OHSS- CURRENT ACCEPTABLE PREVENTION STRATEGIES
Neena Malhotra
Professor, ART Centre, Department of Obstetrics and Gynecology
All India Institute of Medical Sciences, New Delhi
malhotraneena@yahoo.com
Ovarian Hyper stimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction or
ovarian stimulation for assisted reproductive techniques (ART). In severe forms affects 1 to 3% of ART
cycles and is a potentially life threatening complication. Prevention strategies for OHSS can be classified
as primary and secondary. Primary prevention is initiated before stimulation and includes personalizing
stimulation protocols to suit individuals identified at high risk of OHSS ie high responders. Secondary
prevention includes strategies, as withdrawal, delay, or modification in stimulation protocols during the
course of stimulation cycle. Primary and secondary prevention strategies include:
PRIMARY PREVENTION
1. Identifying women at high risk of OHSS before start of stimulation. These include
a. Women with PCOS
b. History of OHSS in prior cycles
c. High responders on initial assessment as in high S.AMH (> 4.0 ng/ml), AFC (>20 in total) in
absence of PCOS features
2. Choosing protocols-Antagonist protocols are preferred as are associated with lower risk of OHSS.
Besides reducing the incidence of hospital admission consequent to OHSS, antagonist protocol
reduces the need for secondary interventions such as coasting, or cycle cancellation (1).
3. Insulin sensitizers – use of insulin sensitizers including Metformin reduces the incidence of
OHSS during ovarian stimulation (2).
4. In-vitro-maturation (IVM) - This technique stands to lower OHSS in women with PCOS or those
with past history of sever OHSS. However this strategy is not picked up owing to lower live birth
rates as compared to standard IVF technique.
SECONDARY PREVENTION
During the course of stimulation patients can be identified at risk of developing OHSS by
monitoring response with estradiol levels or follicular tracking. Strategies of secondary
prevention include:
1. Coasting- This involves withdrawing gonadotropins and withholding HCG trigger until the
estradiol levels decrease to a safe level(<3,500 pg/ml).This method has the great attraction of the
cycle not being cancelled, fresh embryos still being transferred and no additional gonadotrophins
or medications being used (3). Although coasting is a very effective method to reduce the
incidence of severe OHSS, it does not abolish the syndrome completely, as 2.5% of hyperresponders, still present with the severe form of the syndrome. The duration of coasting can vary
between 3-9 days until the estradiol levels fall, however longer duration of coasting are associated
with lower pregnancy outcome.
2. Alternative agents to triggering ovulation
3.
4.
5.
6.
7.
a. Agonist trigger-In GnRH antagonist cycles the use of agonist to trigger oocyte maturation is a
recent and recommended strategy to prevent OHSS. Data from randomized controlled trial
comparing agonist with hCG trigger have suggested a reduced but not eliminated incidence of
severe OHSS after agonist trigger. The problem after agonist trigger is luteal insufficiency
consequent to it. Luteal phase can be rescued by low dose hCG in doses after oocyte recovery
(4). Further supplementation with estrogens and progesterone for luteal support improve
pregnancy rate by correcting the luteal insufficiency.
b. Recombinant LH- This appears an effective option, but excess costs and commercial nonavailability are limiting factors to substitute this for hCG.
Albumin- while initial experience suggested benefit recent evidence from RCT does not support
the use of intravenous albumin to prevent OHSS (5).
Hydroxyethyl starch (HES) - Intravenous use of HES at the time of ovum pick up and in the
initial 24 hrs has been suggested to benefit in prevention of OHSS (5).
Cryopreservation of embryos- Freezing all embryos and avoiding fresh transfer is a plausible
strategy to prevent OHSS as pregnancy worsens the development of OHSS. This strategy is even
advocated after agonist trigger when > 20 oocytes are recovered as despite agonist trigger the
patient is still at a high risk of developing OHSS> Combined use of agonist with freeze all policy
seems to near eliminate the risk of OHSS in women at a higher risk (6).
Dopamine agonist- The use of cabergolin, a dopamine agonist has proved useful in preventing
severe OHSS however does not completely eliminate it. Used in patients at high risk of
developing OHSS it can be started on the day or even before oocyte retrieval (7).
Cycle cancellation- This is one of the strategies advocated, but with currently available methods,
availability of other options the need for cycle cancellation to avert OHSS is by far less in current
times.
CONCLUSION- While no single strategy can eliminate the development of OHSS, combination
helps to prevent t. Identification of women at high risk, use of antagonist protocol, agonist trigger,
use of low dose hCG and freeze all would prevent OHSS and improve reproductive outcome in
these women.
REFERENCES
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