Ectopic pregnancy (tubal, interstitial, cornual, abdominal, cesarean-scar)
PLANNED dossier — no manifest, package, or design brief on disk yet. Drug regimen captures ACOG 193 single-dose MTX 50 mg/m² IM with day 4/7 β-hCG surveillance + 2-dose / multi-dose MTX with leucovorin rescue + surgical pathway (laparoscopic salpingostomy vs salpingectomy per ESEP) + Rh prophylaxis + symptom management. Eligibility gate explicit: β-hCG <5000 (preferred <3500), no FCA, mass <3.5 cm, hemodynamically stable, normal renal/hepatic/CBC, no contraindications, reliable follow-up. GAPS — no RxCUIs (validate via npm run research:rxnav:validate); registry lacks ectopic-specific workup adapter (uses workup.pelvic_pain); no test_files; multi-dose MTX protocol simplified — production should include leucovorin schedule with stop rules; Rh dosing for very-early gestation (<12 wk = 50 µg) needs guideline cross-check before PRODUCTION. Deepened 2026-05-14 (shard-5-obped-id depth-pass-1): added co-located _briefs/ob.ectopic-pregnancy.v1.depth.md companion brief (non-.depth. slot held by 2026-04-27 Playbook-0.5 brief) + _research-bundles/ob.ectopic-pregnancy.v1.md. design_brief pointer repointed to the new .depth.md companion (in-scope per shard contract). Phenotype matrix surfaced (location: tubal-ampullary/isthmic/fimbrial/interstitial-cornual / non-tubal-cervical/ovarian/abdominal/cesarean-scar / PUL × hCG-tier <1000 expectant / 1000-5000 MTX-single / 5000-10000 MTX-2-dose-or-multi / >10000 surgical × hemodynamic-stable/unstable/ruptured × symptom-severity × prior-history × heterotopic). First-class TS field for phenotype matrix remains schema-blocked. Added new outpatient setting playbook covering methotrexate clinic follow-up (β-hCG day 4 + day 7 + weekly to <5; CBC + LFT at 1 wk; 2nd MTX dose if persistence; surgical fallback if MTX fails), RhoGAM verification (ACOG CO 818 2021; 50 µg <12 wk; 300 µg ≥12 wk), contraception counseling (≥ 3 months no pregnancy post-MTX due to teratogenicity; LARC / combined OC / barrier), preconception counseling (recurrence 10-15 % per prior ectopic; cumulative ≈ 25 % after 2 ectopics; early TVUS at 6-7 wk in next pregnancy), psychosocial screen (pregnancy-loss grief, PTSD risk after rupture, infertility-related distress), fertility evaluation (HSG / laparoscopy + ART counseling if 2nd ectopic), and post-bleed iron repletion (oral or IV). Added 'outpatient' to settings[] framing list. Severity-trigger cross-walk confirmed: all 7 user-required triggers (hemodynamic_instability_or_rupture, mtx_failure_day_4_to_7, mtx_contraindication_present, non_tubal_ectopic_location, heterotopic_pregnancy_suspected, rh_negative_unprotected, pul_with_rising_hcg_no_iup) are represented by existing severity_triggers[] rows; no new severity_trigger rows added this pass (existing rows pass audit lint). Appended 2 canonical PMIDs — Barnhart hCG curves 2004 (PMID 15466057) and ACOG Practice Bulletin 191 (2018, reaffirmed 2024) — PMID 29528616 when indexed via local PubMed mirror — bringing evidence.pmids from 5 to 7. Bayesian linkage (documented in co-located _briefs/ob.ectopic-pregnancy.v1.depth.md): pre-test priors per Barnhart 2004 (general first-trimester ectopic ≈ 1.5-2 %; pelvic pain + positive β-hCG in ED ≈ 6-16 %; prior ectopic 10-15 % recurrence; IVF 2-5 % with heterotopic 1-3 %). LR data: β-hCG rise < 53 % in 48 h LR+ ≈ 4-5 for ectopic vs IUP (Barnhart 2004 PMID 15466057); β-hCG > discriminatory zone (2000-3500 mIU/mL) + no IUP on TVUS LR+ ≈ 6-12 for ectopic (Connolly 2013); TVUS visualisation of extra-uterine sac + yolk sac LR+ > 100 (pathognomonic); hemodynamic instability + positive β-hCG LR+ ≈ 20 for ruptured ectopic (mandates emergent OR without imaging). Decision thresholds: T_treat = methotrexate at hCG < 5000 + asymptomatic + mass < 3.5 cm + no FCA + reliable follow-up (NNT ≈ 1.1-1.2 for treatment success in selected stratum); T_treat = surgical at hemodynamic instability OR rupture OR MTX contraindication OR MTX failure × 2 OR location-not-MTX-amenable (non-tubal); T_test = expectant at hCG < 1000 + falling + asymptomatic (NICE NG126 2019; ≈ 70 % success). Cross-dossier routing: gyn.ovarian-torsion.v1 (RLQ pain + reproductive-age — whirlpool sign distinguishes), gi.acute-appendicitis.core.v1 (β-hCG negative differential — always check β-hCG before CT in reproductive-age women), ob.postpartum-hemorrhage.core.v1 (intra-op massive bleeding overlay for ruptured ectopic — MTP 1:1:1 + TXA-within-3h-of-bleeding-onset is reasonable off-label adjunct), and Rh prophylaxis (ACOG CO 818 2021). Prehospital recognition state-of-play: encoded via severity_triggers[].fires (setting:OR_now in rupture_with_hemodynamic_instability row) + transitions-equivalent (ED escalation_triggers in ed playbook); a first-class 'prehospital' DossierSetting value is schema-blocked. Permissive hypotension during pre-hemostasis transport (SBP target 80-90 mmHg) is the prehospital fluid posture; full volume + 1:1:1 product replacement begins at OR. Fluids field (ectopic-rupture aggressive-resuscitation-after-OR pattern) blocked on FLUID_COMMAND_ENGINES allowlist decision — not landed this pass. Removed 2026-05-26: DELIVER 36027571 / ProMISe 25776532 / POINT 29766750 / REDUCE 23900119 PMIDs were copy-paste-template carryover from 2026-04-27 baseline — none are ectopic-pregnancy-specific trials — removed per the orchestrator-gated audit (docs/superpowers/notes/2026-05-26-citation-deep-audit.md).
Entry points (5)
- symptomPelvic / lower-abdominal pain with positive β-hCG (ACOG PB 193, 2018)pelvic_pain_with_positive_hcg
- symptomFirst-trimester vaginal bleeding (ACOG PB 193, 2018)first_trimester_vaginal_bleeding
- lab_abnormalityAbnormal β-hCG trend (rise <53% in 48 h or plateau — Barnhart NEJM 2009)abnormal_hcg_trend
- imagingNo IUP on TVUS with β-hCG above discriminatory zone (~3500 — ACOG PB 193, 2018)no_iup_at_discriminatory_zone
- symptomSyncope, shoulder-tip pain, or hemodynamic instability in known/possible pregnancy (suspected rupture — RCOG GTG 21, 2016)syncope_or_shock_pregnant
Required inputs (13)
- lmp_or_garequireddemographic • used at CONTEXTEstimated gestational age frames discriminatory β-hCG zone and TVUS expectations (ACOG PB 193, 2018)
- beta_hcg_quantrequiredlab • used at INITIAL_WORKUPQuantitative β-hCG drives MTX eligibility (<5000) and surveillance trend (15% drop day 4 → day 7 — ACOG PB 193, 2018)
- tvusrequiredimaging • used at INITIAL_WORKUPDefinitive imaging — IUP, adnexal mass, free fluid, fetal cardiac activity (ACOG PB 193, 2018; NICE 2024 ectopic)
- rh_typerequiredlab • used at TREATMENTRh-negative → RhoGAM 50–300 µg per gestational age and ACOG guidance (ACOG CO 818, 2021)
- cbcrequiredlab • used at INITIAL_WORKUPHemoglobin trend if rupture suspected; baseline for MTX (ACOG PB 193, 2018)
- creatininerequiredlab • used at TREATMENTMTX contraindicated if Cr elevated; renal clearance dependent (ACOG PB 193, 2018)
- ast_altrequiredlab • used at TREATMENTMTX contraindicated if LFT elevated (ACOG PB 193, 2018)
- sbprequiredvital • used at RED_FLAGSHypotension = rupture until proven otherwise (RCOG GTG 21, 2016)
- hrrequiredvital • used at RED_FLAGSTachycardia + hypotension = surgical OR now (RCOG GTG 21, 2016)
- prior_ectopicrequiredhistory • used at CONTEXT~10% recurrence; lower threshold for surgical management (Barnhart NEJM 2009)
- prior_tubal_surgery_pid_ivf_iudhistory • used at CONTEXTMajor risk factors — PID, prior tubal surgery/sterilization, IVF, IUD, smoking, age >35 (ACOG PB 193, 2018; Barnhart NEJM 2009)
- desires_future_fertilityrequiredhistory • used at TREATMENTSalpingostomy preserves tube but slightly higher persistence; salpingectomy if other tube healthy (ESEP Mol Lancet 2014)
- breastfeeding_or_immune_diseaserequiredmedication • used at TREATMENTMTX contraindicated in breastfeeding, immunodeficiency, active liver/renal disease, peptic ulcer, blood dyscrasia (ACOG PB 193, 2018)
12-phase flow (12)
- 1FRAMESuspect ectopic in any pregnant patient with pelvic pain, vaginal bleeding, or abnormal β-hCG trend; risk factors compound suspicion (ACOG PB 193, 2018; Barnhart NEJM 2009)inputs: lmp_or_ga, beta_hcg_quantadvance: pregnancy confirmed and ectopic on differential (ACOG PB 193, 2018)
- 2ENTRYCapture trigger: pelvic pain + β-hCG, abnormal trend, no IUP at discriminatory zone, or rupture features (ACOG PB 193, 2018)inputs: beta_hcg_quant, sbp, hradvance: trigger documented (ACOG PB 193, 2018)
- 3CONTEXTRisk-factor inventory (PID, prior ectopic, tubal surgery, IVF, IUD, smoking, age >35 — Barnhart NEJM 2009); fertility desires; allergies; current meds (ACOG PB 193, 2018)inputs: prior_ectopic, prior_tubal_surgery_pid_ivf_iud, desires_future_fertility, breastfeeding_or_immune_diseaseadvance: context complete (ACOG PB 193, 2018; Barnhart NEJM 2009)
- 4RED_FLAGSHypotension, tachycardia, syncope, peritoneal signs, shoulder-tip pain, free fluid on US → emergent OR with type-and-cross (RCOG GTG 21, 2016; ACOG PB 193, 2018)inputs: sbp, hradvance: rupture treated OR ruled out (RCOG GTG 21, 2016; ACOG PB 193, 2018)
- 5INITIAL_WORKUPQuant β-hCG, TVUS, CBC, BMP (Cr), LFT, Rh type, T&S; serial β-hCG q48h if PUL (ACOG PB 193, 2018; NICE 2024 ectopic)inputs: beta_hcg_quant, tvus, cbc, creatinine, ast_alt, rh_typeactions: panel.cbc, panel.renal, panel.lftadvance: diagnosis established or PUL surveillance plan (ACOG PB 193, 2018; NICE 2024 ectopic)
- 6BRANCHING_WORKUPPUL → serial β-hCG ± TVUS (NICE 2024 ectopic); suspected heterotopic in ART pregnancies; cesarean-scar / cornual / abdominal ectopic require MFM + IR + surgical consult (RCOG GTG 21, 2016)actions: workup.pelvic_painadvance: site identified or branched (NICE 2024 ectopic; RCOG GTG 21, 2016)
- 7DIFFERENTIALTubal (~95%) vs interstitial / cornual / cervical / cesarean-scar / ovarian / abdominal; rule out IUP missed, miscarriage, heterotopic, gestational trophoblastic disease, ovarian torsion, appendicitis (ACOG PB 193, 2018; Barnhart NEJM 2009)advance: phenotype assigned (ACOG PB 193, 2018; Barnhart NEJM 2009)
- 8RISK_STRATIFICATIONMTX eligibility checklist (β-hCG <5000, ideally <3500; mass <3.5 cm; no fetal cardiac activity; hemodynamically stable; normal Cr/LFTs/CBC; reliable for follow-up; no contraindications — ACOG PB 193, 2018); surgical indications (instability, rupture, MTX failure, contraindication, fertility complete — RCOG GTG 21, 2016)inputs: beta_hcg_quant, creatinine, ast_altadvance: pathway chosen (ACOG PB 193, 2018; RCOG GTG 21, 2016)
- 9TREATMENTMTX 50 mg/m² IM (single-dose — ACOG PB 193, 2018; consider 2-dose or multi-dose for higher β-hCG) OR laparoscopic salpingostomy (preserve tube) OR salpingectomy (other tube healthy or massive bleeding — ESEP Mol Lancet 2014); RhoGAM if Rh-negative (ACOG CO 818, 2021); expectant only in highly selected falling β-hCG <1500 with shared decision-making (NICE 2024 ectopic)inputs: beta_hcg_quant, rh_typeadvance: treatment delivered (ACOG PB 193, 2018; ESEP Mol Lancet 2014)
- 10DISPOSITIONOR for unstable / ruptured / MTX contraindication / failed MTX; outpatient with strict return precautions for MTX recipients with reliable follow-up; admit for observation if borderline stable (ACOG PB 193, 2018; NICE 2024 ectopic)advance: disposition assigned (ACOG PB 193, 2018; NICE 2024 ectopic)
- 11MONITORINGMTX: β-hCG day 4 and day 7 — expect ≥15% drop day 4→7; weekly until <5 mIU/mL (ACOG PB 193, 2018); surgical: weekly β-hCG until <5 if salpingostomy or any conservative procedure (ESEP Mol Lancet 2014); pain re-evaluation at 24, 48, 72 h post-MTX (separation pain expected — NICE 2024 ectopic)inputs: beta_hcg_quantadvance: β-hCG trending down or zeroed
- 12FOLLOWUPContraception counselling (avoid pregnancy ≥3 mo after MTX due to teratogenicity — ACOG PB 193, 2018); preconception counselling on recurrence risk (~10% — Barnhart NEJM 2009); early ultrasound in any future pregnancy; mental-health screening (pregnancy loss); future-fertility plan (NICE 2024 ectopic)advance: contraception + future-fertility plan documented