: 7.329

3.  Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo.

Authors:  A Trounson; L Mohr
Journal:  Nature       Date:  1983 Oct 20-26       Impact factor: 49.962

4.  Birth after transfer of cryopreserved embryos.

Authors:  B G Downing; L R Mohr; A O Trounson; L E Freemann; C Wood
Journal:  Med J Aust       Date:  1985-04-01       Impact factor: 7.738

  4 in total

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