- Preimplantation Diagnosis: Basic Science and Clinical Practice
- New guidelines for best practice preimplantation genetic diagnosis and screening
- Preimplantation genetic diagnosis - Wikipedia
This reintroduction of PGS in the form of PGS 2 is mostly based on allegedly improved techniques and technologies, with ability to diagnose aneuploidies more accurately. In a review of PGS 1 we recently reached the conclusion that the failure of PGS 1, likely, was not, as suggested by proponents of PGS 2, the consequence of inadequate PGS 1 techniques and technologies but, primarily, due to incorrect patient selection.
Preimplantation Diagnosis: Basic Science and Clinical Practice
We, therefore, cautioned from uncritically accepting the notion that improvements in PGS 1 techniques and technologies, alone, would improve IVF outcomes [ 12 ]. We reviewed the medical literature via PubMed and Medline searches under appropriate keyword and phrases up to year-end The primary review was performed by one of the authors N. The primary review of the literature revealed 93 relevant articles.
Amongst those, 39 were chosen as reflective of published data on PGS 2, and as references with relevance to the presentation of context. Five of these references, providing context, were added based on suggestions received during the manuscript review process. It is important to note that all published papers in the English literature addressing PGS 2 during the search years were reviewed. This study presents all published data on PGS 2, independent of our quality assessment. In addition, we reviewed reference lists of reviewed papers for additional appropriate articles.
While this finding, alone, suggests that so far available PGS 2 data are insufficient to support the uncontrolled utilization of PGS 2 as a routine feature of IVF practice, our research did discover published studies, claiming to be represent results of clinical trials demonstrating outcome benefits for IVF following utilization of PGS 2. To make sure no relevant studies were overlooked, we also reviewed all currently registered PGS trials, cross-referencing the names of principal investigators under above noted key words and phrases in our literature search.
Here obtained results, therefore, are not necessarily surprising. Only one then registered clinical trial has, since, been completed in , has been reported, and will be discussed in detail below. The statistical methodologies utilized in this trial fully confirmed our then voiced concerns [ 12 ]. Absence of properly designed clinical trials is especially noteworthy as patient surveys suggest willingness to participate in such trials [ 13 ].
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- New guidelines for best practice preimplantation genetic diagnosis and screening.
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Though results of this systemic review, thus, have failed to demonstrate adequate supportive evidence for the clinical utilization PGS 2 outside of experimental frameworks, this review, nevertheless, offers additional potentially important insights into the current practice of PGS 2, presented below in the discussion section of this manuscript. Two studies, receiving extraordinary attention for claiming outcome benefits for PGS 2, appeared in print during In addition, at least one editorial opinion was supportive of PGS 2 [ 14 ], though others [ 15 ] and we [ 16 ] disagreed.
In this discussion section we, therefore, pay special attention to these two studies, partially reassessing their data, as reported by the investigators. A few major technical and methodological changes differentiate between the two:. Unless viable embryos reach blastocyst stage, patients are not even given a chance of embryo biopsy and chromosomal analysis in association with PGS 2. Not all embryos, however, reach blastocyst stage. Especially embryos from older women and younger females with prematurely low ovarian reserve often do not.
PGS 2 and PGS 1 outcomes can, and should, therefore, not be compared without statistically adjusting for difference in patient population. PGS 2 patients are clearly favorably selected in comparison. Older women and younger females with prematurely diminished ovarian reserve reach blastocyst stage with greatly diminished embryo numbers. Those patients who do reach embryo transfer in PGS 2 are, thus, automatically twice favorably selected. This is a principal reason why all so far published PGS 2 studies, including those claiming outcome benefits for IVF, have been reporting outcomes in highly favorably selected patients.
Only two so far published small studies have, however, pointed out this fact, one a small clinical trial of PGS 2 [ 17 ] and a small case control study, utilizing PGS 1, from our center [ 18 ]. That PGS 2, thus, automatically excludes significant patient populations, including older women who, in the initial utilization as PGS 1 represented the primary target population [ 4 ] is, therefore, neither communicated to the scientific community nor to patients receiving such treatments.
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This means that pregnancy rates have to be calculated with denominator cycle start rather than embryo transfer. Yet, every single paper so far published in the literature, claiming any kind of outcome benefit for PGS 2, reported pregnancy outcomes with reference point embryo transfer. All of these studies, therefore, breach one of the most basic rules of statistical outcome reporting in IVF and, simply, misrepresent outcomes.
Misleading outcome reporting is, unfortunately, increasingly prevalent in the U. Amongst a small number of U. Various companies and their respective assays now compete in the market place, with accuracy i. Some suggestions about efficacy can, however, be derived from a recently published study [ 20 ], though how individual testing platforms compare to each other also, still, needs to be established. In addition, increasing human evidence suggests that blastocyst stage cultures are associated with increased premature delivery risk in comparison to earlier stage embryo transfers [ 24 , 25 ].
Combined, these observations raise further questions about PGS 2, which is dependent on blastocyst stage embryo biopsy. The study by Harton et al. While there are technical differences between these newly reported testing techniques, and comparative studies between different commercial platforms are not available, they share the claim that by allowing for assessments of a complete chromosome complement they are more accurate in determining embryo aneuploidy than the prior exclusively on post-fertilization d-3 utilized FISH.
Results of this study, in at least general terms, should therefore also be applicable to other reported platforms allowing for aneuploidy testing of a complete chromosome complement.
New guidelines for best practice preimplantation genetic diagnosis and screening
If the study is viewed in this way, it does offer potentially important new insights into efficacy of PGS 2. A careful analysis of reported data, actually, offers further support for lack of therapeutic efficacy of PGS in general, and PGD 2 in particular.
This conclusion was, however, once again based on implantation and pregnancy rates with reference embryo transfer rather than cycle start. The study does, however, offer some interesting additional findings: Aneuploidy rates were Yet, implantation rates, even in those selected women who did reach embryo transfer, improved only by 9. The same question also arises in regards to presented data on pregnancy loss. Here, miscarriages after day-3 biopsy occurred in 9.
Since pregnancy outcome data in the study are not presented in total, like implantation and miscarriage rates, but stratified by age groups, these data are somewhat difficult to interpret. They are also presented with two different reference points, per embryo biopsy i. This statistical observation, therefore, represents the most convincing evidence in the manuscript of Harton et al.
Even considering previously noted obvious methodical weaknesses, this study, therefore, offers rather convincing evidence that a major argument of PGS 2 proponents, almost with certainty, is inaccurate. This, of course, raises further doubts about the hypothesis that PGS 2 represents a diagnostic clinical improvement over PGS 1, and that PGS 1 failed for technical reasons. Since, as noted earlier, embryo culture to blastocyst stage results in definite and significant clinical as well as cost disadvantages, the study by Harton et al.
Since published studies have so far been unable to prove pregnancy outcome benefits for PGS 2, proponents of the procedure have started to promote the procedure for new indications. A prime example is the alleged PGD 2-driven ability of reducing twin pregnancies by facilitating embryo selection for elective single embryo transfer eSET [ 27 ].
Preimplantation genetic diagnosis - Wikipedia
Forman et al. As this failed, their original intent was replaced by the listed secondary goal of the study, the reduction of twin pregnancies via eSET. We would argue that under generally accepted study reporting guidelines, such an unreported switch in study goals is inappropriate. Specifically, the original Clinical Trial Registration lists as Primary Outcome Measures: i Live birth rate per randomized patient; and ii Comparative live birth rates of patients with elective single embryo transfer eSET of chromosomally normal embryos after utilizing chromosome copy analysis, given the acronym Comprehensive Chromosome Screening, CCS and 2-embryo 2-ET transfer without CCS.
Only their Secondary Outcome Measures related to the risk of twinning. The published paper, however, does not refer to pregnancy rates in title of manuscript, and barely refers to pregnancy rates in the body of the manuscript. The manuscript, however, describes itself in the title as a randomized controlled trial of single blastocyst stage embryo transfer, and it really is neither. The study design per initial registration see above was for a non-inferiority trial, demonstrating non-inferiority of transfer of a single embryo after PGS 2 in comparison to transfer of two embryos at blastocyst stage without trophectoderm biopsy and aneuploidy determination.
In other words, even Pregnancy rates with single embryo transfer were, however, in absolute terms actually 4.
Basically leaving this fact unaddressed in their manuscript, and claiming non-inferiority, the authors concentrated on above described secondary goal of their study, assessing in the literature already well-described effects of single embryo transfer on reducing twin pregnancy rates in association with IVF. Reducing twin pregnancies represent a distinctively separate subject of considerable complexity from the primary goal of PGS 2 to improve IVF pregnancy and delivery rates.
We, indeed, have extensively addressed the concept of single embryo transfer in the literature [ 28 , 29 ]. As a topic of further discussion, it is beyond the framework of this commentary. Much more likely, their participation was solicited with the intent of improving IVF pregnancy and delivery chances, a proposition infertility patients are supportive of [ 13 ].
Patients who did not have at least one euploid embryo for embryo transfer in controls at least two blastocyst-stage embryos were removed from outcome considerations. Selection biases in favor of favorable patients, thus, occurred in this study at three separate stages. As in many previously reported studies, single embryo transfer thus, even after PGS 2, resulted in lower IVF pregnancy rates than double-blastocyst stage embryo transfer with chromosomally unscreened embryos.
Single embryo transfer, therefore, apparently will always reduce twin pregnancies but also always result in lower pregnancy rates than a 2-embryo transfer, raising significant questions about the utility of performing chromosomal analysis of embryos in even favorably selected women.
At minimum, these data suggest that even favorably selected patients, still, require further selection to identify sub-populations who may benefit from PGS 2 [ 12 , 18 ]. Who these patients are if such women, indeed, exist remains, however, to be determined. Even a suggestion that PGS 2 is responsible for the observed reduction in twin pregnancies in this study appears incorrect.
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checkout.midtrans.com/piedrahta-app-conocer-gente.php Appeared in BioNews Baby born with genetic disease after embryo test 'mistakes'. First baby born from 'cheaper' gene sequencing of IVF embryos. First study of chromosome test suggests increase in IVF success. Progress Educational Trust conference: Making the grade. Report backs role of PGS in assisted reproduction. Celebrating 20 years of preimplantation genetic diagnosis. The case for case-by-case regulation of PGD. By posting a comment you agree to abide by the BioNews terms and conditions Syndicate this story - click here to enquire about using this story.
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