EARLY PREGNANCY P-530 Wednesday, October 16, 2013 A PROSPECTIVE EVALUATION OF THE EFFECT OF HERPESVIRUS-ASSOCIATED UBIQUITIN-SPECIFIC PROTEASE (HAUSP) GENE POLYMORPHISM GENOTYPES ON RECURRENT MISCARRIAGE. C. G. Petersen,a,b,c L. D. Vagnini,b A. L. Mauri,a,b J. B. A. Oliveira,a,b,c R. L. R. Baruffi,a,b J. G. Franco, Jr.,a,b,c aCenter for Human Reproduction Prof. Franco Jr, Ribeirao Preto, Sao Paulo, Brazil; bPaulista Center for Diagnosis Research and Training, Ribeirao Preto, Sao Paulo, Brazil; cDepartment of Gynecology and Obstetrics, Botucatu Medical School -Sao Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil. OBJECTIVE: An association between the HAUSP gene guanine(G)/adenine(A)(rs1529916) polymorphism in women and human fertility has been previously reported. However, these studies have not considered the genotypes of the men or of the embryos. The objective of this study was to analyze whether this HAUSP G/A polymorphism in couples and their embryos indicated susceptibility to recurrent miscarriage(RM). DESIGN: Genetic evaluation. MATERIALS AND METHODS: A total of 23 couples with RM (R2consecutive miscarriages) were included. The control group consisted of 55 couples who had experienced at least two live births (without any treatment). The DNA of all of the participants was extracted from peripheral blood. The HAUSP G/A single nucleotide polymorphism(rs1529916) was genotyped using real-time PCR with the Taqman Universal PCR Master Mix and a Taqman SNP genotyping assay. The genotypes/alleles distributions were evaluated using the c2 test. RESULTS: Table 1 summarizes the results. TABLE 1. Results Genotypes and allele frequencies of the HAUSP G⁄A polymorphism in women and men with RM and controls Women RM Group
Control Group
Men
P
RM Group
Control Group
P
Genotypes(%): 0.50 0.13 G/G 65.2 52.7 56.5 34.6 G/A 26.1 40 30.4 54.5 A/A 8.7 7.3 13.1 10.9 Alleles(%): 0.60 0.31 G 78.3 72.7 71.7 61.8 A 21.7 27.3 28.3 38.2 Couples’ genotype combinations and possible HAUSP G⁄A polymorphism genotypes in the embryos RM Control P Offspring Couple Group Group Genotype Genotype Combination G/GxG/G 43.5% 23.6% 0.25 100%G/G G/GxG/A 30.5% 36.4% 0.80 50%G/G, 50%G/A G/GxA/A 4.3% 3.6% 0.90 100%G/A G/AxG/A 8.7% 21.8% 0.29 25%G/G, 50%G/A, 25%A/A G/AxA/A 8.7% 14.6% 0.73 50%A/A, 50%G/A A/AxA/A 4.3% 0 0.66 100%A/A
CONCLUSION: There were no differences in the frequencies of the HAUSP G/A (rs1529916) polymorphism in couples with RM and the controls. In addition, the embryonic HAUSP G/A polymorphism was not associated with RM. P-531 Wednesday, October 16, 2013 A CASE OF EARLY ONSET CHOLESTASIS OF PREGNANCY ASSOCIATED WITH IN VITRO FERTILIZATION (IVF) AND MODERATE OVARIAN HYPERSTIMULATION SYNDROME (OHSS). M. Erdem, A. Erdem, K. Aslan, Y. Oguz. Gazi University Medical Faculty, Obstetric and Gynecology, Ankara, Turkey. OBJECTIVE: To determine the exact diagnosis in patients with moderate OHSS, elevated liver enzymes (ELE) and pruritis in a case af early pregnancy.
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ASRM Abstracts
DESIGN: Case report. MATERIALS AND METHODS: An infertile patient conceived after IVF. RESULTS: A 24 years old primary infertile woman had IVF with long suppression. She used recFSH with step-down and coasting. Twenty-seven oocytes were retrieved, 17 were fertilized and a grade I blastocyst was transferred. She applied with complaints abdominal distension and pain two days after embryo transfer (ET). She had moderate OHSS and followed conservatively. Abdominal distension worsened after the diagnosis of pregnancy and she was hospitalized again for moderate late onset OHSS. On admission mildly ELE with normal bilirubine levels were observed. Blood levels of bile acids were increased (166.8 mmol/L). Her symptoms diminished after fluid restriction. However, liver enzymes reached a peak value of AST:400 ALT:903 at 6th weeks of pregnancy. Her complaints diminished except pruritus. The pregnancy was terminated with a diagnosis blighted ovum and liver enzyme and bile acid levels were normal after. The patient was diagnosed as CP. CONCLUSION: CP is a rare condition in first trimester of pregnancy, almost all the cases reported were associated with OHSS after controlled ovarian hyperstimulation. P-532 Wednesday, October 16, 2013 IMPACT OF SUPRAPHYSIOLOGIC SERUM ESTRADIOL LEVEL ON CLINICAL PREGNANCY AND MISCARRIAGE RATES FOLLOWING IVF CYCLES. R. H. Goldman,a A. N. Imudia,a A. O. Awonuga,b D. L. Wright,a A. K. Styer,a T. L. Toth.a aVincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA; bDivision of Reproductive Endocrinology and Infertility, Wayne State University School of Medicine, Detroit, MI. OBJECTIVE: To investigate the relationship between elevated peak serum estradiol (E2) levels during controlled ovarian hyperstimulation (COH) and peri-implantation embryo development, clinical pregnancy (CPR) and spontaneous miscarriage rates (SMR) following IVF ICSI cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: A total of 2,995 consecutive IVF cycles with autologous oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by peak serum E2 level on the day of hCG administration into those with levels >90th percentile [>2,991 pg/mL, (Group 1, n¼299)] and % 90th percentile [% 2,991 pg/mL (Group 2, n¼2,696)]. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, CPR and SMR were compared using SPSS version 21. RESULTS: Cycles with E2 levels >90th percentile were associated with aspiration of a greater number (meanSD) of total (15.05.0 vs. 10.05.0, p¼0.001) and mature oocytes (12.05.0 vs. 8.05.0, p¼0.001). Rates of normal fertilization with conventional insemination (58.020.1 vs. 62.321.5, p¼0.001) or ICSI (68.620.0 vs. 71.620.8, p¼0.02) were significantly lower in Group 1. Rate of progression of 2PN to 6-8 cell embryos on day 3 between the groups was not different. Although rates of positive pregnancy test (55.2% vs. 57%), implantation (26.4% vs. 28.5%) and clinical pregnancy (45.5% vs. 49.4%) were lower in Group 1, the difference was not statistically significant. Similarly, SMR was higher in Group 1 (8.4%) compared with Group 2 (7.1%), but this difference was not significant. CONCLUSION: Elevated peri-implantation E2 during IVF is associated with lower normal fertilization rates with both conventional insemination and ICSI. The non-significant decrease in CPR and increase in SMR reported in Group 1 may be due to a type 2 error and suggests that a larger study is needed to confirm or refute the association between elevated serum peak E2 levels and rates of spontaneous early pregnancy failure. P-533 Wednesday, October 16, 2013 THE SAFETY OF OFFIE MANUAL VACUUM ASPIRATION IN TREATING GESTATIONAL TROPHOBLASTIC DISEASE ASSOCIATED WITH EARLY PREGNANCY FAILURE. E. L. Dickson, V. Dalton, K. Pasque. Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI. OBJECTIVE: Compare complication rates among women with molar pregnancy undergoing uterine aspiration in the office with those treated in the operating room. DESIGN: We conducted a chart review of patients undergoing manual vacuum aspiration or electric vacuum aspiration with a molar pregnancy from January 1st 2001 to December 31st 2011.
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MATERIALS AND METHODS: Women with molar pregnancies were identified using ICD codes. The medical record was reviewed to confirm the diagnosis which required histopathology. Women were included in the study if they had confirmed molar pregnancy diagnosis and were less than 14 weeks gestation. Procedure location was determined from the operative note and appointment schedule. Charts were reviewed for complications including: need to stop procedure due to pain, conversion to general anesthesia, postabortal syndrome, estimated blood loss greater than 300ccs, blood transfusion, hospital admission, uterine perforation, endometritis, retained products of conception, and visit to the emergency department within 2 weeks. Additionally, the incidence of recurrent gestational neoplastic disease, metastases and need for chemotherapy was recorded. Risk factors for complications including uterine size, gestational age, mean sac diameter by ultrasound, suspicion for mole preoperatively and maximum b-hcg values were also examined. RESULTS: We identified 136 women with histopathology confirmed molar pregnancy of which 49 underwent office MVA. Patients undergoing office based procedures had slightly smaller gestational ages (53.0 vs 63.7 days for OR group, p 0.03). B-hcg values were also lower for office based procedures (56,203 vs. 161,478, p<0.001). Patients undergoing evacuation in the clinic were less likely to have blood loss greater than 300ccs (4.1% vs. 42.5% in the OR group, p <0.001). There were no other significant differences in complication rates. CONCLUSION: Based on this small series of patients, complication rates were not increased if treated in the office as compared to in the operating room. P-534 Wednesday, October 16, 2013 EMBRYONIC KARYOTYPE AS A PROGNOSTIC INDICATOR IN WOMEN WITH UNEXPLAINED RECURRENT PREGNANCY LOSS. J. A. M. Massiea R. B. Lathi.b aReproductive Endocrinology and Infertility, San Antonio Military Medical Center, Fort Sam Houston, TX; b Reproductive Endocrinology and Infertility, Stanford University Medical Center, Palo Alto, CA. OBJECTIVE: To ascertain if women with unexplained recurrent pregnancy loss (RPL) who experience euploid miscarriages have a similar prognosis for live birth as women with aneuploid miscarriages. DESIGN: Cohort study. MATERIALS AND METHODS: Women with unexplained RPL who had chromosomal analysis of a miscarriage specimen and subsequently conceived a clinical pregnancy were included. RPL was defined as R2 clinical pregnancy losses, <20 weeks. Patients were excluded if they had an identifiable cause of RPL, such as uterine cavity abnormality, parental chromosome abnormality, or Antiphospholipid Antibody Syndrome. Those that utilized PGS, donor oocytes or gestational carrier were also excluded. Live birth rate (LBR) in the first subsequent pregnancy was compared between patients with euploid and aneuploid miscarriages. Statistical analysis utilized Student’s t-test or X2 tests, with logistic-regression to adjust for potential confounders. RESULTS: 391 women with a history of RPL between April 1998 and November 2011 were identified. Of these, 95 satisfied all inclusion and exclusion criteria. Demographic characteristics are shown in Table 1. There was a non-significant trend toward a lower LBR after a euploid loss compared to aneuploid loss (52% vs 67%). TABLE 1.
Euploid (n¼40)
Aneuploid (n¼55)
Age (time of intake loss) 35.9 36.7 (range 26-43) (range 25-42) # SABs 2 21 (52.5%) 26 (47.3%) 3 11 (27.5%) 21 (38.2%) R4 8 (20.0%) 8 (14.5%) Method of Conception Spontaneous 22 (55%) 25 (45%) IUI 7 (18%) 14 (25%) IVF 11 (27%) 16 (29%) BMI <25 27 (67.5%) 36 (65.5%) R25 13 (32.5%) 19 (34.5%) Primary RPL 26 (65.0%) 37 (67.3%)
FERTILITY & STERILITYÒ
p-value 0.15
CONCLUSION: Counseling patients with unexplained RPL is based largely on age and previous number of losses. Embryonic karyotype may offer an additional prognostic marker in women with unexplained RPL. Further research is needed into the etiology of euploid losses in patients with RPL, as the prognosis seems to be worse for these patients. P-535 Wednesday, October 16, 2013 HUMAN CHORIONIC GONADOTROPIN (hCG) TRENDS IN THE MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY WITH SINGLE-DOSE (SD) AND TWO-DOSE (2D) METHOTREXATE PROTOCOLS: A DIFFERENCE OF RISK. M. C. Mergenthal,a S. Senapati,b J. Zee,c L. Allen-Taylor,d M. D. Sammel,c K. T. Barnhart.b a Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA; bDepartment of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; c Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; dCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. OBJECTIVE: To evaluate the association between methotrexate (MTX) protocol, hCG trends, and time to resolution of ectopic pregnancy (EP). DESIGN: Retrospective multicenter cohort study. MATERIALS AND METHODS: Women diagnosed with EP in 20072009 who underwent management with either SD or 2D MTX protocol were included. Data on center, age, race, ethnicity, parity, body mass index, gestational age, ultrasound findings, hCG levels on days 0, 4, and 7, and treatment outcome were collected. Successful resolution was hCG<5 mIU/mL while failure was need for surgical management after MTX. A propensity score analysis was used to address confounding by indication. Linear regression models were used to assess hCG change from day 0 to 7 and day 4 to 7 by protocol while Cox proportional hazards models were used to assess time to success. RESULTS: 162 women were included; 114 received SD and 48 received 2D. Protocol differed by center, race, and ethnicity (p<0.001, p¼0.011, and p<0.001, respectively). hCG levels declined faster in the SD compared to 2D group from day 0 to 4 (-10.8% vs. +5.14%, p¼0.03); however, the change from day 4 to 7 was no different between groups (p¼0.11). Success rates were comparable between the two groups (83% vs. 79%, p¼0.53). There was no difference in time to success (HR 0.67, p¼0.44). CONCLUSION: We hypothesized that 2D protocol would have a greater effect on hCG decline and would result in a faster time to resolution. However, outcomes were similar due to confounding by indication in clinical practice. SD protocol was given to patients with better prognosis as demonstrated by the larger hCG drop from day 0 to 4, when MTX exposure is the same between the two protocols. Ultimately, there was no difference in success rates or time to success between the two groups, suggesting that the 2D protocol may be attenuating the expected poor prognosis and subsequent risk of failure. Randomized trials are needed to elucidate differences between protocols. Supported by: T32HD007440 (SS), K24HD060687 (KB). P-536 Wednesday, October 16, 2013 HOW LOW CAN YOU GO? INTERPRETING LOW BETA HUMAN CHORIONIC GONADOTROPIN (hCG) LEVELS FOLLOWING IN VITRO FERTILIZATION (IVF) AND FROZEN EMBRYO TRANSFER (FET). J. Buldo-Licciardi,a K. N. Goldman,a D. McCulloh,a F. Licciardi,a J. Goldfarb,b J. A. Grifo.a aObstetrics and Gynecology, Reproductive Endocrinology and Infertility, New York University Langone Medical Center, New York, NY; bUniversity Hospitals of Cleveland Fertility Center, Beachwood, OH.
0.76
0.57
0.42 0.41
OBJECTIVE: To assess outcomes in patients with low (<50mIU/ml) initial hCG levels on cycle day 28 following IVF and FET. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: From October 2010 through March 2013, 368 women were identified who underwent IVF (n¼269) and FET (n¼99) at our center and presented with a cycle day 28 hCG level R5 and <50mIU/ml. We sought to determine the incidence of biochemical pregnancy, spontaneous abortion or anembryonic gestation, ectopic pregnancy, and ongoing pregnancy(OP)/live birth in patients presenting with low initial hCG following frozen versus fresh cycles. Data were analyzed using Fisher’s Exact and Student’s T-test.
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