Do high estradiol levels during IVF affect thyroid function?

CONCLUSION: Weekly increments of 25 IU in the daily rFSH dose were more effective and efficient than 50-IU increments and resulted in higher ongoing pregnancy rates. Ovulation induction with 25-IU increments in women with anovulatory infertility resulted in a significant decrease in the amount of gonadotropin used. Supported by: Financial support for this study was provided by Merck, Sharp and Dohme & Co. P-37 Tuesday, October 18, 2011 DO HIGH ESTRADIOL LEVELS DURING IVF AFFECT THYROID FUNCTION? S. L. Reinblatt, B. Hererro, E. Shalom-Paz, A. Wiser, D. Morris, H. Holzer. Obstetrics and Gynecology, McGill University Health Center, Montreal, QC, Canada. OBJECTIVE: The purpose of this study was to determine whether the supra-physiologic levels of estradiol (E2) induced during in vitro fertilization (IVF) affect thyroid function. DESIGN: Prospective study MATERIALS AND METHODS: All patients undergoing IVF between April 2009-Oct 2010 were eligible. Their baseline characteristics, medical history as well as hormonal profiles were collected. Sample size calculation required a minimum of 150 patients to detect a change in TSH of 0.5 mIU/L from the mean with a power of 80%. We collected samples from 180 patients in order to account for those whose cycles were cancelled or did not proceed to embryo transfer. Blood was collected at each visit during the IVF treatment cycle as well as on the day of pregnancy test. Samples were frozen at -20oC and analyzed together using the same assay kit once all patients had completed their cycles. The TSH according to increasing E2 levels as well as the TSH and E2 levels at pregnancy test were recorded. ANCOVA test was used to determine whether there was an effect of high E2 levels on TSH, both for patients with and without anti-thyroid antibodies. We also examined whether some patients with previously normal TSH levels became hypothyroid during or after treatment. The study received internal review board approval. RESULTS: We found that as E2 levels rose from baseline to supra-physiologic levels during treatment, TSH did not change significantly, regardless of the presence or absence of antibodies (p-value 0.71 and 0.07, respectively). CONCLUSION: The results of this study suggest that the supra-physiologic E2 levels induced by controlled ovarian hyperstimulation (COH) do not acutely affect thyroid function. Whether this lack of effect is due to the short time period of observation or because there is truly no effect of high E2 levels on thyroid function remains to be studied. Supported by: This project was funded by the ‘‘Academic Enrichment Fund’’ at McGill University, Montreal, Quebec. P-38 Tuesday, October 18, 2011 HUMAN CHORIONIC GONADOTROPIN TRIGGERS ANGIOGENESIS VIA THE MODULATION OF ENDOMETRIAL CELL RECEPTIVITY TO INTERLEUKIN 1: A NEW MECHANISM UNDERLYING EMBRYO-MATERNAL CROSSTALK. A. Akoum, A. Bourdiec, E. L. Calvo, M. Al-Akoum. Obstetrics and Gynecology, Faculty of Medicine, Laval University, Quebec, QC, Canada; Anatomy and Physiologiy, Faculty of Medicine, Laval University, Quebec, QC, Canada. OBJECTIVE: Embryo implantation is orchestrated by embryonic and maternal signals. Secretion of interleukin 1 (IL1) in response to the receptive endometrium induces molecular changes that are essential for embryonic implantation. Our objective was to investigate whether human chorionic gonadotropin (hCG), a major embryonic signal, modulates endometrial stromal cell receptivity to IL1 and assess the impact on tissue remodeling and angiogenesis. DESIGN: Cell treatment with hCG and/or IL1 and assessment of cell receptivity to IL1 and angiogenesis in vitro. MATERIALS AND METHODS: Expression of IL1 receptors and angiogenic factors was analyzed by ELISA and qRT-PCR. Endothelial cell proliferation was evaluated using 3H-thimidine incorporation into DNA. For microarray analysis, RNA quality was assessed using Agilent Bioanalyzer. Reverse transcription to cDNA, fragmentation, labeling and hybridization with Human Gene 1.0 ST arrays were performed according to Affymetrix protocols. Functional grouping was carried out using the Ingenuity Pathway Analysis (IPA). Some of the most significantly (P<0.01) regulated genes (R3-fold) were chosen for validation by qRT-PCR. RESULTS: hCG (100 ng/ml) significantly downregulated IL1R2 expression (P<0.01) in stromal cells; and effect which was maintained in cells subsequently exposed to IL1 (P<0.01) and accompanied by a significant

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Abstracts

increase in IL1R1 expression (P<0.001), MCP1 secretion (P<0.0001) and endothelial cell growth-promoting activity (P<0.01). Functional grouping (IPA) revealed significant changes in angiogenesis/tissue remodeling, immuno-inflammatory and cell signaling pathways and identified several genes that may play an important role in embryo-maternal signaling. CONCLUSION: hCG modulates endometrial cell receptivity to IL1, and act in synergy with IL1 to promote angiogenesis and tissue remodeling and modulate immune function at the embryo-maternal interface. This reveals a new mechanism by which hCG sustains human pregnancy and promotes embryonic growth. Supported by: NSERC discovery grant to AA.

P-39 Tuesday, October 18, 2011 ANTI-MULLERIAN HORMONE UPREGULATES CYP17 EXPRESSION IN HUMAN THECA CELLS. W. S. Vitek, L. A. Underhill, S. A. Carson, J. C. Robins. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School at Brown University, Providence, RI. OBJECTIVE: While AMH has been identified as an autocrine and paracrine regulator of steroidgenesis in granulosa cells and leydig cells, little is known regarding the effects of AMH on theca cells. The objective of this study was to determine the effect of AMH on theca cell activity. We hypothesized that AMH would be a potent stimulator of theca cell androgen biosynthesis. DESIGN: Experimental, in-vitro. MATERIALS AND METHODS: Human theca interna cells from antral follicles were isolated from a reproductive-aged woman undergoing oophorectomy for a benign indication and propagated at 37  C and 5% CO2 in DMEM supplemented with 10% FBS and antibiotics. Immunocytostaining was performed for calretinin and AMH receptor, type II (AMHR2). Theca cells were cultured for 24 hours in serum-free media supplemented with vehicle (negative control), 100 ng/ml recombinant human AMH or 20 mM forskolin (positive control). Expression of AMHR2 and cytochrome P450 17-alpha-hydroxylase/lyase (CYP17) transcripts were quantified for each condition by real time PCR. RESULTS: Calretinin staining demonstrated the isolation of theca interna cells. The majority of the cells contained the AMHR2 by immunocytostaining. AMH treatment induced the expression of CYP17 by 30%. AMH also induced the expression of AMHR2 by 6.7 fold. CONCLUSION: We have demonstrated the presence of AMHR2 on theca cells by both PCR and immunocytostaining. Our data demonstrates that AMH stimulates theca cell androgen biosynthesis in contrast to its suppressive effect on leydig cell androgen biosynthesis. This effect may be enhanced by AMH-induced synthesis of its receptor. These findings suggest a dimorphic role of AMH and may implicate AMH as a factor contributing to the androgen excess observed in polycystic ovarian syndrome (PCOS). Supported by: NEFS/Ferring Pharmaceuticals REI Fellow Research Grant.

REPRODUCTIVE HORMONES P-40 Tuesday, October 18, 2011 EFFECTS OF ENDOGENOUS AND EXOGENOUS ESTROGENS ON VAGINAL MUCOSAL HISTOLOGY. S. Nambiar, J. van Leeuwen, H. J. van Dessel, E. A. McGee. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, VA; Department of Obstetrics and Gynecology, TweeSteden Ziekenhuis, Tilburg, NB, Netherlands; Institute of Womens Health, Virginia Commonwealth University, Richmond, VA. OBJECTIVE: The vaginal epithelium undergoes remarkable changes during menopause, presumably due to the physiologic estrogen reduction. Surprisingly few studies however, have quantified the histologic changes associated with estrogen supplementation. The current study was undertaken to investigate basic histologic differences between pre- and postmenopausal women and compare those with postmenopausal women using exogenous estrogen thus providing insight into both endocrinologic and age-related changes in vaginal epithelium. DESIGN: Analysis of histologic specimens discarded following vaginal surgery.

Vol. 96., No. 3, Supplement, Sepetmber 2011