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Low-dose hCG is useful in preventing OHSS without adversely affecting the outcome of IVF cycles

Low-dose hCG is useful in preventing OHSS without adversely affecting the outcome of IVF cycles. Geeta Nargund Head of Reproductive Medicine St George’s Hospital, London Medical Director The Centre for Reproduction & Advanced Technology

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Low-dose hCG is useful in preventing OHSS without adversely affecting the outcome of IVF cycles

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  1. Low-dose hCG is useful in preventing OHSS without adversely affecting the outcome of IVF cycles Geeta Nargund Head of Reproductive Medicine St George’s Hospital, London Medical Director The Centre for Reproduction & Advanced Technology London

  2. Reprod Biomed Online. 2007 Jun;14(6):682-5 Low-dose HCG is useful in preventing OHSS in high-risk women without adversely affecting the outcome of IVF cycles Nargund G, Hutchison L, Scaramuzzi R, Campbell S. .

  3. Ovarian Hyperstimulation Syndrome (OHSS) Mild/moderate OHSS(5-20%) Morbidity Bloatedness PMT like symptoms Abdominal discomfort Nausea Severe OHSS (1-5%) Potentially fatal Women die due to severe OHSS. This is unacceptable

  4. OHSS: Prevention • No / Low & tailored dose of stimulation • IVM • GnRH agonist for trigger • Unilateral early (pre-hCG) aspiration • Coasting • Freezing all embryos • Low dose luteal dopamine agonist

  5. OHSS: Identifying Risk Clinical History and Examination • PCO/PCOS/MFO • BMI (Thin women!) • Previous over-response to clomid/FSH • Previous OHSS • No ovarian surgery/diathermy • Herbal medicine!

  6. Doppler ovarian USS Two ovaries ↓Accessibility of ovary ↑Ovarian volume & PCO morphology ↑Early (2-5mm) AFC ↑Stromal vascularity (Velocity) ↑Follicular vascularity (Velocity) OHSS: Identifying risk

  7. Angiogenesis in the ovary • Physiologic angiogenesis (capillary growth) • Follicles & Corpora Lutea contain VEGF and FGF • Periodic growth & regression of vessels • Striking changes in rates of flow • Corpus luteum has the highest blood velocity Redmer DA & Reynolds LP Rev Reprod 1996;1(3) 182-92

  8. Ovarian vascularity & Doppler • Follicle specific(Peri-follicular) -Oocyte collection (↑ velocity =↑ quantity &quality) -Infollicular VEGF correlate with vascularity • Stromal -Prediction of response to stimulation -OHSS Nargund et al,Hum Reprod,1996;11:109-12 Jarvela,Nargund et al,Fertil Steril,2004;82(5):1358-63 Nargund et al,RBM online 2007

  9. The role of VEGF in OHSS • OHSS is a dramatic complication of OI • VEGF mRNA is expressed by granulosa & theca cells • Ovarian VEGF levels correlate with the dose of gonadotrophins administered • Excess of bioactive VEGF in FF increases OHSS risk • VEGF expression is dependent on LH • There is an association between hCG & OHSS • VEGF is increased by hCG in a dose-& time-dependent fashion Rizk B et al,HR Update.1997;(3):255-66 Neulen J et al,Hum Reprod,2001;16(4):621-6 Gomez et al Bio Repro 2003

  10. Ovarian & Follicular vascularisation in PCO • Normal vs. PCO in IVF cycles • 3D-Doppler technique used • Ovarian stromal & Follicular vascularisation • Follicles less vascularised in PCO after GnRH analogue treatment • Increased stromal velocity and total ovarian vascularisation in PCO JarvelaI,Sladkevicius P,Nargund G et al,Fertil Steril,2004;82(5):1358-63

  11. High stromal vascularity can predict the risk of OHSS

  12. Low-dose hCG & OHSS Patients • 21 Women (aged 28-36 ) at risk of severe OHSS • 6 of them previously admitted with severe OHSS (elsewhere) • One had a pulmonary embolus as part of OHSS • All previous severe OHSS were given hCG 5000 iu Protocol • Long protocol • Daily FSH dose 100/112.5 iu • Daily 150 iu if no response to the above dose in the past (3 women) • hCG 2500 iu was administered

  13. Low-dose hCG & OHSS Patients & protocol: In all cases, at the time of hCG: • Leading follicle ≥ 18mm • ≥20 per ovary & 4-5 follicles> 16mm in each ovary • Ovarian volume≥92ml • High ovarian vascularity (power Doppler) • High serum E2 levels

  14. Low-dose hCG & OHSS Results: • Mean duration of stimulation 9.4 days • Total FSH used varied: 750 – 1650iu • Mean no. follicles = 38, of those, 10>16mm • Mean serum E2 >17k pmol/l • Minimum ovarian volume 92mls • Power Doppler-Grade 4 vascularity

  15. Low-dose hCG & OHSS Results: Serum E2 levels No E2 range (pmol/l) 1 8000-10000 9 11000-15000 3 16000-20000 5 21000-25000 2 26000-30000 1 31000-40000 (3 women with E2 >31k coasted ,E2 at hCG 27k)

  16. Low-dose hCG & OHSS Results: • Mean no of oocytes -24 • No of embryos transferred- 2 • 11 had blastocyst transfer • 10 had day 3 transfer • 10 had spare embryos for freezing • 13 conceived (61.9%/cycle) • 10 had live births (47.6%/cycle) & 3 with twins • One developed symptoms of mild OHSS • None developed moderate-severe OHSS

  17. Low-dose hCG & OHSS Conclusions: • We have completed a larger cohort in this study • Low-dose hCG at 2500 iu may be useful in preventing OHSS • Low-dose hCG does not seem to adversely affect the pregnancy rate of IVF cycles • The current minimum dose of hCG could be reduced from 5000 iu to 2500 iu • Further large randomised studies are required

  18. About Yokohama The City of Yokohama is a beautiful resort and port city located on the Tokyo Bay, where you discover the truly Japanese beauty and the futuristic view of the waterfront skyscrapers. The city is located south of Tokyo, less than half and hour’s journey by train. With a population of over three million people, Yokohama is Japan's second largest city and is the capital of Kanagawa Prefecture. Towards the end of the Edo Period (1603-1867), during which Japan maintained a policy of self-isolation, Yokohama's port was one of the first to be opened to foreign trade in 1859. Consequently, Yokohama quickly grew from a small fishing village into one of Japan's major cities. Until today, Yokohama remains popular among expats, has one of the world‘s largest Chinatowns and preserves some former Western residences in the Yamate district. As annual event, large-scale fireworks displays will be held in Yokohama on August 1, 2010. The Third World Congress on Mild Approaches in Assisted ReproductionEmbracing Mild IVF and IVMJuly 30 and 31, 2010At the Pacifico Yokohama, Yokohama, JAPAN Join us in Japan July 30 and 31, 2010At the Pacifico Yokohama, Yokohama, JAPAN The 28th Annual meeting of Japan Society of Fertilization and Implantation (JSFI) will be held on July 28-29, 2010 at the same venue. www.ismaar.org Osamu Kato Congress President Geeta Nargund President, ISMAAR René Frydman Chairperson, ISMAAR Bart Fauser Head of Scientific Committee, ISMAAR ISMAAR2010 Congress Secretariat c/o Kato Ladies Clinic, 7-20-3, Nishi-Shinjuku, Shinjuku, Tokyo, 160-0023, Japan E-mail: ismaar2010@ismaar-japan.com http://2010.ismaar-japan.com/ www.ismaar.org Supported by(Tentative) The Japan Society of Fertilization and Implantation HER Trust – Women’s Health Foundation (UK) ISMAAR HER Trust Excel House, 6 Pepys Road, West Wimbledon, London SW20 8NH, UK www.hertrust.org

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