Medical Management of Ovarian Hyperstimulation Syndrome (OHSS) In 1500 IUI Cycles Practical tips
1. Dr. Sharda Jain
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar
Dr. Aruna Saxena
Dr Abhishek S. Parihar
Medical Management
of Ovarian Hyperstimulation Syndrome (OHSS)
In 1500 IUI Cycles
Practical tips
Directors:
2. Review this Lecture at:
Slideshare. net :
Medical Management
of Ovarian Hyperstimulation Syndrome (OHSS)
In 1500 IUI Cycles
Practical tips
3. Goals of Ovulation induction
in IUI
Minimize RISK
Complications
AIM
Ideal Outcome
Singleton live
Birth at term
Cycle
Cancellation
Multiple
Pregnancy OHSS
4. IMPORTANCE of OHSS in IUI
WHAT IT means to US & to You ?
• Totally Iatrogenic problem
Induced by clinician – when GT is used for OI
• Without HCG Trigger OHSS is extremely rare.
• 100% prevention impossible
• It has Profound Economical impact &
Profound Psychological Impact
FATAL
CASES
In IUI
are RARE but
Is a REALITY & a possibility !!!
(Though not reported)
5. OHSS in IUI is Not Reported
in Literature as it should be
In IVF : MORTALITY : 3 / 1,00,000
CYCLES
1 Aboulghar. Fertil Steril. 2012;97:523-6;
2 Confidential Enquiry into Maternal and Child Health, 2007;
1-5 million IVF cycles / year
500 death (last 10 years)
Grossly Underreported
6. CLINICS providing ovarian stimulation
with Gonadotrophins
for IUI/IVF -
Protocol should be in place for preventing,
diagnosing and managing
OHSS
Nice Guideline 2004
80% Gynaecologists in
India Practise IUI
9. Classification
Mathur et al - 2005.
• THE EARLY FORM (<10 days after the
HCG trigger.
• THE LATE FORM (>- 10 days after HCG).
• COMBINATION of the early form , followed
by pregnancy is SERIOUS AND LONG
LASTING
(Papnikolaou et al., 2004)
10. Classification and staging of ovarian
hyperstimulation syndrome (Whelan 2000)
•Grade 1: Abdominal distension /discomfort
•Grade 2: grade 1 plus nausea and vomiting or diarrhea
ovaries enlarged 5-12 cm
•Grade 3: Sonograding evidence of ascites
•Grade 4: clinical evidence of ascites or hydrothorax or
difficult breathing
•Grade 5 :All of the above puls decrease blood volume
nemoconcertration, diminished renal perfusion and
function , and coagulation abnormal
•From whelan , with permission
Followed in Lifecare IVF
M
I
L
D
S
E
V
E
R
E
MODERATE
11. Mild
Mild abdominal pain
Abdominal bloating
Ovarian size usually <8 cm
Moderate
Moderate abdominal pain
Nausea +/- Vomiting
Ultrasound Evidence of ascites
Ovarian size 8-12 cm
HCT > 41% , WBC>15,000, Hypoproteinemia
GRADING
12. Mild
Mild abdominal pain
Abdominal bloating
Ovarian size usually <8 cm
Moderate
Moderate abdominal pain
Nausea +/- Vomiting
Ultrasound Evidence of ascites
Ovarian size 8-12 cm
GRADING
13. Moderate OHSS i.e ultrasound evidence
of Ascites on day of IUI warns
gynecologist to take action
• Infact , Action should be taken on
day of trigger itself
PCOD Ascites
14. Severe
N & V ++, pain ++ ,
Clinical ascites (rarely hydrothrorax)
Ovarian size > 12 cm, Oliguria
heamoconcentration - HEAMATOCRIT > 45%
Hypoproteinaemia
Critical
Ovarian size > 12 cm
TENSE ASCITES ± HYDROTHORAX
WHITE CELL COUNT > 25 000/ ML
PCV > 55 gm %
OLIGURIA / ANURIA
Venous thrombosis ± Thromboembolism
Acute respiratory distress syndrome
Very
Very
Rare
15. Etiology
The Etiology of OHSS is complex,
HCG
Development of OHSS involves increase vascular permeability
and loss of fluid , protein and electrolytes into the peritoneal
cavity, which leads to hemoconcentration.
Either exogenous or endogenous
(from resulting pregnancy is believed to be
an early contributing factor).
16. HCG
Albert et al. Mol Hum Reprod. 2002;8:409; Chen et al. Hum Reprod.
2000;15:1037; Gómez et al. Endocrinology. 2002;143:4339
17. OHSS INCIDENCE in IUI
Clomiphene + IUI
Very Low Incidence
Mostly mild !!
Upto 13.5% of mild form of OHSS
In OI with Clomiphene
LITERATURE : Very few reports
Inspite of 90% Gynaecologists doing it
Delvigne & Rozenberg
Hum Reprod Update. 2003;9:77-96;
Cantineau et al.,
Cochrane database Syst.Rev
2007;18:CD005356
18. Mild OHSS around 10%
Cycle Cancellation
due to moderate OHSS in IUI : 2 - 10%
Database Syst Rev. 2007; 18:CD005356 OHSS
OHSS INCIDENCE in IUI
(Clomiphene+ GT)
LITERATURE : Scant
•Lower Incidence
• Mild to Moderate only
19. Lifecare IVF EXPERIENCE
on INCIDENCE of OHSS
in OI with Clomiphine + IUI
N 1000 Cases
• Lower Incidence
• Mostly mild form !!
Mild – 3%
Moderate
Severe Not Seen
OHSS
(Pain , > ovarian size)
20. Mild – became
Moderate : 4.8%
(N =15)
LIFECARE IVF EXPERIENCE
With CC + GT + IUI
N-320
Lower Incidence
Mostly mild to Moderate
Mild – 5.5 % (N=17)
Severe : Nil
OHSS
After trigger
21. Lifecare IVF Experience
CC+GT+ IUI (N-320 cases)
MODERATE OHSS (after trigger) in 4.8%
(N-15)
A)Cycle Cancellation 11 cases , 1 pregnancy
Advice given in all cases - for no intercourse bcz.
of risk Multiple pregnancy & late OHSS
B) Converted to IVF i.e.
OPU + Freezing of embryo : 4 cases , Pregnancy : Nil
(Cabergoline + antagonist for 3 days)
No freezing was possible in 3 due to poor quality embryos
22. Mild : 6% (N-11)
Mild become Moderate after trigger = 4.4% (N- 8)
A Cycle cancellation = 6, Preg. : Nil
(Cabergoline + antagonist2 days)
B Converted to IVF 2 cases, Preg : 1
(Caberboline +antagonist 2 days)
Lifecare IVF INCIDENCE of OHSS
in OI with
Pure Gonadotrophins + IUI
(N-180)
23. The Truth is that
OHSS MUST
BE PREVENTED RATHER
than treated
25. HOW TO PREVENT ?
• Steps Before stimulation
• Step During Stimulation
• Step on Impending severe OHSS
26. Young patients
Lean women
Polycystic Ovarian
PCOS
Previous OHSS
• High number of follicle in both ovaries at the quiescent state before
Stimulation
(>- 10 follicle of 4-10mm in each ovary)
• Raised AMH over 25.0 pmol/l for a high response NICE Guidelines
or >7 ng/ml
Easily
Recognized
WHO are AT HIGH RISK BEFORE OI – IUI & IVF
PRIMARY RISK FACTORS
SENSITIVE OVARIES
27. Monitoring for OHSS should be
• Easy
• Reliable
• Patient friendly
• Not Expensive
• Can be done by
Gynaecologist herself doing
ovulation Induction + IUI
28. MONITORING
ASSESSING THE
FOLLICULAR MATURITY
• The follicles normally grow at a rate
of 2- 3 mm / day in a stimulated cycle.
• Definitive size of the follicle which
confirms the maturity of oocytes is
still controversial.
• A follicle measuring 18—20 mm has
been found to contain a mature
oocyte.
29. MONITORING
CORELATION WITH SERUM
OESTRADIOL LEVELS
• Plasma estradiol levels correlates closely
with the stage of development of the
dominant follicle
• Serum estradiol levels >200 pg / ml on day 8
of stimulation indicates adequate dose of
gonadotropins.
Ultrasound monitoring has totally
replaced estradiol monitoring in most
centers.
30. TREATMENT options in
Moderate OHSS case
in IUI cycle for Gynaecologists
• Cancel IUI and reinitiate with lower dose
GT next time (give cabergoline +
antagonist for 2 days in this cycle)
• Convert to IVF i.e.
* GnRH trigger,
* OPU (Cabergoline + antagonist + HES)
* Freezing of all embryos
31. Low dose step up protocol
- Ideal in PCOS
First Line
Next time start with lower dose of Gonadotropins
Starting dose of Gonadopropins Varies between
37.5-75 iu, followed by step – wise increase in
dose.
• Monofollicular development is aimed
• Increase pregnancy rates
• Lower risk of OHSS and multiple pregnancies
(Homberg et al 1995)
32. STEP DOWN protocol in PCOS
(Second line)
• Mimics hormonal pattern in natural cycle.
• Starting dose - once dominant follicle of
around 10 mm is seen on ultrasound
• Then reduce dose by 37.5iu sequentially
• NOT PREFFERED
33. Options for trigger at Lifecare IVF
In Mild to Moderate OHSS
In cases at high risk of OHSS we usually
give GnRH agonist trigger .
If we convert to IVF + freeze all embryos
and then transfer embryos in next cycle
(as cases with very high estradiol levels are not
only at high risk for OHSS but also lead to “out of
phase endometrium”
with lower implantation rates).
34. What Luteal support Modified
Luteal phase if we are saving the
cycle?
A. INTENSIVE ESTRADIOL AND PROGESTERONE
SUPPORT
B. IF WE ARE CONVERTING TO IVF
1. One bolus of 1500 iu hcg administered on the
day of OPU if the total number of follicle (12-14
mm) are <16
2. OR, a total of three boluses of hcg (250-500 iu)
during the luteal phase
3. OR, recombinant luteinising hormone 300 iu
administered every second day until a positive
pregnancy test
(chen et al 2012)
35. How would you counsel patient for IVF ?
What is the extra cost?
• In one mathematical model, the cost -
effectiveness ratios for IVF alone Unstimulated
IUI followed by IVF and stimulated IUI followed
by IVF were £ 12600, £ 13100 and £15100 per
live birth , respectively.
• the authors concluded that for couple with
unexplained infertility and mild male factor, a
primary offer of an IVF cycle was cheaper and
more cost effective that starting with IUI
stimulated IUI followed by IVF
(Pashayan et al 2006)
We had only pregnancy in our 6 IVF
converted cycles – in rest embryo work
poor quality
36. PRIMARY PREVENTION
* Identify patients at risk
* Close Monitoring
* Mild ovarian stimulation (CC+ GT)
* Low dose step up GT protocol
* With hold HCG trigger
* GnRH- agonist for ovulation trigger
only in mild cases where we want to
save the cycle + MODIFIED LUTEAL PHASE SUPPORT
or
* Cycle cancellation (if Mod- OHSS on IUI day is detected)
No intercourse + cabergoline (5 days) + antagonist 2 day
SECONDARY PREVENTION
* Dopamine agonist - Cabgoline
* Antagonist in the luteal phase
*Plasma Expanders – HES, IV albumin
7
3
38. 38Dr Razia S
If This picture on day of trigger
should warn - not to give HCG
Biggest
39. Give GnRH – agonist
Trigger
if Wish to Save Cycle
WHICH Drug AND HOW:
Triptorelin 0.2 mg
Leuprolide acetate 1 mg
Buserelin 0.2-0.5 mg
When :
Same criterion of hCG
40. • GnRH – agonist rather than hCG trigger ± Cabergoline
(A) Cycle cancellation
Daily Monitoring 2-3 days
• No intercourse
• Cabergoline 0.5 mg x 5 days
• HES 6% slow
• Luteal phase GnRH Antagonists
Moderate Cases on day of IUI
Mild Cases
(B) Convert to IVF
Pateint frustation/ waste of Money is addressed
• Agonist trigger for ovulation
• Cabergoline 0.5 mg X 5 days
• Antagonist after OPU for 2-3 days
• FREEZING OF EMBRYOS
•EMBRYOS
Management of OHSS
Our
41. Close Monitoring in MODERATE
CASES by IVF unit staff
• Abdominal girth daily
• Strict I/O chart
• Hb, PCV, s. electrolytes
• Keep Eye for venous thrombosis
Critical Values
PCV > 45
Hb >15 gm%
Our In MODERATE OHSS
42. Role of Cabergoline in OHSS
prevention
• Cabergoline appears to reduce that risk of
OHSS in high – risk women especially in
moderate OHSS.
• But there is no evidence that it reduces
the chances of severe OHSS.
• The use of cabergoline does not affect the
pregnancy outcome risk of adverse.
Events
(Chocrane reviews 2012)
43. Role of Cabergoline in OHSS
Prevention
• Cabergoline 0.5 mg tablet daily
starting on the day of hcg (just
before) injection and continued for
total of 8 days have been shown to
reduce the risk of OHSS
44. Role of Metformin in OHSS
Prevention
• Metformin has also been used for the
prevention of OHSS.
• In a meta – analysiss of eight
randomized controlled trials of women
with PCOS metforming given 2 months
before strating COS significantly
reduced the risk of severe OHSS (odd
ratio(OR))OF 0.21,95% confidence
interval (CI)0.11-0.41,p<0.00001)
(costello et al 2006)
45. Role of Metformin in OHSS
prevention
• The mechanism of action of
metformin is not completely clear,
but reduction of
Anti – Mullerian Hormone (AMH)
values and a reduced insulne
dependent VEGE production has
been suggested
(Tang et al 2006)
46. Key Take home Messages
Ten Commandments to prevent
& treat MODERATE OHSS in IUI cycles
1. Identify cases with primary risk factor
for OHSS
2. Gradual and Low dose HMG protocol
3. Ovarian drilling for PCOS
4. Withholding HCG trigger if S/S of
mild OHSS
5. Use of GNRH Agonist – to trigger ovulation
(to save the cycle) in mild OHSS
6. Modified Luteal phase support
47. Key Take home Messages
7.Cabergoline 0.5 mg daily
Bromocriptine 2.5 mg daily from the
day of hcg for 8 days
8.HES 6% slow
9.Luteal phase GnRH Antagonists 2-5 days
10 Close Close monitoring of the
patients stimulated with GT is must
48. ADDRESS
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Morh Flyover, Delhi - 51
CONTACT US
9650588339, 011-22414049,
WEBSITE :
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www.lifecareivf.com
E-MAIL ID
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