Ovarian Hyperstimulation Syndrome (OHSS) Risk Factors and Prevention

Abdulmagid Sarhan, MD, MRCOG.
Zagazig University
Ovarian Hyper-stimulation Syndrome
(OHSS)

OVARIAN HYPERSTIMULATION SYNDROME
(OHSS)
Ovarian hyper-stimulation syndrome (OHSS) is
an uncommon but serious complication
associated with assisted reproductive
technology (ART).
A SARHAN, OHSS

(OHSS)
Mild Ovarian Hyperstimulation Syndrome
(OHSS) is a very common and trivial condition
while its severe form can be a life threatening
condition.
A SARHAN, OHSS

(OHSS)
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Classifications
Rabu et al 1967
Schenker and Wienstien 1978
Golan et al 1989
Risk and Aboulghar 1999
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INCIDENCE
 Mild : 20-40 %
 Moderate : 2-8%
 Severe : 0.5-2%
In one series of 3500 ART cycles the incidence
of moderate and sever OHSS was 5.7% and
1.7% respectively (Serour et al 1998, Fertil.
Steril.)
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Classifications
 Mild:
Increased urinary steroids
Nausea , vomiting, abdominal discomfort
 Moderate:
Ovarian enlargement (8-12 cm) US ascitis
nausea , vomiting , diarrhea, abdominal pain
 Severe:
Severe symptoms
Ascitis hydrothorax, ovarian enlargement >12 cm
Hemoconcentration, coagulation,
Possible different complications
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Natural History
Clinical picture
Early OHSS
 Develops within 11 days of HCG injection.
Late OHSS
 Develops after 11 days of HCG injection
Self limited
Regression takes place spontaneously over 10 –14 days ( parallel to decrease in
HCG)
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WHO IS AT HIGH RISK FOR SEVERE OHSS?
Demographics
(Age, BMI, Race, Infertility Diagnosis)
Ovarian Reserve Markers
(AMH, AFC, Inhibin A/B)
Ovarian Stimulation Parameters
(Follicles, Oocytes, Estradiol)
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Demographics
 Society of Assisted Reproductive Technology (SART) database
(214,219 ART cycles)
- Younger age,
- Black race,
- Ovulation, Tubal factor, and Unexplained infertility
were all associated with an increased risk of OHSS.
(Luke et al., Fertil Steril 2010)
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Demographics
 Younger age was associated with an increased risk. In the largest of
these studies, more than 60% of women who developed OHSS were
less than 35 years old.
Rretrospective studies
(Sousa et al., Fertil Steril 2000; Luke et al., Fertil Steril 2010, Ashrafi
et al., Arch Gynecol Obstet 2015,)
Prospective studies
(Mathur et al., Fertil Steril 2000, Aramwit et al., Am J Health Syst
Pharm 2008)
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Demographics
 BMI and rates of OHSS,
Two studies supported a correlation between a lower BMI and OHSS
(Aramwit et al., Am J Health Syst Pharm 2008)
Other four studies showed no predictive value.
(Ashrafi et al., Arch Gynecol Obstet 2015, Sousa et al., Fertil Steril
2000 , Delvigne et al., Hum Reprod 1993, Lee et al., Hum Reprod
2008)
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Demographics
 PCOS
Several observational studies have shown a higher incidence of
OHSS in women with (PCOS).
Delvigne et al., Hum Reprod 1993;
Sousa et al., Fertil Steril 2000;
Mathur et al., Fertil Steril 2000;
Luke et al., Fertil Steril 2010;
Swanton et aly. Eur J Obstet Gynecol Reprod Biol 2010;
Jayaprakasan et al. Fertil Steril 2012
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Ovarian Reserve Markers
 AMH levels
Using a prospective cohort of 262 women (IVF), higher serum AMH levels
(cut-off value 3.36 ng/mL) predicted OHSS better than age and BMI with
a sensitivity of 90.5% and specificity of 81.3%.
(Lee et al., Hum Reprod 2008)
 In another study, AMH levels in women with OHSS were 6-fold higher than
age- and weight-matched controls.
(Nakhuda et al. Fertil Steril 2006)
 In a retrospective cohort study of 134 women with elevated AMH levels
(>5 ng/mL), women with AMH of >10 ng/mL had significantly higher rates
(>3-fold) of OHSS.
(Tal et al. Am J Obstet Gynecol 2014)
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 Antral follicle count (AFC):
In a prospective analysis of 1,012 first ART cycles, the risk of OHSS
increased from 2.2% with an AFC <24 to 8.6% with an AFC >24.
(Jayaprakasan et al. Fertil Steril 2012)
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 Inhibin A and B:
Only 2 studies have assessed the predictive value of inhibin, and both have
shown no correlation between serum (or follicular) inhibin concentrations and
the development of OHSS.
(Moos et al. Reprod Biol Endocrinol 2009; Ocal et al. J Assist Reprod
Genet 2011)
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Stimulation Protocols
 GnRH agonist :
Allows more hMG stimulation and production of more follicles leading to OHSS
 Dose of hMG:
- Narrow margin between the dose required to produce satisfactory ovarian response and OHSS
- OHSS patients require less ampoules than other patients in the same center
- Increased incidence of OHSS in centers using higher doses of gonadotropins
 FSH:
Using FSH alone versus hMG
 Recombinant FSH
No difference compared to purified urinary FSH
 Luteal support:
Progesterone should be used alone for luteal support for patients at risk of OHSS
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Ovarian Stimulation Parameters
Number of growing follicles:
A high number of growing follicles is an independent predictor of
OHSS
(Danninger et al. Hum Reprod 1996; Papanikolaou et al. Fertil Steril
2006; Jayaprakasan et al. Hum Fertil (Camb) 2007; Kahnberg et al
Acta Obstet Gynecol Scand 2009)
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Number of growing follicles:
Utilizing the SART registry, analysis of 256,381 cycles demonstrated that
retrieval of >15 oocytes significantly increases the risk of OHSS without
improving live-birth rate in fresh autologous cycles.
(Steward et al. Fertil Steril 2014)
In a prospective cohort study of 624 first IVF cycle in Sweden, multivariate
analysis identified a model to predict OHSS with 82% sensitivity and 90%
specificity if the following thresholds were met:
>25 follicles at retrieval;
>19 large-/medium-sized follicles before hCG; and
>24 oocytes retrieved.
(Kahnberg et al Acta Obstet Gynecol Scand 2009)
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Serum estradiol concentrations:
Several studies showed a significantly association with OHSS.
In the majority of these studies, the mean estradiol value in patients with OHSS was >3,500 pg/mL.
Danninger et al. Hum Reprod 1996;
Mathur et al. Fertil Steril 2000;
Aramwit et al. Am J Health Syst Pharm 2008;
Lee et al. Hum Reprod 2008;
Johnson et al. Gynecol Endocrinol 2014;
Sousa et al. Reprod Biol Endocrinol 2015;
Ashrafi et al. Arch Gynecol Obstet 2015
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Conception
OHSS is more common (4 times) in conceived patients.
OHSS takes longer time to resolve with pregnancy.
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PREVENTION OF OHSS
 The Type of Stimulation Protocol?
 Aspirin?
 Metformin?
 Coasting?
 Choice of Triggering Ovulation?
 Dopamine Agonist
 Albumin?
 Calcium?
 Cryopreservation?
 Miscellaneous Treatments?
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PREVENTION OF OHSS
The Type of Stimulation Protocol
Gonadotropin-releasing hormone (GnRH) antagonists for ovulation
suppression are associated with a lower incidence of OHSS compared
with GnRH agonist.
 RCS
Ludwig et aln. Arch Gynecol Obstet 2000; Firouzabadi et al. Arch
Gynecol Obstet 2010; Borges et al. JBRA Assist Reprod 2016)
 Systematic reviews
(Ludwig et al. Arch Gynecol Obstet 2001; Mancini et al. Gynecol
Endocrinol 2011; Al-Inany et al. Cochrane Database Syst Rev
2011(CD001750); Xiao et al. Gynecol Endocrinol 2013; Xiao et al.
PLoS One 2014)
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Complications oF OHSS
 Thrombo-embolic.
 Renal failure.
 Liver dysfunction.
 Respiratory compromise and ARDS.
 Ovarian torsion.
 Intra-abdominal bleeding
 Early pregnancy loss
 Late obstetric complications
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Vascular complications:
↑ Estrogen produces a hypercoagulable state:
↓CLT - ↑ Fibrinogen - ↓ Antithrombin
In three large series
Belgium, 1 case in 128 cycles, (Delvinge et al 1993, Hum Reprod) Israel, 2 cases in 87 cases
(Abramov et al 1999, Fertil. Steril.) and
Egypt 10 case among 106 cases of severe OHSS (Serour et al 1998, Fertil. Steril.)
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 Abnormal Liver functions:
25-40% of moderate and severe cases
↑Liver enzymes
Ultra structure changes
Persist up to 2 months, completely reversible
 Respiratory complications:
Dyspnea and tachypnea are the commonest symptoms in severe OHSS
90% hydrothorax and pleural effusion
Local pneumonia (4%)
ARDS (2%)
Pulmonary embolism: (2%)
 Renal Complications:
Prerenal failure due to hypovolemia and fluid shift
Obstruction of transplanted kidney by enlarged ovaries
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Early pregnancy loss:
Increased in IVF patients with severe OHSS (38%)
compared to control group (15%).
Late obstetric complications:
Apart from early pregnancy loss, OHSS does not
affect other obstetric complications.
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PREVENTION OF OHSS
Aspirin
Increased platelet activation due to VEGF levels may lead to release of
substances, such as histamine, serotonin, platelet-derived growth
factor, or lysophosphatidic acid, that can further potentiate the
physiologic cascade of OHSS.
(Varnagy et al. Fertil Steril 2010)
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PREVENTION OF OHSS
Aspirin
 Careful ovarian stimulation
 HCG
Avoid HCG (Cancellation)
Delay HCG (Coasting)
Decrease HCG
 I.V albumin & Hydroxy ethyl starch solution
 Dopamine agonist
 GNRH-Antagonists
 Aspirate all follicles
 Embryo cryopresevation
 Avoid HCG in luteal phase
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PREVENTION OF OHSS
Aspirin
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RCS on 395 women with high risk of severe OHSS
97 Patients
100 mg aspirin and prednisolone in
varying doses (10 mg to 30 mg) from
the first day of stimulation until
pregnancy test
298 Patients
Nothing
More retrieved oocytes,
lower incidence of severe OHSS (1.7% ).
Less retrieved oocytes,
higher incidence of severe OHSS (6.5%).
Aspirin decreases the risk of severe OHSS.
(Revelli et al. Fertil Steril 2008)

PREVENTION OF OHSS
Aspirin
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(Varnagy et al. Fertil Steril 2010)
RCS on 1192 women with high risk of severe OHSS
780 Patients
100 mg aspirin and prednisolone in
varying doses (10 mg to 30 mg) from
the first day of stimulation until
pregnancy test
412 patients
Nothing
2, (0.25% )
Similar pregnancy outcomes.
43, (8.4%) P<.001)
Women at high risk for OHSS taking aspirin had a lower incidence of severe OHSS
requiring hospital admission

PREVENTION OF OHSS
Metformin
 Whether metformin (500 mg three times daily or 850 mg twice daily)
during ovarian stimulation for IVF in PCOS patients can reduce OHSS
in this high-risk group?.
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PREVENTION OF OHSS
Metformin
 Metformin from the start of down-regulation until oocyte retrieval for
GnRH protocols decreased the incidence of OHSS in PCOS patients
(3.8% vs 20.4%, P=.023).
(Tang et al. Hum Reprod 2006)
 Subsequent RCTs have supported this conclusion.
(Palomba et al. Fertil Steril 2011; Qublan et al. J Obstet Gynaecol
2009)
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PREVENTION OF OHSS
Metformin
 More recently, a systematic review of 10 RCTs concluded that
metformin decreases the incidence of OHSS in PCOS patients (OR
0.27, 95% CI 0.16–0.46).
(Palomba et al. BJOG 2013)
 A recent meta-analysis included 12 studies of 1,516 participants and
showed that there were no differences in pregnancy rates, live-birth
rates, and spontaneous abortion rates between the metformin
group and placebo group, but that OHSS risk was significantly lower
with metformin use (relative risk [RR] 0.44, 95% CI 0.26–0.77).
(Huang et alures. Int J Gynaecol Obstet 2015)
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PREVENTION OF OHSS
Metformin
Metformin does not decrease OHSS risk in non-obese PCOS
patients or those with PCO morphology only.
(Swanton et al. Hum Reprod 2011)
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PREVENTION OF OHSS
Coasting
 Early cohort studies showed that coasting is associated with a lower
risk of OHSS without compromising the pregnancy rate.
(Al-Shawaf et al. Hum Reprod 2001; Dhont et al. Fertil Steril 1998)
 One cohort study suggested that coasting may lead to a higher
incidence of severe OHSS, though the absolute numbers were small.
(Lee et al. Hum Reprod 1998)
 A systematic review of four RCTs concluded that coasting does not
decrease risk of OHSS, but is associated with fewer oocytes retrieved.
(D'Angelo et al. Cochrane Database Syst Rev 2001:CD002811)
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PREVENTION OF OHSS
Choice of Triggering Ovulation
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hCG dose Results
(Shaltout et al. Middle
East Fertil Soc J 2006)
RCT evaluated 5,000 IU
vs 10,000 IU of hCG in
100 high-risk patients
2% vs 8.3%, but the
results did not meet
statistical significance.
(Lin et al. Eur J Obstet
Gynecol Reprod Biol
2011)
RCT of 164 patients
randomized to 4,000 IU
vs 6,000 IU dose
3.6% vs 4.9%, but the
results did not meet
statistical significance.

PREVENTION OF OHSS
 There is strong evidence that the use of a GnRH agonist trigger results
in a significant reduction in the development of OHSS.
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PREVENTION OF OHSS
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GnRH–a trigger group hCG trigger group
Patients 32 32
OHSS 0% 31% (10/32)
Implantation rate 22/61 [36.0%] 20/64 [31.0%]
Clinical pregnancy rate 17/30 [56.7%] 15/29 [51.7%]
Ongoing pregnancy
rate
16/30 [53.3%] 14/29[48.3%]
(Engmann et al. Fertil Steril 2008)

PREVENTION OF OHSS
 Three RCTs were performed in an oocyte donor population at high risk for
OHSS and found that GnRH agonist trigger almost eliminated the
development of OHSS in these women (0% risk of OHSS with GnRHagonist
vs 7%–16% with hCG trigger).
(Galindo et al. Gynecol Endocrinol 2009;
Sismanoglu et al. J Assist Reprod Genet
Bodri et al. Reprod Biomed Online 2008)
 A Cochrane review of 17 RCTs found that final oocyte triggering with an
agonist resulted in a lower incidence of OHSS in fresh autologous cycles
as well as in donor-recipient cycles. However, agonist trigger was
associated with a lower live-birth rate in fresh autologous cycles.
(Youssef et al. Cochrane Database Syst Rev 2014:CD008046.)
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PREVENTION OF OHSS
Dopamine Agonist
 Dopamine-receptor agonist such as cabergoline results in a
reduction of VEGF production and a subsequent reduction in OHSS.
 This was supported by many randomized controlled studies.
(Tehraninejad et al. J Assist Reprod Genet 2012;
Shaltout et al. Eur J Obstet Gynecol Reprod Biol 2012)
 A review of seven studies in 858 women found that administration of
cabergoline reduced the incidence of OHSS compared with no
treatment (RR 0.38, CI 0.29–0.51, P<.00001), without impacting
pregnancy rates (RR 1.02, 95% CI 0.78–1.34, four studies, 561 women).
(Leitao et al. Fertil Steril 2014)
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PREVENTION OF OHSS
Albumin
Properties:
 low molecular weight
 long half life of 20 daysIncreases plasma oncotic pressure
 Counteract the permeability effect of angiotensin II.
 May bind to vasoactive substances, related to the renin-
angiotensin system and VEGF.
Blood-derived product:
 Allergic Reactions,
 Anaphylactic Reactions,
 Transmission of viral or unidentified diseases.
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PREVENTION OF OHSS
Albumin
 Early RCTs demonstrated that 20% human albumin administered
around the time of oocyte retrieval decreased the incidence of
moderate-to-severe OHSS compared with no treatment.
(Shoham et al. Fertil Steril 1994; Shalev et al. Hum Reprod 1995; Isik
et al. Eur J Obstet Gynecol Reprod Biol 1996)
 However, more recent studies have not found albumin to be
effective in decreasing the incidence of OHSS.
(Ben-Chetrit et al. Hum Reprod 2001; Bellver et al. Hum Reprod 2003;
Isikoglu et al. Fertil Steril 2007)
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PREVENTION OF OHSS
Albumin
 A systematic review concluded that albumin does not prevent OHSS.
(Venetis et al. Fertil Steril 2011)
 Intravenous (IV) albumin not only does not decrease the incidence
of severe OHSS compared with no treatment (RR 0.8, 95% CI 0.57–
1.12), but it also lowers the pregnancy rate (RR 0.85, 95% CI 0.74–
0.98).
(Jee et al. Gynecol Obstet Invest 2010)
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PREVENTION OF OHSS
Calcium
 Calcium decreases cAMP-stimulated renin secretion, which
decreases angiotensin II synthesis and its subsequent effect on VEGF
production.
 Studies have investigated whether an IV calcium infusion (10 mL of
10% calcium gluconate in 200 mL normal saline) on the day of
oocyte retrieval and days 1, 2, and 3 after oocyte retrieval can
decrease OHSS risk.
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PREVENTION OF OHSS
Calcium
 A retrospective cohort study concluded that IV calcium was
effective in reducing OHSS risk in PCOS women.
(Gurgan et al. Fertil Steril 2011)
 Another case-control study suggested that IV calcium is as effective
as cabergoline in preventing OHSS.
(Naredi et al. J Hum Reprod Sci 2013)
 One RCT of 200 women at risk for OHSS demonstrated that the
incidence of moderate and severe OHSS was higher in women who
received normal saline compared with the IV calcium group (23% vs
7%, P=0.002).
( El-Khayat et al. Fertil Steril 2015)
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PREVENTION OF OHSS
Cryopreservation
 Elective cryopreservation of all embryos and their subsequent
transfer in non stimulated cycles may avoid the endogenous hCG
rise in fresh transfer cycles, which can exacerbate late-onset OHSS
symptoms and duration.
 With improved results of embryo freezing by vetrification, freeze all
policy appears as a very accepted option.
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PREVENTION OF OHSS
Miscellaneous Treatments
There are insufficient data to make recommendations
regarding the use of:
 luteal antagonist administration,
 letrozole,
 Methylprednisolone,
 Progesterone, or
 ketoconazole to mitigate OHSS risk.
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PREVENTION OF OHSS
✓ GnRH antagonists
✓ Dopamine agonist (Cabergolide)
✓ GNRH agonist trigerring of ovulation
✓ Coasting
✓ Low dose FSH stimulation
✓ Progesterone for luteal support
✓ Pretreatment with pills
✓ Proper monitoring of E2 level.
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TREATMENT OF OHSS
 Does outpatient paracentesis of women with OHSS improve their
outcome?
 Do volume expanders improve outcome for women with OHSS?
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TREATMENT OF OHSS
Outpatient paracentesis
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Shrivastav et al. Hum Reprod 1994)
Cohort study of 18 women with severe OHSS
8 women
Managed with hospitalization and IV
fluid
10 women
Had outpatient US-guided
paracentesis. 1–3 liters of fluid were
removed over 2–3 hours, with IV
hydration
The average length of stay was 11
days.
None of these patients required a
second procedure, nor admitted to the
hospital.
Outpatient ultrasound-guided paracentesis is a safe alternative to hospitalization
in patients with severe OHSS.

TREATMENT OF OHSS
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(Lincoln et al. Assist Reprod Genet 2002)
A cohort study of 48 women with OHSS and ascites
Treated all the patients with repeated outpatient transvaginal culdocentesis and
rehydration with IV crystalloids and albumin every 1–3 days until resolution of
symptoms or hospitalization was required.
The average number of outpatient treatments was 3.4 (1–14); 91.6% of patients were
managed as outpatients and avoided hospitalization.
Outpatient ultrasound-guided paracentesis shortens the duration of severe OHSS and
reduces hospitalization.

TREATMENT OF OHSS
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(Qublan et al. J Obstet Gynaecol 2012)
Sixty-five women with severe early OHSS were hospitalized and
managed with transvaginal fluid aspiration
<3 occasions (historic control group; n =
29)
>3 occasions (multiple aspirations) (study
group; n = 36)
Patients in the study group had significantly fewer days of hospitalization (4.2 vs 6.7
days, respectively, P<.01).
The pregnancy rate increased significantly along with a significant decrease in the
abortion rate after multiple aspirations compared with <3 aspirations.
Multiple ultrasound-guided paracentesis is safe and does not affect pregnancy rate.

TREATMENT OF OHSS
volume expanders
 A small, prospective observational trial reported non surgical
inpatient management of 13 patients with severe OHSS).
 This trial employed a fairly aggressive use of volume expanders (25%
albumin 250 mL) with diuretic (furosemide20 mg or bumetanide 1
mg) and dopamine IV (2–3 mg/kg/min)every 8 hours in oliguric
patients.
 This protocol was reported to have a comparable length of hospital
stay compared to prior published studies.
(Morris et al. J Reprod Med 1995)
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TREATMENT OF OHSS
volume expanders
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(Abramov et al. Fertil Steril 2001)
Small, retrospective cohort study on 16 patients with severe OHSS.
6% HES (6 patients) human albumin (10 patients)
Patients who received HES had higher urine output, needed fewer
abdominal paracenteses and pleural thoraco-centeses and had a
shorter hospital stay.
No difference in adverse effects was reported.
Due to the small sample size and cohort design, the results are not
definitive

TREATMENT OF OHSS
volume expanders
 These small studies evaluating the use of volume
expanders in women already exhibiting symptoms of
OHSS were not RCTs.
 It is not clear whether the patients’ course would have
resolved in a similar way with crystalloid alone.
 The concomitant use of diuretics in some patients in
these trials further confuses the therapeutic assessment.
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RECOMMENDATIONS
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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)
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RECOMMENDATIONS
 The use of a GnRH agonist to trigger ovulationis recommended to
reduce the risk of OHSS if peak estradiol levels are high or multi-
follicular development occurs during stimulation. (Grade A)
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RECOMMENDATIONS
 Low-dose hCG co-trigger, luteal hormonal support, or
cryopreservation of embryos are strategies that may improve
pregnancy rates in this setting. (Grade B)
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RECOMMENDATIONS
 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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RECOMMENDATIONS
 Additional strategies to prevent OHSS which may be helpful include:
 The use of metformin in PCOS patients (Grade A),
 Aspirin administration (Grade A), and
 Cryopreservation of embryos. (Grade B)
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RECOMMENDATIONS
 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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RECOMMENDATIONS
 Known protocol
 Moderate:
Assurance
Adequate fluid intake
Frequent phone calls
Report any alarming symptoms, Oliguria or dyspnea
 Severe:
Clinical and Biochemical monitoring
Medical treatment
Aspiration of ascetic fluid
Management of complications
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RECOMMENDATIONS
 Severe OHSS:
Clinical and Biochemical monitoring:
 - Vital signs, wt, girth
- US abdomen and chest
- Fluid balance record
- Serum electrolytes Liver and kidney functions
- Blood gases and acid base balance with respiratory complaints
- IV hemodynamic monitoring (CVP, PAP) if volume expanders are
used.
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RECOMMENDATIONS
 Severe OHSS:
Medical treatment:
 - Restoration of circulatory volume
 - Correction of electrolyte balance
 - Anticoagulants
Heparin should be used in all cases with sever OHSS
 - Diuretics:
↑ hemoconcentration, ↑ hypotension, ↑ bl viscosity and thrombosis
Only with pulmonary edema or congestion
 - Dopamine:
↑RBF GFR
↓fluid retention and ARF
Given with caution and under strict supervision
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RECOMMENDATIONS
 Severe OHSS:
Aspiration of ascetic fluid:
 To relieve pulmonary compromise
 improve symptoms ↓weight, ↓ edema ↑ renal function
 Risks are minimal specially with US guide
 Volume aspirated as required to relieve dyspnea and repeated if
required
 Trans-vaginal US guided approach can be used
 Continuous auto transfusion system for ascitis (CATSA) was used to avoid
loss of plasma proteins.
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Ovarian Hyperstimulation Syndrome (OHSS) Risk Factors and Prevention

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