Fetal myocardial morphological and functional changes associated with well-controlled gestational diabetes

Objective

To make a global evaluation of the fetal myocardial changes in a well-controlled gestational diabetic population.

Study design

Twenty-four pregnant well-controlled diabetic patients were selected. Sixteen normal pregnancies were randomly collected as a control group. Measurements of morphological and functional myocardial parameters were performed. Data from the left ventricular outflow tract and peripheral Doppler data were obtained.

Result

The thickness of the interventricular septum was increased in diabetic pregnancies (p < 0.001). Tricuspid E/A index was the only functional parameter showing a significant variation, with lower values in diabetic pregnancies. Doppler parameters from the left ventricular outflow tract and peripheral Doppler waveforms were similar between groups.

Conclusion

A tendency towards interventricular septum hypertrophy was observed even in well-controlled diabetic pregnancies. Mild hypertrophic cardiac changes were not associated with abnormal cardiac function or signs of left ventricular outflow obstruction, although minor changes in right ventricular diastolic function were recorded.     

Reproductive outcome following resectoscope metroplasty in women having a complete uterine septum with double cervix and vagina

Objective

To evaluate reproductive outcomes in women with complete uterine septum with double cervix and vagina following resectoscope metroplasty.

Methods

The pregnancy outcomes of 21 women who underwent vaginal and uterine septum resection were compared with those of 15 untreated women with similar clinical characteristics. The Fisher exact test and the Mann-Whitney test were used for statistical analysis.

Results

Cycle fecundity was better (33.4% ± 28.5% vs 12.2% ± 4.7%; P = 0.046), the rate of term delivery significantly increased (P < 0.05), and the rate of spontaneous abortion decreased (P < 0.05) in the treatment group.

Conclusion

Resectoscope metroplasty was found to improve the pregnancy outcomes of women having primary infertility or a history of pregnancy loss associated with a complete uterine septum with double cervix and vagina.     

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective

To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters.

Study design

We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS.

Results

From all patients, 30 (56.6%) were responders and 23 (43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015).

Conclusion

In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects.     

Serum HE4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women

Objective

Human epididymal secretory protein E4 (HE4) is a new promising tumor marker developed for the diagnostics and follow up of ovarian cancer. It has yet to become widely accepted in clinical practice, and its biological properties have not been inclusively studied. The aim of this study was to investigate whether serum HE4 concentration varies within the normal menstrual cycle and whether common gynecological hormonal treatments have an effect on HE4 values.

Methods

Our study population consisted of 180 women, including 126 endometriosis patients and 54 healthy women. We measured their serum HE4 and CA125 concentrations and evaluated the effect of the menstrual cycle and the possible hormonal medication on these marker concentrations.

Results

We found no significant variation in serum HE4 concentrations in samples taken at different phases of the menstrual cycle. The median HE4 concentrations in proliferative, secretory and menstrual phase were 41.5, 45.1 and 35.3 pM in healthy women, and 43.4, 44.3 and 43.0 pM in endometriosis patients, respectively. The use of combined estrogen and progestin contraceptives did not affect serum HE4 levels significantly.

Conclusions

The present study shows that the HE4 measurement in healthy premenopausal women as well as in women with endometriosis can be carried out at any phase of the menstrual cycle, and irrespective of hormonal medication, extending the benefits of HE4 use in clinical practice.     

Regression of endometrial autografts in a rat model of endometriosis treated with etanercept

Objective

To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in the rat endometriosis model.

Study design

A randomized, placebo-controlled, blinded study using rat endometriosis model. After the peritoneal implantation of endometrial tissue, twenty-eight Wistar female rats were randomized to two equal intervention groups: the control group and the etanercept-treated group. After measuring implant volume, pretreatment blood and peritoneal fluid samples were obtained. A vehicle treatment of 2 mL saline to the rats in control group and 0. 4 mg/kg etanercept SC once weekly were administered in the etanercept-treated group. After four weeks treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate preservation of epithelia. Endometrial explants were evaluated immunohistochemically for tumor necrosis factor receptor type 2 (TNFR2). A scoring system was used to evaluate expression grade of TNFR2.

Results

There was not a significant difference in spherical volume between control (131.0 (60.3-501.2)) and treatment groups (72.8 (31.2-149.6)) (p > 0.025). There was a significant change in between the volumes of implants before and after treatment in etanercept group (p < 0.05). At the end of the treatment significant differences among the groups were found in histopathological and immunohistochemical parameters (p < 0.05) also histologic scores and HSCORES were decreased in the treatment group significantly (p < 0.05).

Conclusion

These results indicate that etanercept was found to effectively reduce the development of endometriosis in this experimental rat model.     

Polycystic ovary syndrome and abnormalities in glucose tolerance

Objectives

To compare the prevalence of abnormal glucose tolerance (AGT) among women with polycystic ovary syndrome (PCOS) and controls, and assess risk factors associated with PCOS.

Method

A fasting oral glucose tolerance test after ingestion of 75 g of glucose was administered to 264 women with and 116 without PCOS. Moreover, fasting glucose, insulin, and testosterone levels were measured in the women with PCOS. Body mass index (BMI), waist-to-hip ratio (WHR), and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated for each woman with PCOS.

Results

The AGT prevalence was 14.4% in the PCOS group and 11.2% in the control group (P = 0.17). The women with both PCOS and AGT had significantly higher BMIs, WHRs, testosterone levels, and HOMA-IR values than those with normal glucose tolerance.

Conclusion

While AGT was not associated with PCOS, the women with both PCOS and AGT were significantly more obese, hyperandrogenic, and insulin resistant than those with PCOS and normal glucose tolerance.     

A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Purpose

This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).

Patients and methods

Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.

Results

Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p = 0.342).

Conclusion

A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.     

Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model

Objective

To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model.

Study design

Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n = 8) and Group 2 (pinealectomy + melatonin, n = 8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution + without pinealectomy (n = 6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken.

Results

There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3.

Conclusion

The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin.     

Delivery delay with neoadjuvant chemotherapy for cervical cancer patients during pregnancy: a series of nine cases and literature review

Objective

Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached.

Methods

Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy.

Results

FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression.

Conclusion

During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained.     

Screening history preceding a diagnosis of cervical cancer in women age 65 and older

Objective

To characterize the antecedent screening of women 65 years of age and older diagnosed with cervical cancer.

Methods

Screening histories of women 65 years of age and older who were diagnosed with cervical cancer between 2003 and 2008 were examined utilizing the organization's databases and the regional Cancer Registry. Stopping screening was recommended at age 65 for members who had either 3 consecutive negative Paps or a single negative Pap plus HPV test (“cotest”).

Results

From 2003 through 2008 there were 56 Kaiser Permanente Northern California members 65 years of age and older diagnosed with cervical cancer. During the same time period there were 1,323,100 woman-years of membership in women age 65 and older. The risk of invasive cancer among women age 65 and older was 4.2/100,000/year in 2003-2008. 33 of 56 (59%) had one or more Pap smears prior to diagnosis. Of the 33, 14 women (25%) had 3 consecutive negative Pap smears prior to diagnosis. Three of 46,401 women with 1 or more negative cotests at age 65 and older were subsequently diagnosed with invasive cancer during 132,639 women-years of follow-up (2.3/100,000/year).

Conclusions

Most cervical cancers diagnosed at age 65 and older occur in women who have not met our criteria for stopping screening. A few cancers will continue to occur at age 65 and older despite multiple negative tests, as is true in other age groups. We currently have no evidence that these cancers would be prevented with continued screening at ages 65 and older.     

Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome

Objective

To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling.

Methods

A total of 110 eligible participants were randomly allocated to diagnostic laparoscopy plus metformin therapy (group 1, n = 55) or laparoscopic ovarian drilling (group 2, n = 55). The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment. The χ² test was used for comparisons of ovulation, pregnancy, and abortion rates.

Results

Groups 1 and 2 showed a significant decline in testosterone, insulin-like growth factor-1 (P < 0.001 vs P < 0.001), and luteinizing hormone (P < 0.05 vs P < 0.001), while the glucose to insulin ratio was significantly increased (P < 0.001 vs P < 0.05) compared with baseline. Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1: 76.4% [42/55] vs 58.2% [32/55], P < 0.04; 50.8% [131/258] vs 33.5% [94/281], P < 0.001; and 38.2% [21/55] vs 20.0% [11/55], P < 0.03, respectively. The difference in the early abortion rate between the groups was not statistically significant.

Conclusion

Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.     

Use of fetal colon thickness for auxiliary term dating of pregnancy

Objective

To verify whether fetal colon thickness can be used as a marker for estimating, independent of biometrics and fetal weight percentile, the gestational age (GA) of fetuses between 37 and 40 weeks.

Methods

The study group was 1296 fetuses aged between 33 and 40 weeks. The correlation between GA and colon thickness was assessed by the Pearson correlation test. For term fetuses (≥ 37 weeks), comparisons among the mean colon thickness for different weight percentiles at each GA (in weeks) were made with an analysis of variance test.

Results

A significant relationship was observed between GA and colon thickness (P < 0.001, r² = 0.6). For term fetuses, significant differences were observed among the mean colon thickness values for different weight percentiles at 38 and 39 weeks. Of the 157 term fetuses for which biometrics would have underestimated GA by 2 weeks or more, 126 (80.3%) had a colon thickness equal to, or greater than, 14 mm. This colon thickness was also observed in 52 (70.3%) of term fetuses weighing less than the 10th percentile (n = 74).

Conclusion

The present study suggested that colon thickness might be a good marker for 37 weeks of gestation, and might identify term fetuses for which biometrics has underestimated the GA.     

Outcome of investigations for postmenopausal vaginal bleeding in women under the age of 50 years

Objective

The objective of this study is to determine the incidence of endometrial cancer in young postmenopausal women presenting with vaginal bleeding.

Methods

Cross-sectional study of postmenopausal women presenting with vaginal bleeding in a gynaecological oncology centre in the United Kingdom. All women underwent transvaginal ultrasound scanning (TVS) as the initial investigation tool to evaluate the endometrium. Endometrial biopsy was performed only in cases where endometrial thickness measured equal to or greater than 5 mm. The patients were divided into two groups based on their age: less than 50 years (Group A) and 50 years or older (Group B).

Results

Over a 57-month period, 4454 women were investigated for postmenopausal vaginal bleeding. Of these, 259 (5.8%) women were diagnosed with endometrial carcinoma. 260 (5.8%) women were younger than 50 years. Endometrial biopsy was not performed in 130 women in Group A that had an endometrial thickness measurement of less than 5 mm on ultrasonography. With a median follow-up period of 3 (1-5) years, we found no cases of endometrial cancer in women under the age of 50 that did not undergo endometrial biopsy at the time of initial evaluation. Overall, no cases of endometrial cancer were diagnosed in postmenopausal women under the age of 50 years.

Conclusions

We found no cases of endometrial cancer amongst 260 women presenting with postmenopausal vaginal bleeding under the age of 50 years. These women could be investigated on a less urgent basis depending on the available resources.     

Maternal myo-inositol, glucose, and zinc status is associated with the risk of offspring with spina bifida

Objective

The purpose of this study was to investigate the maternal and children's myo-inositol, glucose, and zinc status in association with spina bifida risk.

Study design

Sixty-three mothers and 70 children with spina bifida and 102 control mothers and 85 control children were investigated. The maternal and child serum myo-inositol, serum glucose, and red blood cell zinc concentrations were measured when the child was between 1 and 3 years old. These data were compared between cases and control subjects. The association with spina bifida was expressed by the ratio of geometric means and by odds ratios and 95% CI for a cutoff value at the extreme 10th percentile of the control group.

Results

The geometric mean of the maternal myo-inositol concentration tended to be 5% (95% CI, −1% to 11%) lower in cases. Interestingly, the odds ratio for the extreme low maternal myo-inositol concentration was 2.6 (95% CI, 1.1-6.0). The glucose and zinc concentrations were significantly higher at 7% (95% CI, 4%-10%) and significantly lower at 5% (95% CI, 0%-9%), in case mothers compared with control mothers. The odds ratios (95% CI) for maternal high glucose and low zinc concentrations were 4.6 (2.0-10.5) and 2.9 (1.2-7.0), respectively. The geometric mean of the myo-inositol concentration tended to be 7% (95% CI, 0%-14%) lower in children with spina bifida; the glucose and zinc concentrations were comparable.

Conclusion

Maternal myo-inositol, glucose, and zinc status are associated with the risk of spina bifida in offspring. Furthermore, the myo-inositol status of the child seems to contribute to this risk as well.     

Histopathology-based combined surgical approach to rectovaginal endometriosis

Objective

To describe a new surgical approach to rectovaginal endometriosis. Rectovaginal endometriosis can be infiltrative or superficial involving the bowel. Only infiltrative disease should be treated by intestinal resection. However, infiltration of endometriosis cannot be confirmed by preoperative imaging techniques.

Methods

A total of 48 women with infiltrative rectovaginal endometriosis were included in this prospective study. Surgery was performed using a newly developed technique. All bowel resections were indicated according to operative findings and not on the basis of preoperative imaging technique results.

Results

The decision for rectosigmoidal resection was based on the results of the intraoperative dissection of the rectovaginal septum. Histologically, infiltration of the ventral bowel wall was confirmed in all cases.

Conclusion

This new surgical technique for the treatment of rectovaginal endometriosis allows precise diagnosis and treatment with low morbidity. A resection of the mesorectum is not necessary because the endometriotic nodules are always located on the antimesenteric surface of the bowel.     

The significance of surgical staging in intermediate-risk endometrial cancer

Objective

The objective was to evaluate rates of nodal disease in endometrial cancer within risk groups based on uterine factors, and to estimate the rate of potential undertreatment and impact on survival if nodal status was unknown.

Methods

This was a population-based retrospective cohort study of endometrioid-type endometrial cancer in British Columbia from 2005 to 2009. All women with a preoperative grade 2/3 cancer underwent hysterectomy, bilateral salpingo-oophorectomy (HBSO) and lymphadenectomy, and those with intermediate- or high-risk disease based on uterine factors after HBSO alone underwent secondary lymphadenectomy. We compared rates of node-positivity and potential undertreatment in each group if nodal status had been unknown (chi-square test), and estimated the survival benefit from lymphadenectomy.

Results

There were 222 women who underwent primary or secondary lymphadenectomy. Median age was 65 (range 38-86) and median number of lymph nodes was 10 (range 2-39). Of the 66 women with intermediate-risk disease (grade 1 or 2 tumor, deep myometrial invasion), 6 had nodal disease (9.1%) and received adjuvant chemotherapy. They remain disease-free after 24 months (range 8-55). They would not have qualified for chemotherapy based on uterine factors alone, and would have been undertreated compared to other risk groups (chi-square p = 0.071). A 1% survival benefit was estimated from lymphadenectomy.

Conclusion

Women with a grade 1 or 2 tumor and deep myometrial invasion have a 9% risk of nodal disease. Lymphadenectomy is significant for this subgroup as they would have been undertreated based on uterine risk factors alone, although the survival benefit is limited.     

Assessment of HPV infection among female university students in Honduras via Roche linear array

Objective

To determine the prevalence of specific types of human papillomavirus (HPV), and the association with possible risk factors, among female university students at university in Honduras.

Methods

In a cross-sectional study, cervical samples from 400 women aged 18-35 years were tested using a Roche HPV linear array to differentiate 37 genotypes of HPV. Associations with risk factors were assessed.

Results

Of the 400 participants, 393 completed the study. HPV DNA was detected in 45% of these women, of whom 73% were infected with high-risk types of HPV and 46% had multiple infections. Overall, 36 HPV genotypes were identified, of which HPV types 16, 51, 84, 66, and 39 were the most common. There was a marked decrease in the prevalence of multiple and high-risk infections with age. The factors that were independently associated with risk of being infected were related to sexual behavior and smoking habits.

Conclusion

The study showed that genital HPV infection is common among sexually active women at university in Honduras. In addition, the Roche linear array was shown to be a valuable tool for HPV genotyping, which will be useful for monitoring the future effectiveness of an HPV vaccine in the population.     

Comparing effectiveness of combined transobturator tension-free vaginal mesh (Perigee) and transobturator tension-free vaginal tape (TVT-O) versus anterior colporrhaphy and TVT-O for associated cystocele and urodynamic stress incontinence

Objective

To evaluate the efficacy and safety of transobturator tension-free vaginal mesh (Perigee) and concomitant transobturator tension-free vaginal tape (TVT-O) for treating cystocele with urodynamic stress incontinence (UDSI).

Study design

A retrospective study of 115 patients with symptomatic stages 2-3 cystocele and UDSI who were treated with a Perigee system (Group I, n = 68) plus TVT-O procedure or traditional anterior colporrhaphy (Group II, n = 47) plus TVT-O procedure. All patients were followed up for more than one year. Objective and subjective symptoms were evaluated at one year postoperatively. Statistical analysis was performed using SPSS software.

Results

The objective cure rates for cystocele at one year were significantly higher in Group I than in Group II (98.5% and 86.9%, P = 0.018), respectively. The cure rates for UDSI in the two groups were 91.0% vs. 91.3% (P = 1.000). Symptomatic improvement of frequency was better in Group I than Group II (87.7% vs. 70.0%, P = 0.030). There were no significant differences with regard to intraoperative and postoperative complications between the two groups.

Conclusions

The combination of the Perigee system and TVT-O offers a safe and effective treatment for cystocele with UDSI and may be performed as first-line treatment.     

Vaginal mesh colpopexy for the treatment of concomitant full thickness rectal and pelvic organ prolapse: a case series

Objective

To present our case series of concomitant rectal and pelvic organ prolapse (POP) treated with vaginal colpopexy with synthetic mesh.

Study design

Charts of patients with full thickness rectal prolapse and POP were reviewed for presenting symptoms, physical examination with POP-Q including rectal prolapse evaluation, and perioperative complications and outcomes.

Results

Four patients aged 63-78 were identified with full thickness rectal prolapse and POP. All of them had symptoms related to both conditions. Rectal prolapse protrusion ranged from 2 cm to 3 cm outside the anus. All patients had vaginal mesh colpopexy; two of them with anterior and posterior vaginal mesh and 2 with posterior mesh only. At a follow-up of 6-44 months, all patients had resolution of both POP and rectal prolapse signs and symptoms.

Conclusion

Vaginal colpopexy with mesh may be a unique treatment to address both POP and full thickness rectal prolapse in selected patients. Further research is needed to determine the safety and efficacy of this method.