Ovarian hyperstimulation syndrome is an important cause of severe morbidity and
mortality in assisted reproduction.
(a) Which factors predispose to OHSS? (3marks)
(b) What steps will you take to minimise the risk of OHSS? (8 marks)
(c) How will you recognise OHSS? (4 marks)
(d) Briefly discuss its management. (5marks)
Common mistakes
● Classification and details of OHSS
● Treatment and management of the causes of OHSS
● Mentioning irrelevant points, e.g. OHSS does not occur with GnRH analogues (this is
not true and if you are uncertain do not mention it) – OHSS occurs in natural cycles!
● Vaginal examination is contraindicated in OHSS
● Scanning before induction of ovulation to determine suitability for induction. Listing
investigations for OHSS
● Inaccurate facts, e.g. features of OHSS include hirsutism, irregular periods and vaginal
bleeding
● Use of clomifene for more than 6 months inadvisable because of OHSS
● Stating that it only occurs in PCOS patients in whom injudicious use of gonadotropins
has occurred
● Defining the features of OHSS (enlarged ovaries, abdominal distension, nausea, vomiting, diarrhoea, and, in severe forms, ascites, pleural effusions, hypovolaemia, hypotension and polycythaemia)
A good answer will include some or all of these points
(a) Which factors predispose to OHSS? (3 marks)
● Predisposing factors:
● Large number of follicles (especially induced by gonadotropins and βhCG)
● βhCG administration
● Younger patients
● Pregnancy – four times higher incidence in conception cycles. Pregnancy is three
times more likely in OHSS cycles
● Low body mass index (weight) (BMI <19) ● PCOS (b) What steps will you take to minimise the risk of OHSS? (8 marks) ● Serial follicular tracking to ensure no hCG administration for more follicles ● Oestradiol levels >6000 pmol, do not administer βhCG
● Advice against sexual intercourse if oestradiol levels high or large number of follicles
● Progestogens rather than βhCG to support pregnancy
● Ovarian drilling/diathermy for PCOS
● Clomid® rather than gonadotropins
● hMG + GnRH agonists decrease the risk of OHSS compared to gonadotropins alone
(c) How will you recognise OHSS? (4 marks)
● Symptoms – mild, moderate or severe (abdominal pain, vomiting, chest pain, enlarged
abdomen)
● Ultrasound – follicles, ascites
● Biochemistry – deranged urea and electrolytes (U&Es), hypovolaemia, low urine output, pleural effusion – chest X-ray (CXR)
(d) Briefly discuss its management. (5 marks)
● Should be protocol driven:
● Mild cases may be managed at home – moderate to severe cases to be admitted
● Divided into several aspects:
● Symptom control:
● Pain relief – avoid non-steroidal anti-inflammatory drugs (NSAIDs) as these
may precipitate renal failure
● Nausea and vomiting – metoclopramide/prochlorperazine
● Fluid replacement – most of the fluid is in the extravascular compartment, hence the
intravascular volume is constricted and needs replacing:
● Oral if mild and no vomiting/nausea
● Intravenous – if moderate to severe and/or there is nausea and vomiting – colloids preferred to crystalloids
● Fluid accumulation:
● Drainage if necessary – ascites or hydrothorax
● Thromboprophylaxis:
● Thromboembolic deterrent (TED) stocking
● Low-molecular-weight heparin (Fragmin®)
Sample answer
(a) Which factors predispose to OHSS? (3 marks)
The factors predisposing to OHSS include the age of the patient (the younger the patient, the
greater the risk), PCOS, low body mass index (BMI <19), βhCG administration, high serum oestradiol levels during ovulation induction, and a larger number of follicles (>18–20 mm in
diameter) during ovulation and pregnancy.
Pregnancy is three times more likely in OHSS cycles.
(b) What steps will you take to minimise the risk of OHSS? (8 marks)
Minimising the risk of OHSS must involve reducing the predisposing factors. First, ovulation
induction is best undertaken by drugs that are least likely to induce the condition, e.g. use antioestrogen agents such as clomifene citrate instead of gonadotropins. However, this may not
necessarily be the case, as these drugs may be ineffective. Therefore, alternatives to
gonadotropins, such as ovarian drilling, must also be considered.
Where gonadotropins are
employed, the ovulation induction process must be monitored closely. This will include follicular tracking with ultrasound to ensure that there are not too many follicles ready to rupture.
This can be complemented with serum oestradiol estimations.
If the number of follicles above 12 mm in diameter is more than 15, or serum oestradiol levels are above 2000 pg/mL, then βhCG should be withheld.
This will delay, or prevent, release of the ova from the follicles.
In some cases, it has been suggested that delaying rather than omitting the βhCG may also
minimise the risk of OHSS.
Where ovulation induction is for a natural conception, advising against sexual intercourse
will minimise the risk of OHSS.
This will prevent pregnancy and therefore reduce the chances
of OHSS developing. If pregnancy does occur, the use of progestogens rather than βhCG to
support the early phase of pregnancy will significantly minimise the risk of OHSS.
Ovulation induction with GnRH agonists with βhCG or hMG is associated with a lower risk
of OHSS compared to the use of hMG and hCG.
Used in a pulsatile fashion, this has been
shown to result in successful pregnancy without the risk of developing the condition. In
patients who have raised oestradiol levels, GnRH agonists with βhCG or hMG may be used
during induction of ovulation with gonadotropins.
Imoedemhe et al. (1991) used 8-hourly
intranasal buserelin in patients with >4000 pg/mL oestradiol levels and achieved a 22 per cent
pregnancy rate with no case of OHSS.
Alternatively, follicular aspiration may be used.
Pregnancies after IVF are rarely complicated by OHSS, because of aspiration of the follicles.
Therefore, where there are many follicles above the threshold diameter, repeated aspiration
will minimise the risk of OHSS.
Although other methods of minimising the risk of OHSS have been employed, e.g. intravenous administration of albumin and also corticosteroids, these are not commonly used.
The most effective method of minimising this complication of superovulation is to monitor
the patient closely and to offer interventions that will minimise it.
It is also important to
identify early symptoms and signs of OHSS and to take the steps necessary to prevent progression.
(c) How will you recognise OHSS? (4 marks)
Ovarian hyperstimulation syndrome consists of ovarian enlargement, abdominal distension,
ascites, nausea, vomiting and diarrhoea, and, in severe forms, pleural effusion, hypovolaemia,
hypotension and polycythaemia. If improperly managed, it could be fatal.
Recognition should
start with a high index of suspicion and then the clinical features enumerated above. This can
be confirmed by ancillary investigations which must include USS for ascites, U&Es, liver function tests and, if indicated, a CXR.
(d) Briefly discuss its management. (5 marks)
Treatment should be protocol driven and intensive as this is a recognised cause of mortality.
Mild cases may be managed at home but moderate and severe cases should be admitted into
hospital. Treatment should be directed at the control of symptoms, fluid replacement,
removal of accumulated fluids and thromboprophylaxis.
With regards to symptoms, pain
should be treated with simple analgesics (avoiding NSAIDs) and nausea and vomiting treated
with antiemetics such a metoclopramide and prochlorperazine. Occasionally, something
stronger may have to be administered.
In OHSS there is constriction of the intravascular compartment, hence plasma expanders should be considered. If there is no nausea/vomiting and it
is mild, oral fluids should be prescribed. Where there is nausea and vomiting or if it is more
than mild, intravenous plasma expanders such as colloids may be offered. Drainage of extracellular fluid, especially that which affects the woman’s health, should be considered (e.g.
drainage of a pleural effusion).
An important cause of mortality in these patients, especially those with severe disease, is
venous thromboembolism.
Prophylaxis in the form of TED stockings, appropriate mobilisation and prophylactic low-molecular-weight heparin should be offerred.
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