Pregnancy specific stress experienced by women who conceived pregnancies via in-vitro fertilization: a mixed-methods approach

POSTER SESSION MENOPAUSE P-1 Tuesday, October 23, 2012 PERSISTENCE OF OVARIAN FUNCTION AND VASCULAR MAINTENANCE IN POSTMENOPAUSAL FEMALES. R. Maruoka, A. Tanabe, A. Watanabe, K. Nakamura, M. Takai, M. Ohmichi. Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan. OBJECTIVE: Menopause is defined as the permanent cessation of menses. Although several previous studies demonstrated that there was a slight production of androgens and estrogens by the postmenopausal ovaries, the impact of the hormone production on vascular protection is still uncertain. DESIGN: Prospective observational study. MATERIALS AND METHODS: Serum specimens were collected from the ovarian veins of 21 premenopausal females (mean age 43.4 years), 12 early-menopausal females with less than 10 years of amenorrhea (56.8 years) and 15 late-menopausal females with more than 10 years of amenorrhea (69.0 years), undergoing total hysterectomy and bilateral oophorectomy (BSO). Serum specimens were also collected from the peripheral veins preoperatively and postoperatively. Estrone (E1), estradiol (E2), testosterone (Ts) and dehydroepiandrosterone sulfate (DHEAS) were measured in all serum samples by an electrochemiluminescence immunoassay. The flow-mediated dilatation (FMD) of the brachial artery was measured before and one week after surgery to evaluate the vascular endothelial damage. Comparisons of the hormone levels were made using the Wilcoxon signed-rank test. Differences with P<0.05 were considered to be statistically significant. RESULTS: Statistically significant gradients were seen between the ovarian venous and peripheral samples for E2 and Ts, but not for DHEAS, in all groups. In premenopausal and early-menopausal females, the postoperative levels of E1, but not E2, Ts or DHEAS, were lower than the preoperative levels. The ovarian vein level of E2 showed a decline with age after menopause, and E2 production was seen until about the age of 65. However, ovarian vein levels of E1, Ts and DHEAS showed no significant changes with age after menopause. Significant decreases in the FMD were observed one week after BSO in premenopausal and early-menopausal females. CONCLUSION: The postmenopausal ovary is hormonally active, thereby contributing to the maintenance of the vascular endothelium.

P-2 Tuesday, October 23, 2012 ASSOCIATIONS BETWEEN LEVELS OF SEX STEROID HORMONES AND INFLAMMATORY CYTOKINES BY HORMONE REPLACEMENT THERAPY (HRT) STATUS IN ETHNIC MINORITY B. Chen,a POSTMENOPAUSAL WOMEN. K. M. Brennan,a,b a a,b,c a A. Goto, S. Liu. Epidemiology, UCLA, Los Angeles, CA; bOB/ GYN, UCLA, Los Angeles, CA; cMedicine, UCLA, Los Angeles, CA. OBJECTIVE: Elevated levels of inflammatory markers have been associated with metabolic diseases such as type 2 diabetes (DM) and cardiovascular disease. Inflammation associated with aging may be mediated by changes in hormonal milieu, as seen with menopause. Whether HRT modifies the relationships between levels of sex hormones and inflammatory cytokines is largely unknown, especially in minority women. DESIGN: Cross-sectional. MATERIALS AND METHODS: Among 82,069 postmenopausal women aged 50 to 79 years enrolled in the Women’s Health Initiative Observational Study, we selected 1791 ethnic minority women who were apparently healthy at baseline for a nested case-control study of DM. We examined the relationships between baseline levels of sex hormones (total estradiol [E2], total testosterone [TT], and sex hormone-binding globulin [SHBG]) and inflammatory markers (CRP, IL-6, and TNF-a), and assessed whether these associations were modified by HRT. All hormone levels were log transformed. RESULTS: E2 levels were directly associated with CRP levels in the entire cohort (b¼0.29, P<0.0001), even after adjusting for potential confounding factors including DM status, BMI, and levels of insulin, IL-6, and TNF-a. A weak, but significant negative association was found between TT and TNF-a in current users of HRT (b¼-0.04, P¼0.04), persisting when controlling for potential confounders. Higher SHBG levels were associated with lower levels of CRP in women who had never used HRT (b¼-0.47, P<0.0001), and in past users (b¼-0.38, P¼0.04), but not in current users

FERTILITY & STERILITYÒ

of HRT (b¼-0.02, P¼0.86). Higher SHBG levels were associated with lower IL-6 levels in the entire cohort (b¼-0.18, P<0.0001). CONCLUSION: HRT did not modify the relationship between E2 and inflammatory marker levels, but it did modify the associations for TT and SHBG in relation to inflammatory markers. The inverse association between levels of CRP and SHBG only held in non-users of HRT. Supported by: NIH (R01 DK066401), Burroughs Wellcome Fund, and NHGRI (T32-HG002536). P-3 Tuesday, October 23, 2012 ASSOCIATION OF BRCA-1 AND -2 MUTATIONS WITH FMR1 GENOTYPES: EFFECTS ON MENARCHE AND MENOPAUSE AGE. M.-K. M. Tea,a A. Weghofer,a,b A. Kim,b K. Wagner,c C. F. Singer.a aDepartment of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; bCenter for Human Reproduction, New York, NY; cDepartment for Genetics, Medical University of Graz, Graz, Steiermark, Austria. OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, malignancies, in turn, associated with female infertility. BRCA-1 mutations (genotypes) have also been associated with occult primary ovarian insufficiency (OPOI), as have different mutations of the FMR1 gene. We, therefore, hypothesized that FMR1 genotypes may be associated with menarcheal and menopausal ages of BRCA mutation carriers. DESIGN: Controlled cohort study. MATERIALS AND METHODS: We analyzed FMR1 genotype status in 99 BRCA-positive (50 BRCA-1 and 49 BRCA-2 carriers) and 182 healthy random control women and evaluated the relationships between BRCA1/2 mutations, menarche and menopausal age in reference to FMR1 genotypes (sub-genotypes were assessed as previously reported: PLoS ONE 2010; 5: e 15303; PLoS ONE 2011; 6: e18781). T-test was used to assess differences in menarcheal and menopause ages, with times of menarche and menopause as continuous variables. RESULTS: FMR1 genotypes/sub-genotypes and BRCA status were significantly related (P%0.001). 78.8% of the BRCA1/2 positive but only 24.7% of controls had het-norm/low FMR1 sub-genotype; 52.7% of controls but only 6.1% of the BRCA1/2 positives had norm genotypes. BRCA-1 and -2 did not differ in FMR1 genotype/sub-genotype distribution. Age at menarche in BRCA1/2 and control patients did not differ (P¼0.22). BRCA-1 (age 41.77.4 years) demonstrated a trend towards earlier menopause than BRCA 2 (48.06.9; P¼0.07). In women with low FMR1 alleles (CGGn<26), menopausal age (%vs.>39) was, however, significantly lower with BRCA-1 (P¼0.018). CONCLUSION: While preliminary, these data suggest an interplay between BRCA1/2 and the FMR1 gene. Considering the statistical association between BRCA-1 and low FMR1 sub-genotypes, it appears reasonable to conclude that previously reported association of BRCA-1 with OPOI may be FMR1-mediated. Supported by: The Foundation for Reproductive Medicine and intramural funds from CHR. NURSING

P-4 Tuesday, October 23, 2012 PREGNANCY SPECIFIC STRESS EXPERIENCED BY WOMEN WHO CONCEIVED PREGNANCIES VIA IN-VITRO FERTILIZATION: A MIXED-METHODS APPROACH. E. L. Stevensona C. M. Bergh.b aSchool of Nursing, Duke University, Durham, NC; bReproductive Medicine Associates of New Jersey, Morristown, NJ. OBJECTIVE: Research supports that IVF is stressful; however, little is known if that stress carries into resulting pregnancies. This study utilized a mixed method approach to understand pregnancy specific stress in women pregnant via IVF. DESIGN: Prospective, cross-sectional. MATERIALS AND METHODS: Subjects were recruited from a private infertility center in New Jersey. Women between the ages of 25 and 40, single or twin gestation, no history of selective reduction, deemed medically and/or obstetrically low-risk, and able to read/write English were selected for further evaluation at a single time point between 12 and 18 weeks gestation. Subjects completed an electronic survey that included demographic data, Pregnancy Related Anxiety Measure (PRAM) Scale, and the question: ‘‘Are you

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currently experiencing any additional anxieties related to this pregnancy that have not previously been asked?’’ Descriptive statistics and Cronbach’s alpha were calculated on the PRAM and content analysis was conducted on the open-ended question responses. RESULTS: 144 subjects completed the PRAM. 31 subjects provided a narrative response to the question. The average score of the PRAM was 20.49 (SD¼5.96) and demonstrated higher scores than non-IVF, non-high-risk pregnant populations. Several themes emerged from the content analysis including anxiety about the health of their unborn baby(ies), anxiety about their own health and safety, anxiety about women’s perception of their own ability in the role of mother, and anxiety about finances. CONCLUSION: Women who conceive via IVF experience increased anxieties specific to the pregnancy. Content analysis of narrative responses confirmed some of the findings of the PRAM. This research is an important step in better understanding this patient population and helps inform REI and Obstetrical nursing practice when caring for women pregnant via IVF. Supported by: This study was supported by a $1000 grant from the McRae Foundation and a $1000 grant from Sigma Theta Tau, Upsilon Chapter. P-5 Tuesday, October 23, 2012 THE EFFECT OF GUIDED IMAGERY TO REDUCE PAIN AT THE TIME OF IN VITRO FERTILIZATION EGG RETRIEVAL: A RANDOMIZED CONTROLLED TRIAL. Y. Nagaoka. Ibaraki Prefectural University of Health Sciences, Inashiki-County, Ibaraki, Japan. OBJECTIVE: This study was undertaken to clarify the effects of guided imagery on subjective pain at the time of egg retrieval in infertile women undergoing IVF treatment. DESIGN: Randomized single-blind study. MATERIALS AND METHODS: The study candidates were inpatients receiving treatment in a private IVF clinic in Kanagawa, Japan. After passing the IRB, 91 eligible women were randomized into an imagery group (IG) (n¼45), in which the intervention primarily consisted of listening to an imagery CD (20 min), or a music group (MG) (n¼46), whose primary task was to listen to a music CD.Interventions were conducted 3 times at the clinic: (i) at the start of treatment, (ii) the 7th days, and (iii) on the night before egg retrieval. Visual Analog Scale (VAS) was used to measure subjective pain. The data analysis was carried using SPSS and t-test. RESULTS: 1. In total, 6 out of the 91 women (9.9%) withdrew from the egg retrieval. 2. The VAS scores for pain during egg retrieval were 55.7226.78(n¼44) for the IG and 62.5320.34(n¼41) for the MG; no significant difference was observed (t¼-1.33, P¼0.189). In addition, there was no significant difference observed between the two groups in the VAS score 90 min after egg retrieval. 3. In this study, because the number of times participants listened to the CD at home differed, subgroup analysis was carried out on the ‘high-frequency listening group’, which listened to the CD twice or more in a three-day period up until the egg retrieval, and the ‘low-frequency listening group’. The VAS scores at the time of egg retrieval for the high-frequency group were 45.9626.05(n¼25) for the IG and 63.9821.64(n¼29) for the MG. Scores were significantly lower in the IG (t¼-2.74, P¼0.009). CONCLUSION: Results of the study suggest that confidence and a sense of security brought on by egg-retrieval image training and the implementation of guided imagery raised the pain threshold.Guided imagery can be used as a nursing care for women undergoing IVF. Supported by: Fumiko Yamaji professional nursing educational research fund.

OVARIAN RESERVE

P-6 Tuesday, October 23, 2012 ANDROGEN RECEPTOR POLYMORPHISMS ARE ASSOCIATED WITH POOR OVARIAN RESPONSE. J. Llacer,a J. A. Ortiz,b J. Guerrero,a B. Lledo,b J. Ten,a R. Bernabeu.a aReproductive Medicine, Instituto Bernabeu, Alicante, Spain; bIB Biotech, Instituto Bernabeu, Alicante, Spain. OBJECTIVE: To evaluate the association of Androgen Receptor (AR) polymorphism and Poor Ovarian Responders (POR). DESIGN: Observational case-control study.

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ASRM Abstracts

MATERIALS AND METHODS: Number of repeats CAG in the exon 1 the AR gene was assessed in 56 women involved. We include 20 in the POR group, all were under 36 and met the criteria to consider POR in our institution (2 of the following criteria: AMH levels<1 ng/ml, AFC less than 6 and one or more cycles cancelled for low response or with less than 5 eggs collected using standard doses of gonadotropins). The control group consisted of 36 women with proven fertility and that both the antral follicle count and AMH levels are normal. DNA is purified from peripheral blood lymphocytes or buccal swabs. The CAG repeat region in the AR is amplified by fluorescent PCR and analyzed by capillary electrophoresis (ABI PRISM 310, Applied Biosystems). Two-tailed X2 test was used to compare allelic frequency between POR and control group. RESULTS: Women with POR showed a maximum number of repeats at the beginning (19 CAG repeats) that decreases slowly over the interval. On the other hand, the control group showed a maximum mid-range (21 CAG repeats) with two tails along which decreases relative frequency. The relative frequency in distribution of number CAG repeats in POR group is shifted to the right, compared to controls. Only 15% of the group of patients have alleles with repeat number below 20, compared with 50% of controls (P<0.05). CONCLUSION: Women labelled as POR have a number of CAG repeats in exon 1 of AR significantly higher than the control group. These results suggest that this polymorphism would affect ovarian function and therefore the activity of de receptor could be related to ovarian response. This fact could explain the improvement in ovarian response with androgen priming published so far. Polymorphisms in AR gen are candidates to explain some cases of POR. Supported by: Supported by Instituto Bernabeu. P-7 Tuesday, October 23, 2012 CORRELATION BETWEEN ANTI-MULLERIAN HORMONE AND NUMBER OF CGG REPEATS. E. Cervantes,a M. Luna,a G. Vela,a M. Whitehouse,a B. Sandler,a,b A. B. Copperman.a,b aReproductive Medicine Associates of New York, New York, NY; bObstetrcis, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, NY. OBJECTIVE: Approximately 20% of patients who are FMR1 premutation carriers present with premature ovarian failure (POF) compared to 1% of the general population (Gallagher, 2012). The risk of POF in female carriers appears to increase with increasing CGG repeat size up to 99, after which the risk plateaus or decreases for women with repeat size>100 (Uzeil, 1999; Wittenberger, 2007). Recently, Anti-Mullerian hormone (AMH) has been evaluated as a novel clinical marker of follicular reserve in the prediction of quantitative oocyte response (La Marca, 2010). Therefore we conducted this study to evaluate whether there was a correlation between low AMH levels and the number of CGG trinucleotide repeats. DESIGN: Retrospective data analysis. MATERIALS AND METHODS: Women with clinical suspicion of diminished ovarian reserve (DOR) who had completed both fragile X screening and AMH determination between 2008 and 2012 were included for analysis. AMH levels and CGG repeats in the study population were correlated regardless of age. A second correlation for both variables was performed in selected patients with an AMH<1 ng/ml and%38 years of age. Pearson correlation was used for testing. RESULTS: A total of 74 patients with both AMH testing and fragile X screening were included for analysis. The mean age of the study population was 38.34.5 yrs. The mean AMH level and CGG repeats were 1.21.4 ng/ml and 32.45.7 repeats, respectively. The first correlation analysis, which included all patients regardless of age and AMH level, revealed a trend towards a greater number of CGG repeats as AMH levels decreased (P¼0.0793). Forty patients met criteria of being%38 years (mean 35.52.8 yrs) and AMH<1 ng/ml (mean 0.440.26), however no correlation no trend was found to CGG repeat size (mean 32.75.8 repeats) (P¼0.1178). CONCLUSION: AMH is an important prognostic variable in counseling and treating patients in a reproductive setting. We have confirmed that the FMR1 premutation is both predictive of and correlated with reproductive potential.

P-8 Tuesday, October 23, 2012 OVEREXPRSSION OF UROMODULIN-LIKE 1 ACCELERATES OVARIAN AGING. W. Wang, Y. Tang, L. Ni, E. J. Kim, H.-C. Liu, Z. Rosenwaks. CRMI Endocrine Research Laboratory, Weill Medical College of Cornell University, New York, NY.

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