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Nick Macklon Chair, Department of Reproductive Medicine and Gynaecology UMC Utrecht

Nick Macklon Chair, Department of Reproductive Medicine and Gynaecology UMC Utrecht The Netherlands. PCOS throughout life. history complaints future concerns. GP Pediatrician Gynecologist Dermatologist Internal Medicine Cardiology.

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Nick Macklon Chair, Department of Reproductive Medicine and Gynaecology UMC Utrecht

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  1. Nick Macklon Chair, Department of Reproductive Medicine and Gynaecology UMC Utrecht The Netherlands

  2. PCOS throughout life history complaints future concerns GP Pediatrician Gynecologist Dermatologist Internal Medicine Cardiology low birth weight precocious pubarche obesity cycle abnormalities hirsutism infertility pregnancy complications type 2 DM cardiovascular events Birth puberty adolescence reproductive life ageing

  3. PCOS BASICS • Prevalence of PCOS is 7% -and rising Norman et al ,Lancet 2007 • Increases risk of cardiometabolicdisturbances • Insulinresistance • Dyslipidaemia • Diabetes Ehrmann et al, JCEM 2006 • Obesity present in 50-70% of cases Azziz et al, JCEM 2004

  4. Lecture Summary Why consider lifestyle? Which interventions? Outcomes Conclusions

  5. Endocrine Impact of Obesity • Obesity associated with increased insulin resistance • High serum insulin may drive increased androgen production • Insulin resistance associated with suppression of SHBG Women with PCOS and obesity have higher T4 than PCOS alone Peripubertal obesity associated with 2 fold increase in T4 levels Hoeger K, Clin Obstet Gynecol, 2007

  6. Impact of obesity of clinical, hormonal and metabolic features of PCOS Hoeger K, Clin Obstet Gynecol, 2007

  7. Ovulatory infertility and Obesity Mulders et al. Hum Reprod Update 2003

  8. Fedorcsák et al, Hum Reprod 2004,19:2523 What is the impact of obesity on IVF/ICSI outcomes ?

  9. What is the impact of obesity on IVF/ICSI outcomes ? Fedorcsák et al, Hum Reprod 2004,19:2523

  10. Risks of Infertility Treatment in the Obese Patient • Difficulty in ultrasound monitoring • Complications during oocyte retrieval • Difficult embryo transfer • Increased risk thromboembolic complications

  11. 80 120 60 100 SOX2 hTERT CDX2 NANOG 100 80 60 80 40 % cells +ve 60 40 60 40 40 20 20 20 20 0 0 0 0 15 20 25 30 35 15 20 25 30 35 15 20 25 30 35 15 20 25 30 35 BMI BMI BMI BMI Maternal BMI affects early embryo phenotype Relationship between embryonic potency protein marker expression and maternal BMI Eckert et al, 2008

  12. Meta-analysis: 720 women with PCOS vs 4505 controls OR 95% CI Gestational Diabetes: 2.94 1.70-5.08 Pregnancy induced hypertension: 3.67 1.98-6.81 pre-eclampsia 3.47 1.95-6.17 Pre-term birth 1.75 1.16-2.62 Peri-natal mortality 3.07 1.03-9.21

  13. SO: WHAT SHOULD WE DO ABOUT IT? ..and why bother?

  14. Treatment Controls Endocrinology & Weight Loss(Guzick et al., Fertil Steril, 1994) SHBG SHBG - T Insuline Glucose Total T 90 .9 16 90 120 80 .8 14 80 110 70 .7 12 70 100 60 .6 10 60 90 50 .5 8 50 40 .4 6 40 Pre Post Pre Post Pre Post Pre Post Pre Post

  15. Which diet? 12 week energy restriction diet Randomised to high or low protein diet RESULTS: Both interventions improved cyclicity, lipid profile and IR : Mean weightloss 7.5% LP diet: HDLs decreased 10% : FAI increased 44% CONCLUSIONS: Both diets work! High protein diet may have slight advantages

  16. Diet or Exercise- or both?

  17. Why Bother? Hoeger K, Clin Obstet Gynecol, 2007

  18. Moment of caution…

  19. 10 women, 18-40 years, BMI >28, indication for IVF Diet from day14 or day 21 of previous cycle to day of OPU 4 patients withdrew Mean duration of diet: 27-41 days Weight loss: 5.3-8.2 kg (mean 6.3% of body weight) 3 patients : total fertilization failure Tsegareli et al 2006 Fertil Steril

  20. Do womenwith PCOS have poorerpericonceptionaldiet? • Cross-sectional study in patients about to undergo IVF • 25 women with PCOS and 222 control women. • Linear regression analysis of validated dietary questionnaire Brussel, ter Schouw, Macklon

  21. Do womenwith PCOS have poorerdiet in general? • Case control study in 84 cases versus 79 age matched controls • Linear regression analysis of validated dietary questionnaire PCOS Controls p Age 47 48 NS BMI 32 29 0.004 Fasting Insulin (uIU/ml) 17.8 14.7 0.006 Energy intake (kcal) 1754 1762 NS Protein(g) 66 63 NS CHO(g) 205 211 NS Fat(g) 75 73 NS Ever smoker 48% 48% NS Wright et al, Int J Obesity 2004

  22. CONCLUSIONS 1

  23. CONCLUSIONS 2

  24. ´Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption´.

  25. CONCLUSIONS 3 • Larger RCTS needed to assess impact • of interventions. • 2. MORE EMPHASIS ON PREVENTION: • focus on lifestyle and diet in adolescent girls • 3. Build lifestyle interventions into reproductive treatment pathways • 4. Invest effort and money into lifestyle programs

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