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Abstract

STUDY QUESTION

What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies?

SUMMARY ANSWER

The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy.

WHAT IS KNOWN ALREADY

There have been no data in the literature on the effect of letrozole in termination of human pregnancies.

STUDY DESIGN, SIZE, DURATION

This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT–PCR analysis of ERα and estrogen receptor-β (ERβ), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERβ, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis.

MAIN RESULTS AND THE ROLE OF CHANCE

Real-time RT–PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): −0.643–8.443] in the letrozole group versus 4.714 (95% CI: 1.776–7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333–1.069) in the letrozole group versus 1.774 (95% CI: 1.07–2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103–119) in the letrozole group versus 217 (95% CI: 214–290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98–105) in the letrozole group versus 210 (95% CI: 200–286) in the control group, in cytotrophoblasts; P = 0.004], while the expression levels of ERβ, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the two groups.

LIMITATIONS, REASONS FOR CAUTION

Only the placentae from the second trimester termination of pregnancy were collected in this study. Information from first trimester terminations is still lacking.

WIDER IMPLICATIONS OF THE FINDINGS

The results shed some light on the mechanism of action of letrozole pretreatment in termination of pregnancies.

STUDY FUNDING/COMPETING INTEREST(S)

This study was funded by the GRF/RGC and CRCG grants of the University of Hong Kong.

TRIAL REGISTRATION NUMBER

HKClinicalTrials.com with trial number HKCTR-695.

letrozole pretreatment, misoprostol, second trimester, termination of pregnancy, steroid receptors
© The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]
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Original Articles > Early Pregnancy
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