- Email: [email protected]
Miscarriage rates in women with recurrent pregnancy loss and untreated chronic endometritis
O-158 Tuesday, October 21, 2014 05:00 PM ASSOCIATION OF ANTI-MULLERIAN HORMONE (AMH) AND LIVE BIRTH: RESULTS FROM THE EFFECTS OF ASPIRIN ON GESTATION AND REPRODUCTION (EAGER) TRIAL. E. F. Schisterman,a S. M. Zarek,a E. M. Mitchell,a N. Galai,b c a a b J. M. Townsend, S. L. Mumford. NIH, Rockville, MD; University of Haifa, Haifa, Israel; cThe Commonwealth Medical College, Buffalo, NY. OBJECTIVE: Although AMH has been studied as a predictor of live birth in assisted reproductive technology (ART), less is known about the association in women with normal fertility. The objective was to assess a possible association between preconception AMH levels with live birth. DESIGN: Secondary analysis of a multicenter, block-randomized, doubleblind, placebo-controlled clinical trial. MATERIALS AND METHODS: 1228 women attempting pregnancy, aged 18–40 years, with one to two prior pregnancy losses and no history of infertility, pelvic inflammatory disease, tubal occlusion, endometriosis, anovulation, uterine abnormality, or polycystic ovarian syndrome were included. Women were block-randomized by center and eligibility stratum in a 1:1 ratio to preconception-initiated daily low-dose aspirin or placebo. The primary outcome was live birth (defined as a living infant born after 23 weeks’ gestation). AMH was assayed using the Gen II ELISA assay (Beckman-Coulter) at the baseline visit before randomization. AMH was clinically categorized and verified by data analysis into low (<1.25 ng/mL), normal (1.25 to 4.0 ng/mL), and high (>4.0 ng/mL). The Mann Whitney test was utilized to evaluate differences in AMH levels by live birth status. Relative Risk (RR) and 95% confidence intervals (CIs) for live birth by AMH categories were estimated using generalized linear models adjusted for age. RESULTS: Women were followed for up to six menstrual cycles with N¼776 (72%) achieving pregnancy and N¼582 (55%) with a live birth. Women were predominately of white race (95.6%) with a mean age of 28.9 years (standard deviation (SD) 4.7) and body mass index (BMI) of 26.1 (SD 6.5). Among women with a single recent loss, the live birth rate was 53.6% among women with low AMH, 53.9% among normal AMH, and 65.9% among high AMH (p¼0.04). After adjusting for age, women with a single recent loss and high (>4.0 ng/mL) AMH levels had an increased risk of live birth (RR¼1.2, 95% CI 1.1, 1.4) compared to women with normal levels, whereas women with low AMH (<1.25) were not significantly different from women with normal AMH levels (RR¼ 1.04, 95% CI 0.81, 1.3). CONCLUSION: High AMH was associated with live birth in women with normal fertility. These findings are consistent with previous studies in the ART population, confirming that AMH is associated with live birth in women with normal and subfertility. Supported by: Intramural Research Program, DIPHR, PRAE.
O-159 Tuesday, October 21, 2014 05:15 PM MISCARRIAGE RATES IN WOMEN WITH RECURRENT PREGNANCY LOSS AND UNTREATED CHRONIC ENDOMETRITIS. D. McQueen,a C. Perfetto,b F. Hazard,b R. Lathi.b a Obstetrics and Gynecology, University of Chicago, Chicago, IL; bObstetrics and Gynecology, Stanford University, Stanford, CA. OBJECTIVE: To evaluate the prevalence of chronic endometritis (CE) and subsequent pregnancy outcomes in women with recurrent pregnancy loss (RPL). DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 107 women with 2 or more pregnancy losses received an endometrial biopsy as part of their work up for RPL. Hematoxylin and eosin (H&E) staining was performed and treatment decisions were made based on the identification of plasma cells by morphology alone. Immunohistochemical staining was later applied to archived paraffin samples in order to detect CD138 (syndecan-1), an antibody marker of plasma cells. A single blinded pathologist reviewed all slides. CE was defined as the presence of at least 1 plasma cell per high power field by CD138 staining. Charts were
FERTILITY & STERILITYÒ
TABLE 1. Group Characteristics
Miscarriage Rate Mean BMI (SD) Mean Age (SD) Mean number of prior losses (SD) RPL work up Unexplained Uterine Parental Translocation APA
CE (n¼30)
No CE (n¼27)
P value
36.7% (11/30) 24.0 (4.5) 36.0 (5.0) 3.0 (1.3)
14.8% (4/27) 23.3 (3.5) 34.9 (4.2) 2.7 (0.8)
0.08 0.52 0.38 0.31
83.3% (25/30) 3.3% (1/30) 6.7% (2/30) 6.7% (2/30)
74.1% (20/27) 11.1% (3/27) 7.4% (2/27) 7.4% (2/27)
0.52 0.34 1 1
CE defined as positive CD138 staining on IHC.
reviewed to evaluate the outcome of the next clinical intrauterine pregnancy. RESULTS: The use of CD138 staining to identify women with CE resulted in a significantly higher prevalence of CE compared to the use of H&E staining and morphology alone, 56% (60/107) vs 13% (14/107) (p ¼ <0.01). 11 women received antibiotic treatment for CE and were excluded, leaving 51 women with untreated CE and 45 women without CE for outcome analysis. At least one subsequent pregnancy was documented in 71% (36/51) of women with untreated CE and 73% (33/45) of women without CE (NS). 6 pregnancies were lost to follow up in each group. The miscarriage rate in the next clinical intrauterine pregnancy was 36.7% (11/30) in women with untreated CE vs 14.8% (4/27) in women without CE (NS). Age, BMI, results of RPL evaluation and number of prior losses were not significantly different. CONCLUSION: There was a high prevalence of CE when it was defined as the presence of CD138 positive plasma cells. CD138 may provide increased sensitivity when screening for CE compared to H&E staining and morphologic evaluation alone. Although we did not see a statistically significant difference in miscarriage rates between women with untreated CE and women without CE, this subject deserves further study with a larger study sample.
O-160 Tuesday, October 21, 2014 05:30 PM TROPHOBLAST RETRIEVAL AND ISOLATION FROM THE CERVIX (TRIC) TO PREDICT RISK FOR SPONTANEOUS ABORTION. R. Fritz,a J. Bolnick,a A. Bolnick,a M. Modi,a B. Kilburn,a M. P. Diamond,b D. R. Armant.1,c aWayne State University, Detroit, MI; bGeorgia Regents University, Augusta, GA; cNational Institute of Child Health & Human Development, Bethesda, MD. OBJECTIVE: Spontaneous abortion (spAb) is one of the most common pregnancy complications and is associated with abnormal trophoblast invasion. Our objective was to evaluate whether abnormal protein expression occurs in first trimester extravillous trophoblast cells isolated from
Proteins Altered by Spontaneous Abortion
ENG*
FLT-1*
AFP*
PP14*
Control 20.44 5.61 18.50 4.05 11.68 1.93 54.77 6.71 Patients Spontaneous 70.71 14.60 79.27 15.01 52.23 5.94 38.19 5.33 Abortion P Value 0.009 0.001 <0.001 0.02 * Mean Fluorescence Intensities SEM
e55
O-159 Tuesday, October 21, 2014 05:15 PM MISCARRIAGE RATES IN WOMEN WITH RECURRENT PREGNANCY LOSS AND UNTREATED CHRONIC ENDOMETRITIS. D. McQueen,a C. Perfetto,b F. Hazard,b R. Lathi.b a Obstetrics and Gynecology, University of Chicago, Chicago, IL; bObstetrics and Gynecology, Stanford University, Stanford, CA. OBJECTIVE: To evaluate the prevalence of chronic endometritis (CE) and subsequent pregnancy outcomes in women with recurrent pregnancy loss (RPL). DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 107 women with 2 or more pregnancy losses received an endometrial biopsy as part of their work up for RPL. Hematoxylin and eosin (H&E) staining was performed and treatment decisions were made based on the identification of plasma cells by morphology alone. Immunohistochemical staining was later applied to archived paraffin samples in order to detect CD138 (syndecan-1), an antibody marker of plasma cells. A single blinded pathologist reviewed all slides. CE was defined as the presence of at least 1 plasma cell per high power field by CD138 staining. Charts were
FERTILITY & STERILITYÒ
TABLE 1. Group Characteristics
Miscarriage Rate Mean BMI (SD) Mean Age (SD) Mean number of prior losses (SD) RPL work up Unexplained Uterine Parental Translocation APA
CE (n¼30)
No CE (n¼27)
P value
36.7% (11/30) 24.0 (4.5) 36.0 (5.0) 3.0 (1.3)
14.8% (4/27) 23.3 (3.5) 34.9 (4.2) 2.7 (0.8)
0.08 0.52 0.38 0.31
83.3% (25/30) 3.3% (1/30) 6.7% (2/30) 6.7% (2/30)
74.1% (20/27) 11.1% (3/27) 7.4% (2/27) 7.4% (2/27)
0.52 0.34 1 1
CE defined as positive CD138 staining on IHC.
reviewed to evaluate the outcome of the next clinical intrauterine pregnancy. RESULTS: The use of CD138 staining to identify women with CE resulted in a significantly higher prevalence of CE compared to the use of H&E staining and morphology alone, 56% (60/107) vs 13% (14/107) (p ¼ <0.01). 11 women received antibiotic treatment for CE and were excluded, leaving 51 women with untreated CE and 45 women without CE for outcome analysis. At least one subsequent pregnancy was documented in 71% (36/51) of women with untreated CE and 73% (33/45) of women without CE (NS). 6 pregnancies were lost to follow up in each group. The miscarriage rate in the next clinical intrauterine pregnancy was 36.7% (11/30) in women with untreated CE vs 14.8% (4/27) in women without CE (NS). Age, BMI, results of RPL evaluation and number of prior losses were not significantly different. CONCLUSION: There was a high prevalence of CE when it was defined as the presence of CD138 positive plasma cells. CD138 may provide increased sensitivity when screening for CE compared to H&E staining and morphologic evaluation alone. Although we did not see a statistically significant difference in miscarriage rates between women with untreated CE and women without CE, this subject deserves further study with a larger study sample.
O-160 Tuesday, October 21, 2014 05:30 PM TROPHOBLAST RETRIEVAL AND ISOLATION FROM THE CERVIX (TRIC) TO PREDICT RISK FOR SPONTANEOUS ABORTION. R. Fritz,a J. Bolnick,a A. Bolnick,a M. Modi,a B. Kilburn,a M. P. Diamond,b D. R. Armant.1,c aWayne State University, Detroit, MI; bGeorgia Regents University, Augusta, GA; cNational Institute of Child Health & Human Development, Bethesda, MD. OBJECTIVE: Spontaneous abortion (spAb) is one of the most common pregnancy complications and is associated with abnormal trophoblast invasion. Our objective was to evaluate whether abnormal protein expression occurs in first trimester extravillous trophoblast cells isolated from
Proteins Altered by Spontaneous Abortion
ENG*
FLT-1*
AFP*
PP14*
Control 20.44 5.61 18.50 4.05 11.68 1.93 54.77 6.71 Patients Spontaneous 70.71 14.60 79.27 15.01 52.23 5.94 38.19 5.33 Abortion P Value 0.009 0.001 <0.001 0.02 * Mean Fluorescence Intensities SEM
e55