Cookbook 354: Offline Clinical Reproductive Medicine OHSS Golan Staging & Cabergoline Prophylaxis Engine

"""
Cookbook 354: Offline Reproductive Medicine OHSS Golan Staging & Cabergoline Prophylaxis Engine
OpenPHR Clinical AI Working Group (https://openphr.org)
"""

import math
import numpy as np
import pandas as pd
from typing import Dict, List, Tuple, Optional
from dataclasses import dataclass

@dataclass
class OHSSTelemetry:
    patient_id: str
    age_years: float = 29.0
    bmi: float = 21.5 # Low BMI / PCOS phenotype = high risk
    has_pcos: bool = True
    antral_follicle_count: int = 34 # High baseline reserve
    # Controlled Ovarian Stimulation Telemetry
    total_follicles_ge_11mm: int = 24 # >= 20 follicles is high risk!
    peak_serum_estradiol_pg_ml: float = 5400.0 # > 4,000 pg/mL is high risk!
    oocytes_retrieved_count: int = 26 # >= 20 oocytes
    trigger_agent_planned_or_used: str = "hCG 10,000 IU" # "hCG 10,000 IU", "GnRH Agonist (Leuprolide 1mg)", "Dual Trigger"
    fresh_embryo_transfer_planned: bool = True # Freeze-all recommended!
    # Physical Exam & TVUS Telemetry
    clinical_symptoms: List[str] = None # ["Abdominal distension", "Nausea", "Dyspnea"]
    ovarian_diameter_max_cm: float = 13.5 # > 12 cm = Severe
    sonographic_ascites_location: str = "Gross ascites extending to upper abdomen" # "None", "Pelvic cul-de-sac", "Gross ascites extending to upper abdomen", "Pleural effusion"
    # Laboratory & Hemodynamic Telemetry
    hematocrit_percent: float = 48.2 # > 45% = Severe hemoconcentration!
    white_blood_cell_count_per_ul: float = 17500.0 # > 15,000 /uL
    serum_sodium_meq_l: float = 132.0 # Hyponatremia < 135
    serum_potassium_meq_l: float = 5.2 # Hyperkalemia > 5.0
    serum_creatinine_mg_dl: float = 1.2 # Mild renal impairment
    urine_output_ml_kg_hr: float = 0.40 # Oliguria < 0.5 mL/kg/h
    thromboembolic_event_present: bool = False

@dataclass
class OHSSEvaluationReport:
    patient_id: str
    golan_ohss_stage: str # "SEVERE OHSS (Grade 5)"
    ohss_risk_profile: str
    prevention_and_trigger_guidance: List[str]
    cabergoline_prophylaxis_order: str
    inpatient_resuscitation_protocol: List[str]
    safety_sentinels: List[str]
    clinical_asrm_eshre_directive: str

class OvarianHyperstimulationDecisionEngine:
    """
    Offline clinical engine for Golan OHSS staging, cabergoline VEGFR-2 prophylaxis,
    ASRM/ESHRE primary prevention gating, and hemoconcentration safety audit.
    """

    def stage_golan_ohss(self, d: OHSSTelemetry) -> Tuple[str, str, List[str]]:
        features = []

        is_critical = (
            d.hematocrit_percent >= 55.0 or
            d.white_blood_cell_count_per_ul >= 25000.0 or
            d.serum_creatinine_mg_dl >= 1.6 or
            d.urine_output_ml_kg_hr < 0.15 or
            d.thromboembolic_event_present or
            "Pleural effusion" in d.sonographic_ascites_location
        )

        is_severe = (
            d.ovarian_diameter_max_cm > 12.0 or
            "Gross ascites" in d.sonographic_ascites_location or
            d.hematocrit_percent >= 45.0 or
            d.white_blood_cell_count_per_ul >= 15000.0 or
            d.urine_output_ml_kg_hr < 0.50 or
            d.serum_creatinine_mg_dl >= 1.0 or
            d.serum_sodium_meq_l < 135.0
        )

        is_moderate = (
            d.ovarian_diameter_max_cm >= 8.0 or
            "Pelvic cul-de-sac" in d.sonographic_ascites_location
        )

        if d.hematocrit_percent >= 45.0: features.append(f"Severe Hemoconcentration (Hct {d.hematocrit_percent:.1f}% >= 45%)")
        if d.white_blood_cell_count_per_ul >= 15000.0: features.append(f"Leukocytosis ({d.white_blood_cell_count_per_ul:.0f} /uL >= 15,000)")
        if d.ovarian_diameter_max_cm > 12.0: features.append(f"Massive Ovarian Enlargement ({d.ovarian_diameter_max_cm:.1f} cm > 12 cm)")
        if "Gross ascites" in d.sonographic_ascites_location: features.append("Clinical Gross Ascites")
        if d.urine_output_ml_kg_hr < 0.50: features.append(f"Oliguria ({d.urine_output_ml_kg_hr:.2f} mL/kg/h < 0.50)")

        if is_critical:
            stage = "CRITICAL OHSS (Grade 6)"
            risk = "Life-threatening complication with acute organ failure, massive third-spacing, and high thromboembolism mortality."
        elif is_severe:
            stage = "SEVERE OHSS (Grade 5)"
            risk = "Severe hyperpermeability state requiring immediate hospital admission, volume expansion, and thromboprophylaxis."
        elif is_moderate:
            stage = "MODERATE OHSS (Grade 3)"
            risk = "Moderate fluid shift with ultrasonic ascites requiring outpatient surveillance and cabergoline prophylaxis."
        else:
            stage = "MILD OHSS (Grades 1-2)"
            risk = "Mild ovarian enlargement and distension; self-limiting with conservative hydration."

        return stage, risk, features

    def generate_prevention_plan(self, d: OHSSTelemetry) -> List[str]:
        plan = []

        is_high_responder = d.total_follicles_ge_11mm >= 18 or d.peak_serum_estradiol_pg_ml >= 4000.0 or d.oocytes_retrieved_count >= 20

        if is_high_responder:
            plan.append("1. PRIMARY PREVENTION - GnRH AGONIST TRIGGER:")
            plan.append("   • If prior to trigger: CANCEL hCG trigger. Administer Leuprolide acetate 1.0 - 2.0 mg SC (or Triptorelin 0.2 mg) to induce endogenous LH surge with rapid luteal regression.")
            plan.append("2. ELECTIVE 'FREEZE-ALL' EMBRYO CRYOPRESERVATION:")
            plan.append("   • CANCEL fresh embryo transfer. Cryopreserve all 2PN zygotes / blastocysts. Eliminates pregnancy-derived endogenous hCG and prevents late-onset OHSS.")
        else:
            plan.append("1. Standard stimulation protocol with close monitoring.")

        return plan

    def generate_cabergoline_order(self, d: OHSSTelemetry) -> str:
        return "Cabergoline 0.5 mg PO once daily at bedtime for 8 consecutive days (starting day of trigger / oocyte retrieval) to inhibit VEGFR-2 phosphorylation and reverse microvascular permeability."

    def generate_inpatient_protocol(self, stage: str, d: OHSSTelemetry) -> Tuple[List[str], List[str]]:
        protocol = []
        sentinels = []

        # Inpatient Medical Resuscitation for Severe/Critical OHSS
        if "SEVERE" in stage or "CRITICAL" in stage:
            protocol.append("1. INTRAVASCULAR VOLUME EXPANSION:")
            protocol.append("   • Administer Isotonic Normal Saline (0.9% NaCl) or Plasmalyte at 125-150 mL/h to restore renal perfusion.")
            protocol.append("   • If Hct remains >= 45% despite crystalloids: Administer 20-25% Human Albumin (50-100 mL IV over 2 hours) to increase intravascular oncotic pressure.")
            protocol.append("2. THROMBOPROPHYLAXIS (MANDATORY):")
            protocol.append("   • Enoxaparin 40 mg SC once daily + Graduated Compression Stockings (due to hypercoagulable third-spacing).")
            protocol.append("3. ULTRASOUND-GUIDED PARACENTESIS / CULDOCENTESIS:")
            protocol.append("   • Indicated for tense ascites, intractable pain, oliguria unresponsive to fluids, or respiratory compromise (relieves renal vein compression).")

            # Safety Sentinels
            if d.hematocrit_percent >= 45.0:
                sentinels.append("🚨 ABSOLUTE DIURETIC PROHIBITION: NEVER administer Loop Diuretics (e.g. Furosemide) to an intravascularly depleted patient with elevated Hematocrit (Hct >= 45%). Diuretics precipitate acute hypovolemic collapse, acute tubular necrosis, and FATAL THROMBOEMBOLISM!")

            if d.serum_potassium_meq_l >= 5.0:
                sentinels.append(f"🚨 HYPERKALEMIA ALERT (K+ {d.serum_potassium_meq_l:.1f} mEq/L): Withhold potassium-containing IV fluids and potassium-sparing agents. Maintain continuous ECG monitoring.")

        return protocol, sentinels

    def evaluate_case(self, data: OHSSTelemetry) -> OHSSEvaluationReport:
        stage, risk, features = self.stage_golan_ohss(data)
        prev_plan = self.generate_prevention_plan(data)
        cab_order = self.generate_cabergoline_order(data)
        inpatient_plan, sentinels = self.generate_inpatient_protocol(stage, data)

        directives = []
        directives.append(f"STAGING: {stage}.")
        directives.append("PRIMARY ACTIONS: GnRH agonist trigger + Elective Freeze-All + Cabergoline 0.5mg x 8d.")
        directives.append("INPATIENT: Volume expansion + Albumin + Enoxaparin VTE prophylaxis.")

        return OHSSEvaluationReport(
            patient_id=data.patient_id,
            golan_ohss_stage=stage,
            ohss_risk_profile=risk,
            prevention_and_trigger_guidance=prev_plan,
            cabergoline_prophylaxis_order=cab_order,
            inpatient_resuscitation_protocol=inpatient_plan,
            safety_sentinels=sentinels,
            clinical_asrm_eshre_directive=" ".join(directives)
        )

# Example Execution & Verification
if __name__ == "__main__":
    engine = OvarianHyperstimulationDecisionEngine()

    print("=" * 80)
    print("OpenPHR Clinical Reproductive Medicine OHSS Golan & Cabergoline Engine")
    print("=" * 80)

    # Test Case 1: 29-year-old female with PCOS undergoing IVF COS.
    # Telemetry: 24 follicles >= 11mm, E2 5400 pg/mL, 26 oocytes retrieved.
    # Exam & TVUS: Gross ascites, max ovarian diameter 13.5 cm.
    # Labs: Hematocrit 48.2% (Severe hemoconcentration), WBC 17.5k, K+ 5.2, Oliguria 0.40 mL/kg/h.
    # Staging: SEVERE OHSS (Grade 5).
    # Actions: Elective Freeze-All + Cabergoline 0.5mg x 8d + Albumin/NS expansion + LMWH Enoxaparin!
    # Sentinel: ABSOLUTE DIURETIC CONTRAINDICATION!
    ohss1 = OHSSTelemetry(
        patient_id="REI-IVF-9901",
        age_years=29.0,
        bmi=21.5,
        has_pcos=True,
        antral_follicle_count=34,
        total_follicles_ge_11mm=24,
        peak_serum_estradiol_pg_ml=5400.0,
        oocytes_retrieved_count=26,
        trigger_agent_planned_or_used="hCG 10,000 IU",
        fresh_embryo_transfer_planned=True,
        ovarian_diameter_max_cm=13.5,
        sonographic_ascites_location="Gross ascites extending to upper abdomen",
        hematocrit_percent=48.2,
        white_blood_cell_count_per_ul=17500.0,
        serum_sodium_meq_l=132.0,
        serum_potassium_meq_l=5.2,
        serum_creatinine_mg_dl=1.2,
        urine_output_ml_kg_hr=0.40
    )

    rep1 = engine.evaluate_case(ohss1)

    print(f"\n[Patient {rep1.patient_id} - OHSS Clinical Assessment]")
    print(f"Golan OHSS Stage: {rep1.golan_ohss_stage}")
    print(f"Risk Profile: {rep1.ohss_risk_profile}")
    print("\nPrevention & Trigger Guidance:")
    for p in rep1.prevention_and_trigger_guidance:
        print(f"  {p}")
    print(f"\nVEGFR-2 Prophylaxis Order:\n  {rep1.cabergoline_prophylaxis_order}")
    print("\nInpatient Medical Resuscitation:")
    for r in rep1.inpatient_resuscitation_protocol:
        print(f"  {r}")
    if rep1.safety_sentinels:
        print("\nSafety Sentinels:")
        for s in rep1.safety_sentinels:
            print(f"  🚨 {s}")
    print(f"\nASRM / ESHRE Consensus Directive:\n{rep1.clinical_asrm_eshre_directive}")