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Ovarian Hyperstimulation Syndrome How to Prevent
What is it ,[object Object],[object Object]
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Severity ,[object Object],[object Object]
Classification of OHSS Study Mild Moderate Severe Rabau  et al . (1967)  grade 1:  estrogen > 150   g and  grade 2 : + enlarged ovaries grade 3 : grade 2 +  palpable cysts  grade 4 :  grade 3 + vomiting grade 5 : grade 4 +  Ascites  grade 6 :  grade 5 + changes in blood Volume  Golan et al. (1989)  grade 1 :  distension and discomfort  grade 2 :  grade 1 + nausea, vomiting, enlarged ovaries  grade 3 :  grade 2 + US evidence of ascites  grade 4 :  grade 3 + clinical evidence of ascites and/or breathing difficulties  grade 5 :  grade 4 + haemoconcentration,
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Life Threatining ,[object Object]
 
How to prevent ,[object Object],[object Object],[object Object]
Steps before stimulation ,[object Object],[object Object],[object Object]
Before stimulation
After Stimulation
Steps during Stimulation ,[object Object],[object Object],[object Object]
Steps during Stimulation ,[object Object],[object Object],[object Object]
Low Gonadotropin doses Starting with 150 IU for all patients at risk is recommended Type of gonadotropins :  urinary vs recombinant No significant difference in the occurrence of OHSS
Stop hMG and continue down regulation. This is the only complete prevention. (Aboulghar and Mansour, 2003) Not a preferred choice  for both doctors or patients Active Steps
Cryopreservation of Embryos ,[object Object],[object Object],[object Object],[object Object]
Coasting ,[object Object],[object Object]
Mature follicles can survive for a few days without exogenous FSH/hMG while small follicles will undergo apoptosis / necrosis  33
In the absence of gonadotropin stimulation, dominant follicles will continue their growth, while intermediate and small ones will undergo atresia. Coasting diminishes the granulosa cell cohort E2
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What happens when you start coasting? ,[object Object],[object Object]
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The number of days of coasting IS NOT the key issue The focus should be on the E 2  level  We should wait until it drops to 3000 pg/mL
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The   Egyptian IVF-ET Center (May 2001 – May 2003) No. of Cycles  4969 No. of Coasting  560 Mean E 2  on hCG day   3742  +  1074 Days of Coasting 2 – 6 No. of Oocytes 18  +  7 No. of Cancelled ET (cryopreservation of all embryos) 3 OHSS (%) 6 (1.2 per 1000) Clinical Pregnancy (%) 265 (47.32%)
Problems with coasting ,[object Object],[object Object]
However ,[object Object]
Why ,[object Object]
The role of GnRH antagonist in the prevention of  OHSS
GnRH antagonist In a Cochrane review by Al-Inany et al (2006) comparing agonist and antagonist, significant difference in the incidence of OHSS was found
(GnRH) antagonists  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Value ,[object Object]
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GnRH antagonist vs GnRH agonist In patients at high risk of OHSS Multicenter prospective comparative study   Ragni et al., 2005 Hum Reprod GnRH agonist GnRH antagonist cycles cancelled cycles severe OHSS E 2  on day of hCG pregnancy (%) per ET 87 49 (56.3%) 6 4322 87 28 (32.2%) 1 2538  18 (31.6%) P<0.001 P=0.006 P<0.001
Metformin ,[object Object]
Evidence ,[object Object],[object Object]
Metformin & OHSS ,[object Object]
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possible Mechanisms ,[object Object]
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The use of metformin for  women with PCOS Prospective randomized placebo-controlled double-blind study Tang et al., 2006 Hum Reprod Metformin Group control Group Patients Mean total FSH Occytes retrieval Fertilization rate Clinical PR per ET Clinical PR>12 weeks Severe OHSS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],P=0.022 P=0.023 P=023
A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotropins ovulation induction in PCOS patients Significant reduction in OHSS (OR=0.21; 95% CI = 0.11-0.41 P<0.00001) Does not significantly improve the pregnancy rate Costello et al., 2006 Hum Reprod
Luteal support ,[object Object],[object Object],[object Object]
.) OHSS is a preventable disease
What if it Happens ,[object Object]
Always remember ,[object Object],[object Object],[object Object],[object Object],[object Object]
Always remember ,[object Object]
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Ovarian Hyperstimulation Syndrome Prevention and Management

  • 2.
  • 3.
  • 4.
  • 5. Classification of OHSS Study Mild Moderate Severe Rabau et al . (1967) grade 1: estrogen > 150  g and grade 2 : + enlarged ovaries grade 3 : grade 2 + palpable cysts grade 4 : grade 3 + vomiting grade 5 : grade 4 + Ascites grade 6 : grade 5 + changes in blood Volume Golan et al. (1989) grade 1 : distension and discomfort grade 2 : grade 1 + nausea, vomiting, enlarged ovaries grade 3 : grade 2 + US evidence of ascites grade 4 : grade 3 + clinical evidence of ascites and/or breathing difficulties grade 5 : grade 4 + haemoconcentration,
  • 6.
  • 7.
  • 8.  
  • 9.
  • 10.
  • 13.
  • 14.
  • 15. Low Gonadotropin doses Starting with 150 IU for all patients at risk is recommended Type of gonadotropins : urinary vs recombinant No significant difference in the occurrence of OHSS
  • 16. Stop hMG and continue down regulation. This is the only complete prevention. (Aboulghar and Mansour, 2003) Not a preferred choice for both doctors or patients Active Steps
  • 17.
  • 18.
  • 19. Mature follicles can survive for a few days without exogenous FSH/hMG while small follicles will undergo apoptosis / necrosis 33
  • 20. In the absence of gonadotropin stimulation, dominant follicles will continue their growth, while intermediate and small ones will undergo atresia. Coasting diminishes the granulosa cell cohort E2
  • 21.
  • 22.
  • 23.
  • 24. The number of days of coasting IS NOT the key issue The focus should be on the E 2 level We should wait until it drops to 3000 pg/mL
  • 25.
  • 26. The Egyptian IVF-ET Center (May 2001 – May 2003) No. of Cycles 4969 No. of Coasting 560 Mean E 2 on hCG day 3742 + 1074 Days of Coasting 2 – 6 No. of Oocytes 18 + 7 No. of Cancelled ET (cryopreservation of all embryos) 3 OHSS (%) 6 (1.2 per 1000) Clinical Pregnancy (%) 265 (47.32%)
  • 27.
  • 28.
  • 29.
  • 30. The role of GnRH antagonist in the prevention of OHSS
  • 31. GnRH antagonist In a Cochrane review by Al-Inany et al (2006) comparing agonist and antagonist, significant difference in the incidence of OHSS was found
  • 32.
  • 33.
  • 34.
  • 35. GnRH antagonist vs GnRH agonist In patients at high risk of OHSS Multicenter prospective comparative study Ragni et al., 2005 Hum Reprod GnRH agonist GnRH antagonist cycles cancelled cycles severe OHSS E 2 on day of hCG pregnancy (%) per ET 87 49 (56.3%) 6 4322 87 28 (32.2%) 1 2538 18 (31.6%) P<0.001 P=0.006 P<0.001
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43. A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotropins ovulation induction in PCOS patients Significant reduction in OHSS (OR=0.21; 95% CI = 0.11-0.41 P<0.00001) Does not significantly improve the pregnancy rate Costello et al., 2006 Hum Reprod
  • 44.
  • 45. .) OHSS is a preventable disease
  • 46.
  • 47.
  • 48.
  • 49.