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Ohss
Ovarian hyper stimulation syndrome (OHSS) is an exaggerated response to ovulation induction that is usually associated with exogenous gonadotropin stimulation. It is typically a self-limiting condition, but can progress to become severe and be associated with increased pregnancy complications. OHSS is classified based on severity of symptoms and managed through prediction, prevention strategies like using a GnRH antagonist protocol or cryopreserving all embryos, and treatment of symptoms for mild-moderate cases or intensive care for critical OHSS. Further research aims to reduce OHSS risk while allowing for fresh embryo transfers.
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Ohss
- 1. www.company.com AICOG 2015 OVARIAN HYPER STIMULATION SYNDROME D ARADR SUNDAR NARAYANAN YANAN
- 2. www.company.com AICOG 2015 • Ovarianhyper stimulation syndrome (OHSS) is an exaggerated response to ovulation induction. • The OHSS is typically associated with exogenous gonodotrophin stimulation and is rarely observed with oral ovulation induction agents.
- 3. www.company.com AICOG 2015 • OHSSis usually a self-limiting disorder • Milder forms resolves spontaneously within few days, but may persist for longer periods and progress to severe disease especially if conception occurs.
- 4. www.company.com AICOG 2015 • Moreover there is a significant increase in pregnancy related complications among OHSS affected pregnancies. • There fore it is the responsibility of the treating physician to well aware of this iatrogenic disease, prevention and management of its complications.
- 5. www.company.com AICOG 2015 • Ratesof occurrence • Mild : 8-23% • Moderate : 1-7% • Severe : 0.25% • Mortality • 3/100,000 cycles
- 6. www.company.com AICOG 2015 The essentialcoexisting factors CO Over response HCG simple model Over stimulation pregnancy, AETIOLOGY
- 7. www.company.com AICOG 2015Humaidan Pet al (2010) PATHOGENISIS
- 8. www.company.com AICOG 2015 •Vascular endothelialgrowth factor (VGEF)is the main mediator of these exaggerated response. •Secondary mediators include renin - angiotensin system and platelet‐derived factors. •Associated increased capillary permeability leads to ASCITES, Pleural /Pericardial effusions. •Ovarian enlargement may lead to torsion or cyst rupture.
- 9. www.company.com AICOG 2015 CLASSIFICATION • Accordingto the time of onset classified into • Early OHSS: Occurs within 9 days of oocyte retrieval due to exogenous hCG trigger. • Late OHSS: Occurs after 10 days of ovum pickup due to endogenous hCG produced by implanting embryo. It is more likely to be severe and lasts longer. (mathur et al Fertil Steril 2000)
- 10. www.company.com AICOG 2015 CLASSIFICATION (Golanet 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
- 11. www.company.com AICOG 2015 Modification ofNavot et al (1992) CRITICAL OHSS Variable enlarged ovary Tense ascites Hydrothorax Hct >55% WBC >25 000 Oliguria Creatinine >1.6 Creatinine clearance <50ml/min Renal failure; Thromboembolic phenomena; ARDS
- 12. www.company.com AICOG 2015 MANAGEMENT • PREDICTION •PREVENTION – Primary – Secondary • POST - OHSS MANAGEMENT
- 13. www.company.com AICOG 2015 PREDICTION • Youngpatients • 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)
- 14. www.company.com AICOG 2015 PRIMARY PREVENTION •Insulin- Sensitizing agents • Reducing dose of gonadotropins • GnRH antagonists protocols • Low dose of hCG /r hcg/r LH • Alternative agents to hcg • Avoiding hCG for Luteal support • In vitro oocyte maturation (IVM)
- 15. www.company.com AICOG 2015 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)
- 16. www.company.com AICOG 2015 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)
- 17. www.company.com AICOG 2015 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)
- 18. www.company.com AICOG 2015 LOW DOSEHCG / 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)
- 19. www.company.com AICOG 2015 GNRH AGONISTTRIGGER • 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)
- 20. www.company.com AICOG 2015 OVAIDING HCGFOR 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)
- 21. www.company.com AICOG 2015 IN VITROMATURATION • 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 Reviews 2013
- 22. www.company.com AICOG 2015 SECONDARY PREVENTION •Cyclecancellation •Coasting •Cryopreservation • Intravenous albumin and HES •Dopamine agonists •Calcium gluconate infusion •Luteal phase antagonist
- 23. www.company.com AICOG 2015 CANCELLATION • Cyclecancellation 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.
- 24. www.company.com AICOG 2015 COASTING • Coastinginvolves 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)
- 25. www.company.com AICOG 2015 CRYOPRESERVATION • Cryopreservationinvolves 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)
- 26. www.company.com AICOG 2015 IV ALBUMINvs 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)
- 27. www.company.com AICOG 2015 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)
- 28. www.company.com AICOG 2015 CA GLUCONATE/ ANTAGONIST • Calcium infusion (10 ml of 10% IV Ca gluconate in 2oo 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).
- 29. www.company.com AICOG 2015 RECOMMENDED • Metforminco‐treatment in PCOS. • Lower starting dose of FSH • GnRH antagonist protocol • GnRH agonist trigger • Avoiding hCG for luteal support • Dopamine agonists • Elective single embryo transfer • Cryopreservation of all embryos (Canadian task force 2014)
- 30. www.company.com AICOG 2015 NOT RECOMMENDED •Intravenous albumin during OPU • Coasting > 3 days • Using one type of FSH versus another • Lowering dose of hCG for final oocyte maturation • Using rec LH instead of hCG for trigger (Canadian task force 2014)
- 31. www.company.com AICOG 2015 MANAGEMENT • Outpatient 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 • GNRH antagonist & dopamine agonist to control early OHSS.
- 32. www.company.com AICOG 2015 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.
- 33. www.company.com AICOG 2015 • Antagonistprotocol with agonist trigger and vitrification of all embryos for subsequent transfer in natural / estrogen administered cycles (segmentation of IVF) seems to be the best available option at present to reduce the incidence and severity of OHSS. • Further research is needed to explore possibilities of fresh embryo transfer to reduce the cost and improve outcome.
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