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503: Rate of sonographic cervical shortening and biologic pathways of spontaneous preterm birth
www.AJOG.org
Doppler Assessment, Fetus, Prematurity
500 Non-invasive prediction of chorioamnionitis in women with preterm premature rupture of membranes Kyo Hoon Park1, Shi Nae Kim1, Eun Ha Jeong1, Sung Youn Lee1, Aeli Ryu1, Kyung Joon Oh1 1 Seoul National University College of Medicine, Seoul National University Bundang Hospital, Department of Obstetrics and Gynecology, Seongnam-si, South Korea
OBJECTIVE: To develop a model based on non-invasive clinical and ultrasonographic parameters to predict the probability of subsequent chorioamnionitis in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of subsequent chorioamnionitis based on the non-invasive model. STUDY DESIGN: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 106 consecutive women with PPROM at 23 0/7-33 6/7 weeks of gestation. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. Outcome measures were histologic and clinical chorioamnionitis. The placentas were examined histologically for presence of chorioamnionitis and women were evaluated for evidence of clinical chorioamnionitis. RESULTS: The non-invasive model (model 1) for prediction of histologic chorioamnionitis included serum C-reactive protein (CRP), gestational age, and parity. The model was shown to have an adequate goodness of fit, and the area under the receiver operating characteristic curve (AUC) was 0.756. When adding AF IL-6, AF culture, and AF WBC as invasive markers to the non-invasive model, serum CRP and parity were excluded from the final model (model 2) as not significant, whereas AF IL-6 and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. For the outcome of clinical chorioamnionitis, no parameters studied could be identified to predict women at high risk for its development, although the association with AF culture results was borderline statistically significant (P⫽0.055). CONCLUSION: In women with PPROM, the non-invasive model based on serum CRP, gestational age, and parity was shown to be moderately predictive of developing histologic chorioamnionitis. However, invasive test results did not add predictive information to the non-invasive model in this setting.
501 Prediction of spontaneous preterm delivery based on sonographic cervical length and gestational age at cervical length measurement in asymptomatic women with twin pregnancies Kyung Joon Oh1, Kyo Hoon Park1, Sung Youn Lee1, Aeli Ryu1, Eun Ha Jeong1, Shi Nae Kim1 1 Seoul National University College of Medicine, Seoul National University Bundang Hospital, Department of Obstetrics and Gynecology, Seongnam-si, South Korea
OBJECTIVE: To estimate the risk of spontaneous preterm delivery within 14 and 28 days based on sonographic cervical length and gestational age at which cervical length was measured in asymptomatic women with twin pregnancies. STUDY DESIGN: Two hundred forty-nine women with twin pregnancies were prospectively enrolled in a longitudinal cohort study between 19-24 weeks of gestation. Serial transvaginal ultrasonographic assessments of cervical length were made until 34 weeks of gestation. Exclusion criteria were cerclage and iatrogenic preterm delivery. Primary outcome measure was spontaneous preterm delivery within 14 days of examination. Data were analyzed using generalized estimating equation (GEE) models. RESULTS: A total of 1269 cervical sonographic measurements were made. The incidences of spontaneous preterm delivery before 32, 34, and 36 weeks were 4.0% (10/251), 5.7% (14/246), and 15.2% (34/
Poster Session III
223), respectively. Using GEE model, independent factors associated with delivery within 14 days were cervical length and gestational age at cervical length measurement. The risk of spontaneous preterm delivery within 14 days decreased by approximately 8% for each additional millimeter of cervical length (odds ratio 0.92, 95% confidence interval, 0.87-0.97, P⫽.001) and increased by approximately 40% for each additional week of pregnancy at which the cervical length was measured (odds ratio 1.40, 95% confidence interval, 1.17-1.67, P⬍.001). Similar results were obtained for delivery within 28 days. CONCLUSION: In asymptomatic women with twin pregnancies, the risk for spontaneous preterm delivery within 14 days increases as the length of the cervix declines and as the gestational age at which cervical length was measured increases. These risks of spontaneous preterm delivery within 14 days can be used to effectively counsel and manage women with different degrees of short cervical length at different gestational ages.
502 Prediction of preterm birth in twin gestations through analysis of maternal plasma at 24-30 weeks gestation Leonardo Pereira1, Phil Wilmarth2 1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network, Bethesda, MD, 2Oregon Health & Science University, Department of Biochemistry and Molecular Biology, Portland, OR
OBJECTIVE: The majority of morbidity and mortality in twins occurs with delivery 34 wk. STUDY DESIGN: Secondary analysis of maternal plasma samples from an RCT of 17 ␣-hydroxyprogesterone caproate in twins and triplets. Samples obtained at randomization from twins in the placebo group with PTB 34 wk (Group 2, N⫽7), matched by maternal age, ethnicity, and gestational age at sample collection were compared. Differentially expressed proteins were identified by multidimensional liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS). Pair-wise comparison was performed using 2 goodness-of-fit tests and a pvalue ⬍0.05 was considered significant. Fold-change between the 2 groups was determined after differential candidates passed the calculated Z-score thresholds. RESULTS: 29 proteins were significantly differentially expressed between the groups (p ⬍0.05). Of those, 15 were overexpressed in Group 1 (PTB⬍34) compared with Group 2. Overexpressed proteins of interest included 5 cell-cell adhesion proteins (Ficolin-3, Gelsolin, Tenascin-X, Galectin-3-binding protein, and Insulin-like growth factor-binding protein complex acid liable subunit). Expression of Profilin-1 and Plastin-2 was two-fold higher in Group 2 than Group 1 although these differences did not reach statistical significance. Cellular Fibronectin was not different between groups. CONCLUSION: Increased maternal plasma levels of cell-cell adhesion proteins are associated with subsequent PTB ⬍34 wk in twin gestations, confirming our earlier findings in CVF. These include both positive (Ficolin-3 and Gelsolin) and negatively associated (Profilin1) proteins that are distinct from markers of recurrent PTB in singletons.
503 Rate of sonographic cervical shortening and biologic pathways of spontaneous preterm birth Leslie Moroz1, Hyagriv Simhan1 1 Magee-Womens Hospital of UPMC, Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA
OBJECTIVE: Rate of change of sonographic cervical length (CL) during the early third trimester is associated with the risk of spontaneous preterm birth (SPTB). The biologic pathways implicated in the relationship between CL and SPTB are poorly understood. We sought to explore the relation between the change in sonographic CL and thrombosis-hemostasis (Antithrombin III (TAT) complexes), activation of the placental stress pathway (Corticotropin Releasing Hor-
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S227
Poster Session III
Doppler Assessment, Fetus, Prematurity
mone (CRH)), and maternal systemic inflammation (C-Reactive Protein(CRP)). STUDY DESIGN: This is a secondary analysis of a multicenter prospective observational cohort study designed to study predictors of preterm birth. In this analysis, women with a singleton gestation from the general obstetric population underwent two study visits (visit 1 at 24 and visit 2 at 28 weeks gestation) at which sonographic CL and maternal plasma CRH, CRP, and TAT were assessed. The relationships between change in CL and plasma levels of these proteins were evaluated using logistic regression. RESULTS: 334 women completed both study visits. In the cohort overall, there was no significant association between the change in cervical length and concentrations of CRP, TAT, or the rate of rise of CRH. 52 (16%) had CL at visit 1 ⬍25mm. Among women with sonographic short CL at visit 1, there was a significant correlation between cervical shortening and rise of CRH (r2⫽ ⫺0.34, p⫽0.014), and rise of CRP(r2⫽ ⫺0.44, p⫽0.001). The magnitude of the association was greatest with the rate of rise of CRH (Figure 1a and 1b). There was no association with change in TAT concentration. CONCLUSION: Among women with a sonographic short CL around 24 weeks gestation, the rate of change in CL is associated with rate of rise of CRH and an increase in maternal CRP concentration, but not TAT concentration. The mechanisms and causal relations between cervical shortening and placental endocrine activation and maternal systemic inflammation warrant further study.
S228
www.AJOG.org
504 Reduction in dichorionic twin pregnancy, a retrospective cohort study Sheila Everwijn1, Lidewij van de Mheen2, Anita Ravelli3, Maarten Knapen4, Dick Oepkes5, Melanie Engels6, Gwendolyn Manten7, Hans Zondervan8, Soetinah Wirjosoekarto9, John van Vught10, Jan Jaap Erwich11, Maria van Pampus12, Christianne de Groot13, Eva Pajkrt14, Ben Willem Mol15 1 Academic Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, 2Onze Lieve Vrouwe Gasthuis Amsterdam, Obestetrics and Gynaecology, Amterdam, Netherlands, 3Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, 4Erasmus Medical Centre, Obstetrics and Gynaecologie, Rotterdam, Netherlands, 5Leiden University Medical Center, Obstetrics, Leiden, Netherlands, 6VU University Medical Center, Obstetrics and Gynaecologie, Amsterdam, Netherlands, 7University Medical Centre Utrecht, Obstetrics and Gynaecologie, Utrecht, Netherlands, 8 Rijnstate hospital, Obstetrics and Gynaecology, Arnhem, Netherlands, 9 Maastricht University Medical Centre, Obstetrics and Gynaecology, Maastricht, Netherlands, 10Radboud University Medical Centre, Obstetrics and Gynaecology, Nijmegen, Netherlands, 11University Medical Centre Groningen, Obstetrics and Gynaecology, Groningen, Netherlands, 12Onze Lieve Vrouwe Gasthuis, Obestetrics and Gynaecology, Amsterdam, Netherlands, 13VU Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, 14Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands, 15 Dutch consortium AMPHIA trial, Netherlands
OBJECTIVE: To assess the outcome of dichorionic twin pregnancy managed expectantly versus those reduced to singletons. STUDY DESIGN: We studied in a retrospective study consecutive cases of twin pregnancies that were reduced to singletons in the Netherlands between 2000-2010. The reductions were performed between 10-23 weeks by transabdominal injection of KCL. The outcome of these pregnancies was compared to twin pregnancies that were collected from a previous RCT (AMPHIA ISRCTN 40512715) and to singleton pregnancies born in 2008 retrieved from the Dutch perinatal registration. The two groups were compared for median gestational age, pregnancy loss ⬍24 weeks, preterm delivery ⬍32 weeks, neonatal birth weight and number of stillbirths. Statistical tests were performed in SPSS 18. Mann-Whitney U test was use to compare mean neonatal birth weight and Chi Square test was used to compare delivery rates ⬍24 and ⬍32 weeks and number of stillbirths. RESULTS: We identified 98 twin pregnancies that were reduced to singletons, 91 for congenital anomalies and 7 for social indications. Median gestational age for these pregnancies was 39.0 weeks (SD 3.8). Ongoing twin pregnancies had a median gestational age of 37.0 weeks (SD 5.8). Pregnancy loss ⬍24 weeks was significantly higher in the reduction group compared to ongoing twins (6.6% vs 2.5% respectively). For delivery ⬍32 weeks there was no significant difference between the two groups (15.4% vs 11% respectively). The median birth weight at birth of the first child was 3120 gram in the reduction group and 2500 gram in the ongoing twin group (p-value 0.00). In the reduction group the percentage of stillbirths was significantly higher compared to the ongoing twin group (9% vs 2%). CONCLUSION: In this study, selective reduction of twin pregnancy to singletons gave a higher risk of pregnancy loss than in ongoing twins, but it significantly improved gestational age and neonatal birth weight. Women opting for selective reduction on social indication should realise there is a significant risk in losing the complete pregnancy before making this decision.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
Doppler Assessment, Fetus, Prematurity
500 Non-invasive prediction of chorioamnionitis in women with preterm premature rupture of membranes Kyo Hoon Park1, Shi Nae Kim1, Eun Ha Jeong1, Sung Youn Lee1, Aeli Ryu1, Kyung Joon Oh1 1 Seoul National University College of Medicine, Seoul National University Bundang Hospital, Department of Obstetrics and Gynecology, Seongnam-si, South Korea
OBJECTIVE: To develop a model based on non-invasive clinical and ultrasonographic parameters to predict the probability of subsequent chorioamnionitis in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of subsequent chorioamnionitis based on the non-invasive model. STUDY DESIGN: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 106 consecutive women with PPROM at 23 0/7-33 6/7 weeks of gestation. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. Outcome measures were histologic and clinical chorioamnionitis. The placentas were examined histologically for presence of chorioamnionitis and women were evaluated for evidence of clinical chorioamnionitis. RESULTS: The non-invasive model (model 1) for prediction of histologic chorioamnionitis included serum C-reactive protein (CRP), gestational age, and parity. The model was shown to have an adequate goodness of fit, and the area under the receiver operating characteristic curve (AUC) was 0.756. When adding AF IL-6, AF culture, and AF WBC as invasive markers to the non-invasive model, serum CRP and parity were excluded from the final model (model 2) as not significant, whereas AF IL-6 and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. For the outcome of clinical chorioamnionitis, no parameters studied could be identified to predict women at high risk for its development, although the association with AF culture results was borderline statistically significant (P⫽0.055). CONCLUSION: In women with PPROM, the non-invasive model based on serum CRP, gestational age, and parity was shown to be moderately predictive of developing histologic chorioamnionitis. However, invasive test results did not add predictive information to the non-invasive model in this setting.
501 Prediction of spontaneous preterm delivery based on sonographic cervical length and gestational age at cervical length measurement in asymptomatic women with twin pregnancies Kyung Joon Oh1, Kyo Hoon Park1, Sung Youn Lee1, Aeli Ryu1, Eun Ha Jeong1, Shi Nae Kim1 1 Seoul National University College of Medicine, Seoul National University Bundang Hospital, Department of Obstetrics and Gynecology, Seongnam-si, South Korea
OBJECTIVE: To estimate the risk of spontaneous preterm delivery within 14 and 28 days based on sonographic cervical length and gestational age at which cervical length was measured in asymptomatic women with twin pregnancies. STUDY DESIGN: Two hundred forty-nine women with twin pregnancies were prospectively enrolled in a longitudinal cohort study between 19-24 weeks of gestation. Serial transvaginal ultrasonographic assessments of cervical length were made until 34 weeks of gestation. Exclusion criteria were cerclage and iatrogenic preterm delivery. Primary outcome measure was spontaneous preterm delivery within 14 days of examination. Data were analyzed using generalized estimating equation (GEE) models. RESULTS: A total of 1269 cervical sonographic measurements were made. The incidences of spontaneous preterm delivery before 32, 34, and 36 weeks were 4.0% (10/251), 5.7% (14/246), and 15.2% (34/
Poster Session III
223), respectively. Using GEE model, independent factors associated with delivery within 14 days were cervical length and gestational age at cervical length measurement. The risk of spontaneous preterm delivery within 14 days decreased by approximately 8% for each additional millimeter of cervical length (odds ratio 0.92, 95% confidence interval, 0.87-0.97, P⫽.001) and increased by approximately 40% for each additional week of pregnancy at which the cervical length was measured (odds ratio 1.40, 95% confidence interval, 1.17-1.67, P⬍.001). Similar results were obtained for delivery within 28 days. CONCLUSION: In asymptomatic women with twin pregnancies, the risk for spontaneous preterm delivery within 14 days increases as the length of the cervix declines and as the gestational age at which cervical length was measured increases. These risks of spontaneous preterm delivery within 14 days can be used to effectively counsel and manage women with different degrees of short cervical length at different gestational ages.
502 Prediction of preterm birth in twin gestations through analysis of maternal plasma at 24-30 weeks gestation Leonardo Pereira1, Phil Wilmarth2 1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network, Bethesda, MD, 2Oregon Health & Science University, Department of Biochemistry and Molecular Biology, Portland, OR
OBJECTIVE: The majority of morbidity and mortality in twins occurs with delivery 34 wk. STUDY DESIGN: Secondary analysis of maternal plasma samples from an RCT of 17 ␣-hydroxyprogesterone caproate in twins and triplets. Samples obtained at randomization from twins in the placebo group with PTB 34 wk (Group 2, N⫽7), matched by maternal age, ethnicity, and gestational age at sample collection were compared. Differentially expressed proteins were identified by multidimensional liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS). Pair-wise comparison was performed using 2 goodness-of-fit tests and a pvalue ⬍0.05 was considered significant. Fold-change between the 2 groups was determined after differential candidates passed the calculated Z-score thresholds. RESULTS: 29 proteins were significantly differentially expressed between the groups (p ⬍0.05). Of those, 15 were overexpressed in Group 1 (PTB⬍34) compared with Group 2. Overexpressed proteins of interest included 5 cell-cell adhesion proteins (Ficolin-3, Gelsolin, Tenascin-X, Galectin-3-binding protein, and Insulin-like growth factor-binding protein complex acid liable subunit). Expression of Profilin-1 and Plastin-2 was two-fold higher in Group 2 than Group 1 although these differences did not reach statistical significance. Cellular Fibronectin was not different between groups. CONCLUSION: Increased maternal plasma levels of cell-cell adhesion proteins are associated with subsequent PTB ⬍34 wk in twin gestations, confirming our earlier findings in CVF. These include both positive (Ficolin-3 and Gelsolin) and negatively associated (Profilin1) proteins that are distinct from markers of recurrent PTB in singletons.
503 Rate of sonographic cervical shortening and biologic pathways of spontaneous preterm birth Leslie Moroz1, Hyagriv Simhan1 1 Magee-Womens Hospital of UPMC, Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA
OBJECTIVE: Rate of change of sonographic cervical length (CL) during the early third trimester is associated with the risk of spontaneous preterm birth (SPTB). The biologic pathways implicated in the relationship between CL and SPTB are poorly understood. We sought to explore the relation between the change in sonographic CL and thrombosis-hemostasis (Antithrombin III (TAT) complexes), activation of the placental stress pathway (Corticotropin Releasing Hor-
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S227
Poster Session III
Doppler Assessment, Fetus, Prematurity
mone (CRH)), and maternal systemic inflammation (C-Reactive Protein(CRP)). STUDY DESIGN: This is a secondary analysis of a multicenter prospective observational cohort study designed to study predictors of preterm birth. In this analysis, women with a singleton gestation from the general obstetric population underwent two study visits (visit 1 at 24 and visit 2 at 28 weeks gestation) at which sonographic CL and maternal plasma CRH, CRP, and TAT were assessed. The relationships between change in CL and plasma levels of these proteins were evaluated using logistic regression. RESULTS: 334 women completed both study visits. In the cohort overall, there was no significant association between the change in cervical length and concentrations of CRP, TAT, or the rate of rise of CRH. 52 (16%) had CL at visit 1 ⬍25mm. Among women with sonographic short CL at visit 1, there was a significant correlation between cervical shortening and rise of CRH (r2⫽ ⫺0.34, p⫽0.014), and rise of CRP(r2⫽ ⫺0.44, p⫽0.001). The magnitude of the association was greatest with the rate of rise of CRH (Figure 1a and 1b). There was no association with change in TAT concentration. CONCLUSION: Among women with a sonographic short CL around 24 weeks gestation, the rate of change in CL is associated with rate of rise of CRH and an increase in maternal CRP concentration, but not TAT concentration. The mechanisms and causal relations between cervical shortening and placental endocrine activation and maternal systemic inflammation warrant further study.
S228
www.AJOG.org
504 Reduction in dichorionic twin pregnancy, a retrospective cohort study Sheila Everwijn1, Lidewij van de Mheen2, Anita Ravelli3, Maarten Knapen4, Dick Oepkes5, Melanie Engels6, Gwendolyn Manten7, Hans Zondervan8, Soetinah Wirjosoekarto9, John van Vught10, Jan Jaap Erwich11, Maria van Pampus12, Christianne de Groot13, Eva Pajkrt14, Ben Willem Mol15 1 Academic Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, 2Onze Lieve Vrouwe Gasthuis Amsterdam, Obestetrics and Gynaecology, Amterdam, Netherlands, 3Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, 4Erasmus Medical Centre, Obstetrics and Gynaecologie, Rotterdam, Netherlands, 5Leiden University Medical Center, Obstetrics, Leiden, Netherlands, 6VU University Medical Center, Obstetrics and Gynaecologie, Amsterdam, Netherlands, 7University Medical Centre Utrecht, Obstetrics and Gynaecologie, Utrecht, Netherlands, 8 Rijnstate hospital, Obstetrics and Gynaecology, Arnhem, Netherlands, 9 Maastricht University Medical Centre, Obstetrics and Gynaecology, Maastricht, Netherlands, 10Radboud University Medical Centre, Obstetrics and Gynaecology, Nijmegen, Netherlands, 11University Medical Centre Groningen, Obstetrics and Gynaecology, Groningen, Netherlands, 12Onze Lieve Vrouwe Gasthuis, Obestetrics and Gynaecology, Amsterdam, Netherlands, 13VU Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, 14Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands, 15 Dutch consortium AMPHIA trial, Netherlands
OBJECTIVE: To assess the outcome of dichorionic twin pregnancy managed expectantly versus those reduced to singletons. STUDY DESIGN: We studied in a retrospective study consecutive cases of twin pregnancies that were reduced to singletons in the Netherlands between 2000-2010. The reductions were performed between 10-23 weeks by transabdominal injection of KCL. The outcome of these pregnancies was compared to twin pregnancies that were collected from a previous RCT (AMPHIA ISRCTN 40512715) and to singleton pregnancies born in 2008 retrieved from the Dutch perinatal registration. The two groups were compared for median gestational age, pregnancy loss ⬍24 weeks, preterm delivery ⬍32 weeks, neonatal birth weight and number of stillbirths. Statistical tests were performed in SPSS 18. Mann-Whitney U test was use to compare mean neonatal birth weight and Chi Square test was used to compare delivery rates ⬍24 and ⬍32 weeks and number of stillbirths. RESULTS: We identified 98 twin pregnancies that were reduced to singletons, 91 for congenital anomalies and 7 for social indications. Median gestational age for these pregnancies was 39.0 weeks (SD 3.8). Ongoing twin pregnancies had a median gestational age of 37.0 weeks (SD 5.8). Pregnancy loss ⬍24 weeks was significantly higher in the reduction group compared to ongoing twins (6.6% vs 2.5% respectively). For delivery ⬍32 weeks there was no significant difference between the two groups (15.4% vs 11% respectively). The median birth weight at birth of the first child was 3120 gram in the reduction group and 2500 gram in the ongoing twin group (p-value 0.00). In the reduction group the percentage of stillbirths was significantly higher compared to the ongoing twin group (9% vs 2%). CONCLUSION: In this study, selective reduction of twin pregnancy to singletons gave a higher risk of pregnancy loss than in ongoing twins, but it significantly improved gestational age and neonatal birth weight. Women opting for selective reduction on social indication should realise there is a significant risk in losing the complete pregnancy before making this decision.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012