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Comparison of outcomes for women with endometriosis undergoing surgical fertility procedures
O-228 Wednesday, October 22, 2014 11:45 AM SYSTEMIC AND FOLLICULAR OXIDATIVE STRESS IN INFERTILE WOMEN WITH ENDOMETRIOSIS UNDERGOING CONTROLLED OVARIAN STIMULATION FOR ICSI: IS THERE A ROLE IN THE ETIOPATHOGENESIS OF INFERTILITY? M. G. Da Broi,a F. O. Albuquerque,a A. Z. de Andrade,a R. L. Cardoso,a A. A. Jord~ao, Jr.,b P. A. Navarro.a aDepartment of Obstetrics and Gynecology, Human Reproduction Division, Faculty of Medicine of Ribeir~ao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil; b Nutrition and Metabolism Laboratory, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeir~ao Preto, Sao Paulo, Brazil. OBJECTIVE: Controversial studies have suggested that impaired oocyte quality and oxidative stress (OS) may be involved in the pathogenesis of endometriosis-related infertility. No study to date has evaluated jointly different pro and antioxidant markers in serum and follicular fluid (FF) of women with endometriosis-related infertility. The aim of the study was to compare eight OS markers in serum and FF of infertile women with and without endometriosis (E) undergoing controlled ovarian stimulation (COS) for intracytoplasmic sperm injection (ICSI). DESIGN: Prospective case-control study. MATERIALS AND METHODS: From October 2009 to October 2010, 275 patients started COS: 151 were eligible for the study, 132 signed the informed consent, 99 underwent oocyte retrieval, and 87 serum samples (43 with E and 44 without E - with male or tubal factor of infertility) and 61 FF samples (29 with E and 32 without E) were collected in the day of oocyte retrieval and had data analyzed. Total hydroperoxides (FOX1), malondialdehyde (MDA), advanced oxidation protein products (AOPP), glutathione (GSH), superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were determined by spectrophotometry, vitamin E (Vit E) by high performance liquid chromatography, and 8-hydroxy-2’ –deoxyguanosine (8OHdG) by ELISA. Total protein (pt) levels were determined by Labtest Kits. Significance level was set on 5%. RESULTS: We observed higher serum concentrations of GSH (220.3243.2 nmol/g pt) and SOD (677.9282.21 U/mL), lower serum concentrations of TAC (0.340.17 mEq Trolox/L), and higher follicular concentrations of 8OHdG (23.196.8 ng/mL) and Vit E (13.05.33 mmol/L) in infertile women with E compared to those without E (193.9243.25 nmol/ g pt, 563.04169.82 U/mL, 0.460.15 mEq Trolox/L, 17.225.6 ng/mL and 8.712.51 mmol/L, respectively). CONCLUSION: We evidenced the occurrence of systemic and follicular OS in infertile patients with E undergoing COS for ICSI. For the first time it was demonstrated the presence of higher follicular 8OHdG concentrations in women with E, a marker of DNA oxidative damage, which may be related to compromised oocyte quality. We suggest that the OS may be involved in the etiopathogenesis of infertility-related disease. Supported by: CNPq, FAPESP (2008/58197-6), Brazil. O-229 Wednesday, October 22, 2014 12:00 PM OVARIAN HORMONES INDUCE DIFFERENTIAL DNA METHYLOME IN DECIDUALIZING VERSUS NON-DECIDUALIZING FIBROBLASTS IN PATIENTS WITH ENDOMETRIOSIS. S. Houshdaran, J. C. Irwin, L. C. Giudice. Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, CA. OBJECTIVE: To investigate molecular differences between decidualizing versus non-decidualizing endometrial stromal fibroblasts from women with endometriosis to better understand hormone-responsiveness in women with disease. DESIGN: Eutopic endometrium of endometriosis patients is estrogen (E2)responsive and progesterone (P4)-resistant. With hormonal treatment in culture, a subset of eutopic endometrial stromal fibroblasts (eSF) of patients with disease decidualize, independent of stage. We hypothesized that the decidualization potential of endometriosis eSF in response to ovarian hormones is due to molecular differences suggestive of distinct disease subtypes. Thus, we assessed epigenetic profiles of both groups, since epigenetic modifications represent both hormone-induced changes as well as pre-existing differences. MATERIALS AND METHODS: Eutopic eSF samples from patients with severe endometriosis (endo) and controls without uterine pathology were collected through the NIH UCSF Human Endometrial Tissue and DNA Bank after informed consent. Cells were treated for 14 days in culture with E2, P4, E2+P4, or vehicle. Decidualization was assessed by IGFBP1 maker by ELISA after 14 days of E2+P4 treatment. Decidualized control (n¼4) and endo (Dendo, n¼4) and non-decidualized endo (ND-endo, n¼4) were selected for
FERTILITY & STERILITYÒ
global DNA methylome analysis using the Illumina 450K platform. In-group methylation values at CpG sites for each hormone were compared to vehicle before inter-group comparisons. Data were analyzed using R. RESULTS: We found that D-endo and ND-endo have different DNA methylation modifications, in extent and in pattern, in response to each hormonal treatment and both differ from the controls: E2, results in vast changes in D-endo, followed closely by controls, but much less changes in ND-endo. P4, and E2+P4, also result in large differences in D-endo, but with less changes in control, followed by ND-endo. The pattern is also different: in D-endo, for all hormones, almost all changes are gain of methylation, different from controls with more loss of methylation in E2 and E2+P4 and more gain of methylation in P4. ND-endo showed more gain of methylation in E2 and P4 but more loss of methylation in E2+P4. CONCLUSION: Differences in DNA methylation profiles in response to E2, P4 and E2+P4 in D-endo vs. ND-endo suggest distinct disease subtypes with varying hormone responsiveness which may result in varying fertility potential of endometriosis patients. Supported by: NIH SCCPIR U54HD 05576407 (LCG). O-230 Wednesday, October 22, 2014 12:15 PM COMPARISON OF OUTCOMES FOR WOMEN WITH ENDOMETRIOSIS UNDERGOING SURGICAL FERTILITY PROCEDURES. W. M. Bannister. Healthcare Analytics, Optum, Minneapolis, MN. OBJECTIVE: To compare differences between women with and without endometriosis in maternal and newborn outcomes of pregnancies resulting from surgical fertility procedures. DESIGN: We conducted a retrospective study of commercially insured US women using administrative data. Pregnancy and newborn outcomes were compared between women with and without endometriosis, where both groups had undergone surgical fertility procedures. Risk adjusted models were developed to compare outcomes including delivery and newborn costs as well as rates of neonatal intensive care unit (NICU) newborns, cesarean deliveries, multiple births, gestational hypertension, placenta previa, and gestational diabetes. MATERIALS AND METHODS: The study included women undergoing surgical fertility treatments within 30 days of their final treatment cycle before delivery. The women were split into two groups: those with an endometriosis diagnosis up to one year prior to delivery (n¼126) and those without (n¼478). Propensity score models were developed to account for differences in age, demographic characteristics, socioeconomic factors, and concurrent treatment types such as in vitro fertilization, superovulation, or hysterosalpingogram. Using the resulting propensity score weights, logistic regression models were developed to estimate differences in rates of adverse outcomes and general linear models were developed to compare delivery and newborn costs. RESULTS: Women with endometriosis were significantly less likely (p < 0.001) to have multiple births than women without endometriosis. Further controlling for that difference in multiple births, we find that women with endometriosis were significantly less likely (p < 0.05) than those without endometriosis to have pregnancies involving gestational diabetes and placenta previa and no significant difference between groups in rates of NICU newborns, cesarean deliveries, or gestational hypertension. We also find that those with endometriosis had significantly lower (p < 0.001) newborn costs than those without endometriosis and no significant difference in delivery costs. CONCLUSION: After controlling for demographic, treatment, and socioeconomic differences it appears that women with endometriosis who undergo surgical fertility procedures have lower rates of multiple births and similar or lower rates of adverse maternal outcomes than women without endometriosis. While larger studies are needed, these results suggest that endometriosis may not by itself result in adverse outcomes. Supported by: Author is employed by Optum. O-231 Wednesday, October 22, 2014 12:30 PM ANDROGEN REGULATION OF PROGESTERONE RECEPTOR (PR) EXPRESSION IN ENDOMETRIUM: IMPLICATIONS FOR ENDOMETRIOSIS. C. Park, S. Babayev, B. R. Carr, P. W. Keller, R. A. Word, O. Bukulmez. OB/Gyn, UT Southwestern Medical Center, Dallas, TX. OBJECTIVE: It has been reported that endometriosis may be associated with progesterone resistance impacting its treatment with progestins.
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FERTILITY & STERILITYÒ
global DNA methylome analysis using the Illumina 450K platform. In-group methylation values at CpG sites for each hormone were compared to vehicle before inter-group comparisons. Data were analyzed using R. RESULTS: We found that D-endo and ND-endo have different DNA methylation modifications, in extent and in pattern, in response to each hormonal treatment and both differ from the controls: E2, results in vast changes in D-endo, followed closely by controls, but much less changes in ND-endo. P4, and E2+P4, also result in large differences in D-endo, but with less changes in control, followed by ND-endo. The pattern is also different: in D-endo, for all hormones, almost all changes are gain of methylation, different from controls with more loss of methylation in E2 and E2+P4 and more gain of methylation in P4. ND-endo showed more gain of methylation in E2 and P4 but more loss of methylation in E2+P4. CONCLUSION: Differences in DNA methylation profiles in response to E2, P4 and E2+P4 in D-endo vs. ND-endo suggest distinct disease subtypes with varying hormone responsiveness which may result in varying fertility potential of endometriosis patients. Supported by: NIH SCCPIR U54HD 05576407 (LCG). O-230 Wednesday, October 22, 2014 12:15 PM COMPARISON OF OUTCOMES FOR WOMEN WITH ENDOMETRIOSIS UNDERGOING SURGICAL FERTILITY PROCEDURES. W. M. Bannister. Healthcare Analytics, Optum, Minneapolis, MN. OBJECTIVE: To compare differences between women with and without endometriosis in maternal and newborn outcomes of pregnancies resulting from surgical fertility procedures. DESIGN: We conducted a retrospective study of commercially insured US women using administrative data. Pregnancy and newborn outcomes were compared between women with and without endometriosis, where both groups had undergone surgical fertility procedures. Risk adjusted models were developed to compare outcomes including delivery and newborn costs as well as rates of neonatal intensive care unit (NICU) newborns, cesarean deliveries, multiple births, gestational hypertension, placenta previa, and gestational diabetes. MATERIALS AND METHODS: The study included women undergoing surgical fertility treatments within 30 days of their final treatment cycle before delivery. The women were split into two groups: those with an endometriosis diagnosis up to one year prior to delivery (n¼126) and those without (n¼478). Propensity score models were developed to account for differences in age, demographic characteristics, socioeconomic factors, and concurrent treatment types such as in vitro fertilization, superovulation, or hysterosalpingogram. Using the resulting propensity score weights, logistic regression models were developed to estimate differences in rates of adverse outcomes and general linear models were developed to compare delivery and newborn costs. RESULTS: Women with endometriosis were significantly less likely (p < 0.001) to have multiple births than women without endometriosis. Further controlling for that difference in multiple births, we find that women with endometriosis were significantly less likely (p < 0.05) than those without endometriosis to have pregnancies involving gestational diabetes and placenta previa and no significant difference between groups in rates of NICU newborns, cesarean deliveries, or gestational hypertension. We also find that those with endometriosis had significantly lower (p < 0.001) newborn costs than those without endometriosis and no significant difference in delivery costs. CONCLUSION: After controlling for demographic, treatment, and socioeconomic differences it appears that women with endometriosis who undergo surgical fertility procedures have lower rates of multiple births and similar or lower rates of adverse maternal outcomes than women without endometriosis. While larger studies are needed, these results suggest that endometriosis may not by itself result in adverse outcomes. Supported by: Author is employed by Optum. O-231 Wednesday, October 22, 2014 12:30 PM ANDROGEN REGULATION OF PROGESTERONE RECEPTOR (PR) EXPRESSION IN ENDOMETRIUM: IMPLICATIONS FOR ENDOMETRIOSIS. C. Park, S. Babayev, B. R. Carr, P. W. Keller, R. A. Word, O. Bukulmez. OB/Gyn, UT Southwestern Medical Center, Dallas, TX. OBJECTIVE: It has been reported that endometriosis may be associated with progesterone resistance impacting its treatment with progestins.
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