1. An OHSS – Free Clinic :
to Manage ERROR – TERROR
International conference on Reproduction fertility &surrogacy
AIIMS, New Delhi 24-25 may 2014
Dr. Sharda Jain
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar
Dr. Aruna Saxena
Dr Abhishek S. Parihar
Directors:

2. An OHSS – Free Clinic
to Manage
ERROR – TERROR
Review this Lecture at:
Slideshare.net :

3. Goals of Ovulation induction
in IUI / IVF
Minimize Complications &
Risk
AIM
Ideal Outcome
Singleton live
Birth at term
Cycle
Cancellation
Multiple
Pregnancy OHSS

4. OHSS – Risk is a reality
OHSS - Mortality is also a reality
- Grossly Underestimated
(Bewley et al 2011)
DEVROEY 2011
OHSS is ↑ in numbers with
↑in IVF /ICSI cycles all over the globe

5. are RARE but
Is a REALITY !!!
(Though not reported)
FATAL
CASES

6. Mortality due to
critical OHSS
in IVF
is Unacceptable
DEVROEY 2011

7. Clinics providing ovarian stimulation
with Gonadotrophins for IUI/IVF -
Protocol should be in place for preventing,
diagnosing and managing
Ovarian Hyperstimulation Syndrome
Nice Guideline 2004

8. Classification

9. Early < 10Early < 10
 Correlated to
ovarian response
to stimulation.
 Acute effect of
exogenous hCG
administration
 Occurs within
10 days after
oocyte retrieval
LATE <10LATE <10
1. Poorly correlated
to the ovarian
response
2. More correlated to
the endogenous
hCG produced by
the implanting
embryos
3. Administration of
hCG for LPS
4. After the initial 10
Mathur et al - 2005.

10. 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

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
Grading

12. 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

13. • Mild OHSS is common
(~33% of stimulated IVF cycles
Almost all in IVF normal & hyper responders)
• moderate (3 - 6%)
• severe (0.3 – 2%) - uncommon.
13
Incidence of OHSS in IVF Cycles
Most Serious Complications of OI
(Dreadful – Hospitalisation & ? Death)
(Papanikolaou et al.2005)

14. MATERNAL MORTALITY RATES
Due to OHSS
Netherland & UK – 2007
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

15. Aetiopathogenesis
Exact Pathogenesis is not clear

16. IMPORTANCE of OHSS
WHAT IT means to ME & to You ?
• Totally IATROGENIC problem of OI with GT
Induced by clinician
• 100% PREVENTION IMPOSSIBLE
• Profound Economical impact
• Profound Psychological Impact
Without HCG Trigger OHSS is
extremely rare.

17. 3 Facts
• HCG Triggerfor ovulation creates HAVOC
• Long protocol of Down regulation
With GnRH agonist in IVF is associated
↑ OHSS
– Compels IVF experts to use
long protocol
Supposedly ↑ PR
With long protocol

18. 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

19. hypovolemia ascites
hemoconcentration ovarian volume (cysts, edema)
albumine loss pleural/pericardial
effusion
hydro ureter
anasarca
Vascularcompartiment 3th space
19Dr Razia S

20. The Truth is that
OHSS MUST
BE PREVENTED RATHER
than treated

21. Dale Carnegi Said
“The successful man
profits from his mistake
and
tries again in a different way”.
“That’s true for errors of OHSS
events in IVF – a dangerous emergency

22. HOW TO PREVENT IT ?
• Steps Before stimulation
• Step During Stimulation
• Step on Impending Severe OHSS

23. 23Dr Razia S

24. 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
Easily
Recognized
WHO are AT HIGH RISK BEFORE OI – IUI & IVF
PRIMARY RISK FACTORS
SENSITIVE OVARIES
25.0 pmol/l for a high response
( >7 ng/ml

25. OHSS Monitoring should be
• Easy
• Reliable
• Patient friendly
• Not Expensive
• Can be done by IVF Team

26. IDEA

27. Welcome Protocol
to manage Error Terror
Paul Devrory et al -2011
Human Reproduction
An OHSS-Free Clinic
by segmentation of IVF Treatment
OHSS

28. Proposed Protocol of
Zero% OHSS
• The use of the GnRH antagonist protocol
for OI instead of long protocol
• Ovulation Triggering with GnRH agonist
Instead of HCG trigger
• Cryopreservation of all oocytes and embryos
↓
ET in frozen – thawed cycle
3 Steps

29. STEP - 1
Use of GnRH antagonist
Protocol for OI
• Patients friendly
- Fewer injection of OI
- Short duration of stimulation
- Absence of side effects
Uses
• ↓↓ OHSS rate
• No difference in Term LB Rates
Between antagonist & agonist
Al- Inany et al 2006- 20011, Kolibisnskis et al 2006
Devroey et al 2009 2011

30. STEP - II
Ovulation Triggering
- ↓↓↓↓ OHSS Rate
- but can’t eliminate it all
together
GOLD STANDARD as ovulation triggering
agent because of long half life with levels
remaining elevated even after six days of
administrations
NO
HCG
TRIGGER
Antagonist
protocol
GnRH
Agonist
trigger
For triggering final Oocyte maturation
• Effective in preventing OHSS
(Segal and Casper ,1992

31. ZERO % OHSS (Severe / Critical)
is achieved
• Incidence of Severe OHSS is GnRH
antagonist cycles is 0% when triggered with
a GnRH agonist.
• This was tested in OOCYTE DONORS
(Melo et al ,2009)
Major Disadvantages
↑ Luteal phase defect &
significant ↓ Pregnancy Rate

32. It is EASIER Said Than Done
to cancel a cycle !!
↓
GnRH AGONIST
as a triggering agent
Luteal phase defect - ↓ PR
Negative effect on corpus luteum function
Negative effect on function of endometrium
BY GIVING HCG1500 units on O.P.U.
day – P.R. ↑ (NORMALISED)
↑
Cryo
Preservation
↑

33. Step III
CRYO PRESERVATION
of oocytes & embryo
A valuable modality…
But Skill - is the key
Oocyte / embryo vitrification –
↑ P.R. (40% - 80%)
↓ Severe OHSS to 0%
Results better than COASTING
Ethical Issue of freezing embryo

34. CDC Report 2008
Pregnancy Rate same
in FRESH / FROZEN – thawed
cycles

35. Endometrum Preparation in
frozen – thawed cycles
(A) Natural Cycle
(B) GnRH agonists (Day 21)
+ E2
+ progesterone from OPU Day

36. SPECIAL TIPS
for Donar stimulation
• Always use GnRH ANTAGONIST PROTOCOL
• Give GnRH AGONIST TRIGGER for ovulation
• If Suspicious of Moderate OHSS
* Give cabergoline before trigger
* After OPU give antagonist inj. for 2-3 days
* Give progesterone withdral inj MPA
Before discharge or Tablets.
* Follow - up is must

37. Key : Take Home messages
• SAFETY OF PATIENT in IVF is public
& doctors TOP PRIORITY
Concept has to be accepted sooner than
later by FOGSI / ICMR
Strict guidelines to follow
OHSS FREE IVF CLINIC Can be reality ?
Yes ofcourse Hospitalization / ICU care can be prevented!!

38. Replace Long protocol of GnRH agonist
with short antagonist protocol
+
Agonist ovulation trigger
+
Oocyte & embryo freezing
+
ET in
Natural cycle
Or Artificially prepared Endometrium
Key Take Home Messages

39. OHSS : an IATROGENIC problem
must never hold you back if you face it.
Instead - these problems can help you shine brighter
in the next take off –
of your PROFESSIONAL MATURITY & support
OHSS Free Clinic

40. Future Strategy for Safe IVF
Practice
• 100% antagonist cycle
• 100% freezing of
embryos
• 100% frozen-thawed
IVF cycles
Zero % OHSS Free Clinic

41. IS A REALITY

42. Thank You