498: Characterization of 20α reductases and 5α reductase enzyme expression in human fetal...
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498 Characterization of 20 reductases and 5 reductase enzyme expression in human fetal membranes Jennifer McIntosh 1 , Eric Knudtson 1 , Daniel Jackson 1 , Kimberly Pecinosky 1 , Dean Myers 1 1 University of Oklahoma Health Sciences Center, Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Oklahoma City, OK OBJECTIVE: Progesterone is essential for maintaining pregnancy. In the fetal membranes, progesterone limits prostaglandin (PG) produc- tion during pregnancy. One potential mechanism for a local proges- terone withdrawal in fetal membranes is a local progesterone metab- olism to inactive metabolites via 20 reductases (aldoketo reductase (AKR) 1C1, C2 and C3) and 5 reductase (5RDT). However, the expression of these enzymes in the fetal membranes has not been described. We hypothesized that members of the AKR1C and/or 5RDT enzymes are expressed in one or more components of the fetal membranes. STUDY DESIGN: Placentas from were obtained under sterile conditions from consented subjects (n3) undergoing term, scheduled cesarean delivery without having undergone labor. For each, the fetal mem- branes were then separated into the amnion, chorion and decidua and snap frozen at -80. The presence of messenger RNA (mRNA) for AKR1C1, AKR1C2, AKR1C3 and 5RDT-type II was assessed by us- ing reverse transcription PCR (RT-PCR) in triplicate followed by aga- rose gel electrophoresis with ethidium staining. Human cervical fi- broblasts were used for comparison, as presence of all of these enzymes have previously been found and described. Cyclophilin was used as a housekeeping gene. RESULTS: AKR1C2, AKR1C3 as well as 5RDT-II were expressed in amnion, chorion and decidua. AKR1C1 was not expressed in these tissues. The relative mRNA levels of AKR1C1, 2 and 5RDT-type II were similar in amnion, chorion and decidua (Figure). CONCLUSION: AKR1C2, AKR1C3 and 5RDT-II were expressed in the amnion, chorion and decidua of normal term pregnancies. This may imply that a local progesterone withdrawal facilitates removal of pro- gesterone action in these tissues facilitating PG production at term. Future studies examining progesterone metabolism via these path- ways and expression of these enzymes in non-laboring vs. laboring membranes may provide another avenue of local progesterone with- drawal in the final common parturition pathway. 499 Use of cervical pessary for prevention of preterm birth in the short cervix population: a cost-effectiveness analysis Jessica Page 1 , Allison Allen 1 , Jenna Emerson 1 , Jessica Fowler 1 , Jonathan Snowden 1 , Leonardo Pereira 1 , Alison Cahill 2 , Aaron Caughey 1 1 Oregon Health & Science University, Obstetrics & Gynecology, Portland, OR, 2 Washington University in St. Louis, Obstetrics & Gynecology, St. Louis, MO OBJECTIVE: Cervical length (CL) less than 25mm is associated with an increased risk of preterm birth. A recent RCT by Goya, et al. showed a significant decrease in the risk of preterm birth with the use of a cer- vical pessary in women with CL25mm. We sought to investigate the cost-effectiveness of the pessary as an intervention to prevent preterm birth. STUDY DESIGN: A decision-analytic model was built using TreeAge software comparing cervical pessary to expectant management in the short cervix (25mm) population. The baseline risk of preterm birth was adjusted to reflect the increased risk associated with a short cervix. The Cervical Pessary in Pregnancy Women with a Short Cervix (PECEP) RCT was used to estimate the relative risk of preterm deliv- ery with pessary. Costs of pessary use, neonatal care and cerebral palsy were derived from the literature. Outcomes included preterm birth, cerebral palsy and neonatal death. Cost-effectiveness was set at a threshold of $100,000/QALY. RESULTS: The pessary was found to be a dominant intervention (i.e. costs less with better outcomes). The costs were $8437 less in the pessary group ($7709.20 vs. $16146.66). Overall, treatment with pes- sary resulted in fewer preterm births and improved neonatal out- comes with NNT of 4 women to prevent one preterm birth. The in- tervention was cost-effective at more than 10 times the estimated cost of the pessary up to $13,992 per pessary. In univariate sensitivity anal- ysis, the pessary intervention remained cost-effective down to a risk reduction of as little as 8% (e.g. RR of 0.92) in the risk of preterm birth. CONCLUSION: The cervical pessary is a cost-effective and relatively non-invasive intervention for the prevention of preterm birth in the short cervix population defined by a CL25mm. Given the high risk of preterm birth in this group and relatively few available treatments, this represents a promising intervention warranting further study and characterization. Outcomes and costs: treat all vs test none for uncertain PPROM In a theoretical cohort of 10,000 patients www.AJOG.org Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases Poster Session III Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology S215
Transcript of 498: Characterization of 20α reductases and 5α reductase enzyme expression in human fetal...
498 Characterization of 20� reductases and 5� reductaseenzyme expression in human fetal membranesJennifer McIntosh1, Eric Knudtson1, Daniel Jackson1,Kimberly Pecinosky1, Dean Myers1
1University of Oklahoma Health Sciences Center, Obstetrics and Gynecology,Division of Maternal Fetal Medicine, Oklahoma City, OKOBJECTIVE: Progesterone is essential for maintaining pregnancy. Inthe fetal membranes, progesterone limits prostaglandin (PG) produc-tion during pregnancy. One potential mechanism for a local proges-terone withdrawal in fetal membranes is a local progesterone metab-olism to inactive metabolites via 20� reductases (aldoketo reductase(AKR) 1C1, C2 and C3) and 5� reductase (5�RDT). However, theexpression of these enzymes in the fetal membranes has not beendescribed. We hypothesized that members of the AKR1C and/or5�RDT enzymes are expressed in one or more components of the fetalmembranes.STUDY DESIGN: Placentas from were obtained under sterile conditionsfrom consented subjects (n�3) undergoing term, scheduled cesareandelivery without having undergone labor. For each, the fetal mem-branes were then separated into the amnion, chorion and decidua andsnap frozen at -80. The presence of messenger RNA (mRNA) forAKR1C1, AKR1C2, AKR1C3 and 5�RDT-type II was assessed by us-ing reverse transcription PCR (RT-PCR) in triplicate followed by aga-rose gel electrophoresis with ethidium staining. Human cervical fi-broblasts were used for comparison, as presence of all of theseenzymes have previously been found and described. Cyclophilin wasused as a housekeeping gene.RESULTS: AKR1C2, AKR1C3 as well as 5�RDT-II were expressed inamnion, chorion and decidua. AKR1C1 was not expressed in these
tissues. The relative mRNA levels of AKR1C1, 2 and 5�RDT-type IIwere similar in amnion, chorion and decidua (Figure).CONCLUSION: AKR1C2, AKR1C3 and 5�RDT-II were expressed in theamnion, chorion and decidua of normal term pregnancies. This mayimply that a local progesterone withdrawal facilitates removal of pro-gesterone action in these tissues facilitating PG production at term.Future studies examining progesterone metabolism via these path-ways and expression of these enzymes in non-laboring vs. laboringmembranes may provide another avenue of local progesterone with-drawal in the final common parturition pathway.
499 Use of cervical pessary for prevention of preterm birthin the short cervix population: a cost-effectiveness analysisJessica Page1, Allison Allen1, Jenna Emerson1,Jessica Fowler1, Jonathan Snowden1, Leonardo Pereira1,Alison Cahill2, Aaron Caughey1
1Oregon Health & Science University, Obstetrics & Gynecology, Portland,OR, 2Washington University in St. Louis, Obstetrics & Gynecology, St. Louis,MOOBJECTIVE: Cervical length (CL) less than 25mm is associated with anincreased risk of preterm birth. A recent RCT by Goya, et al. showed asignificant decrease in the risk of preterm birth with the use of a cer-vical pessary in women with CL�25mm. We sought to investigate thecost-effectiveness of the pessary as an intervention to prevent pretermbirth.STUDY DESIGN: A decision-analytic model was built using TreeAgesoftware comparing cervical pessary to expectant management in theshort cervix (�25mm) population. The baseline risk of preterm birthwas adjusted to reflect the increased risk associated with a short cervix.The Cervical Pessary in Pregnancy Women with a Short Cervix(PECEP) RCT was used to estimate the relative risk of preterm deliv-ery with pessary. Costs of pessary use, neonatal care and cerebral palsywere derived from the literature. Outcomes included preterm birth,cerebral palsy and neonatal death. Cost-effectiveness was set at athreshold of $100,000/QALY.RESULTS: The pessary was found to be a dominant intervention (i.e.costs less with better outcomes). The costs were $8437 less in thepessary group ($7709.20 vs. $16146.66). Overall, treatment with pes-sary resulted in fewer preterm births and improved neonatal out-comes with NNT of 4 women to prevent one preterm birth. The in-tervention was cost-effective at more than 10 times the estimated costof the pessary up to $13,992 per pessary. In univariate sensitivity anal-ysis, the pessary intervention remained cost-effective down to a riskreduction of as little as 8% (e.g. RR of 0.92) in the risk of preterm birth.CONCLUSION: The cervical pessary is a cost-effective and relativelynon-invasive intervention for the prevention of preterm birth in theshort cervix population defined by a CL�25mm. Given the high riskof preterm birth in this group and relatively few available treatments,this represents a promising intervention warranting further study andcharacterization.
Outcomes and costs: treat all vs testnone for uncertain PPROM
In a theoretical cohort of 10,000 patients
www.AJOG.org Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases Poster Session III
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology S215
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