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Ovarian Hyperstimulation Syndrome (OHSS)

Introduction

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproductive technology (ART) characterised by ovarian enlargement and third-space fluid shift. Incidence of moderate to severe OHSS ranges from 1% to 5% of stimulated cycles. Early recognition and evidence-based prevention are critical to minimise morbidity and mortality.

Pathophysiology

OHSS is driven by exaggerated ovarian response to controlled ovarian stimulation:

• Administration of exogenous follicle-stimulating hormone (FSH) leads to multi‑follicular development.
• Triggering of final oocyte maturation with human chorionic gonadotrophin (hCG) or, less commonly, luteinising hormone (LH) surge analogue increases vascular endothelial growth factor (VEGF) and cytokine release.
• VEGF-mediated capillary permeability causes fluid shift from intravascular to third spaces (ascites, pleural effusion), haemoconcentration and hypovolaemia.

Classification

Based on clinical and laboratory findings:

Severity	Clinical Features	Laboratory / Imaging
Mild	Abdominal discomfort, ovaries 5–12 cm	Ultrasound: ovarian enlargement
Moderate	Nausea, vomiting, ascites, ovaries >12 cm	Haematocrit > 45%, US: moderate ascites
Severe	Oliguria, haemoconcentration, pleural effusion, thromboembolism risk	Haematocrit > 55%, creatinine > 1.2 mg/dL, liver enzymes elevated

Risk Factors

• Young age (< 35 years)
• Polycystic ovary syndrome (PCOS)
• High antral follicle count (> 24)
• Elevated serum oestradiol on trigger day (> 3 500 pg/mL)
• Use of hCG for luteal support or trigger
• Prior OHSS episodes

Prevention Strategies

1. Individualised ovarian stimulation with antagonist protocols and lower FSH doses to avoid excessive follicle numbers.
2. GnRH agonist trigger instead of hCG in antagonist cycles reduces OHSS risk by shortening luteotropic stimulus.
3. Dopamine agonists (e.g., cabergoline 0.5 mg daily for 8 days from trigger) attenuate VEGF receptor phosphorylation.
4. Coasting: withholding gonadotrophins when oestradiol levels are excessive until values decline.
5. Segmentation (‘freeze-all’): cryopreservation of all embryos and deferral of transfer until endometrial environment stabilises.

Clinical Features

• Abdominal distension and pain from ovarian enlargement and ascites.
• Gastrointestinal symptoms: nausea, vomiting, diarrhoea.
• Respiratory compromise: dyspnoea, pleural effusion.
• Haemodynamic changes: tachycardia, hypotension, oliguria, haemoconcentration.
• Thromboembolic events due to hypercoagulability.

Management

General Measures

• Monitoring: daily weight, abdominal girth, fluid balance, vital signs, haematocrit, electrolytes, renal and hepatic function.
• Hospitalisation for moderate to severe OHSS; mild cases may be managed outpatient with close follow-up.

Fluid and Haemodynamic Management

• Intravenous fluids: isotonic crystalloids; avoid excessive volume to prevent worsening ascites.
• Albumin infusion (20%, 100 mL at oocyte retrieval) in high‑risk patients may reduce progression to severe OHSS.
• Vasoactive support: judicious use of vasopressors if hypotension persists despite volume resuscitation.

Third-Space Fluid Removal

• Paracentesis: ultrasound‑guided abdominal drainage for tense ascites; replace intravascular volume with 4–8 mL/kg of crystalloids per litre removed.
• Thoracentesis for symptomatic pleural effusion.

Thromboprophylaxis

• Low molecular weight heparin (LMWH) prophylaxis until mobilisation and clinical resolution, given high risk of venous thromboembolism.

Anaesthetic Considerations

• Airway and ventilation: ascites and pleural effusion may compromise functional residual capacity; consider upright positioning and careful induction to avoid hypoxaemia.
• Fluid management: invasive monitoring (arterial line, central venous pressure) guides resuscitation; avoid fluid overload.
• Coagulation: assess for haemoconcentration and hypercoagulable state; ensure thromboprophylaxis peri‑operatively.
• Renal function: monitor urine output; adjust drug dosing for renal impairment.
• Regional anaesthesia: large ovarian cysts and ascites may increase intra‑abdominal pressure—consider ultrasound guidance for neuraxial blocks.

Links

• Oxytotics
• Gynaecological Surgery
• Maternal conditions

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References:

1. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634–1637.
2. Griesinger G, et al. 2019 ESHRE Guideline: Ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2019;2019(4):hoz022.
3. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome: a review. Hum Reprod Update. 2016;22(6):684–692.
4. Alvarez C, et al. Use of dopamine agonists in the prevention of OHSS: a systematic review and meta‑analysis. Reprod Biomed Online. 2020;40(3):401–409.
5. Seyhan A, Yücesoy İ, Berker B. Luteal phase support with GnRH agonist trigger: prevention of severe OHSS. Gynecol Endocrinol. 2021;37(5):467–472
6. The Calgary Guide to Understanding Disease. (2024). Retrieved June 5, 2024, from https://calgaryguide.ucalgary.ca/
7. FRCA Mind Maps. (2024). Retrieved June 5, 2024, from https://www.frcamindmaps.org/
8. Anesthesia Considerations. (2024). Retrieved June 5, 2024, from https://www.anesthesiaconsiderations.com/
9. Namavar Jahromi B MD, Parsanezhad ME MD, Shomali Z MD, Bakhshai P MD, Alborzi M MD, Moin Vaziri N MD PhD, Anvar Z PhD. Ovarian Hyperstimulation Syndrome: A Narrative Review of Its Pathophysiology, Risk Factors, Prevention, Classification, and Management. Iran J Med Sci. 2018 May;43(3):248-260. PMID: 29892142; PMCID: PMC5993897.

Summaries:

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