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Progesterone supplementation in women with otherwise unexplained recurrent miscarriages.

ABSTRACT: CONTEXT:Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%-1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages. AIMS:The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages. SETTINGS AND DESIGN:This was a 9-year cohort study of women with otherwise unexplained recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary care university hospital. SUBJECTS AND METHODS:Women with at least three unexplained recurrent miscarriages were included in the study. They were divided into three groups according to their initial and 48-h repeat progesterone levels. For women with inadequate endogenous progesterone secretion, natural progesterone vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation. STATISTICAL ANALYSIS:Proportions and 95% confidence intervals calculated for categorical variables and the chi-square test were used to show statistical significance. Medians and ranges were calculated for noncontinuous variables. RESULTS:Pregnancy cycles (n = 203) were analyzed to examine the miscarriage rate following progesterone supplementation. Overall live birth and miscarriage rates were 63% and 36%, respectively. When analyzed by the number of previous miscarriages there was a reduction in the miscarriage rate following progesterone supplementation in women with 4 previous miscarriages when compared with historical data. CONCLUSIONS:Progesterone supplementation may have beneficial effects in women with otherwise unexplained recurrent miscarriages.

SUBMITTER: Hussain M

PROVIDER: S-EPMC3604830 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Progesterone supplementation in women with otherwise unexplained recurrent miscarriages.

Hussain Munawar M El-Hakim Samawal S Cahill David J DJ

Journal of human reproductive sciences 20120901 3

<h4>Context</h4>Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%-1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages.<h4>Aims</h4>The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages.<h4>Settings and design</h4>This was a 9-year coho ...[more]

PMID: 23533097

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Project description:BackgroundWe recently demonstrated the increased abundance of anti-trophoblast antibodies (ATAB) in sera of patients with unexplained recurrent miscarriages (uRM). Further, the ATAB-positive sera bound to JEG-3 human choriocarcinoma cells in vitro, resulting in decreased productions of β-human chorionic gonadotropin (β-hCG) and progesterone in these cells. However, the specific antigenic epitopes of ATAB have remained unknown. Therefore, it was the aim of this study to determine specific targets of ATAB in uRM patients.MethodsPotential targets of ATAB were analyzed by 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry, and thereby identifying α-Enolase (ENO1). ATAB targeting of ENO1 was further confirmed in a competitive binding assay. Levels of anti-ENO1 antibodies as well as β-hCG and progesterone were quantified with enzyme-linked immunosorbent assay (ELISA). Additionally, expression of ENO1 was analyzed in first trimester placentas by immunohistochemistry and immunofluorescence analysis.FindingsWe here identified ENO1 as a prominent target of ATAB. Serum levels of anti-ENO1 antibodies were increased in ATAB-positive compared to ATAB-negative patients. Further, increased expression of ENO1 and its co-expression with β-arrestin was found in the extra villous trophoblasts of uRM patients in first trimester placentas. In vitro, anti-ENO1 antibodies decreased the secretion of β-hCG and progesterone in JEG-3 and primary human villous trophoblast cells.InterpretationSerum anti-ENO1 antibodies might be an autoimmune biomarker for uRM. Targeting the formation of anti-ENO1 antibodies or inhibition of ENO1 expression could potentially represent therapeutic strategies for these patients. FUND: All authors declare no conflict of interest. Yao Ye was supported by the China Scholarship Council. Hellen Ishikawa-Ankerhold and Christian Schulz were supported by the SFB914, projects Z01 and A10. None of the rest authors has any conflict of interest to declare.

Dataset Information

Progesterone supplementation in women with otherwise unexplained recurrent miscarriages.

Publications

Progesterone supplementation in women with otherwise unexplained recurrent miscarriages.

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