- Email: [email protected]
Repeat use of the LNG-IUS: results of a European multicenter prospective study
CONTRACEPTION SPECIAL INTEREST GROUP O-134 Tuesday, October 20, 2009 4:15 PM TREATMENT WITH DOXYCYCLINE DOES NOT DECREASE UNSCHEDULED BLEEDING IN CONTINUOUS ORAL CONTRACEPTIVE USERS. B. Kaneshiro, A. Edelman, K. Morgan, M. Nichols, J. Jensen. Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, HI; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR. OBJECTIVE: Matrix metalloproteinases (MMPs) are known to play a role in uterine bleeding. The objective of this study was to determine whether doxycycline, an MMP inhibitor, will decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill. DESIGN: This was a randomized, placebo controlled, double blind study that was conducted over four 28 day cycles (112 days of hormonally active pills). MATERIALS AND METHODS: All women took the same oral contraceptive (20mcg ethinyl estradiol/90mcg levonorgestrel) administered in a continuous fashion, without a placebo week. Women were randomized to doxycycline 100 mg orally twice a day for 5 days or placebo taken at the onset of each bleeding/spotting episode. After the first 84 days, bleeding was observed on the oral contraceptive alone for 28 days. The number of bleeding/spotting days for the first 84, last 28, and all 112 days of the trial were compared using a Mann Whitney U test. The length of bleeding and amenorrheic episodes was also compared. Our sample was calculated to detect a difference of 9 days over 84 days with 80% power and a significance of p¼0.05. RESULTS: Administration of doxycycline at the time of bleeding did not result in a reduction in the median bleeding/spotting days in the first 84 days [doxycycline 18.0 (SD 19.3), placebo 12.0 (SD 18.4), p¼ 0.46], last 28 days [doxycycline 4.0 (SD 9.16), placebo 4.0 (SD 9.48), p¼0.98] or all 112 days [doxycycline 24.0 (SD 27.38), placebo 17.0 (SD 26.3), p¼0.47]. There was no difference in the median length of the longest bleeding/spotting episode [doxycycline 3.0 (SD 14.3), placebo 7.0 (SD 11.3), p¼0.64)] or the longest amenorrheic episode [doxycycline 29.0 (SD 21.6), placebo 33.5 (SD 24.8), p ¼ 0.16]. CONCLUSIONS: Despite initial studies which suggested that doxycycline could treat unscheduled bleeding, this randomized trial shows that this MMP inhibitor does not decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive. Supported by: Family Planning Fellowship, Wyeth.
O-135 Tuesday, October 20, 2009 4:30 PM LEVONORGESTREL EFFECT ON VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND B-FIBROBLAST GROWTH FACTOR (B-FGF) IN SERUM, AND UTERINE FLUID, AND ENDOMETRIAL VEGF. D. F. Archer, S. Zhao, Y. Zhao, C. Choksuchat, F. Stanczyk. Obstetrics and Gynecology, Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA; Epidemiology and Biostatistics Core, Graduate Program of Public Health, Eastern Virginia Medical School, Norfolk, VA; Obstetrics and Gynecology, Prince of Songla Medical School, Hat-Yai, Songkla, Thailand; Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: To determine the effects of levonorgestrel (LNG) on VEGF and bFGF in serum and uterine fluid and endometrial VEGF. VEGF and bFGF are involved in endometrial angiogenesis. LNG-subcutaneous implant (LNG-SI) users have altered vascularity by hysteroscopy. DESIGN: Randomized double-blind clinical trial in women using a LNGSI who were randomized to doxycycline or placebo. MATERIALS AND METHODS: 44 women between 18-40 years with regular menstrual cycles had a LNG-SI inserted and were then randomization to oral doxycycline (DOX) 20mg or placebo (PL) twice a day. Serum LNG levels were quantified by radioimmunoassay, serum and uterine fluid levels of VEGF and bFGF were estimated using enzyme-linked immunosorbent assays and endometrial VEGF levels were assessed by immunohistochemistry (IHC). RESULTS: Serum LNG levels were significantly higher at 1 month compared to 6 months following LNG-SI insertion (p¼0.003) (see Table 1). VEGF levels in serum were unchanged from baseline and between treatment groups. VEGF in uterine wash increased in the PL group at 1 month compared to baseline and higher than the levels found in the DOX group
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(p¼0.012). VEGF IHC intensity at 6 months following insertion increased in the PL compared to DOX (p¼0.02). The bFGF PL level in uterine wash increased at 6 months compared to 1 month (p¼ 0.043) Table 1. The bFGF level in the DOX group at 6 months was less compared to the PL group (p¼ 0.02).
VEGF, bFGF, and LNG Levels in Serum and Uterine Wash
Serum Serum Uterine Uterine
LNG pg/mL VEGF pg/mL Dox PL VEGF pg/mL Dox PL bFGF pg/mL Dox PL
Baseline
1
2
67.8 70.9 19.6 23.6 275.2 247.8
763.3 74.0 66.4 14.7 49.2 201.4 172.9
640.7 74.7 69.8 8.4 22.1 157.7 482.7
CONCLUSIONS: LNG increased VEGF and bFGF levels in the uterine wash while DOX inhibited VEGF and bFGF in uterine wash and VEGF in endometrial tissue. DOX may play a role in angiogenesis by inhibiting endometrial angiogenic factors induced by LNG. Supported by: The study supported by Grants NIH R01 HD43175-01 and Jones Institute Foundation 572822. O-136 Tuesday, October 20, 2009 4:45 PM COMBINED ORAL CONTRACEPTIVES AND BODY WEIGHT: DO ORAL CONTRACEPTIVES CAUSE WEIGHT GAIN? A PRIMATE MODEL. A. B. Edelman, J. T. Jensen, M. Bulechowsky, J. Cameron. Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR; Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR. OBJECTIVE: To determine if oral contraceptive (OC) use effects body weight, composition, and metabolic rate in female rhesus macques and if this effect differs depending on the baseline weight. DESIGN: Prospective cohort study MATERIALS AND METHODS: Reproductive-age female monkeys of normal (n ¼ 5, mean weight ¼ 5.76 kg) and obese (n ¼ 5, mean weight ¼ 8.11 kg) weight were followed for 12 weeks to document baseline weight and metabolic stability, and then placed on 24 weeks of OC dosed to achieve equivalent human serum levels for a 30 mcg ethinyl estradiol/150 mcg levornorgestrel preparation. Monkeys were monitored for changes in body weight, activity levels (triaxial Actical accelerometer), food/caloric intake, body composition (DEXA), and metabolic biomarkers (24 hour metabolic rate and plasma samples). RESULTS: All monkeys completed the study protocol with no adverse events. No significant changes in study outcomes were found for the entire group except an increase in metabolic rate (p < 0.01). The obese group was found to have several changes with OC use including a decrease in weight (-0.7 kg, p < 0.01), a decrease in % body fat (-12%, p ¼ 0.02) with no change in % lean muscle mass, and a decreasing trend in metabolic rate (p ¼ 0.08). No changes were seen in food intake or activity level with OC use in either BMI-based group. CONCLUSIONS: Overall, OC use appears to increase 24 hour metabolic rates in female monkeys which in turn appears to differentially affect weight and % body fat depending on baseline weight. Supported by: Grant funding from the Society of Family Planning. O-137 Tuesday, October 20, 2009 5:00 PM REPEAT USE OF THE LNG-IUS: RESULTS OF A EUROPEAN MULTICENTER PROSPECTIVE STUDY. O. Heikinheimo, K. Gemzell-Danielsson, P. Inki, M. Kunz, L. Boubli, M. O’Flynn. Dept Ob&Gyn, University of Helsinki, Helsinki, Finland; WHO-center/Karolinska Sjukhuset, Stockholm, Sweden; Bayer Schering Pharma AG/Global Medical Affairs Women´s Health, Berlin, Germany; Bayer Schering Pharma AG/Global Clinical Statistics, Berlin, Germany; Hoˆpital Nord, Marseille, France; The Practice, Cork, Mallow, Ireland. OBJECTIVE: Levonorgestrel-releasing intrauterine system (LNG-IUS) is increasingly used for contraception, treatment of heavy menstrual bleeding
Vol. 92., No. 3, Supplement, September 2009
and endometrial protection during hormone replacement therapy. LNG-IUS has been available in most European countries since early / mid 1990’s. Due to its high acceptability and efficacy, many women opt for consecutive use of the LNG-IUS. However, published data on the repeated use of the LNG-IUS is limited. DESIGN: Prospective single group multicenter study performed in four European countries. MATERIALS AND METHODS: Fertile aged women who had used their 1st LNG-IUS between 4 years and 3-9 months and who opted for an immediate insertion of a 2nd IUS. The main outcome measure was the bleeding profile of the 2nd LNG-IUS during its first year of use. Additionally, the acceptability, efficacy and safety of the LNG-IUS was assessed. Bleeding data were recorded on a daily basis and analyzed per 90-day reference period (RF). The bleeding data obtained during the last 90 days of the 1st IUS (baseline) and the first 4 RFs after insertion of the second Mirena were analyzed descriptively. RESULTS: Median age of the 204 subjects that entered the study was 39 years (range 23-45), and median number of births was 2 (range 0-4). 191 subjects (93.6%) completed the study. The median number of bleeding/spotting days at baseline was 7 (25th to 75th percentiles 0-15). Due to bleeding associated with the insertion procedure, this increased to 8 days (range 4-18) during the 1st RF, thereafter decreasing to 4 days (range 0-10/11) during the 2nd - 4th RF. One expulsion and no pregnancies, pelvic inflammatory diseases or perforations occurred. A total of 12 subjects (5.9%) prematurely discontinued the study: 5 due to an adverse event and 7 due to other reasons (incl. loss to follow-up). CONCLUSIONS: This study confirms the favourable bleeding profile, high acceptability, efficacy and safety of repeat use of the LNG-IUS. Supported by: This study was financially supported by Bayer Schering Pharma AG, Berlin, Germany.
OBJECTIVE: Features of the vaginal epithelium and local immune response play an important role in HIV receptivity. Potentially modifiable local factors that might influence the risk of vaginal transmission of HIV infection include the thickness of the vaginal epithelium and the distribution of specific immune cell types. Our objective was to determine the impact of combination hormonal contraception administered orally or vaginally on the thickness and Langerhan cell populations of the vaginal epithelium. DESIGN: Randomized, single blind pilot study MATERIALS AND METHODS: Sexually active, reproductive-aged women with no recent hormonal exposure were randomized to receive either the vaginal ring (R) (120mcg etonogestrel/15mcg ethinyl estradiol (EE)) or an oral contraceptive pill (P) (150mcg desogestrel/ 30mcg EE) for six 28day cycles. Punch biopsies of the vaginal fornicies were obtained prior to initiation of hormonal contraception (V1) and repeated after three (V2) and six months (V3) of hormonal exposure. Specimens were fixed in formalin and paraffin-embedded. Serial 3um sections were cut for hematoxylin and eosin staining and for immunohistochemistry. Mucosal thickness and Langerhan cell number were compared using independent and paired T tests. RESULTS: A total of 14 subjects (7 R, 7 P) were randomized and had an initial biopsy. Of these, 10 (5 R, 5 P) returned for a biopsy at during the 3rd cycle, and 6 (2 R, 4 P) during the 6th cycle. While the initial mucosal thickness did not differ between groups 185mM Ring and Patch), it tended to be maintained (210mM V1, 175mM V2) in Ring users, but declined slightly in Pill users (160mM V1, 150mM V2); these differences were not significant within or between groups. Langerhan cell populations were similar across all comparisons. CONCLUSIONS: Use of a vaginal ring contraceptive may maintain vaginal mucosal thickness better than oral contraceptives, but there is no impact on Langerhan cell population. Supported by: Oregon Clinical and Translational Research Institute UL1 RR024140, Tarter Foundation.
O-138 Tuesday, October 20, 2009 5:15 PM A NON-HORMONAL MODEL FOR EMERGENCY CONTRACEPTION: PROSTAGLANDIN SYNTHESIS INHIBITOR EFFECTS ON LUTEAL FUNCTION AND LIFESPAN, A PILOT STUDY. A. B. Edelman, J. T. Jensen, J. Hennebold. Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR; Reproductive Sciences, Oregon National Primate Research Center (ONPRC), Beaverton, OR. OBJECTIVE: To determine if the use of a specific prostaglandin endoperoxide-2 (PTGS2) inhibitor will prevent luteal development in women. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Ovulatory reproductive-age women not using or needing hormonal contraception were prospectively followed for 3 menstrual cycles. Women were randomized into two groups using a cross over design [Group 1: control cycle, placebo cycle, active drug (Celecoxib 400 mg orally) cycle; Group 2: control cycle, Celecoxib cycle, placebo cycle]. Study drug was dosed daily until the onset of the next menses. Demographics, menstrual cycle length, and twice per week progesterone (P) levels during the placebo and active drug cycles, were recorded. The primary outcome was the change in menstrual cycle length during active drug exposure. RESULTS: A total of 11 women completed the study (Group 1 n ¼ 7, Group 2 n ¼ 4). No demographic differences were found between groups (age, race, parity, BMI, control cycle length). Within group comparisons revealed no statistical differences between the control and placebo cycles, control and active drug cycles, and placebo and active drug cycles for either group. A comparison of the control and active drug cycles for all participants demonstrated a trend towards a longer menstrual cycle with active drug exposure [control 27.2 days (SD 2.4); study drug 28.5 days (SD 2.5), p ¼ 0.09)]. Nine women had a delay in the rise of their luteal phase progesterone levels during their study drug cycle as compared to their placebo cycle. CONCLUSIONS: Daily administration of a prostaglandin synthesis inhibitor may delay the timing of luteal events, and therefore fertility, in women. Supported by: Grant from the Society for Family Planning.
O-139 Tuesday, October 20, 2009 5:30 PM THE EFFECTS OF ORAL VERSUS INTRAVAGINAL HORMONAL CONTRACEPTION ON THE VAGINAL EPITHELIUM. K. Rosenblum, R. Lindsay, A. Edelman, P. Bednarek, T. Morgan, J. T. Jensen. Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR; Pathology, Oregon Health & Science University, Portland, OR.
FERTILITY & STERILITYÒ
O-140 Tuesday, October 20, 2009 5:45 PM INFLAMMATORY CYTOKINES IN THE LOWER GENITAL TRACT: ANALYSES BY ABSOLUTE CYTOKINE LEVELS AND NORMALIZED CYTOKINE/TOTAL PROTEIN RATIOS RESULT IN DIFFERENT OUTCOMES. H. I. Su, C. Fay, L. Martino, A. Shaunik, C. Schreiber, K. T. Barnhart. Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: Cytokines are increasingly used to study the impact of microbicides on immune response in the lower female genital tract. The objective was to test if 2 methods of analyzing cytokine levels in the reproductive tract gave different results. DESIGN: Randomized, assessor-blinded crossover trial. MATERIALS AND METHODS: In a clinical trial assessing the impact of inert and pro-inflammatory topical gels on the vagina and endometrium, 14 subjects underwent baseline evaluation without gel exposure and at least one (and up to two) more set of vaginal lavage (VL) and endometrial lavage (EL) after exposure to two possible conditions: 3 days of nonoxynol-9 (N-9) or placebo gel. 8 pro-inflammatory cytokines (Il-1ra, Il-6, Il-8, MCP-1, MIP1a, MIP-1b, RANTES, and TNF-a 3 anti-inflammatory cytokines (Il-1ra, Il10, Slp-1) and total protein levels were assayed in all VL and EL specimens (RayBio Human Cytokines Array). Cytokines were analyzed as absolute values and cytokine/total protein ratios. These measures were compared by gel exposure using signrank tests. RESULTS: Compared to baseline and placebo, N-9 exposure changed both absolute cytokine levels and cytokine/total protein ratios in the vagina and the endometrium. However, both the magnitude and direction of change in cytokines differed between analyses using absolute values versus normalized ratios. For example, compared to placebo, N-9 was associated with significantly decreased Il-6 (p¼0.01), MCP-1 (p¼0.02), MIP-1a (p¼0.02), TNF-a (p¼0.05) Il-10 (p¼0.02) and Slp-1 (p¼0.03) cytokine/total protein ratios in the vagina. In contrast, N-9 was only associated with decreased Il-6 (p¼0.05) and increased Il-8 (p¼0.001)when analyzed by absolute levels. CONCLUSIONS: When analyzing the inflammatory impact of topical vaginal agents, results are highly impacted by the method of cytokine analyses. If the evaluation of microbicides candidates is to incorporate surrogates of markers of inflammation, a standardization of methodology is paramount. Supported by: USAID.
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O-135 Tuesday, October 20, 2009 4:30 PM LEVONORGESTREL EFFECT ON VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND B-FIBROBLAST GROWTH FACTOR (B-FGF) IN SERUM, AND UTERINE FLUID, AND ENDOMETRIAL VEGF. D. F. Archer, S. Zhao, Y. Zhao, C. Choksuchat, F. Stanczyk. Obstetrics and Gynecology, Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA; Epidemiology and Biostatistics Core, Graduate Program of Public Health, Eastern Virginia Medical School, Norfolk, VA; Obstetrics and Gynecology, Prince of Songla Medical School, Hat-Yai, Songkla, Thailand; Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: To determine the effects of levonorgestrel (LNG) on VEGF and bFGF in serum and uterine fluid and endometrial VEGF. VEGF and bFGF are involved in endometrial angiogenesis. LNG-subcutaneous implant (LNG-SI) users have altered vascularity by hysteroscopy. DESIGN: Randomized double-blind clinical trial in women using a LNGSI who were randomized to doxycycline or placebo. MATERIALS AND METHODS: 44 women between 18-40 years with regular menstrual cycles had a LNG-SI inserted and were then randomization to oral doxycycline (DOX) 20mg or placebo (PL) twice a day. Serum LNG levels were quantified by radioimmunoassay, serum and uterine fluid levels of VEGF and bFGF were estimated using enzyme-linked immunosorbent assays and endometrial VEGF levels were assessed by immunohistochemistry (IHC). RESULTS: Serum LNG levels were significantly higher at 1 month compared to 6 months following LNG-SI insertion (p¼0.003) (see Table 1). VEGF levels in serum were unchanged from baseline and between treatment groups. VEGF in uterine wash increased in the PL group at 1 month compared to baseline and higher than the levels found in the DOX group
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(p¼0.012). VEGF IHC intensity at 6 months following insertion increased in the PL compared to DOX (p¼0.02). The bFGF PL level in uterine wash increased at 6 months compared to 1 month (p¼ 0.043) Table 1. The bFGF level in the DOX group at 6 months was less compared to the PL group (p¼ 0.02).
VEGF, bFGF, and LNG Levels in Serum and Uterine Wash
Serum Serum Uterine Uterine
LNG pg/mL VEGF pg/mL Dox PL VEGF pg/mL Dox PL bFGF pg/mL Dox PL
Baseline
1
2
67.8 70.9 19.6 23.6 275.2 247.8
763.3 74.0 66.4 14.7 49.2 201.4 172.9
640.7 74.7 69.8 8.4 22.1 157.7 482.7
CONCLUSIONS: LNG increased VEGF and bFGF levels in the uterine wash while DOX inhibited VEGF and bFGF in uterine wash and VEGF in endometrial tissue. DOX may play a role in angiogenesis by inhibiting endometrial angiogenic factors induced by LNG. Supported by: The study supported by Grants NIH R01 HD43175-01 and Jones Institute Foundation 572822. O-136 Tuesday, October 20, 2009 4:45 PM COMBINED ORAL CONTRACEPTIVES AND BODY WEIGHT: DO ORAL CONTRACEPTIVES CAUSE WEIGHT GAIN? A PRIMATE MODEL. A. B. Edelman, J. T. Jensen, M. Bulechowsky, J. Cameron. Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR; Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR. OBJECTIVE: To determine if oral contraceptive (OC) use effects body weight, composition, and metabolic rate in female rhesus macques and if this effect differs depending on the baseline weight. DESIGN: Prospective cohort study MATERIALS AND METHODS: Reproductive-age female monkeys of normal (n ¼ 5, mean weight ¼ 5.76 kg) and obese (n ¼ 5, mean weight ¼ 8.11 kg) weight were followed for 12 weeks to document baseline weight and metabolic stability, and then placed on 24 weeks of OC dosed to achieve equivalent human serum levels for a 30 mcg ethinyl estradiol/150 mcg levornorgestrel preparation. Monkeys were monitored for changes in body weight, activity levels (triaxial Actical accelerometer), food/caloric intake, body composition (DEXA), and metabolic biomarkers (24 hour metabolic rate and plasma samples). RESULTS: All monkeys completed the study protocol with no adverse events. No significant changes in study outcomes were found for the entire group except an increase in metabolic rate (p < 0.01). The obese group was found to have several changes with OC use including a decrease in weight (-0.7 kg, p < 0.01), a decrease in % body fat (-12%, p ¼ 0.02) with no change in % lean muscle mass, and a decreasing trend in metabolic rate (p ¼ 0.08). No changes were seen in food intake or activity level with OC use in either BMI-based group. CONCLUSIONS: Overall, OC use appears to increase 24 hour metabolic rates in female monkeys which in turn appears to differentially affect weight and % body fat depending on baseline weight. Supported by: Grant funding from the Society of Family Planning. O-137 Tuesday, October 20, 2009 5:00 PM REPEAT USE OF THE LNG-IUS: RESULTS OF A EUROPEAN MULTICENTER PROSPECTIVE STUDY. O. Heikinheimo, K. Gemzell-Danielsson, P. Inki, M. Kunz, L. Boubli, M. O’Flynn. Dept Ob&Gyn, University of Helsinki, Helsinki, Finland; WHO-center/Karolinska Sjukhuset, Stockholm, Sweden; Bayer Schering Pharma AG/Global Medical Affairs Women´s Health, Berlin, Germany; Bayer Schering Pharma AG/Global Clinical Statistics, Berlin, Germany; Hoˆpital Nord, Marseille, France; The Practice, Cork, Mallow, Ireland. OBJECTIVE: Levonorgestrel-releasing intrauterine system (LNG-IUS) is increasingly used for contraception, treatment of heavy menstrual bleeding
Vol. 92., No. 3, Supplement, September 2009
and endometrial protection during hormone replacement therapy. LNG-IUS has been available in most European countries since early / mid 1990’s. Due to its high acceptability and efficacy, many women opt for consecutive use of the LNG-IUS. However, published data on the repeated use of the LNG-IUS is limited. DESIGN: Prospective single group multicenter study performed in four European countries. MATERIALS AND METHODS: Fertile aged women who had used their 1st LNG-IUS between 4 years and 3-9 months and who opted for an immediate insertion of a 2nd IUS. The main outcome measure was the bleeding profile of the 2nd LNG-IUS during its first year of use. Additionally, the acceptability, efficacy and safety of the LNG-IUS was assessed. Bleeding data were recorded on a daily basis and analyzed per 90-day reference period (RF). The bleeding data obtained during the last 90 days of the 1st IUS (baseline) and the first 4 RFs after insertion of the second Mirena were analyzed descriptively. RESULTS: Median age of the 204 subjects that entered the study was 39 years (range 23-45), and median number of births was 2 (range 0-4). 191 subjects (93.6%) completed the study. The median number of bleeding/spotting days at baseline was 7 (25th to 75th percentiles 0-15). Due to bleeding associated with the insertion procedure, this increased to 8 days (range 4-18) during the 1st RF, thereafter decreasing to 4 days (range 0-10/11) during the 2nd - 4th RF. One expulsion and no pregnancies, pelvic inflammatory diseases or perforations occurred. A total of 12 subjects (5.9%) prematurely discontinued the study: 5 due to an adverse event and 7 due to other reasons (incl. loss to follow-up). CONCLUSIONS: This study confirms the favourable bleeding profile, high acceptability, efficacy and safety of repeat use of the LNG-IUS. Supported by: This study was financially supported by Bayer Schering Pharma AG, Berlin, Germany.
OBJECTIVE: Features of the vaginal epithelium and local immune response play an important role in HIV receptivity. Potentially modifiable local factors that might influence the risk of vaginal transmission of HIV infection include the thickness of the vaginal epithelium and the distribution of specific immune cell types. Our objective was to determine the impact of combination hormonal contraception administered orally or vaginally on the thickness and Langerhan cell populations of the vaginal epithelium. DESIGN: Randomized, single blind pilot study MATERIALS AND METHODS: Sexually active, reproductive-aged women with no recent hormonal exposure were randomized to receive either the vaginal ring (R) (120mcg etonogestrel/15mcg ethinyl estradiol (EE)) or an oral contraceptive pill (P) (150mcg desogestrel/ 30mcg EE) for six 28day cycles. Punch biopsies of the vaginal fornicies were obtained prior to initiation of hormonal contraception (V1) and repeated after three (V2) and six months (V3) of hormonal exposure. Specimens were fixed in formalin and paraffin-embedded. Serial 3um sections were cut for hematoxylin and eosin staining and for immunohistochemistry. Mucosal thickness and Langerhan cell number were compared using independent and paired T tests. RESULTS: A total of 14 subjects (7 R, 7 P) were randomized and had an initial biopsy. Of these, 10 (5 R, 5 P) returned for a biopsy at during the 3rd cycle, and 6 (2 R, 4 P) during the 6th cycle. While the initial mucosal thickness did not differ between groups 185mM Ring and Patch), it tended to be maintained (210mM V1, 175mM V2) in Ring users, but declined slightly in Pill users (160mM V1, 150mM V2); these differences were not significant within or between groups. Langerhan cell populations were similar across all comparisons. CONCLUSIONS: Use of a vaginal ring contraceptive may maintain vaginal mucosal thickness better than oral contraceptives, but there is no impact on Langerhan cell population. Supported by: Oregon Clinical and Translational Research Institute UL1 RR024140, Tarter Foundation.
O-138 Tuesday, October 20, 2009 5:15 PM A NON-HORMONAL MODEL FOR EMERGENCY CONTRACEPTION: PROSTAGLANDIN SYNTHESIS INHIBITOR EFFECTS ON LUTEAL FUNCTION AND LIFESPAN, A PILOT STUDY. A. B. Edelman, J. T. Jensen, J. Hennebold. Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR; Reproductive Sciences, Oregon National Primate Research Center (ONPRC), Beaverton, OR. OBJECTIVE: To determine if the use of a specific prostaglandin endoperoxide-2 (PTGS2) inhibitor will prevent luteal development in women. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Ovulatory reproductive-age women not using or needing hormonal contraception were prospectively followed for 3 menstrual cycles. Women were randomized into two groups using a cross over design [Group 1: control cycle, placebo cycle, active drug (Celecoxib 400 mg orally) cycle; Group 2: control cycle, Celecoxib cycle, placebo cycle]. Study drug was dosed daily until the onset of the next menses. Demographics, menstrual cycle length, and twice per week progesterone (P) levels during the placebo and active drug cycles, were recorded. The primary outcome was the change in menstrual cycle length during active drug exposure. RESULTS: A total of 11 women completed the study (Group 1 n ¼ 7, Group 2 n ¼ 4). No demographic differences were found between groups (age, race, parity, BMI, control cycle length). Within group comparisons revealed no statistical differences between the control and placebo cycles, control and active drug cycles, and placebo and active drug cycles for either group. A comparison of the control and active drug cycles for all participants demonstrated a trend towards a longer menstrual cycle with active drug exposure [control 27.2 days (SD 2.4); study drug 28.5 days (SD 2.5), p ¼ 0.09)]. Nine women had a delay in the rise of their luteal phase progesterone levels during their study drug cycle as compared to their placebo cycle. CONCLUSIONS: Daily administration of a prostaglandin synthesis inhibitor may delay the timing of luteal events, and therefore fertility, in women. Supported by: Grant from the Society for Family Planning.
O-139 Tuesday, October 20, 2009 5:30 PM THE EFFECTS OF ORAL VERSUS INTRAVAGINAL HORMONAL CONTRACEPTION ON THE VAGINAL EPITHELIUM. K. Rosenblum, R. Lindsay, A. Edelman, P. Bednarek, T. Morgan, J. T. Jensen. Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR; Pathology, Oregon Health & Science University, Portland, OR.
FERTILITY & STERILITYÒ
O-140 Tuesday, October 20, 2009 5:45 PM INFLAMMATORY CYTOKINES IN THE LOWER GENITAL TRACT: ANALYSES BY ABSOLUTE CYTOKINE LEVELS AND NORMALIZED CYTOKINE/TOTAL PROTEIN RATIOS RESULT IN DIFFERENT OUTCOMES. H. I. Su, C. Fay, L. Martino, A. Shaunik, C. Schreiber, K. T. Barnhart. Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: Cytokines are increasingly used to study the impact of microbicides on immune response in the lower female genital tract. The objective was to test if 2 methods of analyzing cytokine levels in the reproductive tract gave different results. DESIGN: Randomized, assessor-blinded crossover trial. MATERIALS AND METHODS: In a clinical trial assessing the impact of inert and pro-inflammatory topical gels on the vagina and endometrium, 14 subjects underwent baseline evaluation without gel exposure and at least one (and up to two) more set of vaginal lavage (VL) and endometrial lavage (EL) after exposure to two possible conditions: 3 days of nonoxynol-9 (N-9) or placebo gel. 8 pro-inflammatory cytokines (Il-1ra, Il-6, Il-8, MCP-1, MIP1a, MIP-1b, RANTES, and TNF-a 3 anti-inflammatory cytokines (Il-1ra, Il10, Slp-1) and total protein levels were assayed in all VL and EL specimens (RayBio Human Cytokines Array). Cytokines were analyzed as absolute values and cytokine/total protein ratios. These measures were compared by gel exposure using signrank tests. RESULTS: Compared to baseline and placebo, N-9 exposure changed both absolute cytokine levels and cytokine/total protein ratios in the vagina and the endometrium. However, both the magnitude and direction of change in cytokines differed between analyses using absolute values versus normalized ratios. For example, compared to placebo, N-9 was associated with significantly decreased Il-6 (p¼0.01), MCP-1 (p¼0.02), MIP-1a (p¼0.02), TNF-a (p¼0.05) Il-10 (p¼0.02) and Slp-1 (p¼0.03) cytokine/total protein ratios in the vagina. In contrast, N-9 was only associated with decreased Il-6 (p¼0.05) and increased Il-8 (p¼0.001)when analyzed by absolute levels. CONCLUSIONS: When analyzing the inflammatory impact of topical vaginal agents, results are highly impacted by the method of cytokine analyses. If the evaluation of microbicides candidates is to incorporate surrogates of markers of inflammation, a standardization of methodology is paramount. Supported by: USAID.
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