Give me new guidelines on NIPT
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NIPT non-invasive prenatal testing guidelines 2024 2025 ACOG SMFM ISPD
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ACOG SMFM NIPT cfDNA guidelines update 2025 recommendations expanded
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Here is a comprehensive summary of the newest NIPT/cfDNA guidelines:
NIPT/cfDNA Screening: Updated Guidelines (2025-2026)
Key Guideline Source
The most current guidance comes from SMFM Consult Series #74: "Cell-free DNA Screening for Aneuploidies: Updated Guidance" (Rink BD, Dugoff L, Kuller JA, 2025), formally endorsed by ACOG in November 2025. This document replaces the previous ACOG Practice Bulletin No. 226 (2020). The term "prenatal cfDNA screening" is now preferred over "NIPT."
Numbered Recommendations (with GRADE levels)
1. Common Trisomies - Universal Offer (GRADE 1B)
cfDNA screening for trisomies 21, 18, and 13 should be made routinely available to all obstetrical patients, regardless of age or baseline risk. It is the most sensitive and specific screening test for these conditions in any patient population. After pretest counseling, every patient has the right to pursue or decline.
- Performance: ~99% sensitivity for T21, ~96% for T18, ~91% for T13
- Available from 10 weeks gestation onward
- Remains a screening test - positive results require confirmation with CVS or amniocentesis
2. Sex Chromosome Aneuploidies - Opt-In Only (GRADE 1C)
Screening for sex chromosome aneuploidies (45,X; 47,XXX; 47,XXY; 47,XYY) should be available as an opt-in consideration with appropriate pretest counseling - not offered by default. Patients with a positive result for 45,X should be referred for posttest genetic counseling and diagnostic testing (consider maternal karyotype assessment).
3. Microdeletions - Not Recommended Routinely (GRADE 1C)
Routine general population screening for microdeletion conditions is NOT recommended. Patients specifically interested in 22q11.2 deletion screening may proceed only after counseling. For those seeking information on copy number variants broadly, diagnostic testing is preferred over cfDNA screening for microdeletion syndromes.
4. Genome-Wide Copy Number Variants - Not Recommended (GRADE 1C)
Routine cfDNA testing for large genome-wide copy number deletions or duplications is not recommended. Evidence for clinical utility remains insufficient.
5. Twin Gestations (GRADE 1B)
- cfDNA is recommended as a first-line screening option for T21 in twin gestations
- Detection rates for T18 and T13 in twins appear consistently high; cfDNA is recommended
- cfDNA for sex chromosome aneuploidies in twins is NOT recommended due to lack of data (GRADE 1C)
- cfDNA for higher-order multiples is NOT recommended (GRADE 1C)
6. Single-Gene Disorders - Not for Routine Use
cfDNA testing for single-gene disorders (e.g., de novo dominant or paternally inherited autosomal dominant conditions) is not recommended for routine use. Laboratories may offer it, but evidence on clinical utility and validity is insufficient, and complex counseling issues remain unresolved.
7. Rare Autosomal Trisomies (RATs)
Neither ACMG nor ISPD recommends routine cfDNA screening for RATs (trisomies other than 21, 18, 13) in unselected populations due to insufficient data.
Counseling Requirements (All Patients)
Pre-test counseling must cover:
- What the test screens for and its limitations
- Performance characteristics including positive predictive value (PPV) - which varies by population prevalence
- The distinction between screening and diagnosis
- Options to decline screening
- Post-test counseling is mandatory for any positive or non-reportable result
Positive results must be communicated clearly with the PPV, and patients should be referred to a provider with genetics expertise (genetic counselor, geneticist, or MFM specialist).
When cfDNA Should NOT Be Used (or Alternatives Preferred)
| Situation | Guidance |
|---|---|
| Vanishing twin syndrome | Serum screening preferred (demised twin placenta may shed aneuploid cfDNA, causing false positives) |
| Maternal organ transplant or stem cell therapy | cfDNA unreliable |
| Maternal mosaicism or translocation | cfDNA cannot capture these |
| Low fetal fraction | No-call result; may require repeat or alternative testing |
| Structural fetal anomalies on ultrasound | Offer diagnostic testing (CMA/karyotype), not cfDNA screening |
Fetal Fraction Considerations
- Inadequate fetal fraction (<4%) is a common cause of no-call results
- Associated with increased risk of adverse outcomes (per 2024 meta-analysis, PMID 39008086)
- Causes: obesity (most common), early gestational age, aneuploidy itself, low-molecular-weight heparin, ART
- A repeat test after 1-2 weeks is reasonable; persistent failure warrants genetic counseling
How This Differs From Previous ACOG 2020 Guidance
- More explicit opt-in framing for sex chromosome aneuploidies
- Stronger language against routine microdeletion and genome-wide CNV screening
- Clearer stance on twin gestations (cfDNA first-line for T21/T18/T13 in twins)
- Preferred terminology shifted from "NIPT" to "prenatal cfDNA screening"
- Single-gene disorder testing explicitly flagged as investigational only
Canadian Guideline (SOGC Guideline No. 456, 2024)
The Society of Obstetricians and Gynaecologists of Canada (SOGC) published an updated guideline in November 2024 (PMID 39419445). Key points:
- cfDNA (NIPS) is the most accurate method for detecting major aneuploidies
- Availability in the public health system is not universal across Canada
- Shared decision-making and counseling are central
- Consistent with SMFM/ACOG on limitations of microdeletion screening
Bottom line: The 2025 SMFM/ACOG guidance strongly endorses universal availability of cfDNA for the three common trisomies, introduces stricter limits on sex chromosome and microdeletion add-ons, and is more explicit about when conventional serum screening remains the better alternative.
Give md new ASRM guidelines for recurrent pregnancy los
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ASRM "recurrent pregnancy loss" "committee opinion" 2026 Fertil Steril definition evaluation antiphospholipid
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Excellent - I now have full data from the ASRM 2026 Committee Opinion (published Fertil Steril, available online April 29, 2026) plus the ScienceDirect abstract with key summary statements. Here is the complete breakdown:
ASRM Recurrent Pregnancy Loss: Committee Opinion (2026)
Source: ASRM Practice Committee. Recurrent pregnancy loss: a committee opinion. Fertil Steril 2026 (available online April 29, 2026). This replaces the previous 2012/2019 ASRM guidelines.
Definition
ASRM defines RPL as the spontaneous loss of two or more pregnancies, excluding confirmed molar or ectopic pregnancies. Pregnancies confirmed by urinary or blood hCG are sufficient to count - biochemical pregnancies are included in the definition. Up to 50% of RPL cases will have no clearly defined etiology.
Evaluation Guidelines
Recommended for ALL Patients
| Test | Method |
|---|---|
| Chromosome evaluation of miscarriage tissue | Array-based chromosome testing (preferred over karyotype) |
| Uterine cavity evaluation | HSG, saline infusion sonogram, or hysteroscopy |
Key update: ASRM now joins ESHRE and ACOG in recommending array-based chromosome testing as the first step in miscarriage evaluation - this replaces traditional G-banding karyotype as the standard approach, as SNP arrays can detect polyploidy and uniparental disomy that aCGH misses.
Recommended in Certain Circumstances
| Test | Indication | Method |
|---|---|---|
| Parental karyotypes | Miscarriage with unbalanced translocation found, OR no miscarriage tissue testing available | Blood karyotype of both partners |
| Antiphospholipid antibodies | Clinical criteria for APS, OR 3+ consecutive losses | Anticardiolipin IgG & IgM; Beta-2-glycoprotein IgG & IgM; Lupus anticoagulant |
| Thyroid (TSH) | Risk factors/symptoms present; euploid miscarriage; or no miscarriage testing available | TSH |
Note on APS testing: APS diagnosis requires BOTH clinical criteria (thrombosis or adverse pregnancy outcomes) AND persistent aPL antibodies confirmed on two occasions at least 12 weeks apart. RPL patients with true APS face serious obstetric complications.
Not Recommended (Explicitly)
| Test | Reason |
|---|---|
| MTHFR mutation testing | No proven clinical utility in RPL |
| NK cell testing | Insufficient evidence |
| Thrombophilia panel (inherited) | Treatment of inherited thrombophilia not beneficial |
| Microbiome testing (including mycoplasma/ureaplasma) | Not recommended |
Treatment Recommendations
Standard Recommended Treatments (for all RPL patients)
- Preconception optimization of maternal health conditions (e.g., lupus, hypertension)
- Psychological support
Treatments of Possible Benefit (Limited or Conflicting Evidence)
These are offered with appropriate counseling about the evidence base:
- Correction of uterine cavity abnormalities (uterine septum, polyps, submucosal fibroids, intrauterine adhesions)
- Progesterone support if bleeding occurs in the first trimester
- Empiric progesterone in the luteal phase
- Treatment of chronic endometritis
- Reproductive urology evaluation if elevated sperm DNA fragmentation is found
- Metformin for women with PCOS or insulin resistance
- IVF with PGT-A or PGT-SR (preimplantation genetic testing for aneuploidy or structural rearrangements)
- Donor gametes when a genetic cause is found or in advanced maternal age with diminished ovarian reserve
Treatments Proven Ineffective / No Evidence of Benefit
These should NOT be offered:
- Empiric aspirin and thrombolytics in the absence of positive APS testing
- Treatment of endometriosis and adenomyosis
- Treatment of hyperprolactinemia in the absence of ovulatory disorder
- Treatment of inherited thrombophilia
- Thyroid hormone supplementation in patients with isolated TPO antibodies or TSH < 4 mIU/L
- IVIG, intralipids, or prednisone (immunotherapy - explicitly not recommended)
Key Changes vs. Prior ASRM Guidance
| Topic | Prior (2012/2019) | Updated 2026 |
|---|---|---|
| Definition | 2+ losses | 2+ losses (unchanged); biochemical losses still count |
| Miscarriage tissue analysis | Karyotype | Array-based testing (SNP arrays preferred) |
| APS testing threshold | Often offered after 2 losses | Now tied to clinical APS criteria or 3+ losses |
| Immunotherapy (IVIG, intralipids) | Controversial/limited use | Explicitly not recommended |
| Sperm DNA fragmentation | Not addressed | Now in "possible benefit" category |
| Microbiome testing | Not addressed | Explicitly not recommended |
| Thyroid treatment | Treat if TPO positive | Not recommended for isolated TPO antibodies or TSH < 4 |
Prognosis Context
- Most miscarriages are sporadic and result from chromosomal abnormalities strongly influenced by maternal age
- As number of prior losses increases, the proportion with a chromosomally normal embryo (and therefore unexplained loss) rises - after 7+ losses, ~80% have a normal embryonic karyotype
- Parental chromosomal abnormalities (translocations, inversions) are found in 3-5% of RPL couples vs. 0.2-0.7% in the general population
The 2026 opinion places a stronger emphasis on genomic tissue analysis as the foundation of workup, explicitly discourages several popular but unproven immunological treatments, and carves out a more selective role for APS antibody testing based on clinical criteria rather than reflex testing in all patients.
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