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Wednesday, October 25, 2006 3:45 pm O-255 SEX SELECTION DEMAND AND PREFERENCES AMONG INFERTILITY PATIENTS IN MIDWESTERN UNITED STATES. S. A. Missmer, T. Jain. Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Univ of Illinois Medical Center, Chicago, IL. OBJECTIVE: To determine the demand of infertility patients for sex selection, the sex they would choose, and to investigate the relation between these choices and their demographic and socioeconomic characteristics. DESIGN: Cross-sectional survey. MATERIALS AND METHODS: 743 patients beginning treatment for infertility at a Midwestern university hospital-based fertility center completed a self-administered questionnaire that asked ”If a safe and effective method, that added no additional financial cost to you, existed for being able to choose the sex of your child, would you use it?. If “yes,” they were asked which sex they would choose. We used unconditional multivariable logistic regression to estimate relative risks (odds ratios (OR)) and 95% confidence intervals (CI) to evaluate the relation between sex selection preferences and demographic and socioeconomic characteristics. Wald p-values were twosided. RESULTS: Study participants ranged in age from 21-56 (median ⫽ 35). 41% were Caucasian, 28% African-American, 18% Hispanic. Of respondents, 49% wanted to select the sex of their next child. Of these patients, 49% had no living children and 41% had children all of one sex. Among both nulliparous and parous patients, African-American (OR ⫽ 4.4 and 6.7, respectively) and Hispanic women (OR ⫽ 46.1 and 29.0) were significantly more likely to wish to select the sex of their child compared to Caucasian women. Catholic women were 74% less likely to desire sex selection (95% CI ⫽ 0.08-0.80), while those with a graduate degree were nearly 3-times as likely (OR ⫽ 2.74, 95% CI ⫽ 1.18-6.34). Additionally, as income increased, the desire for sex selection increased, regardless of parity (pvalues ⬍ 0.02). Of the 363 women who would choose the sex of their child, 64% would choose a female child. After adjustment for observed predictors of gender preference and restricting analyses to nulliparous women, African-Americans (OR ⫽ 0.02, 95% CI ⫽ 0.01-0.64) relative to Caucasians, and Catholics (OR ⫽ 0.03, 95% CI ⫽ 0.2-0.83), Muslims (OR⫽ 0.01, 95% CI ⫽ 0.00-0.40), and Agnostics (OR ⫽ 0.02, 95% CI ⫽ 0.76) relative to protestants were significantly less likely to choose to have a daughter. However, when analyses were restricted to parity, if we adjusted for family balancing (i.e. families with children of only one sex), we observed no significant differences in the desire for a male or a female child for any demographic or socioeconomic characteristic. CONCLUSION: There is significant demand among infertility patients for sex selection, with a significant portion of this demand coming from patients who do not have any children or have children all of one sex. Race/ethnicity, religious affiliation, education, and income may play a role in these preferences. Supported by: None.

Wednesday, October 25, 2006 4:00 pm O-256 REDEFINING IN VITRO FERTILIZATION “SUCCESS”: SHOULD TRIPLETS BE CONSIDERED FAILURES? L. Grunfeld, T. Mukherjee, B. Sandler, Y. Nagashima, A. B. Copperman. Reproductive Medicine Associates of New York, New York, NY; Mount Sinai Medical Center, New York, NY; Mount Sinai School of Medicine, New York, NY. OBJECTIVE: Traditional measures of success rate evaluating In Vitro Fertilization have considered live birth rates to be success and all other outcomes to be failures. Given the morbidity of higher order multiple gestations, we undertook this study to evaluate how the “ranking” of IVF programs would change if higher order multiple gestations were considered negative instead of positive outcomes. DESIGN: The 2004 SART data base was utilized. MATERIALS AND METHODS: 385 programs reported IVF results in the 2004 SART report, We focused on patients ⬍⫽ 35 years of age, and for

FERTILITY & STERILITY威

the purpose of this study, focused on the 208 programs that performed ⬎50 cycles in this population. First, the success rate of a program was recorded based on the traditional measure of live born per embryo transfer. All programs were ranked in order of success rate. The programs were then re-ranked after counting the triplet and higher pregnancies as negatives rather than as positives. RESULTS: Success rates ranged from 16.7% to 67.3% live born per embryo transfer, and triplet rates ranged from 0 (in 43 programs) to 40.7%. 52/207 (25.1%) of programs had greater than a 10% triplet rate and 15/207 (7.2%) of programs had greater than a 20% triplet rate. Analysis after re-ranking the programs showed two programs departing from the top 10 (20%) and 5 from the top 20 (25%). The range of “re-ranking” spanned from gaining 48 places to losing 106 places, and can be demonstrated in Figure 1.

CONCLUSION: While the Clinic Specific SART Report is not intended to be used to rank practices or to allow for direct comparisons, it can be helpful to couples who are trying to determine “What are my chances of having a child by using ART?” or “Where can I go to get this treatment?” In addition, it can provide an overview of ART in the United States, and analysis of trends can provide meaningful information. The poor prognosis carried by high order multiple pregnancies should cause ART programs to reevaluate the number of embryos recommended for replacement. Market pressures often induce aggressive emryo replacements to maintain competitive ranking amongst programs. The pressure to transfer high numbers of embryos would be removed if the multiple birth were considered a liability rather than an asset. We propose that a corrected pregnancy rate that accounts for multiple births may offer IVF programs an incentive to limit embryos for transfer. Better embryo assessment will allow the best programs to maintain high rates of success and limit the penalty of high order multiple pregnancy on the outcome. Supported by: None.

Wednesday, October 25, 2006 4:15 pm O-257 CLINICALLY SIGNIFICANT SNPS OF THE MITOCHONDRIAL DNA IN PATIENTS WITH PCOS BY SCREENING THE HYPERVARIABLE REGIONS. S. H. Lee, H. J. Cho, K. H. Baek, H. J. Jeong, T. K. Yoon, K. Y. Cha. Fertility Center of CHA General Hospital, CHA Research Institute, Pochon CHA Univ, “Genome Research Center for Infertility and Reproductive Medicine” of Korea Ministry of Health & Welfare, Seoul, Republic of Korea. OBJECTIVE: The polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder. It affects 5%-10% of women of reproductive age. Significant number of PCOS patients is in potential risk of developing type2 diabetes. However, the etiology of PCOS is still a subject of debate. To investigate the relationship of mitochondria supporting the cell energy and pathogenesis of PCOS, we analyzed mutations in hypervariable region 1 and 2 (HV1 and 2) of the mitochondrial DNA (mtDNA). DESIGN: Prospective observational study. MATERIALS AND METHODS: Peripheral blood samples were collected from 81 patients with PCOS (mean age, 32.5⫾3.1) who were under the inclusion criteria for PCOS and from 80 healthy controls (mean age, 29.4⫾4.8). Genomic DNA was used to amplify the HV1 (16024-16383) and HV2 (57-372), sequenced and aligned. The sequences were compared with those reported in the revised Cambridge Reference Sequence (www.mito-

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map.org). Statistical analysis was assessed by Chi-square and Fisher’s exact test (p ⬍ 0.05). RESULTS: Most of all mutations were single base substitutions. Most of these were transitions (72.87%) and transversions were 19.38%, while insertions and deletions were detected rarely. We also found 31 novel mutations in PCOS patients and 6 in controls.

CONCLUSION: PCOS may be associated with the mutations of mtDNA which is a role in supporting the cell energy. Mitochondrial DNA codes for 13 essential subunits of the respiratory chain complexes that provide the main ATP supply of the cell. Its mutations may affect oxidative energy metabolism. Our analysis shows that novel and known mutations are detected more frequently in PCOS samples than in control group. It suggests that the variation of mtDNA may lead to the development of PCOS. Furthermore, we found statistically significant 3 polymorphisms in HV1 and 7 in HV2. Especially, G366A, a new polymorphism, is detected significantly in PCOS (Chi-square test, p⫽0.01, Fisher’s exact test, p⫽0.0092). These polymorphisms have high frequency in H-strand origin, which is associated with replication of the mtDNA. It also demonstrates that these mutations of H-strand origin may be relevant to pathophysiology of PCOS. Based on this study, we show that polymorphisms identified in the HV1 and 2 affect the development of PCOS caused by abnormalities in the mitochondrial mechanism, such as impaired apoptosis, insulin-stimulated pathways, insulin resistance and anovulation. Our results support that polymorphisms of mtDNA may play a role in patients with idiopathic PCOS. Supported by: Grant of Korea Health 21 R&D Project, Ministry of Health & Welfare Republic of Korea (01-PJ10-PG6-01GN13-0002).

Wednesday, October 25, 2006 4:30 pm O-258 BREAST CANCER INCIDENCE IN INFERTILE WOMEN WITH AND WITHOUT IVF TREATMENT AS COMPARED WITH THE GENERAL POPULATION. L. Lerner-Geva, I. Pappo, L. Olmar, S. Friedler, A. Raziel, R. Ron-El. Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel; The Comprehensive Breast Care Institute, Assaf Harofeh Medical Center, Israel; Infertility and IVF unit, Assaf Harofeh Medical Center, Zerifin, Israel. OBJECTIVE: A clear connection was established between breast cancer risk and the exposure to endogenous or exogenous female hormones. The possible association between ovulation inducing drugs and breast cancer development has been debated. The aim of our study was to evaluate the incidence of breast cancer among infertile women with and without IVF treatment as compared with the general population. DESIGN: A retrospective cohort analysis. MATERIALS AND METHODS: The computerized database of all women who underwent IVF treatment at the Assaf Harofeh Medical Center during the period 1986-2003 was linked to the Israeli National Cancer Registry updated to 31.12.2004. The standardized incidence ratio (SIR) and corresponding 95% confidence intervals (CI) were computed from the observed number of breast cancer cases and the expected cases based on the national breast cancer incidence rates adjusted for age and continent of birth. Breast cancer incidence was also evaluated in a cohort

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Abstracts

of infertile women with similar follow-up since their first visit to the infertility clinic but without IVF treatment and compared to the general population rates. The incidence of breast cancer was compared between the two cohorts of infertile patients using multivariate Poisson regression analysis. RESULTS: The cohort of IVF patients included 3340 women with a mean follow-up of 8.1⫾4.3 years. Thirty five breast carcinomas were diagnosed as compared to 24.9 expected in the general population (SIR⫽ 1.4; 95% CI 0.98-1.95). Anovulatory women (SIR⫽3.1; 95% CI 0.99-7.22) and those who underwent more than 4 IVF cycles (SIR⫽2.0; 95% CI 1.15-3.27) were at high risk for breast cancer compared to the general population. However, these excess risks decreased in multivariate analysis (HR⫽2.4; 95% CI 0.7-6.14 and HR⫽2.0; 95% CI 0.92-4.28 for anovulation and multiple (ⱖ4) IVF cycles respectively). The cohort of infertile women included 2592 women with a mean follow-up of 7.8⫾5.5 years. Eleven breast carcinomas were observed as compared to 11.2 expected in the general population (SIR⫽0.98; 95%CI 0.49-1.75). In multivariate analysis including both cohorts, women with anovulatory infertility (HR⫽2.5; 95%CI 0.62-8.08) and women who were treated with IVF (HR⫽2.1; 95%CI 0.60-9.35) were at insignificant risk for breast cancer development. CONCLUSION: Women who attended IVF program were not at significant increased risk for breast cancer as compared with the general population and infertile women who were not treated with IVF. However, the risk for breast cancer in women who underwent more than 4 IVF cycles should be further investigated. Supported by: The Israel Cancer Association.

Wednesday, October 25, 2006 4:45 pm O-259 CYTOMEGALOVIRUS IN ASSISTED REPRODUCTION - A PROBLEM? A. R. Thornhill, P. Mittal, M. Asaad, A. Berkley, I. L. Craft. London Fertility Centre, London, United Kingdom. OBJECTIVE: Cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection with possible severe neonatal complications. UK regulations discourage CMV seropositive (⫹) gamete donor use for CMV(-) recipients, resulting in rejection of many eligible gamete donors. Since CMV DNA has not been detected in oocytes or embryos from couples in whom CMV serum antibodies are detected, our policy allows treatment in exceptional circumstances for cases of known donation or surrogacy in which the gamete donor is CMV⫹ with no active infection (IgG⫹/IgM-) and the recipient has no possibility of finding an alternative donor or host. We wished to determine the frequency of CMV⫹ status and donor⫹/recipient- CMV incompatibility in unselected patients undergoing third party reproduction. DESIGN: Retrospective data analysis. MATERIALS AND METHODS: Serum CMV IgG/IgM antibody tests for patients undergoing known gamete donation or surrogacy during 2005 were reviewed. For cases, in which incompatibility was between a CMV⫹ sperm donor and CMV- ‘recipient’, semen samples were frozen (for quarantine) and later subjected to CMV viral load (CMV-VL) testing to rule out active infection. Aliquots were thawed, processed (by density gradient, wash and swim-up procedures) and tested for CMV-VL using real-time quantitative polymerase chain reaction (Taqman assay) for CMV DNA. Some samples were washed using a novel sperm washing device to avoid possible sample recontamination. Samples from which an aliquot tested negative were deemed safe for use in IUI/IVF procedures after appropriate counselling. For CMV⫹ known oocyte donors, a negative CMV-VL test made them eligible for use in treatment of CMV- recipients. Pearson’s chi-squared was used to test for differences between CMV⫹ frequency in men and women. Based on observed CMV⫹ frequencies, probability trees were used to predict donor/recipient incompatibility frequencies and these were compared with observed frequencies using T tests. RESULTS: In 2005, 249 samples (221 women, 28 men) were sent for CMV antibody testing. The incidence of CMV⫹ status was no different between women (52.9%) and men (39.2%). Based on these results, donor⫹/ recipient- incompatibility should be common (24.9% - 32.1%). Observed incompatibility frequencies were significantly lower than predicted for oocyte donation (6.2% vs 24.9%; P⬍0.003), but there was no difference

Vol. 86, Suppl 2, September 2006