Prevention and treatment of moderate and severe OHSS: ASRM Guideline 2016

1. Prevention and
treatment
of moderate and
severe OHSS:
ASRM Guideline
2016
Prof. Aboubakr
Elnashar
Benha University Hospital, Egypt
4/22/2017ABOUBAKR ELNASHAR

2. Level I:
Evidence obtained from at least one properly designed RCT.
Level II-1:
Evidence obtained from well-designedcontrolled trials without
randomization.
Level II-2:
Evidence obtained from well-designed cohort or case-control
analytic studies
Level II-3:
Evidence obtained from multiple time series with or without the
intervention.
Level III:
Opinions of respected authorities based on clinical experience,
descriptive studies, or reports of expert committees.
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3. The strength of the evidence was evaluated as follows:
Grade A:
There is good evidence to support the
recommendations, either for or against.
Grade B:
There is fair evidence to support the
recommendations, either for or against.
Grade C:
There is insufficient evidence to support the
recommendations, either for or against.
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4. HIGH RISK
There is fair evidence(Grade B)
increase the risk of OHSS.
PCOS
Elevated AMH values
Peak estradiol levels
Multifollicular development
High number of oocytes retrieved
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5. An increased risk of OHSS
cut points require validation, (Grade B)
1. AMH values >3.4 ng/mL,
2. AFC >24
3. Development of ≥25 follicles
4. Estradiol values >3,500 pg/mL, or
5. ≥24 oocytes retrieved
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6. PREVENTION
There is good evidence (Grade A)
1. GnRHan
2. GnRHa to trigger oocyte maturation
There is good evidence that LBR are lower in
fresh autologous cycles after GnRH trigger
3. Metformin
4. Dopamine agonist
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7. GnRHa trigger
Mechanism of lowered PR in cycles
more rapid and dramatic post-luteal drop in
hormonal LH support, as compared with hCG for
maturation: luteal phase insufficiency.
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8. Strategies to improve PR:
1. Cryopreserving embryos
2. Co-trigger with 1500 IU hCG
single bolus
:reduced OHSS (0%)
second bolus of 1,500 IU of hCG
(one the day of OR and one the subsequent day):
an increase in moderate-to-late onset of OHSS
(3.4%)
3. low-dose hCG for luteal support
(1,000 IU, 500 IU, or 250 IU every third day after
OR): restored the CPR.
4. Supplementing estradiol during luteal phase in
addition to progesterone.
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9.  Poor response to GnRHa for final oocyte maturation
= suboptimal LH surge (LH <15) after trigger with
GnRHa.
5.2% rate of suboptimal response
This strategy should be avoided or used with caution
in this patient population.
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10. Causes:
1. lower (FSH) and LH levels at baseline
2. lower LH levels on the day of GnRHa trigger.
25% chance of suboptimal response if the LH level
was undetectable on the day of trigger.
3. Irregular menses
4. Prolonged oral contraceptive pill use
5. Lower body mass
6, patients who exhibit signs of significant
suppression of the hypothalamic-pituitary axis
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11. Metformin:
By improving intraovarian hyperandrogenism:
reducing the number of nonperiovulatory follicles:
 reduce estradiol secretion
500mg three times daily or
850 mg twice daily during ovarian stimulation for IVF
in PCOS patients
No decrease OHSS risk in
1. non-obese PCOS patients or
2. PCO morphology only.
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12. Dopamine-receptor agonist
Cabergoline
reduction of VEGF production.
0.5 mg/day from the day of hCG for 8 days.
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13. There is fair evidence (Grade B)
1. Aspirin reduces the incidence of OHSS
2. Calcium lowers OHSS risk.
3. Cryopreservation
4. Reproductive outcomes are improved when a
low dose of hCG is co-administered at the time
of GnRHa trigger for LPS
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14. IV calcium infusion
Increased calcium inhibit cAMP-stimulated renin
secretion, which decreases angiotensin II synthesis
and its subsequent effect on VEGF production.
10 mL of 10% calcium gluconate in 200 mL normal
saline) on the day of OR and days 1, 2, and 3 after
OR
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15. Aspirin:
increased platelet activation due to VEGF: release
of: histamine, serotonin, platelet-derived growth
factor, or lysophosphatidic acid, that can further
potentiate the physiologic cascade of OHSS.
(Vamagy et al, 2010).
daily dose of 100 mg aspirin from the first day of
stimulation until the day of the pregnancy test, or the
US detection of embryonic cardiac activity
lower incidence of severe OHSS requiring hospital
admission compared with women who were not on
aspirin (0.25% vs, 8.4%, P<.001)
No difference in pregnancy outcomes between the
two groups.
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16. There is insufficient evidence (Grade C)
1. Coasting
2. Lower dose of triggering hCG
3. Albumin
4. Clomiphene
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17. Coasting
withholding gonadotropins at the end of COS for up
to 4 days.
Early cohort studies:
lower risk of OHSS without compromising PR
(Al-Shawaf et al, 2001 ).
Cohort studies
comparable reduction in OHSS when coasting is
compared with cryopreservation
(Gera et al, 2010),
albumin
(Chen et al, 2003), or,
in one RCT, early unilateral follicular aspiration
(Egbase et al, 1999).
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18. Systematic review of four RCTs
coasting does not decrease risk of OHSS
: fewer oocytes retrieved
(D'Angelo et al, 2001).
Cohort study
coasting may lead to a higher incidence of severe
OHSS, though the absolute numbers were small
(lee et al, 1998).
The optimal length of coasting
not been determined, with limited cohort studies
suggesting that coasting ≥4 days decreases
implantation rates
(Nardo et al, 2006).
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19. Addition of CC as part of a GnRHan stimulation
protocol
Two RCTs:
addition of CC to COS: fewer OHSS compared with GnRH
agonist protocols without CC
(Weigert et al, 2002; Karimzadeh et al, 2010).
Two SR:
CC antagonist protocols have a significant reduction of
OHSS compared with either non-CC protocols
(Figueiredo et al, 2013) or
GnRHa cycles
(Gibreel et al, 2013).
However, these studies are difficult to interpret since the
reduction in OHSS risk is confounded by different
stimulation protocols where ‘‘minimal stimulation’’ may be
the goal.
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20. TREATMENT
There is fair evidence (Grade B)
Paracentesis or culdocentesis for the management of
OHSS in an outpatient setting.
There is insufficient evidence (Grade C)
volume expanders alone in treatment of OHSS.
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21. Culdocentesis
Repeated outpatient TV culdocentesis and
rehydration with IV crystalloids and albumin every 1–
3 days until resolution of symptoms or hospitalization
The average number of outpatient treatments was
3.4
91.6% of patients were managed as outpatients and
avoided hospitalization.
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22. Transabdominal paracentesis.
outpatient ultrasound-guided paracentesis is a safe
alternative to hospitalization in patients with severe
OHSS.
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23. Volume expanders
6% HES Vs human albumin
higher urine output, needed
fewer abdominal paracenteses and pleural
thoracocenteses
(33% vs 80%)
shorter hospital stay
(15.7 5.7vs 19.0 8.2 days)
No difference in adverse effects was reported.
6% HES: superior to albumin as a colloid
solution for the treatment of severe OHSS
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24. RECOMMENDATIONS
Women with PCOS, elevated AMH values, and
elevated AFC may benefit from ovarian stimulation
protocols that reduce the risk of OHSS.
(Grade B)
 Ovarian stimulation protocols using GnRH
antagonists are preferable in women at high risk of
OHSS.
(Grade A)
 The use of a GnRH agonist to trigger oocyte
maturation prior to oocyte retrieval is recommended to
reduce the risk of OHSS if peak estradiol levels are high
or multifollicular development occurs during stimulation.
(Grade A)
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25. Low-dose hCG co-trigger, luteal hormonal support, or
cryopreservation of embryos are strategies that may
improve pregnancy rates in this setting.
(Grade B)
 Dopamine agonist administration starting at the time
of hCG trigger for several days also may be used to
reduce the incidence of OHSS.
(Grade A)
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26. Additional strategies to prevent OHSS which may be
helpful include the use of metformin in PCOS patients
(Grade A)
aspirin administration
(Grade A)
cryopreservation of embryos
(Grade B).
 The mainstay of OHSS treatment includes fluid
resuscitation and prophylactic anticoagulation.
Paracentesis or culdocentesis may be recommended
for management of OHSS when a large amount of
ascites is present.
(Grade B)
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