| Domain | Current finding | Quantitative evidence | Evidence type/source year | Knowledge-base annotations |
|---|---|---|---|---|
| Identifiers | Ovarian hyperstimulation syndrome (OHSS) is a primarily iatrogenic complication of controlled ovarian stimulation/ART; rare spontaneous forms also occur. MONDO identifier available. | MONDO:0011972; MeSH: D016471 (pqac-00000000, pqac-00000002, pqac-00000013) | Database association + clinical review, 2024 | MONDO:0011972; MeSH:D016471; category: complex/iatrogenic ovarian disorder |
| Epidemiology | Current incidence in modern IVF practice is low but not eliminated, with early and late forms recognized. | Danish cohort: 1.2% annual incidence across 186,168 cycles; Chinese study: 1.14% mean annual incidence across 1,581,703 cycles; Australian prospective antagonist-cycle cohort: 2.1% overall, 1.2% early, 0.9% late OHSS (pqac-00000011) | Human cohort/review, 2024 | ICD/phenotype note: early OHSS vs late OHSS; adult female reproductive-age population |
| Main trigger and VEGF mechanism | Final oocyte maturation exposure to exogenous hCG, or endogenous hCG from pregnancy, drives luteinized granulosa-cell VEGF production; VEGF/VEGFR2-mediated vascular hyperpermeability causes third-spacing, hemoconcentration, oliguria, pleural effusion, and thrombosis risk. | Moderate-severe OHSS reported in 3-8% in older mechanistic literature; severe OHSS 0.1-3% in some IVF series; VEGF elevated in OHSS granulosa cells and follicular fluid (pqac-00000003, pqac-00000029, pqac-00000031) | Human clinical + in vitro + animal model, 2022; review 2024 | Genes: VEGFA, KDR, FSHR, LHCGR; GO:0001525 angiogenesis, GO:0001568 blood vessel development, GO:0043114 regulation of vascular permeability; CL: granulosa cell, endothelial cell |
| Major risk factors | Consistently supported risk factors are PCOS/high ovarian reserve, young age, high AMH, high estradiol on trigger day, high follicle count, and high oocyte yield; prior OHSS also used clinically. | High-risk thresholds used in trials/reviews include AMH >3.4 ng/mL, peak E2 >3500 pg/mL, >25 follicles, >24 oocytes; trial eligibility often used E2 >3000-4000 pg/mL or >20 follicles/oocytes (pqac-00000022, pqac-00000023, pqac-00000013, pqac-00000015, pqac-00000019) | Human meta-analysis/trial protocols, 2022-2024 | HPO suggestions: Polycystic ovary morphology, elevated anti-Müllerian hormone, hyperestrogenemia; risk annotation: prior OHSS, PCOS |
| Hallmark phenotypes | Hallmarks are ovarian enlargement, abdominal distension/pain, ascites, nausea/vomiting, dyspnea/pleural effusion, oliguria, hemoconcentration, electrolyte disturbance, and thromboembolism in severe disease. | Severe criteria examples include Hct >45%, WBC >15,000/mm3, ovaries >100 mm, moderate-or-higher ascites; elevated AST/ALT occurs in ~30% of severe cases (pqac-00000008, pqac-00000020) | Human review + trial criteria, 2024/2015 registry text | HPO: Ascites, Pleural effusion, Abdominal distension, Oliguria, Hemoconcentration, Dyspnea, Enlarged ovary; imaging: transvaginal ultrasound |
| Prevention (standard/current) | Standard prevention centers on identifying high-risk patients, using GnRH antagonist stimulation, minimizing hCG exposure, GnRH agonist trigger where appropriate, individualized gonadotropin dosing, and freeze-all/cryopreservation strategies in high responders. | Antagonist-based prospective cohort incidence 2.1%; individualized follitropin-d in PCOS study: moderate OHSS 0% vs 5.9% and severe 0% vs 17.6% versus standard dosing (pqac-00000011, pqac-00000023) | Human review 2024 + case-control study 2024 | NCIT/management concepts: risk-adapted ovarian stimulation, embryo cryopreservation; ontology hints: CHEBI gonadotropins, GnRH agonists/antagonists |
| Prevention (drug evidence, adjunctive) | Among pharmacologic adjuncts, calcium, cabergoline, HES, and metformin have the strongest evidence; albumin is not favored because of limited benefit and possible pregnancy-rate reduction. | Network meta-analysis: calcium RR 0.14 (95% CI 0.04-0.46), HES RR 0.25 (0.07-0.73), cabergoline RR 0.43 (0.24-0.71); earlier network meta-analysis: aspirin RR 0.07, IV calcium RR 0.11, cabergoline RR 0.17, metformin RR 0.20, HES RR 0.26; albumin pregnancy RR 0.85 vs placebo (pqac-00000022, pqac-00000024, pqac-00000025) | RCT network meta-analyses, 2016/2022 | CHEBI/Drug terms: cabergoline, calcium gluconate, hydroxyethyl starch, metformin, aspirin; note: adjunct prophylaxis |
| Established management | Mild-moderate OHSS is generally managed conservatively with monitoring, fluid/electrolyte management, urine output assessment, and thrombosis risk assessment; severe disease may require hospitalization, paracentesis, albumin, and ICU-level support. | Review notes severe complications include renal impairment, respiratory distress, thromboembolism; severe early OHSS trial criteria used regression over 2-21 days and monitored Hct, WBC, ovary size, ascites, E2, progesterone, VEGF (pqac-00000006, pqac-00000020) | Clinical review 2024 + interventional protocol | NCIT suggestions: Paracentesis, Albumin administration, Intensive care unit care, Thromboprophylaxis; HPO: Acute kidney injury/oliguria, hydrothorax |
| Experimental trials | Active/recent interventional research includes calcium+diosmin vs cabergoline regimens, fludrocortisone for presumed mineralocorticoid deficiency physiology, early cabergoline timing, letrozole prophylaxis, montelukast, and luteal-phase cetrorelix for established severe early OHSS. These remain experimental/non-standard. | NCT06333691 (completed, n=180); NCT04351126 (completed, n=107); NCT03996434 (completed, n=300); NCT02670304 (completed, n=100); NCT03794037 (suspended, n=20); NCT02392520 (planned n=40) (pqac-00000013, pqac-00000015, pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000020) | ClinicalTrials.gov records, 2015-2025 updates | Trial annotations: prevention vs treatment; drug terms: diosmin, fludrocortisone, letrozole, montelukast, cetrorelix |
| Genetics/model evidence | Genetic susceptibility is supported but incompletely standardized clinically. FSHR mutations are linked to spontaneous OHSS; common FSHR/LHCGR polymorphisms influence ovarian response and may modify OHSS risk. Functional human-cell/rat evidence supports an EGR1-TIE1-PI3K-AKT axis upstream of VEGF in granulosa cells. | Open Targets disease-target evidence: FSHR (5 literature links), VEGFA (5), LHCGR (3), KDR (1); TIE1 knockdown attenuated OHSS progression in rat models and abolished hCG-induced VEGF in SVOG cells (pqac-00000000, pqac-00000029, pqac-00000031, pqac-00000032, pqac-00000033) | Database + systematic review + in vitro/animal study, 2018-2022 | Genes: FSHR, LHCGR, VEGFA, KDR, TIE1, EGR1; GO:0030335 positive regulation of cell migration/vascular remodeling context, GO:0001933 negative regulation of protein phosphorylation not established clinically; CL: granulosa-lutein cell; model: induced rat OHSS |
| Outcomes/prognosis | Most cases resolve with supportive care, but severe OHSS can be life-threatening. In recent small 2023 case-series data, pregnancy was often achieved but preterm birth was common; evidence remains limited. | 15-patient case series: 73.3% achieved pregnancy; preterm delivery 33.3% at 32-37 weeks, 33.3% at 28-32 weeks, 6.7% before 28 weeks; 73.3% severe OHSS (pqac-00000009, pqac-00000012) | Human case series, 2023 | Outcome annotations: hospitalization, preterm birth, pregnancy continuation; evidence level: limited/small single-center |


*Table: This table condenses the strongest gathered evidence on ovarian hyperstimulation syndrome across identifiers, epidemiology, mechanism, risk, phenotypes, prevention, management, trials, and genetics/models. It is designed to support rapid knowledge-base population while distinguishing established care from experimental approaches.*