Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding.

Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-related bleeding. These findings support the role of the bFGF ligand-receptor system in the pathogenesis of leiomyoma-related bleeding and may have implications for fertility and contraception since the differential FGFR1 expression occurs in the peri-implantation period of the early luteal phase.

Perinatal consequences of maternal hypothyroidism in early pregnancy and inadequate replacement.

UNLABELLED: Maternal hypothyroidism may be associated with a variety of pregnancy complications. OBJECTIVE: We have evaluated the perinatal consequences of maternal hypothyroidism in early and late gestation. DESIGN: Retrospective study of pregnant women, with quasi-experimental design comparing different subjects. SUBJECTS: Forty-three pregnancies in 42 women with hypothyroidism--either biochemically hypothyroid or with a history of hypothyroidism on adequate replacement--and no other preexisting medical conditions. MEASUREMENT: Free thyroxine index (FTI), TSH, and haematocrit at initial antepartum presentation and near term gestation. Pregnancy outcome variables including: rate of Caesarean section performed for fetal distress in labour, neonatal weight percentile, and gestational age at birth. RESULTS: Of 42 hypothyroid pregnancies, six were complicated by fetal distress in labour leading to Caesarean section. Five of these six were severely hypothyroid (defined as FTI < or = 0.6 (normal range 1.1-4.4)) on initial antepartum presentation. In contrast, of the 36 pregnancies without fetal distress, only four initially presented severely hypothyroid (P < 0.001). Conversely, 56% (5/9) of pregnancies which initially presented severely hypothyroid were subsequently complicated by Caesarean section for fetal distress in labour. This compared to 3% (1/33) among those who presented either mildly hypothyroid or euthyroid on replacement (P < 0.0001). Fetal distress correlated with low FTI (P < 0.001) and high TSH at initial presentation. However, it was independent of FTI near term. A relation between fetal distress and TSH near term did not reach statistical significance. Fetal distress also correlated with low maternal haematocrit on admission to labour and delivery (P < 0.05), but was independent of haematocrit and gestational age at initial presentation, neonatal weight percentile, and gestational age at birth. CONCLUSIONS: Severe maternal hypothyroidism early in gestation is strongly associated with fetal distress in labour. This suggests that (1) inadequate maternal replacement leads to fetal distress and (2) maternal thyroid status in early gestation may exert irreversible effects on the fetus, the placenta, and/or on subsequent maternal adaptations to pregnancy. Early adequate replacement therapy is especially prudent in pregnant women presenting with severe hypothyroidism.