OHSS

Question 1

Categories of OHSS

Answer 1

Question 2

Pathophysiology

Answer 2

High serum oestradiol levels suppress expression of KISS1 receptors and increases VEGF and nitric oxide secretion via ER modulation.
Arteriolar vasodilation and an increase in capillary permeability that results in fluid shifting from intravascular to extravascular spaces.
Intravascular volume depletion and hyponatraemia.
VEGF integral to development of OHSS - involved in follicular growth, corpus luteum function, aniogenesis, vascular endothelial stimulation.
VEGF appears to be in responde to hCG.

Question 3

Risk factors

Answer 3

Young age
Thin
PCOs
AMH elevated
plasma estradiol levels during COH act as a guide but do not correlate well with incidence of OHSS.
20 follicles > or = to 11 should be a freeze all cycle.

Question 4

Definition of OHSS (ACCEPT)

Answer 4

Syndrome characterised by ovarian enlargement and fluid accumulation within the peritoneal and/or pleural and/or (rarely) pericardial cavities, following treatment with ovarian stimulating hormones. The action of LH or hCG is required to develop the syndrome.

Question 5

Early versus late OHSS

Answer 5

Early - occurs after COH and ovulatory dose of hCG. Sx begin 4-7 days after hCG trigger, resolve with menses.

Late onset- begins at least 9 days after the hCG trigger in response to the rising hCG of pregnancy, is more severe and lengthy (more likely with a multiple pregnancy).

Question 6

Admission rate from OHSS

Answer 6

1.4-1.9% in the first IVF cycle and 0.04-0.5% with OI.
Risk of death from OHSS is very low.

Question 7

Risk factors for OHSS

Answer 7

Risk factors pre-cycle start: (strong evidence)
1. AMH >24pmol/L, AFC > 24
2. Diagnosis of PCOS
3. Prior OHSS
4. Younger age

Stimulation related risk factors: (strong evidence)
1. Follicle number (>17-19, ≥10mm)
2. Oestradiol level (> 13000-18000pmol/L)
3. Oocytes retrieved (>15-18)

*Insufficient data on the influence of lean bosy weight on the risk of OHSS
follicle-stimulating hormone (FSH) receptor variants rare cause of OHSS

Reduced ovarian resrve reduces risk of OHSS

Other risk factors;
Black women inc risk
UE/tubal factor/ovulatory disorder - incr risk.

Question 8

Cycle managemen to reduce OHSS risk

Answer 8

1. GnRH antag over GnRH agonist cycles (Strong evidence grade A)
   Individualised gonadotrophin dosing to decrease the risk of OHSS (moderate evidence Grade B)
2. Lower starting dose of gonadotrophin and/or supplementing with oral OI meds (clomiphene or letrozole) may decrease risk of OHSS (moderate evidence Grade B)
3. Weak evidence to recommend coasting for prevention of OHSS (weak, grade C) - my interpretation is only in agonist cycle.
4. It is recommended to use a GnRH agonist to trigger oocyte maturation as a first-line strategy to reduce the risk of moderate-to-severe OHSS. (Strength of evidence: A; strength of recommendation: strong).
5. It is not recommended to use a lower dose for the hCG-only
   trigger as a strategy to reduce the risk of moderate-tosevere
   OHSS. (Strength of evidence: C; strength of recommendation:
   weak).
6. There is strong evidence that avoiding a fresh embryo transfer and cryopreserving embryos (freeze-only cycle) significantly reduces the risk of moderate-to-severe OHSS compared with fresh embryo transfer cycles. (Grade A)

Question 9

Evidence for adjuncts

Answer 9

1. Recommended in those at risk of mod-sev OHSS to start a dopamine agonist such as cabergoline on they day of hCG trigger or soon thereafter and continue for several days. 0.5mg daily 7 days in our unti (grade A)
2. Aspirin is not recommended as a primary strategy to reduce the incidence of OHSS (weak evidence that asprin reduces the incidence based on a limited number of mixed studies)
3. There is moderate evidence that metformin reduces the incidence of OHSS in patients with PCOS who are at high risk for OHSS in the setting of GnRH agonists but not antagonist stimulation protocols. (Grade B)
4. Not recommended to use volume expanders she as albumin in those at high risk of developing mod to severe OHSS (weak evidence can reduce rates of mod to severe OHSS grade C)
5. Letrozole in luteal phase not recommended to reduce mod-severe OHSS though one RCT did show a reduction compared to aspirin (Grade C)
6. Not recommended to try inosotol (myo or D-chiro), mifepristone or glucocorticoids - not recommended.