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FEMALE REPRODUCTIVE ENDOCRINOLOGY P-334 Wednesday, October 22, 2014 CREAM INGESTION PROMOTES THE EXPRESSION OF TOLL-LIKE RECEPTOR-2 (TLR-2) AND MATRIX METALLOPRO- TEINASE-2 (MMP-2) IN POLYCYSTIC OVARY SYN- DROME. F. Gonz alez, R. V. Considine, S. L. Pardue, A. J. Acton. Obstetrics and Gynecology and Internal Medicine, Indiana University School of Medicine, Indianapolis, IN. OBJECTIVE: Lipid-stimulated oxidative stress and circulating heat shock protein 70 (Hsp70) are increased in Polycystic Ovary Syndrome (PCOS). 1,2 Hsp70 is induced by oxidative stress and can bind the TLR-2 receptor to stim- ulate proatherogenic inflammation. MMP-2 promotes atherosclerotic plaque rupture. We examined the effect of cream ingestion on serum Hsp70 and TLR-2 and MMP-2 protein content in women with PCOS compared with ovulatory controls; and its relation to the ovarian androgen response to HCG administration and abdominal adiposity (AA). DESIGN: Cross sectional study. MATERIALS AND METHODS: We studied 16 women with PCOS (8 lean, 8 obese) between ages 18-40, diagnosed on the basis of oligomenorrhea and hyperandrogenemia, and 16 ovulatory controls (8 lean, 8 obese) of similar age. Subjects ingested 100 ml of dairy cream and received a 5000 IU IM HCG injection within 5-8 days of menses. Serum Hsp70 was measured by ELISA and TLR-2 and MMP-2 protein content were quantified by Western blotting in mononuclear cells (MNC) isolated from blood samples drawn while fasting and 2 hours after cream ingestion. Androgens were measured from blood samples drawn at 0, 24, 48 and 96 hours after HCG administration. AA was defined as the % ratio of truncal fat to total body fat measured by DEXA. RESULTS: Compared with lean controls, obese controls and lean and obese women with PCOS exhibited a greater change from baseline in Hsp70 (-11.16.4 vs. 2.41.9, 3.22.0, 4.93.7 ng/dl D;p<0.04), TLR-2 (-93 vs. 95, 162, 207 %; p<0.002) and MMP-2 (-143 vs. 112, 153, 194 %; p<0.0001). Compared with weight-matched controls, women with PCOS exhibited a greater area under the curve (AUC) following HCG administration for testosterone (T) (lean: 6933715 vs. 4010340, p<0.03; obese: 70791236 vs. 3173853, p<0.007), and androstenedione (A) (lean: 47130 vs. 31726, p<0.0001; obese: 51114 vs. 29419, p<0.0001). Androgen AUC was positively correlated with the change from baseline in Hsp70 (T: r¼0.42, p<0.05, A: r¼0.41 p<0.05), TLR-2 (T: r¼0.42, p<0.04, A: r¼0.47, p<0.02) and MMP-2 (T: r¼0.40, p<0.04, A: r¼0.58, p<0.002). AA was also positively correlated with the change from baseline in Hsp70 (r¼0.37, p<0.05), TLR-2 (r¼0.42, p<0.03) and MMP-2 (r¼0.41, p<0.03). CONCLUSION: In PCOS, cream ingestion increases Hsp70, TLR-2 and MMP-2 independent of obesity. Lipid-stimulated inflammation may promote atherogenesis in PCOS. This phenomenon may be perpetuated by hyperan- drogenism and excess abdominal adiposity. Supported by: NIH grant HD048535 to FG. P-335 Wednesday, October 22, 2014 EXPECTANT MANAGEMENT IN THE INFERTILE WOMEN UNDER AGED 35 YEARS WITH LOW SERUM AMH LEVELS. H. S. Koo, E. G. Min, J. Y. Kim, I. S. Kang, I. O. Song, H. O. Kim. Division of Reproductive Endocrinology and Infertility, Depart- ment Obstetrics and Gynecology, Cheil General Hospital, Kwandong University College of Medicine, Seoul, Korea. OBJECTIVE: To evaluate natural pregnancy rates and the predictors of natural pregnancy in the infertile women under 35 years old with low serum AMH levels. DESIGN: A total of 157 patients (age range, 27-34 yrs) with regular menstruation were included retrospectively between Feb. 2010 and Dec. 2012 in a single center. MATERIALS AND METHODS: The 82 study women with low AMH level (less than 25 %; %31 yrs, <2.5 ng/mL; 32-34 yrs, <2.0 ng/mL) and 75 control women with normal AMH level (25%-75%; %31 yrs, 2.5-6.65 (ng/mL); 32-34 yrs, 2.0-5.7(ng/mL)) were analyzed (reference levels from Clin Exp Reprod Med,38(2),93-97,2011). Exclusion criteria is followed; 1) abnormal hysterosalpingography (bilateral tubal obstruction, uterine anom- aly, synechia), 2)severe asthenozoospermia, 3)PCOS, 4)irregular menstrua- tion, 5)FSH>40mIU/ml. Follow up period (F/U) was average 5.55.6 months, and F/U loss rates were 12.7% (20/157). RESULTS: The mean age (yr) was 31.61.8 vs. 31.41.9, mean serum AMH levels (ng/ml) was 1.50.6 vs.3.61.3, and duration of infertility (months) was 15.5 9.2 vs. 13.37.6 in low and normal AMH group respectively. The natural pregnancy rate was 40.0% (28/70) in low AMH group and 49.3% (33/67) in normal AMH group. There was no sta- tistical significance (p¼0.305). Miscarriage rates was significantly higher in low AMH group (32.1% (9/28) vs. 6.1% (2/33), p¼0.016). Average time to pregnancy was 8.66.8 months in low AMH group and 6.55.4 months in normal AMH group. Duration of infertility is the borderline significant factor related with natural pregnancy(r¼-0.46, p¼0.051). CONCLUSION: Expectant management could be available in the young patients with low AMH levels who do not have any infertile factors. But rela- tively high miscarriage rates should be considered and counseled. Further large scaled study was needed to clarify. P-336 Wednesday, October 22, 2014 SYNCHRONIZATION OF WOMEN’S CYCLES: A BIG DATA AND CROWDSOURCING APPROACH TO MENSTRUAL CYCLE ANALYSIS. P. Chenette a C. Martinez. b a Pacific Fertility Center, San Francisco, CA; b Glowing, San Francisco, CA. OBJECTIVE: The ubiquity of mobile devices offers a novel paradigm for fertility study, enabling data collection from thousands of users to provide an unprecedented view of menstrual cycles. Glow, a women’s health app available on iOS and Android platforms, collects menstrual cy- cle parameters from users. Over time a very large collection of cycles emerges, with the challenge of sifting data to provide meaningful analysis. In this phase one study, we studied the synchronization of cycles across a large sampling of users, and its relationship to the phase of the moon. DESIGN: The Glow app was developed to track menstrual cycles, and to provide insights into health for women (www.glowing.com). Glow records data related to fertility and offers algorithms to predict optimal fertile pe- riods. Women’s statements of the date menses began were compared across the population of Glow users. MATERIALS AND METHODS: Glow was offered for free download to iOS and Android users beginning in Aug 2013. A daily calendar records men- strual cycle start, ovulation symptoms, and BBT. Cycles included for analysis were from users who had an average cycle length greater than 28 days in length and less than 31 days in length. Menses start date was recorded relative to the date of the nearest full moon (FM) and the distribution of daily menses start relative to all menses calculated. Start dates were grouped into 5-day ranges. RESULTS: 39,541 cycles were selected for analysis from 8,233 users. The mean cycle length was 29.41 days, +- 0.659. Menses start date was related to the phase of the moon, with a distribution that plateaued at 3.5 to 4.0% on days FM-11 through FM+3 then declined over 4 days to a lower plateau of 2.2-2.8% of cycles. Peak menses start date was FM- 9 and nadir FM-14. Peak incidence (4.0%) exceeded nadir (2.2%) by 81.8%. Menses start distribution relative to Full Moon (FM) Days from FM Distribution -2 to 2 18.6% 3 to 7 16.8% 8 to 12 13.9% 13 to -13 13.2% -12 to -8 18.9% -7 to -3 18.8% CONCLUSION: Menstrual cycles showed evidence of global synchroni- zation in this dataset. There was a correlation of menses start to the phase of the moon, with most starting in a range of 11 days before to 3 days after the full moon. A Big Data approach to menstrual cycle analysis provides unique and powerful insights into population fertility, and potent opportu- nities for future study of menstrual cycle dynamics, and patient counseling on fertility, and fertility avoidance. e250 ASRM Abstracts Vol. 102, No. 3, Supplement, September 2014

Synchronization of women’s cycles: a big data and crowdsourcing approach to menstrual cycle analysis

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Page 1: Synchronization of women’s cycles: a big data and crowdsourcing approach to menstrual cycle analysis

FEMALE REPRODUCTIVE ENDOCRINOLOGY

P-334 Wednesday, October 22, 2014

CREAM INGESTION PROMOTES THE EXPRESSION OFTOLL-LIKE RECEPTOR-2 (TLR-2) ANDMATRIX METALLOPRO-TEINASE-2 (MMP-2) IN POLYCYSTIC OVARY SYN-DROME. F. Gonz�alez, R. V. Considine, S. L. Pardue, A. J. Acton.Obstetrics and Gynecology and InternalMedicine, Indiana University Schoolof Medicine, Indianapolis, IN.

OBJECTIVE: Lipid-stimulated oxidative stress and circulating heat shockprotein 70 (Hsp70) are increased in Polycystic Ovary Syndrome (PCOS).1,2

Hsp70 is induced by oxidative stress and can bind the TLR-2 receptor to stim-ulate proatherogenic inflammation. MMP-2 promotes atherosclerotic plaquerupture. We examined the effect of cream ingestion on serum Hsp70 andTLR-2 and MMP-2 protein content in women with PCOS compared withovulatory controls; and its relation to the ovarian androgen response toHCG administration and abdominal adiposity (AA).

DESIGN: Cross sectional study.MATERIALS AND METHODS: We studied 16 women with PCOS (8

lean, 8 obese) between ages 18-40, diagnosed on the basis of oligomenorrheaand hyperandrogenemia, and 16 ovulatory controls (8 lean, 8 obese) of similarage. Subjects ingested 100ml of dairy cream and received a 5000 IU IMHCGinjection within 5-8 days of menses. Serum Hsp70 was measured by ELISAand TLR-2 and MMP-2 protein content were quantified by Western blottinginmononuclear cells (MNC) isolated fromblood samples drawnwhile fastingand 2 hours after cream ingestion. Androgens were measured from bloodsamples drawn at 0, 24, 48 and 96 hours after HCG administration. AAwasdefined as the % ratio of truncal fat to total body fat measured by DEXA.

RESULTS: Compared with lean controls, obese controls and lean andobese women with PCOS exhibited a greater change from baseline inHsp70 (-11.1�6.4 vs. 2.4�1.9, 3.2�2.0, 4.9�3.7 ng/dl D; p<0.04), TLR-2(-9�3 vs. 9�5, 16�2, 20�7 %; p<0.002) and MMP-2 (-14�3 vs. 11�2,15�3, 19�4 %; p<0.0001). Compared with weight-matched controls,women with PCOS exhibited a greater area under the curve (AUC) followingHCG administration for testosterone (T) (lean: 6933�715 vs. 4010�340,p<0.03; obese: 7079�1236 vs. 3173�853, p<0.007), and androstenedione(A) (lean: 471�30 vs. 317�26, p<0.0001; obese: 511�14 vs. 294�19,p<0.0001). Androgen AUC was positively correlated with the changefrom baseline in Hsp70 (T: r¼0.42, p<0.05, A: r¼0.41 p<0.05), TLR-2(T: r¼0.42, p<0.04, A: r¼0.47, p<0.02) and MMP-2 (T: r¼0.40, p<0.04,A: r¼0.58, p<0.002). AA was also positively correlated with the changefrom baseline in Hsp70 (r¼0.37, p<0.05), TLR-2 (r¼0.42, p<0.03) andMMP-2 (r¼0.41, p<0.03).

CONCLUSION: In PCOS, cream ingestion increases Hsp70, TLR-2 andMMP-2 independent of obesity. Lipid-stimulated inflammationmay promoteatherogenesis in PCOS. This phenomenon may be perpetuated by hyperan-drogenism and excess abdominal adiposity.

Supported by: NIH grant HD048535 to FG.

P-335 Wednesday, October 22, 2014

EXPECTANT MANAGEMENT IN THE INFERTILE WOMENUNDER AGED 35 YEARS WITH LOW SERUM AMHLEVELS. H. S. Koo, E. G. Min, J. Y. Kim, I. S. Kang, I. O. Song,H. O. Kim. Division of Reproductive Endocrinology and Infertility, Depart-ment Obstetrics and Gynecology, Cheil General Hospital, KwandongUniversity College of Medicine, Seoul, Korea.

OBJECTIVE: To evaluate natural pregnancy rates and the predictors ofnatural pregnancy in the infertile women under 35 years old with low serumAMH levels.

DESIGN: A total of 157 patients (age range, 27-34 yrs) with regularmenstruation were included retrospectively between Feb. 2010 and Dec.2012 in a single center.

MATERIALS AND METHODS: The 82 study women with low AMHlevel (less than 25 %; %31 yrs, <2.5 ng/mL; 32-34 yrs, <2.0 ng/mL) and75 control women with normal AMH level (25%-75%; %31 yrs, 2.5-6.65(ng/mL); 32-34 yrs, 2.0-5.7(ng/mL)) were analyzed (reference levels fromClin Exp Reprod Med,38(2),93-97,2011). Exclusion criteria is followed; 1)abnormal hysterosalpingography (bilateral tubal obstruction, uterine anom-aly, synechia), 2)severe asthenozoospermia, 3)PCOS, 4)irregular menstrua-tion, 5)FSH>40mIU/ml. Follow up period (F/U) was average 5.5�5.6months, and F/U loss rates were 12.7% (20/157).

e250 ASRM Abstracts

RESULTS: The mean age (yr) was 31.6�1.8 vs. 31.4�1.9, mean serumAMH levels (ng/ml) was 1.5�0.6 vs.3.6�1.3, and duration of infertility(months) was 15.5� 9.2 vs. 13.3�7.6 in low and normal AMH grouprespectively. The natural pregnancy rate was 40.0% (28/70) in lowAMH group and 49.3% (33/67) in normal AMH group. There was no sta-tistical significance (p¼0.305). Miscarriage rates was significantly higherin low AMH group (32.1% (9/28) vs. 6.1% (2/33), p¼0.016). Averagetime to pregnancy was 8.6�6.8 months in low AMH group and6.5�5.4 months in normal AMH group. Duration of infertility is theborderline significant factor related with natural pregnancy(r¼-0.46,p¼0.051).CONCLUSION: Expectant management could be available in the young

patients with low AMH levels who do not have any infertile factors. But rela-tively high miscarriage rates should be considered and counseled. Furtherlarge scaled study was needed to clarify.

P-336 Wednesday, October 22, 2014

SYNCHRONIZATION OF WOMEN’S CYCLES: A BIG DATA ANDCROWDSOURCING APPROACH TO MENSTRUAL CYCLEANALYSIS. P. Chenettea C. Martinez.b aPacific Fertility Center, SanFrancisco, CA; bGlowing, San Francisco, CA.

OBJECTIVE: The ubiquity of mobile devices offers a novel paradigmfor fertility study, enabling data collection from thousands of users toprovide an unprecedented view of menstrual cycles. Glow, a women’shealth app available on iOS and Android platforms, collects menstrual cy-cle parameters from users. Over time a very large collection of cyclesemerges, with the challenge of sifting data to provide meaningfulanalysis. In this phase one study, we studied the synchronization ofcycles across a large sampling of users, and its relationship to the phaseof the moon.DESIGN: The Glow app was developed to track menstrual cycles, and to

provide insights into health for women (www.glowing.com). Glow recordsdata related to fertility and offers algorithms to predict optimal fertile pe-riods. Women’s statements of the date menses began were compared acrossthe population of Glow users.MATERIALS AND METHODS: Glow was offered for free download to

iOS andAndroid users beginning in Aug 2013. A daily calendar recordsmen-strual cycle start, ovulation symptoms, and BBT. Cycles included for analysiswere from users who had an average cycle length greater than 28 days inlength and less than 31 days in length.Menses start datewas recorded relativeto the date of the nearest full moon (FM) and the distribution of daily mensesstart relative to all menses calculated. Start dates were grouped into 5-dayranges.RESULTS: 39,541 cycles were selected for analysis from 8,233 users.

The mean cycle length was 29.41 days, +- 0.659. Menses start date wasrelated to the phase of the moon, with a distribution that plateaued at3.5 to 4.0% on days FM-11 through FM+3 then declined over 4 days toa lower plateau of 2.2-2.8% of cycles. Peak menses start date was FM-9 and nadir FM-14. Peak incidence (4.0%) exceeded nadir (2.2%) by81.8%.

Menses start distribution relative to Full Moon (FM)

Days from FM Distribution

Vol. 102, No. 3, Supplement, Sep

-2 to 2

18.6% 3 to 7 16.8% 8 to 12 13.9% 13 to -13 13.2% -12 to -8 18.9% -7 to -3 18.8%

CONCLUSION: Menstrual cycles showed evidence of global synchroni-zation in this dataset. There was a correlation of menses start to the phaseof the moon, with most starting in a range of 11 days before to 3 days afterthe full moon. A Big Data approach to menstrual cycle analysis providesunique and powerful insights into population fertility, and potent opportu-nities for future study of menstrual cycle dynamics, and patient counselingon fertility, and fertility avoidance.

tember 2014