Ovarian Hyperstimulation Syndrome(OHSS), is a Rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy where a patient's ovaries become swollen and fluid builds up around her abdomen

1. Dr. Laxmi Shrikhande MD; FICOG; FICMU
•Director-Shrikhande Fertility Clinic, Nagpur
•President Menopause Society, Nagpur
•National Corresponding Editor-The Journal of Obstetrics & Gynecology of India
•Senior Vice President FOGSI 2012
•Vice Chairperson ICOG
•Governing Council member ICOG 2012-2017
•Governing Council Member ISAR 2014-2019
•Governing Council Member IAGE for 3 terms
•Patron-Vidarbha Chapter ISOPARB
•Chairperson-HIV/AIDS Committee, FOGSI (2007-09)
•Received Best Committee Award of FOGSI
•Received Bharat excellence Award for women’s health
•President Nagpur OB/GY Society 2005-06
•Associate member of RCOG
•Member of European Society of Human Reproduction
•Visited 96 FOGSI Societies as invited faculty
•Delivered 5 orations
•Publications-Twenty National & eleven International
•Presented Papers in FIGO, AICOG, SAFOG, AICC-RCOG conferences
•Conducted adolescent health programme for more than 15,000 adolescent girls

2. OHSS
Dr Laxmi Shrikhande
Director-Shrikhande IVF & Surrogacy
Centre

3. First reported in the early 1960s by Muller in
patients who developed the syndrome after
administration of pregnant mare's serum
gonadotropins

4. • Rare iatrogenic complication of ovarian stimulation
occurring during the luteal phase or during early
pregnancy.
• It is potentially fatal and is difficult to predict.
• Fortunately, the reported prevalence of the severe form
of OHSS is small, ranging from 0.5 to 5%.
Hugues J. Ovarian stimulation for assisted reproductive technologies, In: Current practices and
controversies in assisted reproduction. Geneva, Switzerland: WHO; 2001, p. 102–126.

5. • More over there is a significant increase in
pregnancy related complications among OHSS
affected pregnancies.
• There fore it is the responsibility of the
treating physician to be well aware of this
iatrogenic disease,

6. • mild 13.5%
• moderate 8%
• Severe- rare
CC & OHSS incidence

7. • mild- 20% and 33%
• moderate - 3 to 6%
• severe - 0.1 to 2%
• Only a few studies have compared the frequency
of OHSS after ovulation induction in IUI to the
frequency after IVF.
OHSS & Gonadotrophins for IVF

8. It seems, however, that serious OHSS is more
prevalent following ovarian stimulation for
IVF treatment rather than COS for non-IVF
purposes
OHSS & Ovulation Induction

9. Early onset OHSS
3 to 7 days after HCG
Excessive response to
stimulation
Late onset OHSS
12 to 17 days after HCG
Due to pregnancy
OHSS is preceded by multiple follicular development
combined with a high serum E2 concentration.
Lyons et al, Hum Reprod. 9: 792, 1994; Mathur et al, Fertil Steril 73: 901, 2000

10. CLASSIFICATION (Golan et al 1989)
MILD Grade 1: abdominal distension and discomfort
Grade 2: grade 1 + nausea,vomiting and/or Diarrhoea,
enlarged ovaries (5-12 cm).
MODERATE Grade 3: grade 2 + ultrasound evidence of ascites
SEVERE Grade 4: grade 3 + clinical evidence of ascites and/or
hydrothorax and breathing difficulties
Grade 5: grade 4 + haemoconcentration, increase
blood viscosity, coagulation abnormality and diminished
renal perfusion
Classification

11. MANAGEMENT-3 Ps
• PREDICTION
• PREVENTION
– Primary (before starting HMG/FSH)
– Secondary (after starting HMG/FSH and
before HCG administration)
• POST - OHSS MANAGEMENT

12. MANAGEMENT-3 Ps
• PREDICTION
• PREVENTION
– Primary (before starting HMG/FSH)
– Secondary (after starting HMG/FSH and
before HCG administration)
• POST - OHSS MANAGEMENT

13. Prediction of OHSS
(A) Clinical Risk factors: PCOS, young
patients, low BMI, previous OHSS, genetic
predisposition
(B) Biochemical indices: Plasma oestradiol
peak, insulin resistance, serum VEGF, von
Willebrand factor, FSH, AMH
(C) Ultrasound indices: PCO pattern, high
AFC, ovarian volume, low intra-ovarian
vascular resistance

14. Prediction
Good predictors Bad predictors
PCOS BMI
Young age Genetic predisposition
PCO pattern Serum VEGF
AFC Von Willebrand factor
E2 level on day of HCG Perifollicular blood flow
Insulin resistance
Large ovarian volume
AMH

15. PCO pattern to predict OHSS
Rizk and Smitz, Hum Reprod 7: 320, 1992;
Delvigne et al, Hum Reprod 8: 1353, 1993

16. Antral follicular count
• Count of total follicles measuring 2 to
5mm in both ovaries on Day 2/3 of
periods.
• Inter observer variation is a limitation.
• cycle to cycle variability
Tomas et al, Hum Reprod 12(2):220, 1997

17. AFC
• 2 D real time TVS by 7 MHz transducer is adequate
• Manual counting on stored 3 D images
• > 15 follicles –risk of OHSS

18. Ovarian volume
• D1xD2xD3x0.52
• Cut off 3.0 MI
• 3 D better than 2 D
• Inter observer variation
• Stand alone- not eligible

19. AMH helps define patient subgroups
<1ng 2-3.5ng >3.5ng
Highly correlates with ovarian response-
97%sensitivity in predicting poor response
98%accuracy in predicting normal response
Current Opin Obstet Gynae 2010 Jan
Hum Reprod Update 2010 Mar-Apr 16(2)
Fertil Steril 2010 Feb 93(3)

20. AMH to predict OHSS
Lee et al. Hum Reprod 23: 160, 2008
AMH Age
BMI
Cut-off value
3.36 ng/ml
Cut-off value
33 years
Cut-off value
18.44 Kg/m2

21. ROC curves comparing AMH and AFC
AFC
AMH
Cut-off
value
=>14
Cut-off
value
3.36
ng/ml

22. Plasma E2 concentration to predict OHSS
Cut-off value
For E2 = 2560 ng/L
For follicles >12
Papanikolau et al, Fertil Steril 85: 112, 2006

23. PREDICTION
• Young patients
• Lean women
• Polycystic Ovarian syndrome
• Previous OHSS
• Increased antral follicular count (> 10 per
ovary)
• Increased anti mullerian hormone levels
(>3.3 ng/ml)
• High or rapidly rising E2 levels (> E2 5,000 pg/ml)
• High number of follicles (≥18)

24. After Prediction-what
next?
PREVENTION HOW???

25. MANAGEMENT-3 Ps
• PREDICTION
• PREVENTION
– Primary (before starting HMG/FSH)
– Secondary (after starting HMG/FSH and
before HCG administration)
• POST - OHSS MANAGEMENT

26. Prevention of OHSS
. Primary prevention (before starting
HMG/FSH)
. Secondary prevention (after starting
HMG/FSH and before HCG
administration)

27. Primary Prevention-before starting
stimulation
• FSH or HMG
• Low dose step-up protocol
• Step-down protocol
• Alternate day HMG/FSH
• Sequential protocol
• In-vitro maturation (IVM)
• GnRH antagonists

28. Reduced gonadotrophin
• Chronic low dose step up protocol results in
better pregnancy rates with reduced incidence of
OHSS compared to high dose regimens in IUI
cycles.
• Minimal stimulation / natural cycle IVF.
• Using r FSH instead of urinary FSH have no effect
in reducing the incidence of OHSS.
Cochrane Database of Systematic Reviews 2011

29. Antagonist protocol
• The use of antagonist compared with long GnRH
agonist protocols was associated with a large
reduction in OHSS and there was no evidence of
a difference in live-birth rates.
• The added advantage being possibility of using
agonist instead of HCG to trigger final oocyte
maturation.
Cochrane Database of Systematic Reviews 2011

30. GnRHa ( long)
n= 85
Cetrorelix
n= 188
P value
OHSS 6.5 % 1.1% 0.03 %
Pregnancy
Rate
26.0 % 22.0% NS
GnRH agonists vs GnRH antogonists
Ludwig e.a. 2001 Gynecol/obstet

31. In vitro maturation
• It is an attractive strategy to prevent OHSS in
PCOS patients. It involves earlier retrieval of
immature oocytes at the germinal-vesicle stage
followed by IVM & ICSI
• Though promising data on the IVM technique have
been published, unfortunately there is still no
evidence from RCTs upon which to base any
practice recommendations.
Cochrane Database of Systematic Reviews2013

32. Prevention of OHSS
Primary prevention (before starting
HMG/FSH)
Secondary prevention (after starting
HMG/FSH and before HCG
administration)

33. Late prevention (after starting HMG/FSH and before HCG)
• Cancellation of the cycle
• Coasting
• Diminish HCG dose
• GnRHa to trigger ovulation
• Metformin
• Albumin
• Cabergoline
• I.V. Calcium
• Cryopreservation of embryos
• GnRH agonists + embryo freezing
• Unilateral follicle aspiration before HCG
• Laparoscopic ovarian electro-cautery

34. Cancellation
• Cycle cancellation before administration of
HCG is an effective strategy for the prevention
of OHSS.
• May be acceptable in an IUI cycle but not in
an IVF cycle because of the financial burden
and psychological stress to the patient.

35. COASTING• Coasting involves withholding further
gonadotropin stimulation & delaying
hCG administration until E2 levels
plateau or decrease significantly
• There was no evidence to suggest a benefit of
using coasting to prevent OHSS compared with
no coasting or other interventions.
Cochrane Database of Systematic Reviews 2011
Coasting

36. Low dose HCG / R- LH
• The trigger of oocyte maturation with low dose
of hCG in high-risk patients reduces the risk of
OHSS. (kolibianakis et al 2007,ying et al 2013).
• No evidence of difference between rHCG or
rhLH and uHCG in achieving final follicular
maturation with equivalent pregnancy rates and
OHSS incidence.
Cochrane Database of Systematic Reviews 2011

37. Gnrh agonist trigger
• Use of GnRH agonists instead of HCG for trigger results
in a lower incidence of OHSS but extremely high early
pregnancy loss due to luteolysis.
• Luteal rescue is still possible with low dose hcg
(1500 IU) with comparable pregnancy rates and
minimal risk of OHSS. (humaidan et al 2012)
• GnRH agonist could be useful for cryopreservation & and
donor/ recipient cycles.
Cochrane Database of Systematic Reviews 2014

38. OVAIDING HCG FOR LPS• Progesterone, hCG or GnRH agonists are used for
LPS but use of hCG was linked to significantly higher
risk of OHSS.
• Progesterone seems to be the best option as LPS in
high risk patients with out the risk of OHSS.
Cochrane Database of Systematic Reviews 2011
Luteal Phase Support

39. Insulin sensitizers
• Metformin suppresses insulin levels &
decreases ovarian androgen
production with improved ovulatory
rates.
• Metformin treatment before or during ART
cycles decreased the risk of OHSS in PCOS
women.
Cochrane Database of Systematic Reviews 2014

40. IV Albumin vs HES
• There is limited evidence of benefit from intra-
venous albumin administration at the time of oocyte
retrieval in the prevention of severe OHSS.
• Where as Hydroxyethyl starch markedly decreases
the incidence of severe OHSS and this is a cheaper,
potentially safer alternative to albumin.
Cochrane Database of Systematic Reviews 2011

41. Review: R.C.T. : 7 studies identified
Conclusion: Clear benefit of IV Albumin in OHSS prevention
Albumin vs. placebo (at OPU) in severe OHSS prevention: a
Cochrane review
Albumin Placebo OR + 95% CI
Severe OHSS 4/193 (2.1%) 14/185(7.6%) 0.28(0.11-0.73)
Aboulghar e.a. Hum. Reprod 2003

42. Dopamine agonist
• Cabergoline appears to reduce the risk of OHSS in
high-risk women, especially for moderate OHSS. (0.5
mg daily for 8 days post hcg trigger)
• The use of cabergoline does not affect the
pregnancy outcome nor is there an increased risk of
adverse events.
Cochrane Database of Systematic Reviews 2012

43. CA GLUCONATE /
ANTAGONIST• Calcium infusion (10 ml of 10% IV Ca gluconate in
200 ml saline for 3 days post OPU) can effectively
prevent severe OHSS and decreases OHSS
occurrence rates. (Naredi & Karunkaran 2013)
• Antagonists 0.25 mg daily from day 5 -8 post OPU
with or without embryo transfer causes rapid
resolution of early onset severe OHSS.
(Lainas et al 2012,2013)
Calcium Infusion

44. Cryopreservation
• Cryopreservation involves freezing of all
embryos to be thawed & implanted at a later
date.
• Early OHSS may occur but it almost eliminates
the risk of late OHSS.
• Though reduced pregnancy rates from frozen-
thawed embryos was a concern, the
introduction of vitrification technique shows
promising results.
CDC Report 2005,Fertil Steril 2008

45. MANAGEMENT-3 Ps
• PREDICTION
• PREVENTION
– Primary (before starting HMG/FSH)
– Secondary (after starting HMG/FSH and
before HCG administration)
• POST - OHSS MANAGEMENT

46. MANAGEMENT
• Out patient management is the norm in mild to
moderate OHSS.
• Monitor hematological & renal parameters
• USG to asses severity of OHSS
• Adequate oral hydration to prevent
haemoconcentration / oliguria
• dopamine agonist to control early OHSS.

47. • Limit activity
• Weigh daily
• Monitor intake(1liter/day) and output
• Daily follow up
• Report if symptoms worsen or
weight gain > 1 kg /day
OUTPATIENT CARE

48. CRITICAL OHSS
• Multi disciplinary management in a intensive care unit
• Strict fluid & electrolyte management
• Crystalloids & HES for hydration
• IV albumin if required
• Thromboprophylaxsis
• Paracentesis/culdocentesis/pleuracentesis relieves
abdominal tension & dysnoea. It also promotes
diuresis & clinical resolution.

49. • Rarely done
• Ovarian torsion, rupture
• Intraperitoneal hemorrhage
SURGERY

50. Summary
• PREDICTION
• PREVENTION
– Primary (before starting HMG/FSH)
– Secondary (after starting HMG/FSH and
before HCG administration)
• POST - OHSS MANAGEMENT

51. Take Home Message
OHSS free clinic is the norm
today

52. “Anyone who stops learning is old,
whether at twenty or eighty. Anyone
who keeps learning stays young.”
Henry Ford―

53. Dr. Laxmi Shrikhande
Shrikhande IVF & Surrogacy Center
Ph-96234 59766 / shrikhandedrlaxmi@gmail.com

54. 'Spiritual blossoming' simply means
blossoming in life in all
dimensions.
Being happy, at ease with yourself
and with everybody around you.
Sri Sri Ravi Shankar
The Art of Living