Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition caused by fertility treatments. It can range from mild to life-threatening. Steps to prevent OHSS include identifying at-risk patients, using low gonadotropin doses, coasting by withholding gonadotropins to lower estrogen levels safely, using GnRH antagonists, and administering metformin. If OHSS occurs, management focuses on investigations, fluid monitoring, and paracentesis if needed.

1. Ovarian Hyperstimulation Syndrome How to Prevent

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,

11. Before stimulation

12. After Stimulation

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

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

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

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%)

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

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

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

45. .) OHSS is a preventable disease