A. Dokras

Meta-Analysis of Intrauterine Device Use and Risk of Endometrial Cancer

PURPOSE We sought to study the association between intrauterine device (IUD) use and endometrial cancer. METHODS A comprehensive search of literature published through April 2007 was conducted, studies reviewed, and data abstracted. Data from ten studies were pooled and analyzed using both fixed- and random-effects models to examine the association of ever use of an IUD and endometrial cancer. RESULTS Based on the random effects model, a protective crude association between IUD use and endometrial cancer was observed (odds ratio [OR] = 0.39; 95% confidence interval [CI] = 0.29-0.51; heterogeneity p < 0.001) with a pooled adjusted risk of OR = 0.54 (95% CI, 0.47-0.63; heterogeneity p = 0.40). A decreased risk of endometrial cancer also was seen for increased years of IUD use (OR for 5 years of use 0.88; 95% CI = 0.84-0.92; n = 5; heterogeneity p = 0.14), increased years since last IUD use (OR for 5 years of use 0.91; 95% CI, 0.86-0.95; n = 4; heterogeneity p = 0.02), and increased years since first IUD use (OR for 5 years of use 0.89; 95% CI, 0.83-0.95; n = 4; heterogeneity p = 0.04). CONCLUSIONS Our results suggest that nonhormonal IUD use may be associated with a decreased risk for endometrial cancer; however, the exact mechanism for this association is unclear. Future investigations should address the difference in the proposed association by specific type of IUDs.

Regulation of Human Cytotrophoblast Morphogenesis by Hepatocyte Growth Factor/Scatter Factor

Abstract In vitro morphogenesis of epithelial cells to form tube-like structures is regulated by hepatocyte growth factor-scatter factor (HGF/SF). The placenta is a rich source of HGF/SF, and its absence in mice has been shown to lead to impaired placental growth and embryonic death. There is no information in the literature regarding in vitro morphogenesis of human cytotrophoblasts or the effect of HGF/SF on this process. In this study, cytotrophoblasts were isolated from human placentae obtained from all three trimesters of gestation and cultured on the recombinant basement membrane matrix (Matrigel). Under these conditions, cytotrophoblasts participated in morphogenetic events including formation of spheroid-like structures, radial linear processes with branching, and invaded Matrigel and formed large, tube-like structures. The presence of a developing lumen was documented in the linear projections arising from spheroids and in the tube-like structures by both confocal and transmission electron microscopy. Immunohistochemistry was used to characterize the phenotype of the cells, and staining with anti-cytokeratin and anti-E-cadherin antibodies confirmed the presence of cytotrophoblasts in both the spheroids and tube-like structures. Recombinant HGF (rHGF) significantly increased the invasive activity of cytotrophoblasts isolated from the first and second (P < 0.001) and third trimesters (P < 0.01). In addition, rHGF significantly increased the percentage of spheroids with branching processes in the first and second trimesters (P < 0.05). Anti-HGF antibody inhibited both these effects in a dose-dependent manner, indicating the specificity of the above findings. This study provides new evidence indicating that HGF/SF regulates invasion and branching morphogenesis of cytotrophoblasts throughout gestation, with maximum effects in the first and second trimester. These findings may help to elucidate the importance of the reduced expression of HGF/SF identified in placentae from women with preeclampsia or intrauterine growth restriction and suggest that HGF/SF may serve as an important candidate in therapeutic intervention strategies.

Bilateral undescended ovaries: association with infertility and treatment with IVF

OBJECTIVE To describe the clinical findings in a patient with bilateral undescended ovaries and infertility who was successfully treated by IVF. DESIGN Case report. SETTING University hospital. PATIENT(S) A 35-year-old woman with bilateral undescended ovaries. INTERVENTION(S) Hysterosalpingography, laparoscopy, and an IVF cycle. MAIN OUTCOME MEASURE(S) Anatomic description and pregnancy test. RESULT(S) This patient conceived and delivered a twin gestation after laparoscopic retrieval of oocytes and transfer of two blastocysts. CONCLUSION(S) Bilateral undescended ovaries is a rare condition that can be associated with infertility but can be successfully treated by IVF.

Testosterone levels in pregnant women correlate with the insulin response during the glucose tolerance test

OBJECTIVE To evaluate the association between insulin/insulin-like growth factor I (IGF-I) systems and androgen levels in pregnancy. DESIGN Prospective cohort study. SETTING Yale University School of Medicine. PATIENT(S) Pregnant women undergoing a 100-gram 3-hour glucose tolerance test (GTT). INTERVENTION(S) Serum samples collected during GTT were analyzed for insulin, androgens, free IGF-I, insulin-like growth factor-binding protein (IGFBP) 1, and estriol. MAIN OUTCOME MEASURE(S) Observing the relationship between insulin/IGFs and androgen levels. RESULT(S) The insulin area under the curve (I(AUC)) during GTT correlated positively with total T and free T, but not with dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), or estriol. The peak insulin values (I(max)) during GTT also correlated positively with total T and free T, but not with DHEA, DHEAS, or estriol. There was no statistically significant correlation of T levels with free IGF-I, IGFBP-1, glucose, DHEAS, or estriol. Multiple linear regression analysis modeling showed that I(AUC) and I(max) did have a statistically significant correlation with free T levels. CONCLUSION(S) This study demonstrates for the first time that I(AUC) and I(max) measured in hyperinsulinemic states such as pregnancy correlate with T levels. In view of the lack of correlation between insulin and DHEAS or estriol, insulin-related T production during pregnancy is likely of ovarian origin.