Ovarian Hyperstimulation Syndrome (OHSS)

Definition and Overview

• Berek & Novak's Gynecology, p. 2100

Pathophysiology

• Increased protein-rich fluid secretion from stimulated ovaries
• Increased renin and prorenin within follicular fluid
• Increased capillary permeability mediated by angiotensin
• Vascular endothelial growth factor (VEGF) - expression in granulosa cells and serum is augmented by hCG, leading to increased vascular permeability
• A variety of inflammatory cytokines also contribute

• Berek & Novak's Gynecology, p. 2100
• Tintinalli's Emergency Medicine

Onset Patterns

• Berek & Novak's Gynecology, p. 2100

Severity Classification (Golan/Navot criteria)

• Berek & Novak's Gynecology, p. 2100-2101

Risk Factors

• Polycystic ovary syndrome (PCOS) or polycystic ovarian morphology
• Elevated anti-Mullerian hormone (AMH) >3.36 ng/mL
• Previous episode of OHSS
• Young age, low BMI

• E2 >3,500 pg/mL at hCG trigger → severe OHSS in 1.5% of patients
• E2 >6,000 pg/mL at hCG trigger → severe OHSS in 38% of patients

• 20 preovulatory follicles → 15% incidence of severe OHSS

• 20-29 oocytes retrieved → 1.4% severe OHSS; ≥30 oocytes → 22.7% severe OHSS
• Use of GnRH agonist protocol (severe OHSS ~9%) vs. antagonist protocol (~5%)
• Berek & Novak's Gynecology, p. 2101

Complications

• Jugular, subclavian, retinal, and extremity vein thrombosis
• Cerebral venous thrombosis
• Stroke, STEMI, sepsis, ARDS, pulmonary embolism

• Tintinalli's Emergency Medicine

Management

Outpatient (mild-moderate, stable)

• Limit activity, daily weight monitoring
• Fluid intake ≥1 L/day of electrolyte-balanced fluid
• Monitor fluid intake and urine output
• Daily telephone follow-up or clinic visit

Indications for Hospitalization

• Inability to tolerate oral hydration
• Hemodynamic instability
• Respiratory compromise
• Tense ascites
• Hemoconcentration, leukocytosis
• Hyponatremia or hyperkalemia
• Abnormal renal or liver function
• Decreased oxygen saturation

Inpatient Management

• IV fluids: Essential to correct hypovolemia, hypotension, electrolyte abnormalities, and oliguria - even though they may worsen ascites
• Albumin 25%: 50-100 mg IV every 4-12 hours if further intravascular volume expansion needed
• Diuretics: Only after hypovolemia is corrected, to address persistent weight gain and oliguria
• Thromboembolic prophylaxis: Mandatory
• Paracentesis (transvaginal or transabdominal, US-guided): For pain relief, hydrothorax, or persistent oliguria - rapid large-volume removal is acceptable in this typically young, healthy population with careful monitoring
• ICU admission for: hyperkalemia, renal failure, respiratory failure, or thromboembolic disease
• Berek & Novak's Gynecology, p. 2101

Prevention

Stimulation Protocol Modifications

• Lower initial gonadotropin doses (150-225 IU) for high-risk patients
• GnRH antagonist protocols rather than agonist protocols (reduce total dosage and duration)
• GnRH antagonists introduced after oocyte retrieval accelerate regression of severe early OHSS without adverse effects on pregnancy/live birth rates

Ovulation Triggering Strategies

• GnRH agonist trigger instead of hCG in antagonist cycles - very short half-life of endogenous LH surge reduces OHSS incidence/severity; preferred when fresh transfer not planned
• Low-dose hCG co-administered with GnRH agonist trigger - maintains acceptable pregnancy rates while reducing OHSS

Coasting

• Considered when E2 >4,500 pg/mL and/or 15-30 mature follicles present
• Gonadotropins withheld; daily E2 monitoring
• Trigger given when E2 falls to <3,500 pg/mL
• Switching from GnRH agonist to antagonist during coasting has been associated with improved outcomes

Other Preventive Measures

• Dopamine agonists (e.g., cabergoline) - a recognized indication for prevention of OHSS
• Metformin in PCOS patients - reduces OHSS incidence in those at risk for severe disease
• Cycle cancellation or freeze-all strategy - embryo cryopreservation with no fresh transfer eliminates the luteal-phase hCG rise that drives late OHSS
• Berek & Novak's Gynecology, p. 2101-2102

Recent Evidence (2024-2026)

OHSS in Pregnancy

Why Pregnancy Makes OHSS Worse

1. Exogenous hCG trigger initiates early OHSS
2. Endogenous hCG from the implanted embryo sustains and amplifies the syndrome, causing late-onset disease

• Comprehensive Clinical Nephrology, 7th Ed.
• Berek & Novak's Gynecology, p. 2100

Late-Onset OHSS (The Pregnancy-Associated Form)

• Comprehensive Clinical Nephrology, 7th Ed.
• Berek & Novak's Gynecology, p. 2100

Pathophysiology in the Pregnant State

• Release VEGF, cytokines, prostaglandins, and histamine
• Increase capillary permeability - causing protein-rich fluid to shift into third spaces
• Result in ascites, pleural effusions, pericardial effusions, and edema
• Produce hemoconcentration (elevated hematocrit) combined with reduced serum osmolality and hyponatremia - a characteristic triad

• Comprehensive Clinical Nephrology, 7th Ed.

Pregnancy Outcomes in OHSS

• Higher rates of biochemical pregnancy losses compared to patients without OHSS
• Similar rates of clinical pregnancy losses (once a heartbeat is established, clinical miscarriage risk is not significantly elevated)
• The presence of OHSS does not mandate termination of pregnancy
• Berek & Novak's Gynecology, p. 2100

Clinical Presentation

• Abdominal bloating and pain (most common initial symptom)
• Nausea and vomiting
• Peripheral edema
• Oliguria - from intravascular volume depletion
• Breathlessness and orthopnea - from ascites pushing up the diaphragm and/or pleural effusions
• Venous thromboembolism manifestations

• Full blood count and hematocrit
• Serum creatinine, electrolytes, and osmolality
• Liver function tests
• C-reactive protein
• β-hCG (confirms pregnancy and monitors hCG trajectory)
• Coagulation profile
• Abdominal ultrasound

Important: OHSS is not a common cause of fever or peritonitis. If these are present, ovarian torsion, rupture, intra-abdominal infection, and ectopic pregnancy must be excluded.

• Comprehensive Clinical Nephrology, 7th Ed.

Management During Pregnancy

General Measures

• OHSS is self-limiting but prolonged (10-20 days in pregnant women vs. ~7 days in non-pregnant)
• Hospital admission for moderate-to-severe disease

IV Fluids

• Crystalloids first-line - with close monitoring because of the risk of third-space accumulation
• Despite worsening ascites, fluids are essential to correct:
  • Hypovolemia and hypotension
  • Electrolyte abnormalities (especially hyperkalemia - a critical complication)
  • Oliguria

Colloids

• Human albumin solution as plasma volume expander - particularly when paracentesis is performed or when crystalloids are insufficient
• Albumin 25%, 50-100 mL IV every 4-12 hours for intravascular expansion

Diuretics

• Only after hypovolemia is corrected - premature diuretic use can worsen intravascular depletion
• Used for persistent weight gain and oliguria once volume status is restored

Paracentesis

• Transvaginal or transabdominal, ultrasound-guided
• Indicated for: symptomatic ascites, respiratory compromise, pleural effusions (hydrothorax), persistent oliguria
• Rapid large-volume drainage is acceptable in this typically young, healthy population with careful monitoring

Thromboprophylaxis - Critical in Pregnancy

• Prophylactic anticoagulation is mandatory - the combination of OHSS and pregnancy creates extreme thrombotic risk
• The risk for VTE is particularly high because:
  • Hemoconcentration increases blood viscosity
  • Pregnancy itself is prothrombotic
  • Immobility from pain/hospitalization
  • Vascular endothelial activation from cytokines
• Reported thrombotic events include jugular, subclavian, retinal, and extremity vein thrombosis, cerebral venous thrombosis, stroke, STEMI, and pulmonary embolism

Analgesia, Nutrition, Psychological Support

• Provided as part of inpatient care
• Respiratory function monitoring

ICU Admission

• Comprehensive Clinical Nephrology, 7th Ed.
• Berek & Novak's Gynecology, p. 2101
• Tintinalli's Emergency Medicine

The Freeze-All Strategy - Preventing Pregnancy-Driven OHSS

• All embryos are cryopreserved after retrieval (freeze-all strategy)
• No fresh transfer means no implantation, no endogenous hCG, and no late OHSS
• A frozen embryo transfer is performed in a subsequent natural or hormone-prepared cycle
• This strategy is particularly recommended in PCOS patients at high risk of severe disease

• Comprehensive Clinical Nephrology, 7th Ed.
• Berek & Novak's Gynecology, p. 3305

Monitoring Parameters in Hospitalized Pregnant OHSS Patients

Current Guidelines

Anaesthetic Management for IVF-Achieved Pregnancy

Why IVF Pregnancy Demands Special Anaesthetic Attention

• Vaginal bleeding
• Caesarean section (markedly elevated rate)
• Hypertension and pre-eclampsia
• Placenta previa
• Premature rupture of membranes

Pre-operative / Antepartum Assessment

Multidisciplinary Planning

• A multidisciplinary team meeting (obstetrician, anaesthetist, neonatologist, haematologist if PAS suspected) should be convened antenatally for all IVF pregnancies - particularly in the third trimester
• A documented peripartum management plan should exist before the patient arrives in labour
• Braunwald's Heart Disease, p. 1066

Baseline Assessment Should Include

Key Obstetric Complications and Their Anaesthetic Implications

1. High Caesarean Section Rate

• Avoids airway manipulation in potentially oedematous airways (pre-eclampsia, OHSS)
• Reduces blood loss vs. general anaesthesia
• Preserves maternal consciousness and neonatal safety
• Allows conversion from labour epidural to surgical block

2. Multiple Gestation (Twins, Triplets)

• Aortocaval compression is more severe and earlier in onset - strict left lateral tilt from 20 weeks; earlier and more exaggerated in multiples
• Respiratory compromise - elevated diaphragm from uterine distension; reduced FRC; rapid oxygen desaturation on induction
• PPH risk - uterine atony is markedly elevated; have oxytocin, ergometrine, carboprost, and tranexamic acid immediately available
• Neonatal team must be present for each infant; NICU notification mandatory
• Epidural placed early in labour in multiples - allows rapid conversion to surgical block for second twin complications

3. Pre-eclampsia

• Airway oedema - laryngeal and upper airway oedema is a specific risk; difficult intubation is more likely; grade the airway serially
• Epidural analgesia is preferred in pre-eclampsia - reduces hypertensive surges with contractions and reduces catecholamine-driven BP spikes
• Spinal anaesthesia for CS in pre-eclampsia is safe (contrary to older teaching) - but use vasopressors (phenylephrine preferred over ephedrine) cautiously
• Coagulopathy must be excluded before neuraxial block: platelets <75,000 is a contraindication to neuraxial; <100,000 is a relative contraindication
• Magnesium sulphate (given for seizure prophylaxis/treatment) potentiates neuromuscular blockers - reduce dose of NMBAs and monitor TOF carefully
• Avoid ergometrine in hypertensive patients - use oxytocin infusion instead

4. Placenta Previa and Placenta Accreta Spectrum (PAS)

• General anaesthesia is usually required for major PAS (percreta/increta) due to:
  • Anticipated massive haemorrhage
  • Prolonged surgical time
  • Likely hysterectomy
  • Need for invasive arterial monitoring
• Cell salvage should be set up and running before incision
• Large-bore IV access (2× 16G minimum) + arterial line pre-induction
• Massive haemorrhage protocol activated pre-emptively
• Interventional radiology (iliac balloon occlusion or embolisation) may be done under regional anaesthesia before conversion to GA
• Blood products (packed RBCs, FFP, platelets, cryoprecipitate) cross-matched and available before start
• Consider cell saver, intraoperative TEG/ROTEM for goal-directed haemostasis
• ICU bed booked pre-operatively

5. Residual OHSS at Time of Delivery

• Ascites raises intra-abdominal pressure - increases aspiration risk (Mendelson's syndrome); use rapid sequence induction (RSI) if GA needed
• Pleural effusions - reduce FRC further; anticipate difficult ventilation; have low threshold for post-op ventilation
• Hypoalbuminaemia - alters protein binding of drugs (opioids, local anaesthetics, benzodiazepines); drug effect may be unpronounced initially then prolonged
• Hyponatraemia/hyperkalemia - must be corrected before elective surgery; can cause arrhythmias during induction
• Oliguria - distinguish pre-renal (still from OHSS) vs. established AKI before oxytocin infusion decisions
• Neuraxial blocks in the presence of coagulopathy from severe OHSS: check coagulation before placing

6. Thromboembolism (VTE)

• Pharmacological thromboprophylaxis (LMWH) should be continued in the antenatal period and resumed 6-12 hours post-delivery
• Regional anaesthesia timing must account for LMWH: last prophylactic dose must be ≥12 hours before spinal/epidural; therapeutic dose ≥24 hours
• Thromboprophylactic stockings + pneumatic compression devices intraoperatively
• Early mobilisation post-delivery

7. Cardiovascular Disease (ART + Heart Disease)

• OHSS leads to fluid shifts that can precipitate cardiac decompensation
• These women fall into mWHO Class III-IV and require cardiac anaesthesia input
• Invasive haemodynamic monitoring (arterial line ± CVP) is standard
• Avoid fluid overload; use albumin judiciously
• Braunwald's Heart Disease, p. 1066

Labour Analgesia

If General Anaesthesia is Required

RSI is mandatory in:

• Any pregnant patient >18-20 weeks
• Especially with residual OHSS ascites (increased aspiration risk)

Key drug considerations:

• Suxamethonium remains the gold standard for RSI (1.5 mg/kg) unless contraindicated
• Rocuronium + Sugammadex is a valid RSI alternative (1.2 mg/kg rocuronium; have sugammadex 200 mg immediately available)
• Magnesium: if patient is on MgSO4 for pre-eclampsia, reduce NMBA dose and monitor TOF
• Volatile agents: maintain at 0.5-0.75 MAC until delivery to limit neonatal depression; increase after cord clamping
• Avoid high PEEP if bilateral pleural effusions from OHSS are present

Postoperative Care

• VTE prophylaxis: restart LMWH 6-12 hours after neuraxial removal / 12 hours after surgery
• Fluid balance: if OHSS history, tight fluid restriction post-CS; avoid aggressive IV crystalloid (worsens third-space accumulation)
• Neonatal considerations: if prematurity (common in IVF multiples and pre-eclampsia-driven early delivery) - NICU coordination essential
• Psychological support: IVF patients have often undergone prolonged fertility treatment; clear communication and emotional support are important in the perioperative period

Summary: Anaesthetic Risk Profile of IVF Pregnancy

Anaesthetic Considerations for Labour Management in IVF-Achieved Pregnancy

Step 1 - Admission Assessment (Anaesthetic Clerking on Labour Ward)

History

• Nature of infertility and IVF protocol used (agonist vs antagonist; number of embryos transferred)
• History of OHSS: severity, duration, any hospitalisation, residual pleural effusions or ascites
• Singleton vs multiple gestation (twins/triplets)
• Underlying cause of infertility: PCOS, endometriosis, uterine anomaly, Turner syndrome, systemic disease
• Previous uterine surgery (myomectomy, previous CS) - raises PAS/rupture risk
• Current medications: LMWH (timing of last dose is critical), aspirin, progesterone supplementation, antihypertensives, MgSO4

Examination

• Airway assessment (Mallampati, mouth opening, neck mobility, thyromental distance) - document formally; IVF patients with pre-eclampsia may develop rapid airway oedema
• Cardiovascular and respiratory examination
• Back examination for neuraxial access (scoliosis, prior epidural, prior back surgery)
• Fluid status (oedema, signs of residual OHSS ascites)

Investigations on Admission

Step 2 - Early Epidural: The Cornerstone of Labour Management

Rationale for Early Epidural in IVF Labour

Epidural Technique

• Epidural placed at L2-3 or L3-4 interspace
• Test dose: 3 mL of 2% lignocaine with 1:200,000 adrenaline - watch for tachycardia (intravascular) or motor block (intrathecal)
• Infusion: Bupivacaine 0.0625-0.1% + fentanyl 2 mcg/mL at 8-12 mL/hr (or PCEA - patient-controlled epidural analgesia)
• Aim: dermatomal level T10 bilaterally (covers uterine pain); advance to T4-6 for surgical conversion
• Document: insertion depth, dermatomal level achieved, motor block assessment (modified Bromage score), haemodynamic response

Timing

• Do not wait for a specific cervical dilatation - early placement is safe and beneficial, especially in high-risk IVF cases
• In pre-eclampsia: place as early as possible in labour, even before active phase if the patient is comfortable, to have a functioning catheter in situ

Step 3 - Specific Conditions During Labour

A. Pre-eclampsia in Labour

• Early epidural is the standard of care in pre-eclampsia in labour
• Epidural reduces blood pressure response to painful contractions
• Vaginal delivery is the safest mode in pre-eclampsia without obstetric contraindications (Bandyopadhyay et al., PMID 38730290)
• Increased invasive monitoring is required during labour and vaginal delivery

• Target: systolic <160 mmHg, diastolic <110 mmHg
• Antihypertensives: labetalol IV bolus (20-80 mg), hydralazine IV (5-10 mg bolus), or oral nifedipine
• Epidural helps reduce BP indirectly; do not rely on it as sole antihypertensive

• Check platelets before placement and recheck if worsening pre-eclampsia
• Platelets >80,000: neuraxial generally safe
• Platelets 50,000-80,000: risk-benefit discussion; consider in pre-eclampsia context
• Platelets <50,000: neuraxial contraindicated; use remifentanil PCA as alternative
• If HELLP syndrome develops: remove epidural catheter when safe (platelets rising); monitor for epidural haematoma

• Given for seizure prophylaxis in severe pre-eclampsia
• Potentiates non-depolarising neuromuscular blockers - if GA required, halve NMBA dose and monitor TOF rigorously
• MgSO4 is safe with neuraxial anaesthesia - no interaction concerns
• Monitor for MgSO4 toxicity: loss of patellar reflexes (first sign, ~5 mmol/L), respiratory depression (~7.5 mmol/L), cardiac arrest (>12 mmol/L)
• Antidote: calcium gluconate 10 mL of 10% IV - always at bedside

• Strict fluid restriction: 80 mL/hr total (IV + oral) to avoid pulmonary oedema
• A pre-eclamptic patient is NOT fluid-depleted despite low urine output - her vascular leak means IV fluid goes to third space
• Cautious vasopressor use for epidural-induced hypotension: phenylephrine is preferred (avoids worsening hypertension from ephedrine's chronotropic effect)

B. Multiple Gestation (Twins/Triplets) in Labour

• Labour and delivery must occur in a theatre-adjacent suite or directly in theatre
• Neonatal resuscitation teams for each infant must be present at delivery
• Anaesthetic team should be scrubbed or immediately available throughout second stage

• An early, well-functioning epidural is not optional in twin labour
• The interval between first and second twin delivery (ideally <30 min) may require:
  • External cephalic version (ECV) of second twin
  • Internal podalic version and breech extraction
  • Emergency CS for second twin - this is the most common reason for urgent conversion
• Without a functioning epidural, emergency GA is required for second twin complications - with all its associated risks in a potentially compromised airway

• Markedly exaggerated in multiple gestation - the uterus is larger and heavier
• Strict left lateral tilt throughout labour
• Wedge under right hip; manual uterine displacement for any supine procedure
• Monitor blood pressure every 5 minutes after epidural dose changes

• Elevated diaphragm from a large uterus significantly reduces FRC
• These patients desaturate faster than singleton patients during any apnoeic period
• Pre-oxygenate thoroughly before any procedure requiring GA
• If intubation is required: titrate PEEP cautiously; have BIPAP/NIV available post-extubation

• Uterine atony risk is markedly elevated
• Oxytocin infusion (not bolus): 40 IU in 500 mL at 125 mL/hr after delivery of last placenta; bolus doses cause cardiovascular collapse
• Have ergometrine, carboprost, misoprostol drawn up and ready
• Activate massive haemorrhage protocol if EBL >500 mL and not slowing

C. Residual OHSS During Labour

• Ascites: raises intra-abdominal pressure and aspiration risk - treat all such patients as having full stomachs; if GA required, RSI is mandatory
• Hypoalbuminaemia: prolongs duration of bupivacaine (protein-bound drug) - use lower concentrations; increased sensitivity to local anaesthetics; monitor for motor block spread
• Electrolytes: correct hypokalaemia/hyperkalemia and hyponatraemia before neuraxial or before any GA - both cause dysrhythmias under anaesthesia
• Oliguria in labour: distinguish pre-renal OHSS (cautious fluid challenge, albumin if severe) from established AKI - avoid aggressive crystalloid loading

D. Placenta Previa / Suspected PAS in Labour

• If previa is known: elective CS is the usual plan - labour itself is typically avoided
• If previa/PAS is suspected incidentally in labour or bleeding occurs:
  • Do not perform vaginal examination without ultrasound confirmation of placental position
  • Activate massive haemorrhage protocol
  • Arrange urgent senior anaesthetic and surgical input
  • Aim for CS under neuraxial if time allows; GA if haemodynamic instability

E. Thromboprophylaxis Timing Around Labour and Neuraxial

• Restart prophylactic LMWH ≥4 hours after catheter removal
• Do not remove epidural catheter within 12 hours of a prophylactic LMWH dose

Step 4 - Second Stage and Delivery

• Continuous CTG is mandatory in IVF labour (these are precious pregnancies, often after years of treatment)
• Consider fetal scalp electrode if external CTG technically difficult (e.g. maternal obesity, multiple)
• Anaesthetist should be physically present in theatre or at bedside for second stage in multiples

• Epidural should be maintained as a low-dose infusion during second stage, not turned off - "walking epidurals" or PCEA allow some motor function while retaining analgesia and the ability to rapidly increase block level

• Oxytocin: give as infusion, not IV bolus (3-5 IU bolus maximum if infusion not ready; bolus causes hypotension and tachycardia which can precipitate cardiac decompensation in pre-eclamptics)
• Monitor blood pressure at delivery - precipitous drop post-delivery from loss of aortocaval compression can cause maternal collapse

Step 5 - Immediate Postpartum Period

• Do not remove epidural catheter until platelet count confirmed adequate in pre-eclampsia (platelets often continue to fall for 24-48 hours postpartum in HELLP)
• Resume LMWH 6-12 hours post-vaginal delivery, 12 hours post-CS
• Monitor for postpartum haemorrhage - IVF patients have elevated PPH risk (uterine atony from multiple gestation, prolonged oxytocin use, placental site abnormalities)
• OHSS may paradoxically worsen postpartum as placental hCG continues briefly - watch for increasing ascites, respiratory compromise, and oliguria for 24-48 hours

Summary: Anaesthetic Labour Checklist for IVF Pregnancy