Ovarian Hyperstimulation Syndrome (OHSS)
The syndrome most commonly associated with In Vitro Fertilization (IVF) is Ovarian Hyperstimulation Syndrome (OHSS), which occurs in 1-10% of IVF cycles for clinically significant cases, with severe OHSS affecting 0.5-2% of cycles. 1
Incidence and Clinical Significance
- Moderate to severe OHSS complicates 1-10% of IVF cycles overall, though only 0.5-2% progress to severe disease 2
- In GnRH antagonist protocols specifically, hospitalization for OHSS occurs in 2.1% of cycles (95% CI: 1.6-2.8%) 3
- Early OHSS presents in 1.2% of cycles (95% CI: 0.9-1.8%), while late OHSS occurs in 0.9% (95% CI: 0.5-1.3%) 3
- The overall absolute incidence of symptomatic thrombosis in standard IVF cycles is low at 0.1-0.3% 1
Risk Stratification by Severity
The risk of thrombosis escalates dramatically in severe OHSS, reaching up to 4.1% (95% CI: 1.1%-13.7%) 1. This represents a critical distinction:
- Without OHSS: VTE risk is approximately 0.2% 1
- With severe OHSS: VTE risk increases to 4.1%, representing a 20-fold increase 1
Thrombotic Complications Pattern
When thrombosis occurs with assisted reproductive technology 1:
- 90% of arterial events are associated with OHSS 1
- 78% of venous events are associated with OHSS 1
- 49 of 61 venous thrombosis cases involved veins of the neck and arm (unusual distribution) 1
- 98% of thrombotic events occurred after ovulation induction 1
- Venous events are delayed compared to arterial (42.4 days vs. 10.7 days post-embryo transfer) 1
High-Risk Patient Identification
Patients with polycystic ovarian disease represent the highest risk group for OHSS and require modified stimulation protocols 4:
- Use small starting doses of HMG with slow escalation 4
- Tailor dosage according to ovarian response 4
- Consider metformin addition, as it reduces OHSS incidence in PCOS patients (Grade I-A recommendation) 5
Pregnancy-Related Risk Amplification
Late OHSS is exclusively pregnancy-associated and carries higher morbidity 3:
- 100% of late OHSS cases occur in pregnancy cycles (vs. 40% of early OHSS) 3
- 72.7% of late OHSS cases are severe (vs. 42% of early OHSS) 3
- 40% are associated with multiple pregnancy 3
Life-Threatening Complications
In extreme cases, OHSS can progress to 2, 6:
- Deep vein thrombosis 2
- Respiratory distress 2
- Acute hepato-renal failure 2
- Death (rare but documented) 6
Critical Clinical Pitfall
The use of GnRH agonists for ovarian stimulation, despite initial expectations, is associated with a higher prevalence of OHSS compared to other protocols 4. This counterintuitive finding emphasizes that protocol selection significantly impacts OHSS risk, with GnRH antagonist protocols now preferred for high-risk patients 5.
Comparison to Other IVF-Associated Conditions
While polycystic ovary syndrome increases cardiovascular disease risk by 1.3-fold in reproductive-age women 1, and fertility treatment itself shows no increased risk of composite cardiovascular disease or stroke 1, OHSS remains the most clinically significant and immediate syndrome specifically caused by the IVF process itself 1, 2.