Hypertension is associated with an increased risk for hysterectomy: a Danish cohort study

OBJECTIVE: To assess whether hypertension is a risk factor for hysterectomy, endometrial resection, and myomectomy. STUDY DESIGN: Self-report questionnaires were collected from 81% of 1959 Danish women aged 30 or 40 years selected at random in 1976-1991, in four different cohort studies. Baseline data included standardized information about cardiovascular diseases, hypertension, use of medicine, gynecologic history, social background, and life style factors. Weight, height and blood pressure were measured. The women were followed via central registers to assess the incidence of hysterectomy, endometrial resection, and myomectomy performed for benign diagnoses. Cox regression analyses were used to control for confounding. RESULTS: The average time to follow-up was 15 years, and 135 operations performed for benign diagnoses were identified. Women with a history of hypertension had a double risk of having an operation compared to women without hypertension, independent of confounders. CONCLUSION: Hypertension seems to be a risk factor for hysterectomy performed for benign diagnoses, and thus contributes to women undergoing hysterectomy having an increased risk of cardiovascular diseases. It might be relevant to pay increased attention to the blood pressure in candidates for hysterectomy, as optimal antihypertensive treatment could decrease their otherwise increased risk of cardiovascular disease years after hysterectomy.     

DNA aneuploidy is associated with increased mortality for stage I endometrial cancer

OBJECTIVE: The current study was undertaken to determine if DNA ploidy is a useful prognostic variable for predicting recurrence in stage I endometrial cancer. For cancer of the endometrium, survival following recurrence may depend on a number of factors, including the pattern of recurrence and the response to second line treatment. Previous studies have demonstrated a worse survival for patients with DNA aneuploid tumors. It remains unclear, however, whether this is necessarily due to a higher risk of recurrence. This study was undertaken to assess DNA ploidy and risk of recurrence in patients with stage I endometrial cancer. METHODS: This is a retrospective study of surgically treated patients with stages IB and IC endometrial cancer treated from 1992 to 2000. All patients underwent definitive surgery, including staging lymphadenectomy. None of the patients received postoperative treatment. DNA ploidy was determined using flow cytometry and image analysis. Grade, lymph-vascular space invasion, stage (stage IB versus IC), and DNA ploidy were analyzed with regard to recurrence and survival. RESULTS: There were 100 patients with stages IB and IC endometrial cancer in this analysis. There were 17 recurrences (17%) and 10 patients that died of cancer (10%). Grade 3 and the presence of lymph-vascular space invasion were associated with increased risk of recurrence; DNA aneuploidy and stage were not. Grade, lymph-vascular space invasion, and DNA ploidy were associated with survival. These findings indicate that DNA aneuploidy does not increase the risk of disease recurrence but is associated with overall survival. CONCLUSION: Although the recurrence risk is not higher for patients with surgical stage I endometrial cancer and aneuploid tumors, overall mortality remains higher.     

The prohibitin 3' untranslated region polymorphism is not associated with risk of ovarian cancer

OBJECTIVE: The 3' untranslated region of the prohibitin gene encodes an RNA molecule that arrests cell proliferation between the G(1) and S phases of the cell cycle, and a C-to-T transition within this region creates a variant lacking antiproliferative activity. The T allele was reported to be associated with an increased risk of breast cancer in North American women, specifically in those under age 50 years reporting a first-degree family history of breast cancer. We assessed the association of the prohibitin 3' untranslated region polymorphism with risk of ovarian cancer in the Australian population by case-control comparison. METHODS: We examined 553 cases of epithelial ovarian cancer and 300 unaffected controls to assess whether this polymorphism was associated with risk of ovarian cancer in Australian women. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Genotype distributions were compared by logistic regression. RESULTS: Stratification of the ovarian cancer cases according to tumour behavior (low malignant potential or invasive), histology, grade, stage, or p53 immunohistochemical status failed to reveal any heterogeneity with respect to prohibitin genotype. There was no difference in genotype distribution between cases and controls, with an odds ratio (95% confidence interval) of 0.99 (0.72-1.35) for the CT/TT genotype. CONCLUSION: The prohibitin T variant does not appear to be associated with risk of ovarian cancer in Australian women.     

Ovulation induction and risk of endometrial cancer: a pilot study

OBJECTIVE: To determine whether women with endometrial carcinoma are more likely to have been exposed to fertility drugs, in particular clomiphene, than healthy population controls. STUDY DESIGN: A nationwide case-control, pilot study. About 128 living women 35-64 years old, with a histologically confirmed diagnosis of endometrial carcinoma that was first diagnosed and reported to The Israel Cancer Registry between 1 January 1989 and 31 December 1992 were enrolled. The controls were 255 women from the same dialing areas selected by random digit dialing. A variety of demographic and clinical parameters were compared between cases and controls. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. RESULTS: About 7 women with endometrial carcinoma (5.5%) and 10 healthy controls (3.9%) reported that they had used any fertility drug (crude odds ratio (OR) 1.4; 95% confidence interval (CI) 0.47-4.2). Use of fertility drugs did not meet the criteria for entry into the logistic model. The following parameters were found to be independently associated with endometrial cancer controlling for age, European-American background OR=2.2, (95% CI 1.3-3.7, P=0.004); nulliparity OR=2.7 (95% CI 1.1-6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI> or =27 OR=2.3 (95% CI 1.4-3.9, P=0.001). The use of oral contraceptives and IUD were found to be protective, OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61, P=0.001 and 0.19-0.70, P=0.003, respectively). CONCLUSIONS: We found no evidence that the use of ovulation induction agents, including clomiphene citrate, are associated with a higher risk of endometrial carcinoma. The association between infertility drugs and endometrial carcinoma should be examined in other, larger studies.     

Maternal periodontal disease is associated with an increased risk for preeclampsia

OBJECTIVE: To determine if maternal periodontal disease is associated with the development of preeclampsia. METHODS: A cohort of 1,115 healthy pregnant women were enrolled at less than 26 weeks' gestation and followed until delivery. Maternal demographic and medical data were collected. Periodontal examinations were performed at enrollment and within 48 hours of delivery to determine the presence of severe periodontal disease or periodontal disease progression. Preeclampsia was defined as blood pressure greater than 140/90 on two separate occasions, and at least 1+ proteinuria on catheterized urine specimen. The potential effects of maternal age, race, smoking, gestational age at delivery, and insurance status were analyzed, and adjusted odds ratios for preeclampsia were calculated using multivariable logistic regression. RESULTS: During the study period, 763 women delivered live infants and had data available for analysis. Thirty-nine women had preeclampsia. Women were at higher risk for preeclampsia if they had severe periodontal disease at delivery (adjusted odds ratio 2.4, 95% confidence interval 1.1, 5.3), or if they had periodontal disease progression during pregnancy (adjusted odds ratio 2.1, 95% confidence interval 1.0, 4.4). CONCLUSION: After adjusting for other risk factors, active maternal periodontal disease during pregnancy is associated with an increased risk for the development of preeclampsia.     

Coupling of uterine contractions during labor: a pilot study

A review of 2167 cardiotocograms revealed 53 (2.5%) with coupling of contractions. The data of these patients was compared to the data of 53 patients with cardiotocograms without coupling. In the coupling group there were more primigravidas (45 vs. 18), and a lower incidence of normal vaginal deliveries (11.3% vs. 83.0%). Vacuum and forceps deliveries occurred in 49.1% in the coupling group and cesarean births in 39.6%. The corresponding figures in the control group were 9.4% and 7.5%, respectively. Coupling seems to be a sign of dysfunctional labor associated with a high incidence of abnormal deliveries, but several confounding variables could not be ruled out.     

Invited commentary: a single nucleotide polymorphism in BMP15 is associated with high response to controlled ovarian hyperstimulation

A report has been published which shows a connection between single nucleotide polymorphisms (SNP) in the bone morphogenetic protein 15 (BMP15) gene and ovarian hyperstimulation syndrome (OHSS) in women, similar to reported effects of heterozygous BMP15 point mutations in sheep. The report also describes the near-significant presence of another BMP15 gene SNP correlated with a low response to ovarian stimulation. Previous studies associated two SNP with anovulation or infertility in women with polycystic ovary syndrome, and heterozygosity for another BMP15 SNP resulted in ovarian dysgenesis and hypergonadotrophic failure. In sheep, homozygous point mutations or immunization against BMP15 led to follicular developmental arrest, ovarian dysgenesis and streak ovaries. In mammalian (including human) ovaries BMP15 and its three receptors were shown to be expressed from primary or primordial follicular stages, suggesting that BMP15 might also be involved in activating primordial follicles, and could possibly serve as a marker of follicular reserve. BMP15 also inhibited follicle stimulating hormone receptor expression, was associated with cumulus expansion and its high follicular-fluid concentration was correlated with improved oocyte and embryo quality. Thus, BMP15 seems to be an important regulator of ovarian function. Further studies are needed to clarify its roles in human female fertility.     

Histidine-rich glycoprotein polymorphism and pregnancy outcome: a pilot study

Histidine-rich glycoprotein (HRG) is involved in fibrinolysis and coagulation, the immune system and angiogenesis. These processes are all crucial in establishing and maintaining pregnancy. The primary aim of this pilot study was to determine if HRG affects pregnancy outcome. The secondary aim was to investigate if a specific genetic polymorphism (rs9898 C/T) in the HRG gene is associated with pregnancy results. The polymorphism leads to expression of either a serine or proline residue at position 186 in the protein sequence. In this study, women undergoing IVF were included. The genetic polymorphism in the HRG gene was analysed by Western blot and single nucleotide polymorphism analysis. None of the women homozygous for the serine at residue 186 became pregnant whereas the women homozygous for proline at residue 186 had higher than expected pregnancy rates. As far as is known,this is the first study to show that a specific genetic polymorphism in the HRG gene of a woman affects her chances of becoming pregnant after IVF. The results may be essential in improving advice and IVF treatment for couples with unexplained infertility.     

Preterm birth is associated with increased risk of maternal and neonatal infection.

Much information suggests that maternal reproductive tract infections, both recognized and unrecognized, account for an important and possibly preventable portion of preterm births. If such infections do mediate instances of preterm labor and premature rupture of the membranes (PROM), then associated risks of subsequent maternal and neonatal infections would be increased, even after controlling for confounding variables. To evaluate possible associations between preterm birth and maternal and neonatal infections, we conducted a retrospective study of 9642 births at the University of Colorado Health Sciences Center between July 1980 and June 1985. Clinical chorioamnionitis occurred more frequently among women delivering before term with intact membranes at the onset of labor (5.8% preterm versus 1.7% term) and among women with PROM (26.5% preterm versus 6.7% term). Among the women delivered by cesarean, the incidence of postpartum endometritis was higher in those with preterm PROM than in those with term rupture of membranes. The incidence of neonatal infection increased significantly as the gestational age of the neonates decreased (P less than .01). The rate of culture-proven neonatal infection was significantly higher following PROM (P less than .01) than after birth without PROM. Both neonatal infection and perinatal mortality were increased in association with chorioamnionitis in both preterm and term pregnancies. These consistent observations complement and support suggestions that reproductive tract infection plays a possibly preventable role in the pathogenesis of preterm birth.