Aberrant HOXA10 Methylation in Patients With Common Gynecologic Disorders: Implications for Reproductive Outcomes.

HomeoboxA10 (HOXA10) is a transcription factor that is crucial for the development and patterning of the uterus during embryogenesis. In the adult endometrium, HOXA10 expression is regulated by steroid hormones and embryonic signals. Expression of sufficient HOXA10 messenger RNA is essential to endometrial receptivity and embryo implantation. Aberrant methylation is believed to alter the expression of HOXA10. Methylation of this gene may be associated with decreased fertility, implantation defects, and/or reproductive wastage seen in certain disease states that affect the female reproductive tract. This study describes the differences in methylation patterns of HOXA10 gene in uterine myomas, endometriosis, uterine septum, Asherman syndrome, or uterine polyps of women undergoing hysteroscopic surgery. In the endometrium of uteri with polyps, submucosal myomas, and intramural myomas, there were CpG sites within the HOXA10 gene that were highly methylated compared to controls. The HOXA10 gene in women with endometriosis was hypomethylated compared to controls. DNA methylation may be a common molecular mechanism that results in reproductive dysfunction seen in gynecologic disease.

A randomized trial to determine the distribution of four topical gel formulations in the human vagina.

BACKGROUND: There is an urgent need for the development of a topical microbicide to protect against sexually transmitted infections. We compared distribution and acceptability of four different gel formulations to be used as a vehicle for a microbicide. STUDY DESIGN: This is a randomized, double-blind comparative study. Six women tested each of the four gels at two different time points. Magnetic resonance imaging (MRI) scans were taken both within 10-15 min following intravaginal gel insertion and 4 h following gel insertion, before and after simulated intercourse at both time points. RESULTS: Vaginal surface contact immediately after insertion ranged from 68% to 92%. Simulated intercourse increased surface contact for all gels (range, 90-106%). After 4 h, surface contact ranged from 86% to 102%. Simulated intercourse at that time resulted in decreased coverage for two gels and increased coverage for two gels. One gel was noted to have consistent broad coverage of the vagina both immediately and 4 h after insertion, increased coverage with simulated intercourse at both time points and the lowest standard deviation of disruption at all time points. CONCLUSION: MRI used in combination with qualitative assessments of acceptability can be used to select optimal gels for use as vehicles for potential spermicides or microbicides. We conclude that a gel consisting of 3% hydroxypropyl methylcellulose and 1.5% of methyl cellulose is the most promising candidate gel.

Prediction of outcome in women with symptomatic first-trimester pregnancy: focus on intrauterine rather than ectopic gestation.

OBJECTIVE: Symptoms of vaginal bleeding and abdominal pain are common in cases of ectopic pregnancy (EP), spontaneous abortions (SAB), and complications of an intrauterine pregnancy (IUP). It is important to determine if efforts should focus on differentiating EP from an IUP (IUP + SAB) or a viable IUP from a nonviable gestation (EP + SAB) in women at risk for EP. METHODS: This is a retrospective cohort study of women who presented with bleeding or pain or both during the first trimester of pregnancy. The cohort was divided into subjects diagnosed with IUP vs. (EP + SAB). The same cohort was then divided into subjects diagnosed with EP vs. (IUP + SAB). Logistic regression models based on risk factors for both outcomes (EP vs. [IUP + SAB] and IUP vs. [EP + SAB]) were obtained. ROC curves as well as Hosmer-Lemeshow goodness of fit and Akaike's information criterion (AIC) were used. RESULTS: Overall, 18.1% (n = 367) of the women were diagnosed with EP, 58.8% (n = 1192) were diagnosed with an SAB, and 23.1% (n = 467) had an ongoing IUP. The area under the ROC curve for the model IUP vs. (EP + SAB) was statistically greater than the model EP vs. (IUP + SAB), p < 0.001. AIC and Hosmer-Lemeshow goodness of fit confirmed the better accuracy of the model comparing IUP vs. (EP + SAB). CONCLUSIONS: Information collected at initial presentation from women at risk for EP to be used for building prediction rules should focus on differentiating a viable from a nonviable pregnancy rather than attempting to distinguish an extrauterine from an intrauterine pregnancy. However, this distinction should not affect current clinical care.

Ectopic pregnancy: diagnosis and management.

The incidence of ectopic pregnancies is increasing, which may be related to better diagnostic tools as well as the increasing use of assisted reproductive technologies. However, the signs and symptoms of ectopic pregnancy can be similar to other complications of early pregnancy such as miscarriage. Diagnosis often requires serial human chorionic gonadotropin levels along with ultrasound and, in some cases, dilation and curettage. Once a diagnosis has been made, treatment options include medical therapy with methotrexate and surgery, which can often be performed via the laparoscope. Fertility rates after therapy are similar for both medically and surgically treated patients.

The accuracy of women performing vaginal pH self-testing.

OBJECTIVE: To determine if women could measure their vaginal pH as accurately as could physicians. METHODS: Each participant measured her vaginal pH using a swab, completed a survey, and then was seen by her physician, who also performed a vaginal pH test. The physician did not have access to the patient's pH reading; only the study coordinator recorded patient results. Accuracy of patient measurements compared with physician results was analyzed by the kappa statistic. RESULTS: A total of 161 women were enrolled in the study. The average difference between the patients' pH readings and the physicians' readings was <0.5. Overall, 85% of the patients' readings were in agreement with the physicians' readings, and the kappa statistic was 0.6. CONCLUSIONS: Study participants could accurately measure vaginal pH through self-testing. Vaginal pH self-testing may be a convenient tool to help women determine whether they should use an over-the-counter (OTC) antifungal medication or go to a physician for diagnostic workup.

Screening for coagulation disorders in adolescents with abnormal uterine bleeding.

STUDY OBJECTIVE: To determine if screening for coagulation disorders was routinely performed during the evaluation of adolescents with abnormal uterine bleeding. DESIGN: A retrospective chart review. Data were analyzed using the chi-square test. P < 0.05 was considered significant. SETTING: Outpatient clinics of an academic center. PARTICIPANTS: Eligible charts of patients age eighteen years and under with abnormal uterine bleeding who were evaluated either by pediatric gynecologists, gynecologists, or pediatricians. INTERVENTIONS: A chart review. MAIN OUTCOME MEASURES: Data on provider type, documented patient history and laboratory tests ordered. RESULTS: In our review, 43% (n= 36) of patients were evaluated by gynecologists, 38% (n=32) by pediatricians and 19% (n=16) by pediatric gynecologists. The mean age of patients whose charts were reviewed was 15 years. Overall 36.6% (n=30) of providers indicated that they screened for a bleeding disorder by documenting at least one screening question in the patient's history. There was a significant difference among providers with 68.8% (n=11) of pediatric gynecologists documenting at least one screening question, compared to 31.4% (n=11) of gynecologists and 25.8% (n=8) of pediatricians (P < 0.05). Overall 14.6% (n=12) of subjects were screened for a coagulation disorder with laboratory testing. CONCLUSIONS: The majority of adolescents with abnormal uterine bleeding were not screened for bleeding disorders. The frequency of evaluation for blood dyscrasias varied by specialty.

Analysis of insulin-stimulated insulin receptor activation and glucose transport in cultured skeletal muscle cells from obese subjects.

Obesity is associated with impaired insulin-stimulated glucose disposal in the skeletal muscle, but whether this is an intrinsic or acquired factor is unknown. In many patients with type 2 diabetes mellitus (T2D) and their nondiabetic relatives, who have a genetic predisposition for diabetes, insulin resistance is maintained in cultured muscle cells. To study the association of obesity with defects in insulin action, we investigated insulin stimulation of both insulin receptor (IR) autophosphorylation and subsequent glucose transport in primary skeletal muscle cell cultures obtained from both nonobese and obese nondiabetic subjects. In these 2 groups, there was no difference in the ability of insulin to induce autophosphorylation of the IR, phosphorylation of the downstream serine kinase Akt/PKB, or stimulation of glucose transport. Moreover, there were no major differences in cultured muscle cell content of either the IR, the IR antagonist PC-1, or GLUT 1 and GLUT 4. These data therefore indicate that the insulin resistance associated with obesity is not maintained in cultured muscle cells and suggest that this insulin resistance is an acquired feature of obesity.

Impact of preventive osteoporosis education on patient behavior: immediate and 3-month follow-up.

OBJECTIVE: To evaluate the effectiveness of an educational video on osteoporosis at increasing knowledge and preventive health behaviors. DESIGN: A total of 195 women between 35 and 80 years of age without documented osteopenia or osteoporosis, who presented for a gynecological examination in an outpatient setting, were enrolled. Of this number, 98 women were randomly assigned to the intervention group that viewed the video before their office visit, and 97 women were assigned to a control group and saw their physician in a routine manner. After their visit, all participants answered a questionnaire that assessed their knowledge of osteoporosis and baseline health-related behaviors. Three months later, a follow-up questionnaire was mailed to participants, eliciting whether preventive behavior had commenced. Frequencies were compared using the Fisher exact test (2-tailed). Continuous variables were analyzed using the Student's t test. RESULTS: The two groups had no statistically significant differences in demographics. The intervention group scored a mean of 92% compared with a mean of 80% in the control group on the initial osteoporosis assessment questionnaire (P < 0.001). The 3-month follow-up questionnaire demonstrated that significantly more women in the intervention group started taking calcium supplements (26.5% v 4.9%; P < 0.001), started taking vitamin D supplements (20.6% v 6.6%; P = 0.02), started a program of weight-bearing exercise (13.3% v 1.7%; P = 0.03), and started hormone therapy (8% v 1%; P = 0.04). CONCLUSION: The use of an educational video on osteoporosis seems to improve patient knowledge and may positively impact health-related behaviors.