1. Diagnosis of PCOS: 3998 Chinese cases NIH, Rotterdam criteria or AES ？ NIH, Rotterdam criteria or AES ？ Zi-Jiang Chen M.D., Ph.D Center for Reproductive Medicine Jinan, China

2. Outline History of diagnostic criteria 1 Clinical study of Chinese PCOS 2 Conclusion 3

3. The history of the criteria 2006 AES 2003 Rotterdam 1990 NIH 1935 S -L PCOS

4. The history of the criteria oligo-/anovulation (AO), hyperandrogenism(HA) and polycystic ovaries (PCO) ROTTERDAM AO+PCO AES HA+ PCO NIH AO+HA

5. Comments on the criteria NIH Rotterdam AES Which is more proper ?

6.  Aim: to have a profound understanding of the features of Chinese PCOS  Time: 2006-  Cases: 3998 PCOS patients from China (13 infertility centers involved)  Screen criteria: Rotterdam criteria, then subgrouped by AES and NIH criteria respectively Clinical study of Chinese PCOS

7. PCOS database

8. Informed consents

9. The clinical phenotypes  3998 patients (Rotterdam criteria) 2798 (70%) cases diagnosed by AES （ 51.53% ） 2715 (67.9%) cases diagnosed by NIH  The clinical characters (Rotterdam criteria) : PCOS from clinical patients PCOS from epidemiological study mentrual dysfunction 97.0 ％ 89.4% polycystic ovaries 94.0% 72.94% hyperandrogenism 70.0% 57.65% hirsutism 16.5% 1.18% acne 18.1% 38.82% Constituent ratio of different phenotypes --- Unpulblished

10. The endocrine of AES and non-AES group (x±s) AES groupnon-AES group tp Age28.54±3.6129.11±3.78-3.872 ＜ 0.01 ** BMI24.97±4.0924.85±4.150.7290.466 FSH6.81±1.826.51±1.764.252 ＜ 0.01 ** LH11.43±6.469.27±5.509.374 ＜ 0.01 ** LH/FSH1.74±1.051.48±0.916.874 ＜ 0.01 ** E255.31±43.2547.68±43.204.428 ＜ 0.01 ** PRL18.82±10.3018.66±10.000.4070.684 --- Unpublished

11. Metabolic features of AES and non-AES group AES groupNon AES grouptp Waistline83.97±10.8283.53±10.701.0310.303 W/H0.864±0.0620.858±0.0582.0140.044 * CHO4.66±0.934.62±0.941.0970.273 TG1.26±0.921.34±1.12-1.7160.086 HDL1.24±2.211.28±0.69-0.3990.690 LDL2.56±2.692.51±0.810.5360.592 FG5.10±0.935.15±1.06-1.3380.181 G308.69±2.708.58±3.300.9690.333 G608.59±4.018.35±3.611.5350.125 G1206.91±2.876.75±2.631.3870.166 G1805.11±2.085.01±1.761.2350.186 F INS10.66±7.8810.43±7.230.7660.444 INS3073.88±49.7969.49±47.612.2370.025 * INS6087.14±64.0881.17±60.342.4320.015 * INS12069.24±60.8961.97±55.653.1910.001 ** INS18026.59±32.5623.70±32.562.2160.027 *

12. DiseasesAES group non-AES group X2X2 p Hypertension 10.6 ％ 11.4 ％ 0.3740.541 Insulin resistance （ HOMA ） 15.2 ％ 15.8 ％ 0.2080.649 Obesity 46.0 ％ 45.2 ％ 0.1510.697 Clinical study of Chinese PCOS --- Unpublished

13. Family history of AES and non-AES group Family historyAES group non-AES group X2X2 p Hypertension 29.8 ％ 29.4 ％ 0.3690.543 Diabetes 11.5 ％ 8.5 ％ 6.0520.014 * Cerebrovascular disease 4.9 ％ 4.5 ％ 0.2010.654 Cardiovascular disease 9.4 ％ 8.8 ％ 0.2760.599 --- Unpublished

14. Endocrine of NIH group and non-NIH group NIH groupnon-NIH group tp Age28.55±3.6429.04±3.72-3.465 ＜ 0.01 ** BMI24.94±4.0924.93±4.160.0410.967 FSH6.81±1.836.53±1.754.090 ＜ 0.01 ** LH11.58±6.469.16±5.4810.696 ＜ 0.01 ** LH/FSH1.76±1.061.46±0.9168.225 ＜ 0.01 ** E255.67±43.8347.65±41.984.774 ＜ 0.01 ** T77.48±20.5246.19±15.8846.460 ＜ 0.01 ** PRL18.79±10.3418.75±9.940.0970.922 Clinical study of Chinese PCOS --- Unpublished

15. NIH groupnon-NIH group tp Waistline 83.89 ±10.74 83.72 ±10.89 0.4200.675 W/H 0.864 ±0.060 0.859 ±0.063 2.1240.034 * CHO 4.66 ±0.92 4.62 ±0.95 1.1590.247 TG 1.26 ±0.91 1.33 ±1.11 -1.6840.092 HDL 1.24 ±2.25 1.28 ±0.67 -0.3690.712 LDL 2.57 ±2.74 2.50 ±0.82 0.6240.533 BG0 5.10 ±0.92 5.15 ±1.67 -1.3810.168 BG30 8.68 ±2.72 8.61 ±3.22 0.5800.562 BG60 8.58 ±4.05 8.40 ±3.56 1.1930.233 BG120 6.91 ±2.88 6.77 ±2.62 1.2880.198 BG180 5.10 ±2.09 5.02 ±1.77 1.1560.248 INS0 10.67 ±7.98 10.40 ±7.08 0.9720.331 INS30 74.06 ±50.06 69.51 ±47.23 2.4200.016 * INS60 87.21 ±64.37 81.51 ±60.08 2.3790.017 * INS120 69.56 ±61.21 62.03 ±55.37 3.3860.001 ** INS180 26.91 ±33.06 23.27 ±31.48 2.9160.004 ** The difference was still statistical significant after excluding the effect of age. (P=0.044)

16. Metabolism results of NIH and non-NIH group DiseasesNIH group non-NIH group X2X2 p Hypertension 10.5 ％ 11.5 ％ 0.6110.434 Insulin resistance （ HOMA ） 15.3 ％ 15.5 ％ 0.0280.868 Obesity 45.8 ％ 0.0000.983 No difference was found between groups about their medical history. Clinical study of Chinese PCOS --- Unpublished

17. Family history of NIH and non-NIH group Family historyNIH group non-NIH group X2X2 p Hypertension 30.5 ％ 28.1 ％ 1.8920.169 Diabetes 11.6 ％ 8.7 ％ 6.2390.012 * Cerebrovascular disease 4.7 ％ 4.9 ％ 0.0440.834 Cardiovascular disease 9.5 ％ 8.6 ％ 0.7030.402 Clinical study of Chinese PCOS --- Unpublished

18.  In AES group and NIH group: Patients are younger, Besides higher T, higher FSH and LH level. LH/FSH ratio is also higher significantly  Similar in both groups: Insulin levels are higher than that of non- groups Prevalence of Diabetes family history is significantly higher More risk of long-term complications Clinical study of Chinese PCOS

19.  The increased level of FSH and hypersensitivity caused by hyperandrogenism can promote the development of mutiple pre-antral follicles. This may be the reason of the morphological change in PCOS.  Elevated LH level will stimulate the production of androgen and form the vicious cycle which will aggravate the ovulatory dysfunction. Sarma HN. 2005 Discussion

20.  A strong association between hyperandrogenism and metabolic syndrome, independent of obesity and insulin resistance. Hyperandrogenism is the independent risk factor of CVD  NIH PCOS is associated with a more adverse metabolic profile. The prevalence of obesity and insulin resistance is higher in NIH group. The risk of CVD and DM was increased. Coviello AD 2006, Legro 2006, Shaw LJ 2008, Cussons 2008, Moran L 2009 Goverde AJ, 2009 Discussion

21.  Our present results: both NIH and AES PCOS are associated with a more adverse metabolic profile. The insulin level are higher than that of non- groups, the insulin sensitivity was impaired in these subgroups. Prevalence of Diabetes family history is significantly higher.  PCOS without polycystic ovaries (non-PCO ) had higher cholesterol and low-density lipoprotein, had a higher incidence of developing long-term complications. ZJ Chen, et al. 2008 Discussion

22. IR Anovulation Hyperinsulinemia IGFBP-1Free IGF-1 Hypersensitivity to FSH Androgen excess Discussion Androgen excess plays an important role in the pathophysiological process and has crucial significance ， but in clinic, how to determine androgen excess ?

23. Serum total Testosterone level in PCOS in different ethnicities Studiesethnicityn T PCOS % increased over Ctl mean T Chang et al., 2005USA mixed31690.02% Hahn et al., 2005German20081.00% Legro et al., 2006USA Caucasian62660.80% Diamanti 2007Greek634103.22% T Iwasa, 2007Japanese49 86±48.00 ng/dl 29.4% D.Y ang 2008 S.Chinese 661 3.20±0.30 nmol/l 88.22% Liou, et al 2008Chinese TW613 3.0±1.4nmol/l 57.88% ZJ Chen, 2010Chinese3155 67.01±24.10 ng/dl 51.9% Orio et al., 2010Italians100 2.6±0.3nmol/l 100.00% M ASUNCIO´ N, 2010Spainish9 1.7 ±0.9 nmol/l 70%

24. Conclusions NIH and AES criteria are stricter than Rotterdam criteria. 1 2 3 In clinic, which is more practical for PCOS diagnosis? 4 We still need more evidence and studies in the future … 2 Which is more proper for Chinese patients with PCOS: AO + HA /+PCO ? (mentrual dysfunction should be necessary condition?)

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