Male and female public opinion regarding a possible male contraceptive pill

Male and female public opinion regarding a possible male contraceptive pill

DESIGN: A randomized, open-label, single center study. MATERIALS AND METHODS: Forty-two women with regular menstrual cycles and normal ovarian morphol...

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DESIGN: A randomized, open-label, single center study. MATERIALS AND METHODS: Forty-two women with regular menstrual cycles and normal ovarian morphology were randomized to use three continuous cycles of oral (n¼13), transdermal (n¼15) or vaginal (n¼14) CCs. Blood sampling was performed on the cycle days 2-4 before the treatment and at 5 and 9 weeks of treatment. For statistical analyses repeated measures ANOVA and paired samples t-test were used. RESULTS: There was a significant decrease in serum anti-M€ullerian hormone (AMH) levels after 9 weeks use of oral, transdermal and vaginal CCs. Similarly to baseline, serum levels of AMH, inhibin B, LH and E2 were comparable after 9 weeks of use of CCs in all groups, whereas serum FSH levels remained higher at 9 weeks in the ring group compared with the patch group. CONCLUSION: The results demonstrate that the use of CCs results in arrest of follicular development independently of hormonal administration route, as serum AMH levels decreased 50% during the use of CCs in all three groups. The higher FSH levels in the ring group during the use of CCs may indicate a less marked negative feedback on pituitary gonadothropin secretion due to lower exposure to EE. The continuous administration may inhibit follicular growth even more significantly than standard cyclic administration and could enable the use of CCs with even lower hormonal doses. Supported by: Grants from the Academy of Finland, the Sigrid Juselius Foundation and Oulu University Hospital. O-18 Monday, October 22, 2012 05:00 PM CONTRACEPTIVE AND FERTILITY PRACTICES IN WOMEN WITH BREAST CANCER COMPARED TO THOSE WITH OTHER MALIGNANCIES. B.-S. L. Maslow, C. B. Morse, A. Schanne, C. Gracia. Obstetrics and Gynecology, Hospital of University of Pennsylvania, Philadelphia, PA. OBJECTIVE: Pregnancy prevention is crucial in women undergoing cancer treatment and particularly challenging for women with breast cancer (BC). Here we describe contraceptive and fertility practices in young women with cancer. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Participants were identified from hospital EMR and invited to an online survey about medical history, contraceptive choice, and counseling. Effective contraception was defined as long-acting reversible contraception, hormonal and barrier methods, or sterilization. RESULTS: 277 women were contacted, 138 agreed to participate and 107 completed the survey. 56 (52.3%) had BC and 51 (47.7%) had other (nonBC) malignancies. BC participants were more likely to be older (P<0.001), married (P¼0.003) and multiparous (P¼0.013). Most participants (82% BC, 80% non-BC) reported contraception as very important during treatment. Use of effective contraception was low and no difference was noted between groups (BC 19/56, 34% vs. non-BC 24/51, 47%; P¼0.17). 6 BC patients (11%) used an IUD compared to none in the non-BC group (P¼0.02). 14/15 (93.3%) BC participants stopped estrogen and progesterone (E/P) containing contraception compared to 5/15 (33.3%) non-BC participants (P¼0.004). No BC participants were initiated on E/P methods compared to 9/51 non-BC participants (P¼0.001). Women with BC were less likely to receive contraceptive counseling (58% vs. 78%, P¼0.04) and less likely to desire future fertility (P¼0.001). Women with cancer pursued fertility preservation at similar rates regardless of their diagnosis (BC 12/ 56,12.2% vs. non-BC 15/51, 30.6%; P¼0.334). CONCLUSION: Contraception is a priority to women with cancer but few use effective methods. The IUD is a highly effective, reversible method and underutilized in this population. Women with BC are less likely to receive counseling and desire future fertility, possibly due to age and parity, but pursue fertility preservation similar to women with a non-BC diagnosis. Supported by: Dept of OBGYN, Hosp Univ of PA. O-19 Monday, October 22, 2012 05:15 PM COMBINATION PHOSPHODIESTERASE (PDE) INHIBITION: A NOVEL APPROACH TO NON-HORMONAL FEMALE CONTRACEPTION. C. B. Hanna,a S. Yao,a J. T. Jensen.a,b aDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR; bDepartment of Obstetrics & Gynecology, Oregon Health and Science University, Portland, OR. OBJECTIVE: The PDE3 inhibitor, ORG9935, blocks cAMP degradation in the oocyte and prevents pregnancy in primates, but side effects associated

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ASRM Abstracts

with pharmacokinetic properties limit the practicality of the approach. cGMP, a physiological inhibitor of PDE3A, is produced in cumulus cells and enters the oocyte via gap junctions. The objective of this study is to determine if inhibitors to cGMP-degrading PDEs [PDE5 (cumulus cells), PDE9 (oocyte)] reduce the dose of ORG9935 needed to inhibit oocyte maturation in vitro. DESIGN: Controlled rodent dose response experiments. MATERIALS AND METHODS: A total of 1,384 cumulus oocyte complexes were collected from 3-week old BDF1 mice and cultured for 24 hours without (control) and with various concentrations of PDE3 (ORG9935) and PDE5 (sildenafil) inhibitors alone and in combination with a PDE9 inhibitor (BAY73-6691). Primary outcome was proportion of oocytes undergoing germinal vesicle breakdown (GVBD) following culture. Significant changes in data were determined by Fisher’s exact 2-tailed test and all cultures were performed in triplicate. RESULTS: ORG9935 showed a dose dependent effect preventing GVBD. While sildenafil alone did not prevent GVBD up to 1 mM, addition of 0.1 mM to media containing ORG9935 reduced the concentration required to arrest GVBD with complete inhibition observed at 0.1 mM ORG9935. The addition of a PDE9 inhibitor did not further augment the effect of the PDE3 and PDE5 inhibitors at the doses evaluated. Proportion GVBD oocytes following culture with PDE inhibitors

Sildenafil (mM)

BAY 73-6691 (mM)

0 0.01 0.1 1 0.1 0.1 0.1 0.1

0 0 0 0 0.1 1 10 100

0

0.001

0.01

0.1

1

96.7 85.5 84.7 86.7

72.1*

75.9*

18.8*

15.3*

50.6*

13.2*

0*

72.7* 66.9* 76.0* 64.6*

* Statistically different from control P<0.05. CONCLUSION: Targeted inhibition of PDE5 reduces the concentration of ORG9935 needed to prevent maturation while blockade of PDE9 has no effect at the levels used in this study. Combining PDE inhibitors may have contraceptive potential. Supported by: 5U54HD055744, P51OD011092. O-20 Monday, October 22, 2012 05:30 PM MALE AND FEMALE PUBLIC OPINION REGARDING A POSSIBLE MALE CONTRACEPTIVE PILL. A. P. Windsperger, K. S. Art, A. Epp, A. Greiner, J. Tash, A. K. Nangia. University of Kansas Medical Center, Kansas City, KS. OBJECTIVE: Reversible male contraception (RMC) is currently limited to the use of barrier methods. A non-hormonal, oral method of RMC is currently on the cusp of clinical trial. Differences in the attitudes and beliefs between men and women towards a RMC have not been examined. DESIGN: A convenience sample survey. MATERIALS AND METHODS: A 40-question survey was administered to men and women over the age of 18 years. Information including demographics, issues of trust, medication and prior contraceptive use, and opinions regarding RMC was obtained. Responses were tabulated according to sex. RESULTS: 132 men and 165 women completed the survey. Sexual activity, distribution of relationship status, and current use and methods of contraception were similar between men and women who responded. 94.9% of respondents believed that contraception was the responsibility of both partners. 92% of men and women surveyed expressed interest in a RMC pill. In terms of trust, 80.9% of men reported they would be compliant with an oral medication, while 65.6% of women believed their male partner could be compliant (P¼0.002). 38.9% and 39.9% of men and women respectively considered better compliance if dosing was daily compared to weekly or monthly. 74.2% of women reported that they would continue their current form of contraception even if their partner was taking a RMC, whereas 58.5% of men reported that they would have their female partner continue their current birth control while they were taking a RMC. The most common reason for having two forms of birth control in the relationship was for double protection against unplanned pregnancy. 48.5% women indicated

Vol. 98, No. 3, Supplement, September 2012

that they would still use condoms for STD protection compared to 35.4% of men. CONCLUSION: The idea of RMC and a non-hormonal oral RMC is generally accepted by both sexes. Men have stronger beliefs in their own compliance in use of such methods. Education of drug profiles will be crucial in achieving overall acceptance and use by the general public with the introduction of RMC. O-21 Monday, October 22, 2012 05:45 PM CELL CYCLE KINETICS, NUCLEAR RECEPTOR AND GENE EXPRESSION IN HUMAN ENDOMETRIAL CELLS: DIFFERENTIAL REGULATION BY PROGESTIN AND SELECTIVE PROGESTERONE RECEPTOR MODULATOR. P. L. Morris,a,b K. Hwang,a R. Hara,a C. Rapelje,a L. Mitchell.a aCenter for Biomedical Research, Population Council, New York, NY; bThe Rockefeller University, New York, NY. OBJECTIVE: Levonorgestrel (LNG) is a progestin used for emergency contraception (EC) within 72h of unprotected sexual intercourse. Selective progesterone receptor (PR) modulators (SPRMs) are PR ligands with agonist or antagonist effects on progesterone-responsive tissues. A dose of SPRM ulipristal acetate (UPA) is an effective EC alternative used up to 5-days after unprotected intercourse. In clinical studies, UPA inhibits follicle growth and ovulation. In other forms, both are effective for long-term contraception. The overall goal of this study is to characterize effects of these regulators on human endometrial genes and cell cycle. DESIGN: Test hypothesis that PR effectors are not only safe and efficacious for contraception but may provide additional benefits; human endometrial cell models used. MATERIALS AND METHODS: RNA and protein levels for steroid receptors, pathways and cycle-proteins evaluated by gene array, qPCR and Western analyses; cell cycle analysis by flow cytometry. E2 or P4 were used to determine responsiveness. RNA and protein extracts characterized. RESULTS: RNA analyses showed significant gene expression alterations by short-term exposure to either drug, with changes in ERa, AR and membrane PR and ER. E2 or P4 responses were differentially affected. After SPRM treatment, cells showed 1433 genes up- and 1464 down regulated; at 72h significant up (926) and 1183 (down) regulation noted. 27 genes were similarly up, 54 down regulated shared between conditions. 30 upand 52 down regulated genes were shared between E2-stimulated control and SPRM-treated. With time, subcellular receptor distributions changed. LNG altered patterns. UPA increased PR cytoplasm/nucleus ratio. E2 responses were significantly altered for cyclins A2, D1, B1 and AR, ERa, PR. UPA increased cells in G0G1, decreased those in S, G2/M. CONCLUSION: Data show changes in subcellular hormone receptors, responsiveness and cell cycle dynamics, suggesting that some PRMs could afford protection against abnormal growth as a health benefit. Supported by: NIH HD029990. O-22 Monday, October 22, 2012 06:00 PM CONTRACEPTION IN AMERICA (CIA) NATIONAL SURVEY: SEGMENT OF RESULTS FOCUSED ON PATIENT AND PHYSICIAN ATTITUDES ABOUT BENEFITS OF INTRAUTERINE DEVICES (IUDs) AS A CONTRACEPTIVE METHOD. M. Ziemana A. Patel.b a Emory University School of Medicine, Atlanta, GA; bFeinberg School of Medicine, Northwestern University, Chicago, IL. OBJECTIVE: The overall CIA survey was designed to describe contraceptive use/preferences from the perspective of US women (18-49 years of age) and physicians; this report specifically addresses how women’s attitudes differ from physicians about IUDs as a contraceptive method. DESIGN: National probability telephone survey of 1000 women of reproductive age and parallel survey of 100 Obstetrics-Gynecology (Ob-Gyn) and 101 Family Practice (FP) physicians. MATERIALS AND METHODS: Questions about IUDs were asked as part of the larger national CIA survey conducted from 12/12/11 to 1/19/12. Dual frame sampling (both landline [n¼800] and cell phone [n¼200]) ensured inclusion of women without landlines. The women’s sample was weighted by telephone status (landline or cell phone only) and age. Physicians were sampled from a list of American medical/osteopathic association members. Expected maximum sampling error (95% confidence) for women and physicians was 3.1% and 9.8, respectively.

FERTILITY & STERILITYÒ

RESULTS: Of 1000 women, 712 familiar with IUDs answered IUD-related questions during the survey and all 201 physicians responded to questions about IUDs. In response to ‘‘What do you think are the benefits of IUDs as a contraceptive method?’’ women were less likely than Ob-Gyns and FPs to view IUDs as convenient (58% vs 79% and 84%), easily reversible (5% vs 20% and 14%), highly-effective (18% vs 47% and 35%), or cost-effective (1% vs 14% and 7%). Although Ob-Gyns and FPs generally shared similar perceptions about the benefits of IUDs, some differences were noted between them that may influence the dialog with women during contraception counseling. CONCLUSION: While IUDs have increased in popularity, misconceptions and gaps in perception about this method of birth control exist among women and physicians. Education is needed to close these gaps and improve physician communication with reproductive-age women about IUDs, with emphasis that IUDs can provide an effective, convenient, and safe contraceptive choice. Supported by: Teva Global Branded Products R&D. FERTILITY PRESERVATION O-23 Monday, October 22, 2012 04:15 PM SIMILAR IN VITRO MATURATION (IVM) AND FERTILIZATION RATES OF OOCYTES RETRIEVED EITHER AT THE FOLLICULAR OR THE LUTEAL PHASE OF THE CYCLE OFFERS FLEXIBLE OPTIONS FOR URGENT FERTILITY PRESERVATION (FP). M. Grynberg,a M. Even,a L. Hesters,b R. Treves,a R. Fanchin,a N. Frydman.b aDivision of Reproductive Medicine, H^opital Antoine Beclere, Clamart, France; bDepartment of Reproductive Biology, H^opital Antoine Beclere, Clamart, France. OBJECTIVE: To compare IVM and fertilization rates of immature oocytes retrieved during the follicular or the luteal phase of the cycle in an urgent FP program. DESIGN: Prospective study. MATERIALS AND METHODS: 94 candidates for urgent FP were studied. Serum AMH levels and antral follicle count (AFC) were measured prior to oocyte retrieval, irrespective of the cycle day. Patients were sorted into 2 groups according to the phase of the cycle in which eggs were harvested (Follicular Group, n¼52 and Luteal Group, n¼42). Oocyte retrieval was performed 36 hours after hCG administration. Number of immature oocytes recovered, maturation rates after 24 hours and 48 hours of culture, fertilization rates and total number of oocytes and embryos cryopreserved were assessed. Moreover, the oocyte output rate (OORT) was calculated by AFCx100/number of immature oocytes recovered. RESULTS: In both groups, women were comparable in terms of age (30(18-39) vs. 30(19-39) years, respectively), BMI (22.20.2 vs. 21.70.4 Kg/m2) and markers of the follicular ovarian status (serum AMH levels (3.1(1.1-8.2) vs. 3.3(0.7-11.7) ng/mL, respectively) and AFC (16(5-44) vs. 16(4-38) follicles, respectively)). In addition, there were no significant difference in the number of oocyte recovered, and in the OORT (8(0-21) vs. 8(0-28) follicles and 48.7%4.8 vs. 47.3%5.0, respectively). Moreover, maturation rates after 24h and 48h of culture (68.4%4.2 vs. 67.4%4.9, and 9.5%1.5 vs. 9.2%2.1, respectively), as well as fertilization rates (87.5%2.1 vs. 88.5%1.9) were comparable in the Follicular and Luteal groups. Finally, the total number of oocytes (6.50.6 vs. 6.20.9) and embryos (5.60.7 vs. 5.40.8) cryopreserved were similar in both groups. CONCLUSION: That no major difference in the IVM and fertilization rates of immature oocytes retrieved during the follicular or the luteal phase of the cycle was noticed suggests that this technique can be offered to patients seeking for urgent FP. O-24 Monday, October 22, 2012 04:30 PM BABY BUDGETING: A COST-EFFECTIVENESS ANALYSIS (CEA) OF ELECTIVE OOCYTE CRYOPRESERVATION (EOC) AS A MEANS TO INCREASE LIVE BIRTH RATES (LBR) IN WOMEN DELAYING REPRODUCTION. K. Devine,a S. Mumford,b B. HodesWertz,c S. Druckenmiller,c A. Propst,d N. N. Noyes.c aProgram in Adult and Reproductive Endocrinology, NICHD, National Institutes of Health, Bethesda, MD; bEpidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, NICHD, National Institutes of Health, Bethesda, MD; cNYU Fertility Center, NYU School of Medicine, New York, NY; d Uniformed Services University of Health Sciences, Bethesda, MD.

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