Are placenta specific protein 1 levels associated with recurrent pregnancy loss or in vitro fertilization failure

with accompanying histone modification, we examined C/EBPb binding to the promoter region of Cyp11a1. The binding of C/EBPb which was analyzed by ChIP assay was significantly higher at 12 h than 0 h. CONCLUSIONS: Changes of histone modification status and chromatin structure in the Cyp11a1 promoter region in addition to DNA hypomethylation status of the promoter are closely associated with the rapid increase of Cyp11a1 mRNA expression in GCs undergoing luteinization during ovulation. In addition, it’s suggested that accompanied by binding of C/EBPb to chromatin structural change, the change of Cyp11a1 mRNA expression is controlled. P-22 Tuesday, October 20, 2015 A RANDOMIZED TRIAL OF WEB-BASED FERTILITY-TRACKING SOFTWARE AND FECUNDABILITY. L. A. Wise,a E. E. Hatch,b J. Stanford,c C. J. McKinnon,a A. Wesselink,b K. J. Rothman.d aDepartment of Epidemiology, Boston University School of Public Health, Boston, MA; b Boston University School of Public Health, Boston, MA; cUniversity of Utah, Salt Lake City, UT; dRTI International, Newton, MA.

P-21 Tuesday, October 20, 2015 CHANGES IN HISTONE MODIFICATION, DNA METHYLATION AND C/EBPB BINDING OF THE CYP11A1 PROMOTER REGION IN RAT GRANULOSA CELLS UNDERGOING LUTEINIZATION H. Asada,b H. Tamura,c DURING OVULATION. M. Okada,a N. Sugino.a aYanaguchi University Graduate School of Medicine, Yamaguchi, Japan; bDepartment of Obstetrics and Gynecology, Yamaguchi, Ube, Japan; cYamaguchi University Graduate School of Mrdicine, Ube, Japan. OBJECTIVE: The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes such as StAR, Cyp19a1 and Cyp11a1 in granulosa cells (GCs). Cyp11a1 codes P450scc and plays an important role in production of progesterone. The ovulatory LH surge induces rapid up-regulation of Cyp11a1 in granulosa cells (GCs) undergoing luteinization during ovulation. Recent evidence has shown that epigenetic mechanisms such as histone modification and DNA methylation are essentially involved in the regulation of gene expression. DESIGN: In this study, we investigated whether epigenetic mechanisms including histone modifications and DNA methylation are involved in the rapid change of Cyp11a1 expression after LH surge and also investigated whether transcription factor is associated with the change. MATERIALS AND METHODS: 21-day-old immature rats were injected with eCG followed by hCG injection 48 h later. The ovaries were removed and luteinized GCs were collected before hCG (0 h), and 4 h, 8 h, and 12 h after hCG injection. RESULTS: 1) In RT-PCR analysis, Cyp11a1 mRNA levels rapidly increased after hCG injection, reached the peak at 4 h, and remained high level until 12 h. 2) Histone modification status in the Cyp11a1 promoter regionwas analyzed by chromatin immunoprecipitation (ChIP) assay. The level of trimethylation of histone-H3 lysine-4, which is an active chromatin marker, was increased and significantly higher at 12 h than 0 h. The level of trimethylation of histoneH3 lysine-9 and trimethylation of histone-H3 lysine-27, which is a suppressive chromatin marker, was decreased and significantly lower at 4 h and 12 h than 0 h. 3) DNA methylation status was analyzed from -1427 bp to -73 bp around Cyp11a1 promoter region by sodium bisulfite sequencing. 5 CpGs were demethylated while the other 3 CpGs, which locate at relatively distal region, were methylated. This DNA methylation profile did not change during luteinization induced by hCG injection. 4) Chromatin accessibility assay showed that the chromatin condensation of the Cyp11a1 promoter region decreased after hCG injection. 5) Since we previously found C/EBPb, which is transcription factor, is involved in the expression of other steroidgenesis-associated genes

FERTILITY & STERILITYÒ

OBJECTIVE: To evaluate whether randomization to use of web-based fertility-tracking software is associated with improved fecundability. DESIGN: Randomized Trial. MATERIALS AND METHODS: The Boston University Pregnancy Online Study (PRESTO) is a prospective cohort study of female pregnancy planners aged 21-45 years in the U.S. and Canada. Women were recruited using internet-based advertisements promoting an incentive to win a premium membership to FertilityFriend.com (FF), a web-based software application that records data on menstrual cycles and fertility signs. At baseline, participants completed a health history questionnaire and were randomized with 50% probability to FF. Women were followed every 8 weeks for up to 12 months or until reported pregnancy. The analysis was restricted to women who were eligible for FF randomization (i.e., non-users of FF) and who had been attempting to conceive for %6 cycles at study entry (N¼1,238). Using an intent-to-treat analysis, we estimated the proportion of women who became pregnant over follow-up and used proportional probabilities regression to estimate fecundability ratios (FR) and 95% confidence intervals (CI). RESULTS: Baseline characteristics were evenly distributed between the two randomization groups. Median follow-up among women randomized to FF was 6.6 months (interquartile range: 3.5-9.4 months) and 6.6 months among non-randomized women (interquartile range: 3.4-10.3 months). Among the 629 women who were randomized to FF, 392 pregnancies (62.3%) were reported during follow-up. Among the 609 women who were not randomized to FF, 379 (62.2%) pregnancies were reported. The overall FR comparing randomized vs. not randomized to FF was 0.95 (95% CI: 0.84-1.08). Among women who had been trying for 0-2, 3-4, and 5-6 cycles at study entry, proportions conceiving among randomized and non-randomized women were 66.4% vs. 69%, 58.7% vs. 57.3%, and 45.6% vs. 30.1%, respectively. FRs for the association between randomization to FF and fecundability were 0.90 (CI: 0.78-1.04), 0.97 (CI: 0.72-1.30), and 1.80 (CI: 1.09-2.99), respectively. Of those randomized to FF, 53.7% actually used the software. The prevalence of FF use was similar across strata of attempt time at entry (55.2%, 47.9% and 54.4%, respectively), but there were differences in time to first use, number/type of features used, and intensity of use. CONCLUSIONS: Overall, there was little evidence that randomization to the FF menstrual cycle charting software program influenced fecundability among pregnancy planners participating in an incentive-based internet study. However, among those who had already been trying to conceive for 5-6 cycles at enrollment, assignment to FF was associated with faster conception. Supported by: This research was Supported by NICHD (R21-HD072326). P-23 Tuesday, October 20, 2015 ARE PLACENTA SPECIFIC PROTEIN 1 LEVELS ASSOCIATED WITH RECURRENT PREGNANCY LOSS OR IN VITRO FERTILH. Timur,a S. Yilmaz,a IZATION FAILURE. N. Yilmaz,a A. S. Erdinc,a S. Erkilinc,b H. A. Inal.c aReproductive Endocrinology Department, ZTB, Dr Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey; bDr Zekai Tahir Burak Education and Research Hospit, Ankara, Turkey; cKonya Education and Research Hospital, Konya, Turkey. OBJECTIVE: To investigate the relationship between the placenta specific protein-1( PLAC 1) levels associated and recurrent pregnancy loss or in vitro fertilization failure.

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DESIGN: A total of 28 patients with recurrent pregnancy loss (group 1), 30 unexplained infertile patients with IVF failure ( group 2), 29 fertil patients ( group 3) were included in this cross- sectional study, from January 2013 to June 2014. MATERIALS AND METHODS: Recruited patients were younger than 40 years and had no systemic disease. Antecubital venous samples were obtained from each woman in the morning. Serum samples were separated and Placenta Specific Protein-1 levels were determined with Human Placenta Specific Protein-1 (Plac-1) (Cusabio) ELISA KIT method. RESULTS: There was no significant difference in terms of age and BMI (p¼ 0.93; 0.20). Serum PLAC 1 levels were significantly higher in group1 when compared to group 3 and 2 (Median of the serum PLAC1 levels: 10.5 vs 1; 10.5 vs 4 ng/ml, respectively) (p <0.001). Also serum PLAC 1 levels in group 2 were significantly higher than group 3 (Median of the serum PLAC1 levels: 4 vs 1ng/ml) (p <0.001). A significant positive correlation was found between serum PLAC 1 levels and abortion rates (r: 0.643; p: 0.001) and a significant negative correlation was found between serum PLAC 1 levels and live birth rates ( r: -0.690; p: 0.001). CONCLUSIONS: Serum Placenta Specific Protein-1 levels might affect negatively on implantation in patients with recurrent pregnancy loss or in vitro fertilization failure. P-24 Tuesday, October 20, 2015 SYSTEMIC OR LOCAL HUMAN CHORIONIC GONADOTROPIN ADMINISTRATION IS NOT BENEFICIAL FOR FROZEN-THAWED EMBRYO TRANSFER IN HORMONE REPLACEMENT CYCLES: TWO PROSPECTIVE RANDOMIZED TRIALS. Y. Matsumoto S. Kokeguchi. Hanabusa Women’s Clinic, Kobe, Japan. OBJECTIVE: Human chorionic gonadotropin (hCG) is important in preparing the endometrium for optimal embryo implantation. However, clinical application of hCG in prior to embryo transfer has been controversial. We evaluated the efficacy of the systemic or local administration of hCG for frozen-thawed embryos transfer in hormone replacement (HR) cycles. DESIGN: Prospective randomized trials MATERIALS AND METHODS: Study1: Systemic administration A total of 173 patients who received frozen-thawed embryo transfer during HR cycle were initially randomized into two groups. In the study group (n¼86), 3000 IU hCG was injected intramuscularly days 17, 20, and 23 of the cycles, in addition to estradiol and progesterone. Patients in the control group (n¼87) were not given hCG. Study 2: Local administration (intrauterine hCG injection before embryo transfer) A total of 198 patients who received single frozen-thawed blastocyst transfer during HR cycles were randomized into two groups. The study group (n¼99) received an intrauterine injection of 100 ml cultured medium containing 1000 IU of hCG. In the control group (n¼99), patients were given only 100 ml intrauterine culture medium. In both groups, intrauterine injections were performed 3 days before blastocyst transfer using an embryo transfer (ET) catheter. The primary outcome measure was the clinical pregnancy rate (CPR). The secondary outcome measure was the miscarriage rate.The study procedures were approved by the Institutional Review Board of Hanabusa Women’s Clinic. RESULTS: No significant differences were found in the baseline characteristics between the two groups in both studies. In study 1, the CPR per ET and the miscarriage rate of the study group were 44% and 13%, while those of the control group were 46% and 15%, with no statistically significant difference. In study 2, the clinical pregnancy and miscarriage rates were 39% and 13%, while those of the control group were 40% and 13%, respectively with no statistically significant difference. CONCLUSIONS: In study 1, systemic administration of 3000IU hCG did not affect on CPR compared with that of control group. In study 2, we used different dosage of hCG from previous studies (1000 IU in this study, and 500 IU in previous studies). However, in spite of two times higher dosage of hCG application, we could not demonstrate any efficacy of hCG on CPR. Therefore, we suggested that neither systemic nor intrauterine administration of hCG were beneficial for frozen-thawed ET in HR cycles. Further investigations will be required to clarify the role of hCG in such treatments. P-25 Tuesday, October 20, 2015 INTERACTIVE CASE-BASED LEARNING IMPROVES RESIDENT KNOWLEDGE AND CONFIDENCE IN REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY (REI). K. N. Goldman,a K. Uquillas,b M. Nachtigall,a M. Fino,a A. Winkel,b V. Lerner.b aReproductive Endocrinology and Infertility, Obstetrics and Gynecology, New York

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ASRM Abstracts

University, New York, NY; bObstetrics and Gynecology, New York University, New York, NY. OBJECTIVE: Residents’ scores on the REI section of the CREOG exam have been traditionally low, and nearly 40% of residents nation-wide perceive their REI knowledge to be poor. We describe the impact of using interactive case-based learning on residents’ knowledge of core REI concepts. DESIGN: An interactive case-based learning curriculum to teach core REI concepts was created. Performance was assessed using a multiple-choice examination before and after the workshop. MATERIALS AND METHODS: A 3-hour case-based workshop was developed to address four primary CREOG objectives: Basic Science/Physiology of the Menstrual Cycle, Menstrual and Endocrine Disorders, Infertility, and Management of Menopause/Primary Ovarian Insufficiency (POI). We evaluated this educational curriculum using a multiple-choice test, assessing both content and confidence, administered immediately before (‘pre’) and after (‘post’) the intervention, as well as 7 weeks post-workshop. Data were analyzed using ANOVA and student’s t-test (p<0.05). RESULTS: 12 (of 29) residents completed both the ‘pre’ and ‘post’ questionnaire including 25% post-graduate year one (PGY1), 41.7% PGY2, 25% PGY3, and 8.3% PGY4. The majority of residents had already completed their REI rotation (66.7%), reported that their REI rotation was too short (58.3%), and self-reported their REI exposure and knowledge as poor (66.7% and 58.3%, respectively). Only one resident reported their REI exposure and knowledge as ‘good’. Following the educational intervention, residents improved their pre-test scores from 50% to 76.5% (p<0.05). A significant improvement in scores was noted in the menstrual cycle physiology section and menopause sections; improvements (NS) were also seen in endocrine and infertility. Mean score-changes indicate that residents benefited the most from menstrual cycle and menopause/POI review. Following the intervention, residents self-reported increased confidence with counseling and treatment of PCOS, ovulation induction cycle monitoring, counseling and treatment of POI, and breaking bad news related to infertility (p<0.05). The multiple-choice content exam was re-administered 7 weeks post-intervention to assess retention, and scores remained significantly improved compared to pre-workshop scores (n¼7, 67.2% vs. 50%, p<0.05). At that time, 71% of residents reported having thought about and/or incorporated the concepts they learned into clinical care, and all residents either strongly agreed (91.7%) or agreed (8.3%) that the case-based interactive format was preferable to traditional lecture-based teaching. CONCLUSIONS: A non-traditional curriculum aimed at teaching core REI concepts to residents through interactive case-based learning can be successfully integrated into a residency curriculum, and significantly improves knowledge and confidence of critical concepts in REI. References: Steiner AZ, Fritz M, Sites CK, Coutifaris C, Carr BR, Barnhart K. Resident experience on reproductive endocrinology and infertility rotations and perceived knowledge. Obstet Gynecol 2011;117:324-30. Supported by: New York University Department of Obstetrics and Gynecology P-26 Tuesday, October 20, 2015 WHO ARE WE? THE 2014 SREI WORK FORCE STUDY. K. T. Barnhart,a S. T. Nakajima,b E. Puscheck,c T. M. Price,d V. L. Baker,e J. Segars.f aObstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; bStanford University, Palo Alto, CA; cObstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI; dDuke University, Durham, NC; eObstetrics and Gynecology, Stanford University School of Medicine, Palo Alto, CA; fJohns Hopkins School of Medicine, Baltimore, MD. OBJECTIVE: The Society for Reproductive Endocrinology and Infertility (SREI) set out to identify the current and future state of the practice of reproductive medicine. DESIGN: Online survey to clarify the current climate and practice of reproductive medicine completed in January 2015. MATERIALS AND METHODS: The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale. RESULTS: 336/1100 (31%) responded: 38% women, 61% men, 76% Caucasian, 9% Asian; 1% AA. The mean age was 53 (range 34-90). Participants averaged 2.3 jobs (range 1-10). 38% worked in academia, 39% in private groups, and 15% solo. The average work week was 53 hrs (1-100). Percent effort included 63% infertility, 9% endocrinology, 10% surgery, 9% research, 5% gyn and 2% preventative health. Respondents performed an average of 12 major surgeries,

Vol. 104, No. 3, Supplement, September 2015