THE GOLD STANDARD OF GENETICS · SPECIALIST STUDY
Treat an embryo-biopsy result as a sample-based decision aid, not a complete portrait of an embryo or future child
Preimplantation genetic testing can help families and fertility teams answer a defined inherited-disease or chromosome question before embryo transfer. Its strength comes from matching the test to that question: PGT-M for a known monogenic condition, PGT-SR for a known structural chromosome rearrangement and PGT-A for chromosome-number assessment. Its limits come from the same biology that makes early development possible. A biopsy samples a few trophectoderm cells, not every cell and not the inner cell mass that forms the fetus. Mosaicism, allele dropout, amplification noise, recombination, contamination and embryo-laboratory handling can therefore change what a result means. A sound pathway confirms family variants and haplotypes before testing, validates the laboratory method, reports uncertainty without converting categories into destiny, preserves alternatives for mosaic and no-result embryos, recommends pregnancy testing appropriate to the question, and makes counselling a continuing process rather than a signature on a form.
This guide belongs to the Genetics subject root, the Gold Standard of Education, and the How X Works hub. It begins with a concrete decision, then tests whether the method still holds when the context changes.
Choose a reading route
Frame the inherited question · chapters 1, 2, 3
Build and control the test · chapters 4, 5
Interpret embryos without overclaiming · chapters 6, 7, 8
Decide and confirm · chapters 9, 10, 11
Counsel, audit and transfer · chapters 12, 13
The whole problem at a glance
| Question | Evidence needed | Unsafe shortcut |
|---|---|---|
| Which PGT pathway? | Known familial variant, rearrangement or defined aneuploidy question | Call every embryo test PGT-A |
| What was sampled? | Biopsy stage, cell number, identity and chain of custody | Biopsy equals whole embryo |
| What can mosaic mean? | Assay threshold, laboratory policy and counselling context | Mosaic equals abnormal child |
| What follows transfer? | Pregnancy screening or diagnostic plan appropriate to the question | PGT guarantees an unaffected birth |
The result is useful only when test design, embryo sampling, uncertainty and follow-up remain connected.
CHAPTER 1 OF 13 · Frame the inherited question
1. Name the reproductive question before ordering PGT
Begin with the family history, molecular diagnosis, chromosome finding or treatment objective. Separate avoiding a known condition from general chromosome-number selection. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A couple with a confirmed pathogenic CFTR variant asks about PGT-M; the team does not substitute PGT-A because the two tests answer different questions. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: pedigree; clinical reports; laboratory reports; variant nomenclature; inheritance pattern; reproductive goals; alternatives; referral question Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: PGT is not one universal test. A broad label can hide a mismatch between the family question and the assay. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Replace the known single-gene condition with a balanced translocation and rebuild the pathway as PGT-SR. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 1 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 2 OF 13 · Frame the inherited question
2. Confirm the familial finding and inheritance model
Review original reports, sample identity, classification, segregation and whether the variant or rearrangement is suitable for a reliable assay. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A research finding is confirmed in an accredited diagnostic laboratory before embryos are created and tested. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: original and confirmatory reports; samples; classification date; inheritance; penetrance; phenotype; segregation; responsible laboratory Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: A database label or family story alone is not a stable assay target, and incomplete penetrance changes counselling even when detection is accurate. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Keep the same variant but introduce uncertain classification and decide whether testing should pause. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 2 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 3 OF 13 · Frame the inherited question
3. Explain PGT-M, PGT-SR and PGT-A distinctly
Describe the target, method and residual uncertainty of each pathway in plain language, including what is not assessed. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A family chooses PGT-M for a known disorder and separately considers whether PGT-A would add a different, evidence-limited selection question. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: test type; target; validation; expected categories; exclusions; optional add-ons; cost; time; alternatives Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: Testing more does not automatically improve the chance of a baby, and an add-on should not be sold as part of the diagnostic target. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Remove PGT-A from the plan and show which monogenic claims remain unchanged. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 3 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 4 OF 13 · Build and control the test
4. Build a family-specific assay and haplotype model
For PGT-M, use direct variant detection with linked markers where appropriate, define informative relatives and test recombination and allele-dropout risks. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: Parental and grandparent samples establish which nearby markers travel with the familial variant before embryo DNA is analysed. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: family samples; marker informativeness; phase; recombination interval; primer or probe design; positive and negative controls; validation acceptance Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: A correct primer is not a complete PGT-M system if amplification failure or recombination can separate the marker from the variant. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Remove one informative relative and state which phase assumptions become weaker. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 4 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 5 OF 13 · Build and control the test
5. Protect embryo, gamete and sample identity
Use witnessing, unique identifiers, separation, traceability and reconciliation from oocyte and sperm through embryo, biopsy tube, result and transfer. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: Two embryos have similar laboratory labels, so the electronic and independent witness trail, not memory, determines which biopsy belongs to which embryo. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: patient identifiers; cycle; dish and tube IDs; witness events; operator; timestamps; storage; transport; deviations; reconciliation Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: Perfect molecular analysis on the wrong biopsy is a wrong result. Identity control is part of genetics, not clerical decoration. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Introduce a label discrepancy and stop interpretation until the chain is reconciled. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 5 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
Worked embryo-result interpretation
| Observation | Possible meaning | Next evidence | Do not claim |
|---|---|---|---|
| PGT-M result is unaffected | Target familial variant was not detected under the validated haplotype model | Review recombination and pregnancy confirmation plan | All genetic conditions are excluded |
| PGT-A result is mosaic | Biopsy contains a mixed copy-number signal | Laboratory review and individual counselling | The fetus will be mosaic |
| No result | Amplification, DNA quantity or quality was insufficient | Discuss re-biopsy risks, transfer or alternative plans | No result means abnormal |
| Euploid PGT-A result | No tested chromosome-number abnormality detected in biopsy | Routine care and advised prenatal options | Implantation or live birth is guaranteed |
Every category keeps the sampled tissue, validation limits and decision alternatives visible.
CHAPTER 6 OF 13 · Interpret embryos without overclaiming
6. Control biopsy stage, cell number and embryo handling
Record whether polar body, cleavage-stage or trophectoderm biopsy was used, how many cells were removed and whether the method is validated. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A day-five trophectoderm biopsy yields several cells, but the report still states that these cells contribute mainly to placenta rather than the fetus. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: embryo stage; morphology; cell number; biopsy operator; laser settings; handling time; cryopreservation; re-biopsy; laboratory validation Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: A larger sample is not the whole embryo, and biopsy can introduce risk even when many embryos continue normal development. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Move the biopsy from trophectoderm to a cleavage-stage single cell and rebuild amplification and error controls. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 6 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 7 OF 13 · Interpret embryos without overclaiming
7. Verify amplification, contamination and quality controls
Check DNA amplification performance, allele dropout, contamination, read or probe quality and control agreement before assigning a category. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: An embryo appears unaffected at the target locus but has marker imbalance and low amplification; it is reported no-result instead of reassuring. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: amplification metrics; allele balance; blank controls; parental contamination markers; read depth; copy-number noise; replicate policy; exclusion reasons Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: A clean-looking final category can conceal weak input. Threshold passing must be shown, not assumed. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Lower DNA quality while keeping the apparent target call fixed and decide whether the category survives. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 7 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 8 OF 13 · Interpret embryos without overclaiming
8. Interpret mosaic and segmental results as sample findings
State how the laboratory defines mosaic range, what copy-number pattern was observed and how platform, algorithm and biopsy composition limit inference. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A 40 percent intermediate chromosome signal is reported under the laboratory’s validated policy, not translated into 40 percent of the fetus. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: platform; algorithm; thresholds; chromosome or segment; noise; cell mixture; policy version; analyst review; alternative explanations Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: Mosaic percentage from bulk biopsy is not a direct cell count or prognosis, and laboratories may classify the same signal differently. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Keep the raw signal but change the laboratory threshold and explain why the label changes while biology does not. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 8 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 9 OF 13 · Decide and confirm
9. Separate embryo ranking from prediction of a child
Use available evidence and local policy to discuss transfer priority, implantation and miscarriage uncertainty without treating category as destiny. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A mosaic embryo is considered only after individual review when no euploid embryo is available; the discussion includes healthy births and lower average success without a guarantee either way. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: embryo cohort; morphology; PGT category; evidence base; maternal factors; clinic policy; patient values; alternatives; decision record Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: PGT-A is a selection tool. It cannot guarantee implantation, prevent every miscarriage or describe a future child’s health in full. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Change the cohort from six embryos to one mosaic embryo and reassess how options and values affect the decision. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 9 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
PGT decision gate
| Gate | Pass evidence | Remain open when |
|---|---|---|
| Indication | Question and PGT type are explicit | Screening and diagnosis are confused |
| Preparation | Family variant, haplotypes and assay validation are complete | Informative relatives or controls are missing |
| Embryo result | Quality, category, mosaic policy and uncertainty are reported | A threshold is treated as natural truth |
| Follow-up | Transfer and pregnancy confirmation plans are recorded | PGT is presented as a guarantee |
Consent must cover both expected categories and plausible surprises before biopsy or transfer.
CHAPTER 10 OF 13 · Decide and confirm
10. Handle no-result and discordant embryos openly
Define repeat analysis, re-biopsy, transfer, storage and non-transfer options, including added handling risk and the value of remaining uncertainty. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: One embryo has no result after adequate controls; the team discusses re-biopsy and transfer pathways instead of silently placing it below every abnormal category. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: failure stage; residual sample; embryo condition; re-biopsy validation; cumulative handling; timing; consent; alternatives; final disposition Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: No result is not positive, negative or low quality as a person. It is an unresolved test outcome. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Make the embryo the only one available and show why the uncertainty conversation becomes more important, not less. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 10 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 11 OF 13 · Decide and confirm
11. Plan pregnancy screening and diagnostic confirmation
Explain that PGT reduces a defined risk but does not replace pregnancy care; offer screening or diagnostic testing appropriate to the PGT type and family question. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: After PGT-M transfer, the family receives a documented plan to discuss chorionic-villus sampling or amniocentesis rather than being told confirmation is unnecessary. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: PGT target; residual risk; transfer record; pregnancy status; screening options; diagnostic options; timing; procedural risks; responsible clinician Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: A normal PGT result does not exclude de novo variants, all chromosome conditions or unrelated congenital problems. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Change from PGT-M to a mosaic PGT-A transfer and rebuild the prenatal counselling questions. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 11 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 12 OF 13 · Counsel, audit and transfer
12. Counsel before, during and after the cycle
Use non-directive, understandable counselling that covers alternatives, limitations, uncertain results, embryo disposition, emotional load and the right to pause. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: The family rehearses how it would respond to unaffected, affected, mosaic and no-result embryos before biopsy rather than deciding for the first time under time pressure. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: counselling notes; interpreter; understanding check; preferences; disposition choices; costs; alternatives; consent versions; follow-up Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: Consent is not a prediction that distress will disappear, and counsellors should not imply one morally correct reproductive choice. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: Add a language barrier and verify that uncertainty and alternatives survive interpretation. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 12 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
CHAPTER 13 OF 13 · Counsel, audit and transfer
13. Audit outcomes, corrections and policy drift
Track diagnostic failures, re-biopsy, implantation, miscarriage, prenatal discordance, births and corrected reports while protecting privacy and avoiding misleading denominators. Work with one family, one reproductive question, one IVF cycle, one embryo biopsy, one validated PGT method, one transfer decision and one confirmation plan. State the decision, specimen, record or person, the time boundary and the responsible owner before interpreting any result.
Worked example: A laboratory reviews all transferred embryos in the denominator and investigates a discordant prenatal result against biopsy, assay and identity records. Put the starting evidence, rule, decision, later observation and consequence on separate lines. This prevents a persuasive narrative from replacing a reproducible pathway.
Evidence to retain: cycle denominator; embryo categories; transfers; follow-up completeness; discordance; complaints; corrections; policy version; review action Preserve provenance, dates, versions, identity checks, responsible people and intended use. If evidence is missing, label the gap instead of turning absence into reassurance.
Boundary and misconception: Success among transferred embryos alone cannot show what happened to excluded or untransferred embryos, and rare outcomes need cautious interpretation. Test the strongest credible alternative explanation and name the new evidence that would change the conclusion. The pass condition is a bounded, reviewable claim, not the removal of uncertainty.
Evidence discipline: record the observation, version or time boundary that supports this chapter’s conclusion. Preserve the rejected alternative as well as the selected action. That makes a later review able to distinguish a changed world from an undocumented change of mind.
Changed-context transfer: A clinic changes its mosaic threshold and must compare policies without mixing old and new categories. The method transfers only if the decision question and measurement meaning survive the change. If either changes, rebuild the comparison rather than copying the earlier threshold or weight.
Chapter 13 check · what should survive an audit
- Name the exact decision, unit, time boundary and responsible authority.
- Preserve the supporting evidence and the strongest credible alternative.
- Record the next action, review date, stop rule and reopening condition.
Verification lab: work the decision twice
Compare a PGT-M referral for a known variant with a PGT-A add-on request. Write the exact question, assay, residual risk and confirmation plan for each.
A trophectoderm biopsy returns a mosaic result. Build two interpretations: one that overclaims a fetal diagnosis and one that preserves sampling, threshold and outcome uncertainty.
A no-result embryo is the family’s only embryo. Map re-biopsy, transfer, storage and stopping options with the evidence and values each requires.
Final review: distinguish family diagnosis, assay validation, biopsy result, embryo-transfer decision and prenatal confirmation. If one checkbox represents all five, the pathway is incomplete.
Limits and misconceptions
A biopsy is a sample
Trophectoderm cells do not represent every embryonic cell or directly measure the future fetus.
Mosaic is a laboratory category
Its threshold and meaning depend on method, signal, policy and evidence; it is not a simple percentage prognosis.
PGT-A is selection, not diagnosis of all disease
It tests chromosome-number patterns in the biopsy and does not guarantee a live birth.
Pregnancy confirmation still matters
PGT reduces a defined risk but does not replace appropriate prenatal counselling and care.
Questions readers ask
What is the difference between PGT-M, PGT-SR and PGT-A?
- PGT-M targets a known monogenic condition, PGT-SR addresses a known structural chromosome rearrangement and PGT-A assesses chromosome-number patterns.
Does a mosaic embryo mean a mosaic baby?
- No. It means the sampled biopsy produced a mixed signal under a defined laboratory policy; the whole embryo and fetal outcome remain uncertain.
Can PGT-A improve the chance of a baby?
- For most patients, authoritative reviews do not show improved cumulative live-birth chances, although miscarriage may be reduced in some settings. Individual circumstances matter.
Why can PGT-M need family samples?
- Linked markers can help detect allele dropout and establish which chromosome copy carries the familial variant.
What does no result mean?
- The laboratory could not make a reliable category under its quality rules. It does not by itself mean affected or unaffected.
Is prenatal testing needed after PGT?
- Pregnancy screening and diagnostic options should still be discussed because PGT has residual error and does not test every condition.
Practise, verify and continue
Build a PGT evidence map with family diagnosis, exact reproductive question, PGT type, assay validation, haplotypes, embryo identity, biopsy method, quality controls, result category, transfer options, pregnancy confirmation and follow-up.
Apply the method to testing a mosaic prenatal sample. Preserve sample identity, tissue biology, thresholds, alternatives and counselling, then rebuild the claims because placental and fetal sampling questions differ.
Practical evidence check
Before implementation, write a one-page evidence map with the decision, unit of analysis, version or time boundary, inputs, outcomes, uncertainty, authority and stop rule. Attach one worked case that passes and one that fails. A reviewer should be able to reproduce the reasoning without relying on the memory of the person who built the system.
Run one changed-context rehearsal before approval. Alter a mechanism rather than a cosmetic detail, then identify which calculation, safeguard or governance gate must change. Record any conclusion that does not transfer. This short rehearsal is often the fastest way to expose a hidden assumption before it becomes an operational dependency.
Related eduKate reading
Carrier screening, residual risk and panel limits
Prenatal diagnostic testing, mosaicism and result limits
De novo variants, parental mosaicism and recurrence risk
Mosaicism, variant allele fractions and tissue-specific detection
Authoritative sources and scope
UK Human Fertilisation and Embryology Authority: PGT-A evidence and risks
ESHRE good-practice recommendations for preimplantation genetic testing
ESHRE good-practice recommendations on chromosomal mosaicism in PGT
ESHRE good-practice recommendations for IVF laboratories
These sources support the testing distinctions and evidence practices described here. They do not replace patient-specific genetic counselling, reproductive counselling, diagnostic evaluation, laboratory validation, consent, local regulation or a clinician’s interpretation. All worked cases are fictional. An educational example, research result or database entry must not be used alone to diagnose, treat or change care.