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OVARIAN
HYPERSTIMULATION SYNDROME (OHSS)
This is a potentially lethal iatrogenic complication occurring as
a consequence of ovarian induction. It is characterised by massive
extravascular exudation of fluid resulting in depletion of the intravascular
volume, and consequent haemoconcentration. The incidence varies
from 0.008% - 23%, severe forms being less common than the mild
form. In IVF cycles the incidence is 1-10%, and less than 4% in
cycles of ovulation induction. It manifests post HCG administration
or post conception usually between D3 and D7 (early OHSS) and, D12
- D17 (late OHSS).
OHSS is categorized as mild, moderate and severe.
Mild OHSS:
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The patient may present with abdominal distention or discomfort,
nausea, vomiting and/or diarrhea.
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The ovaries are enlarged (5-12 cm) with presence of small
cysts.
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Serum estrogen >150 micro gms/day
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Pregnanediol excretion >10 mg/day
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Moderate
OHSS
- Features
of mild hyperstimulation plus ultrasonic evidence of ascites.
Severe
OHSS - This is a life threatening condition.
- Large ovarian
cysts and ascites and/or hydrothorax.
- Haemoconcentration,
coagulation abnormalities and diminished renal perfusion and function.
Increased
estradiol levels and progesterone in the presence of androstendione
are known to provide the stimulus for induction of OHSS. The initiating
event is an increased capillary permeability in the enlarged ovaries
leading to extravasation of fluid into the peritoneal cavity.
Patients at risk of developing this syndrome are young patients
(less than 35 years) with PCOD and oligomenorrheic anovulation,
who have undergone ovulation induction with hMG. Mild OHSS is common
when there are more number of intermediate sized (9 - 15 mm) follicles.
Severe OHSS is more common when there are more number of small (5
- 8 mm) follicles.
No relationship has been defined between the occurrence of OHSS
and abortions, congenital malformations and ovarian cancer.
MILD OHSS usually resolves spontaneously within 2 -3 wks and requires
observation and regular follow up.
Cases of moderate and severe OHSS require hospitalization for investigation
of organ dysfunction, and monitoring to assess progress of the condition.
The woman is given intravenous fluids and 20% albumin solution.
She is advised not to restrict her oral intake. Anticoagulants are
given if there is evidence of hypercoagualability. Organ dysfunction
is dealt with accordingly.
Laparotomy may be necessary in cases of intraperitoneal hemorrhage,
rupture or torsion of ovarian cysts. In cases of massive ascites
abdominal paracentesis is performed.
OHSS may be prevented by the following measures:
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Withholding HCG when serum E2 levels >2000pg/ml with a total
number of more than 12mm diameter. Plasma Estradiol level
is the best predictor of OHSS. OHSS was rarely seen when
the E2 level was less than 1000pg/ml and seen more often
at levels more than 2500pg/ml. Another important factor
to consider is the slope of rise, i.e. the risk of OHSS
increases if the values are more than doubling.
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Delaying HCG - Controlled drift for 4 to 9 days with regular
follicular monitoring. HCG is then administered on day 12
to 16. A higher pregnancy rate was noted.
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GnRH agonists to trigger ovulation - Intra nasal buserlin
200microgms 8th hourly. The initial flare-up response is
used to trigger ovulation.
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Follicular aspiration - This empties the follicles of fluid
and granulosa cells and thus protects against OHSS. However,
this may cause intrafollicular haemorrhage, which could
affect follicular function later on.
- Human
albumin - 50 gms of human albumin I.V. over an hour at the
time of oocyte recovery. The only complication is the appearance
of a Flu-like syndrome (serum sickness). Albumin acts by
sequestering the vasoactive substances released from the
corpora lutea. It also maintains intravascular volume.
- Luteal
phase support - Natural progestogens are preferred for luteal
phase support in patients at risk for OHSS.
- Cryopreservation
of oocytes can ameliorate the severity of late OHSS avoiding
the serious risks but not eliminating occurrence.
- In
PCOs OHSS is prevented by using a combination of dexamethasone
and hMG. A gradual increase in the dosage of the gonadotrophins
lowers the risk of OHSS
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In conclusion
OHSS is a preventable complication of ovulation induction. Vigilance
and careful monitoring will go a long way in avoiding or minimizing
morbidity due to OHSS.
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