Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: The SGSG-012/GOTIC-004/Intergroup study

Objective

The concept of “platinum sensitivity” has been widely applied in the management of recurrent ovarian cancer. This study aimed to evaluate the applicability of this concept to recurrent endometrial cancer.

Patients and methods

In this multicenter retrospective cohort study, the clinical data of patients with recurrent endometrial cancer, who had a history of receiving first-line platinum-based chemotherapy and who received second-line platinum-based chemotherapy at the time of recurrence between January 2005 and December 2009 were reviewed.

Results

A total of 262 patients from 30 centers with initial FIGO stage classifications of I (29), II (23), III (122), and IV (88) were enrolled. In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear cell adenocarcinomas, 36 carcinosarcomas, and 22 “other” tumors were documented. The response rates for patients with platinum-free intervals of < 6 months, 6–11 months, 12–23 months, and ≥ 24 months were 25%, 38%, 61%, and 65%, respectively. The median progression-free survival after second-line platinum-based chemotherapy for patients with platinum-free intervals of < 12 months and ≥ 12 months was 4.4 (95% confidence interval (CI) = 3.7–5.8) months and 10.3 (95% CI = 8.2–12.6) months, respectively (log-rank P < 0.0001), and the median overall survival was 13.8 (95% CI = 10.6–18.1) months and 40.9 (95% CI = 25.3–54.2) months, respectively (log-rank P < 0.0001).

Conclusion

Platinum-free interval is a predictor of response and survival after second-line platinum-based chemotherapy in patients with recurrent endometrial cancer. The concept of “platinum sensitivity” could be applicable to recurrent endometrial cancer.     

Doppler study of uterine hemodynamics in women with unexplained infertility

Objective

To evaluate uterine artery blood flow using pulsed Doppler, and endometrial and subendometrial microvascularization using three-dimensional (3D) power Doppler, in women with unexplained infertility.

Study design

In a prospective clinical trial at a university teaching hospital, 40 women with unexplained infertility were compared to 40 fertile parous controls. In the mid-luteal (peri-implantation) phase, the endometrial thickness and volume, uterine artery pulsatility index (PI) and resistance index (RI), endometrial and subendometrial 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI), and serum estradiol and progesterone levels were measured in both groups.

Results

The uterine artery PI (P = 0.003) and RI (P = 0.007) were significantly increased and the endometrial VI (P = 0.029), FI (P = 0.031), and VFI (P = 0.001) and subendometrial VI (P = 0.032), FI (P = 0.040), and VFI (P = 0.005) were significantly decreased in the unexplained infertility group. The endometrial thickness and volume and serum estradiol and progesterone levels, however, were not significantly different between the two groups.

Conclusion

Peri-implantation endometrial perfusion is impaired in women with unexplained infertility: Doppler study of uterine hemodynamics should therefore be considered in infertility work-up.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.     

Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases

Objective

To assess prognostic factors associated with disease-related survival in endometrial stromal sarcoma (ESS) using the 2009 FIGO staging system.

Methods

From January 1990 to January 2012, 114 patients with ESS were identified at the Samsung and Asan Medical Center and data were retrospectively analyzed.

Results

Ten (8.7%) patients died of the disease and 33 (28.9%) patients relapsed. The 5- and 10-year overall survival (OS) rates for the entire cohort were 92.6% and 87.1%, respectively, and the 5- and 10-year recurrence-free survival (RFS) rates were 71.8% and 52.1%, respectively. The estimated median survival after recurrence for the 33 patients whose tumors relapsed was 133 months (95% CI, 7.7–258.4), and 5-year survival after recurrence was 68.9%. Stage I (P = 0.006), estrogen and/or progesterone receptor (ER/PR) positivity (P = 0.0027), and no nodal metastasis (P = 0.033) were associated with a good prognosis for OS in the univariate analysis. Ovarian preservation was revealed to be an independent predictor for poorer RFS (HR, 6.5; 95% CI, 1.23–34.19; P = 0.027). Positivity for ER/PR (HR, 0.05; 95% CI, 0.006–0.4; P = 0.006) and cytoreductive resection of recurrent lesions (HR, 0.14; 95% CI, 0.02–0.93; P = 0.042) were independent predictors of better survival after recurrence.

Conclusions

Stage, expression of ER/PR, and nodal metastasis are significantly associated with OS in ESS. Bilateral salpingo-oophorectomy (BSO) as the primary treatment and cytoreductive resection of recurrent lesions should be considered for improving survival of patients with ESS.     

Association between delivery of a small-for-gestational-age neonate and long-term maternal cardiovascular morbidity

Objective

To investigate whether delivering a small-for-gestational-age (SGA) newborn is a risk factor for subsequent long-term maternal cardiovascular morbidity.

Methods

Data were analyzed from consecutive pregnant women who delivered at Soroka University Medical Center, Beer-Sheva, Israel, between 1988 and 1999, and were followed-up retrospectively until 2010. Long-term cardiovascular morbidity was compared among women with and without SGA neonates.

Results

During the study period, 47 612 deliveries met the inclusion criteria, and 4411 (9.3%) women delivered an SGA neonate. Delivery of an SGA neonate was a risk factor for long-term complex cardiovascular events, including congestive heart failure, hypertensive heart and kidney disease, and acute cor pulmonale (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.3–4.4; P = 0.006); and long-term cardiovascular mortality (OR, 3.4; 95% CI, 1.5–7.6; P = 0.006). Women who delivered an SGA neonate had a significantly higher risk for cardiovascular mortality during the follow-up period (Kaplan–Meier survival analysis, P = 0.002). Delivery of an SGA neonate remained an independent risk factor for long-term maternal cardiovascular mortality (Cox multivariable regression: adjusted hazard ratio, 3.5; 95% CI, 1.5–8.2; P = 0.004).

Conclusion

Delivery of an SGA neonate is an independent risk factor for long-term cardiovascular morbidity in a follow-up period of more than 10 years.     

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma — Analysis of patient data in the prospective OVCAD study

Objective

Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome.

Methods

Data of 191 patients with advanced serous (FIGO III–IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy.

Results

The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4–158 days). Preoperative performance status (P < 0.001), extent of surgery (P < 0.001), and perioperative complications (P < 0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus > 28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08–2.78), P = 0.022], residual disease [HR 2.95 (95% confidence interval 1.87–4.67), P < 0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41–3.64), P = 0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n = 121), it significantly correlated with overall survival in patients with postoperative residual disease [n = 70, HR 2.24 (95% confidence interval 1.08–4.66), P = 0.031].

Conclusion

Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.     

Premenopausal bleeding: When should the endometrium be investigated?—A retrospective non-comparative study of 3006 women

Objective

There is lack of consensus amongst professional organizations as regards the cut-off age for endometrial sampling of premenopausal women presenting with abnormal uterine bleeding (AUB) to exclude endometrial hyperplasia or carcinoma. Therefore we conducted this study to quantify the prevalence of hyperplasia and carcinoma in different age categories in premenopausal women with AUB to identify the appropriate cut-off age for endometrial sampling.

Study design

A retrospective review of the histopathology reports of endometrial samples taken from 3006 women presenting with AUB and aged from ≥30 to ≤50 years at Ipswich Hospital, UK, from 1 January 1998 to 31 December 2007. Women were divided into three subgroups according to age; group 1: 30 to ≤40 (n = 862), group 2: 40 to ≤45 (n = 1035) and group 3: 45 to ≤50 (n = 1109).

Results

Logistic regression revealed that the prevalence of atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p = 0.01) and carcinoma (OR: 4.03; 95% CI: 1.54, 10.5; p = 0.04) was significantly higher in women in group 3 when compared to younger women. There was no statistically significant difference as regards simple and complex hyperplasia in the different age categories. All but one of the women (n = 23) who had complex atypical hyperplasia or carcinoma under the age of 45 years, presented with irregular rather than cyclical heavy menstrual bleeding.

Conclusion

Our study, the largest in the literature, suggests using the age 45 years as a cut-off for sampling the endometrium in all women with AUB. However, irregular menstrual bleeding justifies investigating women regardless of their age.     

The effect of bisphosphonates on the risk of endometrial and ovarian malignancies

Objective

The use of bisphosphonates has been associated with reduced risk and improved survival of breast and colorectal malignancies. This study was aimed at studying the effects of bisphosphonates on gynecological cancers.

Methods

The Cancer in the Ovary and Uterus Study (CITOUS) is a case–control study of newly diagnosed cases of gynecological malignancies and age/clinic/ethnic-group matched population controls. The use of bisphosphonates prior to, and following, diagnosis was assessed in 424 cases of ovarian and endometrial cancers and 341 controls, all postmenopausal at recruitment, enrolled in Clalit Health Services (CHS), using pharmacy records.

Results

The use of bisphosphonates for more than 1 year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR = 0.49, 95% CI: 0.26–0.93) and endometrial cancer (OR = 0.39, 95% CI: 0.24–0.63). The association with endometrial cancer (OR = 0.48, 0.27–0.84) remained statistically significant after adjustment for a variety of putative effect modifiers (RR = 0.48, 0.26–0.89). The association with ovarian cancer remained significant when adjusted to statin use (0.46, 0.23–0.90) but not for other modifiers (0.58, 0.29–1.18). A strong negative association was found in an adjusted model for the use of either bisphosphonates or statins for more than 1 year (0.40, 0.23–0.68).

Conclusion

The use of bisphosphonates, with or without statins, for more than 1 year before diagnosis was associated with reduced risk of endometrial and ovarian cancers.     

Endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer: Is screening necessary?

Objective

To evaluate the prevalence of endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer and to know if a baseline pretamoxifen endometrial assessment should be taken into consideration in these women at high risk.

Methods

A cross-sectional study was carried out with 201 women with breast cancer. A diagnostic hysteroscopy was performed in all women. All formations suspected as polyps were removed. The prevalence of endometrial polyps was analyzed in all patients (n = 182) and in premenopausal (n = 49) and postmenopausal (n = 118) women with estrogen receptor (ER) positive breast cancer (BC) according to their body mass index (BMI) and other risk factors.

Results

Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and 41.5% were obese (BMI ≥ 30 kg/m²). Endometrial polyps were found in 52 cases (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal patients with ER(+)BC, there were no statistical differences in endometrial polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical differences. In all women the relative risk (RR) of endometrial polyps in obese patients was 2.24 (1.01–4.83), in obese postmenopausal women with ER(+)BC was 2.75 (1.01–7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80–3.29).

Conclusions

Asymptomatic women with breast cancer have a high prevalence of baseline subclinical endometrial polyps and it is very high in obese postmenopausal patients with estrogen receptor positive breast cancer. Therefore, there may be a future role for baseline pretamoxifen screening of some sort for the obese asymptomatic postmenopausal patient, especially if they are elderly and ER positive.     

A large scale population-based cohort study on the risk of ovarian neoplasm in patients with type 2 diabetes mellitus

Objective

To investigate whether the risk of developing ovarian cancer is elevated in women with diabetes mellitus.

Methods

The study is a population-based cohort study. Women with type 2 diabetes (n = 319,310) and age-matched controls (n = 319,308) were selected from the ambulatory care claims and beneficiary registry in 2000, respectively. Selected patients were linked to the in-patient claims (2000–2008) to identify admissions due to ovarian (ICD-9-CM: 183.xx) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of ovarian cancer in relation to diabetes were calculated using multivariate Cox proportional hazard regression model.

Results

The overall incidence density rate of ovarian cancer was estimated at 1.87 (95% confidence interval (CI) 1.70–2.05) per 10,000 patient-years for patients with diabetes. The corresponding figures for controls were slightly lower at 1.79 per 10,000 patient-years. The incidence density of ovarian cancer was increased with age in diabetes but not in controls. The covariate-adjusted HR for ovarian cancer was statistically compared with null (adjusted HR = 1.06, 95% CI = 0.92–1.22) in women with diabetes. Moderately elevated HR was noted in women with diabetes aged < 50 (adjusted HR = 1.17, 95% CI = 0.82–1.65) and in women with diabetes aged > 65 (adjusted HR = 1.10, 95% CI = 0.92–1.42). The null association between diabetes and ovarian cancer remains true regardless of the disease duration of diabetes.

Conclusion

This large-scale cohort study provides little support on the putative association between type 2 diabetes and the risk of ovarian cancer.     

The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: A Gynecologic Oncology Group study

Objectives

The study objective was to determine the prognostic significance of serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC) enrolled in a Phase III study.

Methods

An ancillary analysis of a phase III study of women with advanced epithelial ovarian cancer treated with carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC was used as a surrogate for low-grade serous carcinoma.

Results

Among 3686 enrolled patients, 184 (5%) had grade 1 disease and CA-125 levels available. For those with grade 1 SOC, the median patient age was 56.5; 87.3% had Stage III disease. Median follow-up was 102 months and there was no difference in pre-chemotherapy CA-125 by treatment arm (P = 0.91). Median pretreatment CA-125 for those with grade 1 SOC was lower (119.1) than for patients with grade 2–3 SOC (246.7; P < 0.001). In those with grade 1, pretreatment CA-125 was not prognostic of outcome. However, patients with CA-125 levels that normalized after cycle 1, 2 or 3 were 60–64% less likely to experience disease progression as compared to those who never normalized or normalized after 4 cycles (P ≤ 0.024). Normalization of CA-125 levels before the second cycle was negatively associated with death, with a HR of 0.45 (P = 0.025).

Conclusions

Pretreatment CA-125 level was significantly lower in women with grade 1 SOC compared to those with high-grade SOC. While pretreatment CA-125 was not associated with survival, serial CA-125 measurements during chemotherapy treatment were prognostic, with normalization before the second chemotherapy cycle associated with a decreased risk of death.     

The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer

Objectives

Women with advanced ovarian cancer are treated with chemotherapy either before (neoadjuvant) or after surgery (primary debulking). The goal is to leave no residual disease post-surgery; for women treated with primary debulking surgery this has been associated with an improvement in survival. It has not been shown that the survival advantage conferred by having no residual disease post-surgery is present for women who receive neoadjuvant chemotherapy.

Methods

We reviewed the records of 326 women with stage IIIc or IV serous ovarian cancer. We determined if they received neoadjuvant chemotherapy or primary debulking surgery and we measured the extent of residual disease post-surgery. We estimated seven-year survival rates for women after various treatments.

Results

Women who had neoadjuvant chemotherapy were more likely to have no residual disease than women who had primary debulking surgery (50.1% versus 41.5%; p = 0.03) but they experienced inferior seven-year survival (8.6% versus 41%; p < 0.0001). Among women who had primary debulking surgery, those with no residual disease had much better seven-year survival than women who had any residual disease (73.6% versus 21.0%; p < 0.0001). Women who had no residual disease after debulking surgery and who received intraperitoneal chemotherapy had a seven-year survival of 90%.

Conclusions

Neoadjuvant chemotherapy should be reserved for ovarian cancer patients who are not candidates for primary debulking surgery. Among women with no residual disease after primary debulking surgery, intraperitoneal chemotherapy extends survival.     

Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma

Objective

The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.

Methods

Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed.

Results

Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ in the ascites of the tumor micro-environment were associated with advanced disease (p = 0.012), higher tumor histological grading (p = 0.004), and sub-optimal surgical status (p = 0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85–4.05, p < 0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01–2.93, p = 0.048) for overall survival (OS) for a 10-fold increase in IFN-γ concentration in the ascites. An inverse dose–response relationship between IFN-γ level and survival was also noted (P_trend < 0.001 for DFS and P_trend < 0.042 for OS).

Conclusions

Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.     

Menopausal status: A possible predictive factor for recurrence in women with cancer of the uterine cervix without pelvic lymph node metastasis

Objectives

To evaluate risk factors for recurrence of carcinoma of the uterine cervix among women who had undergone radical hysterectomy without pelvic lymph node metastasis, while taking into consideration not only the classical histopathological factors but also sociodemographic, clinical and treatment-related factors.

Study design

This was an exploratory analysis on 233 women with carcinoma of the uterine cervix (stages IB and IIA) who were treated by means of radical hysterectomy and pelvic lymphadenectomy, with free surgical margins and without lymph node metastases on conventional histopathological examination. Women with histologically normal lymph nodes but with micrometastases in the immunohistochemical analysis (AE1/AE3) were excluded. Disease-free survival for sociodemographic, clinical and histopathological variables was calculated using the Kaplan–Meier method. The Cox proportional hazards model was used to identify the independent risk factors for recurrence.

Results

Twenty-seven recurrences were recorded (11.6%), of which 18 were pelvic, four were distant, four were pelvic + distant and one was of unknown location. The five-year disease-free survival rate among the study population was 88.4%. The independent risk factors for recurrence in the multivariate analysis were: postmenopausal status (HR 14.1; 95% CI: 3.7–53.6; P < 0.001), absence of or slight inflammatory reaction (HR 7.9; 95% CI: 1.7–36.5; P = 0.008) and invasion of the deepest third of the cervix (HR 6.1; 95% CI: 1.3–29.1; P = 0.021). Postoperative radiotherapy was identified as a protective factor against recurrence (HR 0.02; 95% CI: 0.001–0.25; P = 0.003).

Conclusion

Postmenopausal status is a possible independent risk factor for recurrence even when adjusted for classical prognostic factors (such as tumour size, depth of tumour invasion, capillary embolisation) and treatment-related factors (period of treatment and postoperative radiotherapy status).     

The impact of IVF procedures on endometriosis recurrence

Objective

In infertile women with endometriosis requiring an in vitro fertilization (IVF) procedure, the potential risk of an IVF-related progression of the disease remains a matter of debate. Thus, since available data on this issue are scanty and controversial, an observational study has been herein conducted in order to clarify this issue.

Study design

We recruited 233 women with endometriosis who underwent IVF cycles in our unit. Patients were contacted to assess whether they experienced recurrences of the disease after IVF. The main outcome was to evaluate the impact of the number of IVF cycles and the responsiveness to ovarian hyperstimulation on the likelihood of recurrence. Clinical characteristics of women who did and did not have a recurrence were compared.

Results

One hundred and eighty-nine women were included, 41 of whom (22%) had a diagnosis of endometriosis recurrence. The 36 months cumulative recurrence rate was 20%. The number of IVF cycles and the responsiveness to ovarian hyperstimulation were not associated with the risk of disease recurrence. The adjusted OR for recurrences according to the number of started cycles was 0.92 (95% CI: 0.77–1.10) per cycle (p = 0.35). The adjusted OR for recurrences in women with intact versus compromised ovarian reserve was 0.80 (95% CI: 0.40–1.58) (p = 0.52).

Conclusions

IVF procedures do not seem to influence the likelihood of endometriosis recurrence.     

Anti-Müllerian hormone as a marker of ovarian reserve following chemotherapy in patients with gestational trophoblastic neoplasia

Objective

The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels.

Study design

In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents.

Results

The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32–3.94 ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77–6.53 ng/mL, P = 0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30 ng/mL, P = 0.027).

Conclusion

Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve.     

Pregnancy outcomes of expectant management of stable mild to moderate chronic hypertension as compared with planned delivery

Objective

To compare outcomes between elective delivery at 37 weeks of pregnancy and expectant management among pregnant women with mild to moderate chronic hypertension.

Methods

In a two-center study, 76 women with mild to moderate chronic hypertension were randomly allocated to planned delivery at 37 completed weeks (group A) or expectant management for spontaneous onset of labor or reaching 41 weeks (group B) between April 2012 and October 2013. Differences were compared by t test, χ² test, or Fisher exact test. Odds ratios (ORs) with 95% confidence interval (CIs) were determined.

Results

There were no differences in superimposed pre-eclampsia (SPE), severe hypertension, preterm delivery, placental abruption, oligohydramnios, intrauterine growth restriction, or perinatal mortality between the groups. Group B had higher gestational age at delivery (P = 0.001) and birth weight (P = 0.01), but lower cesarean (OR 3.4; 95% CI, 1.2–10.3; P = 0.03) and neonatal care unit admission (OR 5.4; 95% CI, 1.4–21.0; P = 0.01) rates. More women with SPE were diagnosed before than after 37 weeks in group B (P = 0.01). Overall, patients who developed SPE had more adverse pregnancy outcomes than those who did not.

Conclusion

Mild to moderate chronic hypertension could be managed expectantly up to 41 weeks if SPE did not develop.     

Maternal hyperglycemia and adverse pregnancy outcomes in Dar es Salaam,Tanzania

Objective

To evaluate maternal glucose levels during pregnancy as a predictor of adverse perinatal outcomes in Dar es Salaam, Tanzania.

Methods

Random blood glucose measurements were analyzed from 3383 pregnant women enrolled in a randomized trial to assess the impact of multivitamins on pregnancy outcomes in Dar es Salaam between August 2001 and July 2004. Information on maternal and neonatal morbidity was recorded at monthly study visits, delivery, and 6 weeks postpartum. Binomial regression and generalized estimating equations were used to determine the relationship between elevated glucose (> 7.8 mmol/L) and pregnancy outcomes.

Results

In total, 25 women had elevated glucose (0.7%). Hyperglycemia was associated with an increased risk of delivery before 37 weeks [relative risk (RR), 2.11; 95% confidence interval [CI], 1.07–4.13; P = 0.03), delivery before 34 weeks (RR, 4.15; 95% CI, 1.43–12.03, P = 0.009), incident gestational hypertension (RR, 2.90; 95% CI, 1.24–6.76; P = 0.01), low birth weight (RR, 2.87; 95% CI, 1.18–6.99; P = 0.02), reduced newborn head circumference (mean difference, –1.57; 95% CI, –2.51 to − 0.62; P = 0.001), and fetal loss (RR, 3.38; 95% CI, 1.13–10.08; P = 0.03).

Conclusion

Maternal hyperglycemia is uncommon among pregnant Tanzanian women, but nonetheless seems to increase the risk of several adverse perinatal outcomes.     

Effectiveness of GnRH antagonist in intrauterine insemination cycles

Objective

To evaluate the effectiveness of GnRH antagonists in women undergoing controlled ovarian stimulation and intrauterine insemination cycles (COS/IUI).

Study design

Randomized controlled trial. Recruited women were randomized into two groups: GnRH antagonist and control group. The primary outcomes were incidence of premature LH surge and clinical pregnancy rates.

Results

One hundred and forty-one consecutive women were included in the study, with 70 in the antagonist group and 71 in the control arm. The baseline clinical characteristics were similar in both groups. The incidence of premature LH surge and premature luteinization was lower in the antagonist group as compared to the control group (5% vs. 10.3%, P = 0.45 and 5% vs. 13.8, P = 0.31) but not statistically significant. The clinical pregnancy rates were lower in the antagonist group (2.8% vs. 10%, P = 0.12), which was also not statistically significant.

Conclusion

The addition of GnRH antagonist during controlled ovarian stimulation and intrauterine insemination cycles does not lead to improvement in clinical pregnancy rates.     

GnRH-II mRNA expression in tumor tissue and peripheral blood mononuclear cells (PBMCs) in patients with malignant and benign ovarian tumors

Objective

To investigate the expression of the second form of GnRH (GnRH-II) in tumor tissue and peripheral blood mononuclear cells (PBMCs) in malignant and benign ovarian tumors in humans.

Study design

Sixty-six women were studied: 24 with epithelial ovarian carcinomas, 22 with benign ovarian tumors and 20 in the control group undergoing surgery. Malignant, benign and normal ovarian tissue and PBMCs were obtained for measurement of GnRH-II mRNA levels using quantitative real-time RT-PCR.

Result(s)

The expression of GnRH-II was found to be 1.5 times higher in malignant ovarian tumors compared with benign ovarian tumors and the control group in post-menopausal patients (P < 0.01). In the post-menopausal patient group with malignant ovarian tumors, there were significant positive correlations between serum FSH level and ovarian tissue GnRH-II mRNA expression (r = 0.68; P = 0.03), and serum LH level and ovarian tissue GnRH-II mRNA expression (r = 0.71; P = 0.02). Controls, benign and malignant groups were similar in terms of GnRH-II expression in PBMCs in the pre- and post-menopausal periods. There was no significant correlation between ovarian tissue GnRH-II mRNA expression vs. PBMC GnRH-II mRNA expression in patient and control groups.

Conclusion(s)

We have shown increased GnRH-II expression in human ovarian cancer tissue in post-menopausal women in vivo. Expression of GnRH-II in PBMCs did not reflect the local GnRH-II expression levels in ovarian tissue. These preliminary data suggest that local GnRH-II may participate in the regulation of ovarian tumor growth in post-menopausal women.