Fertility outcomes of patients with early stage endometrial carcinoma.

AIM: Three to five percent of endometrial carcinoma patients are younger than 40 years and may desire fertility. Conservative treatment can be employed in these cases. We aimed to review treatment outcomes of patients who were diagnosed with endometrial carcinoma and who wanted to preserve their fertility. MATERIAL AND METHODS: We reviewed nine patients who were diagnosed with early stage endometrial carcinoma and wanted to spare their fertility. The patients were followed up at Baskent University Adana Research Center from January 2004 to December 2011. RESULTS: In all patients the carcinoma presented as polyps, which were resected by hysteroscopy. After being informed about both surgical and medical therapies, four patients preferred surgery and five preferred medical treatment. The mean number of in vitro fertilization trials after conservative treatment was 3.25. One woman, who was on medroxyprogesterone acetate, delivered a healthy term baby from a fresh cycle. Another woman, who was on dydrogesterone, got pregnant from a thawing cycle, which later ended up in a missed abortus. Of all the patients who chose medical treatment, three had surgery at the end. One woman developed an ovarian tumor during the follow-up; one woman had a recurrence of endometrial carcinoma on dilatation and curettage for missed abortus and one woman tried in vitro fertilization several times and could not get pregnant, thus decided to have surgery. Two women had stage IA endometrial carcinoma and one had stage IIB ovarian carcinoma. CONCLUSION: Conservative treatment of endometrial carcinoma is safe in most cases. However, patients should be well-informed about the risks of conservative treatment because delaying definitive treatment sometimes worsens the prognosis.

A Turkish Gynecologic Oncology Group study of fertility-sparing treatment for early-stage endometrial cancer.

OBJECTIVE: To analyze the results of fertility-sparing treatment of early-stage endometrial cancer (EC) in patients treated at Turkish gynecologic oncology centers, and to present a review of the literature. METHODS: Thirteen healthcare centers in Turkey were contacted to determine if they were eligible to participate in the study. Centers that were eligible and agreed to participate were sent a database form to record the demographic characteristics, clinicopathologic findings, and follow-up results for their EC patients. RESULTS: Eleven Turkish healthcare centers provided data on 43 EC patients. Mean duration of treatment was 5 months and mean follow-up was 49 months. In total, 35 (81.4%) patients were tumor free following primary progesterone therapy. Mean time from the end of progesterone therapy to pregnancy was 10.6 ± 4.3 months (range, 3-18 months). Two patients had tumor recurrence during follow-up. The pregnancy rate among the 31 women who actively sought pregnancy was 41.9% (n=13). CONCLUSION: Conservative management of early-stage EC in women of reproductive age using oral progestins was effective and did not compromise oncological outcome. Pregnancy in the study patients was achieved spontaneously and artificially.

Fertility-sparing therapy in young women with endometrial cancer: 2010 update.

Endometrial cancer (EC) in young and especially null gravid women is a challenging problem with increasing frequency due to both detailed investigations for infertile couples seeking treatment in in vitro fertilization centers and women delaying their plans for pregnancy. Considering very low number of such cases in the literature, fertility-sparing therapy for EC in young women is not standard, although it is widely used. In this review we searched the relevant literature, reviewed selection criteria, therapeutic options, response rates to therapy, special challenges, reproductive outcomes, and follow-up strategies for young women diagnosed with EC.

The impact of rescue in vitro fertilization converted from high-response gonadotropin intrauterine insemination cycles in terms of implantation and pregnancy rates as compared with matched controls.

OBJECTIVE: To determine whether conversion of high-response gonadotropin/intrauterine insemination (IUI) cycles to "rescue" in vitro fertilization (IVF) yields a higher implantation and pregnancy rate as found in matched IVF controls. DESIGN: A prospective study with a retrospective controlled section. SETTING: Baskent University Department of Obstetrics and Gynecology. PATIENT(S): Thirty-two patients switched from high response gonadotropin/IUI cycles to "rescue" IVF, 202 women with polycystic ovaries (PCO), and 452 women without PCO from the IVF database. INTERVENTION(S): High-response gonadotropin/IUI cycles were converted to IVF to avoid cycle cancellation and high-order multiple pregnancies. MAIN OUTCOME MEASURE(S): Clinical parameters and characteristics of controlled ovarian hyperstimulation and intracytoplasmic sperm injection results. RESULT(S): The pregnancy rate was 78.1% in the rescue IVF group: 66.3% and 58.2% in the PCO and non-PCO groups, respectively. Clinical pregnancy rates and ongoing pregnancy rates also tended to be higher in the rescue IVF group but the difference was not statistically significant. The main difference between the groups was in the implantation rate: 37.5% in the rescue IVF group, which was greater than that of the PCO and non-PCO groups (27.58% and 24.46%, respectively). CONCLUSION(S): Our study demonstrates that conversion of gonadotropin IUI cycles in patients with excessive follicles to IVF is a safe, effective strategy. Implantation rates are higher than those in hyper-responder and normal responder IVF patients.

Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma.

The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and VEGFD, plays an essential role in the angiogenesis of both pathologic and nonpathologic conditions. Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits motility, invasion, and angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma. Therefore, we investigated the expression and correlation of maspin, VEGFA, VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas, 18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining of cells was scored as +2 if more than 50% of the cells were positive, as +1 if less than 50% of the cells were positive, and as negative if none of the cells stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly associated with high tumor grade (P<.001, P=.004, P<.001, respectively), clinical stage (P=.002, .01, and .001, respectively), the presence of ascites (P<.001, P=.03, and P=.001, respectively), and the presence of metastatic lymph nodes (P=.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA (P=.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively correlated with high tumor grade (P=.04), lymphovascular space invasion (LVSI) (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P=.009), maspin, VEGFC (P=.003), and VEGFD (P=.003), but it was not correlated with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD are expressed in ovarian tumors with a poor prognostic parameters, and seem to play a role in ovarian cancer angiogenesis, progression, and lymph node metastases. Our results indicate that in contrast to most other carcinomas, maspin expression is directly associated with the biological aggressiveness of ovarian carcinoma. These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies.

How best is to discontinue postmenopausal hormone therapy: immediate or tapered?

BACKGROUND: To evaluate the differences between the immediate and tapered cessation protocols of hormone therapy in terms of recurrence of menopausal symptoms. MATERIALS AND METHODS: In this prospective, randomized clinical study 70 consecutive patients in whom hormone therapy was no longer preferred were recruited from the menopause clinic of a university hospital and rank randomized into two groups. In group 1 (n=35) hormone therapy was immediately discontinued and in group 2 (n=35) the medication was tapered. Every patient was questioned about vasomotor symptoms before the initiation of hormone therapy at the first visit, and then revisited at the end of 2 and 4 weeks. RESULTS: We did not find any statistically significant difference between two protocols in terms of symptom severity and frequency at the end of 2 and 4 weeks of discontinuation. Although statistically insignificant, the symptoms tended to recur in fewer patients and in a less severe form in both groups when compared with their pretreatment status. CONCLUSIONS: Tapering or immediate discontinuing of hormone therapy did not affect the recurrence rate and severity of menopausal symptoms at the end of 4 weeks.

COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma.

OBJECTIVES: To investigate the expressions of survivin and Cyclooxygenase-2 (COX-2), and their possible correlations in the development of endometrial adenocarcinoma (EC). We also looked at their association with classical prognostic factors in EC. To our knowledge, this is the first time survivin expression is investigated in terms of its relation to COX-2 in the developmental pathway of EC. METHODS: Archived tissue samples of 50 EC, 30 endometrial hyperplasia and 20 proliferative endometrium were selected and immunohistochemically analyzed for survivin and COX-2 expression. RESULTS: Both survivin and COX-2 were overexpressed in hyperplasia and endometrial adenocarcinoma cases compared to proliferative endometrium, which was statistically significant (p=0.01, p=0.02, respectively). Among EC cases, survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients, respectively. Furthermore, we found survivin and COX-2 to be positively correlated, which was also statistically significant (p=0.0001, r=0.46). Neither survivin nor COX-2 expression was correlated with classical prognostic factors of endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05). CONCLUSIONS: Both survivin and COX-2 are overexpressed, and they seem to be early events in the occurrence of EC. Moreover, protein products of these two genes are positively correlated. COX-2 and survivin might share a common molecular pathway or enhance each other's actions in the developmental pathway of EC. Molecular basis of such a relationship should be further investigated in endometrial carcinogenesis.

Lobular carcinoma of the breast metastatic to the uterus in a patient under adjuvant anastrozole therapy.

This is the first report of breast carcinoma metastatic to the endometrium in a patient on adjuvant anastrozole therapy. We report a case of metastatic lobular carcinoma of the breast in a 63-year-old patient on adjuvant anastrozole therapy for 8 months. She was asymptomatic and metastatic endometrium was diagnosed after transvaginal ultrasound revealed suspicious findings along with elevated Ca 15-3 levels. As further work up showed no other metastatic sites her uterus was taken out along with her ovaries and pelvic lymph nodes. Uterine metastases should be kept in mind in asymptomatic patients on anastrozole therapy.

Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial.

BACKGROUND: The aim of the current study was to assess the effects of B-group vitamins and folic acid administration on serum levels of homocysteine (Hcy) in patients with polycystic ovarian syndrome (PCOS) on short-term metformin treatment. METHODS: Patients were randomly assigned to one of three treatment groups. Group 1 patients (n = 20) received metformin (850 mg twice daily); group 2 patients (n = 20) received metformin (850 mg twice daily) and B-group vitamins (vitamin B1, 250 mg; vitamin B6, 250 mg; vitamin B12, 1000 microg twice daily); and group 3 patients (n = 20) received metformin (850 mg twice daily) and folic acid (174 microg twice daily). In all groups, lipid profiles and plasma total Hcy, vitamin B12, folic acid and glucose levels were recorded at baseline and at 3 months. RESULTS: A 26.5% increase in Hcy levels was seen after 12 weeks of metformin therapy, while 21.17 and 8.33% decreases in Hcy levels were detected when B-group vitamins or folic acid plus metformin were given respectively. There were no statistically significant differences recorded in insulin sensitivity using homeostasis model assessment in the three groups. CONCLUSION: These findings suggest that B-group vitamins and folic acid administration counteract the Hcy-increasing effect seen with metformin therapy.

Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study.

BACKGROUND: Elevated levels of plasma homocysteine (Hcy) have been implicated as a significant risk factor for cardiovascular disease. Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS). In the literature, only one study has demonstrated that metformin increases Hcy levels in PCOS patients, but the effect of other insulin sensitizers on Hcy levels have not been reported previously in women with PCOS. We aimed to assess the effects of metformin and rosiglitazone on plasma Hcy levels in patients with PCOS. METHODS: Thirty women were randomized to two groups: 15 women in group 1 received 850 mg of metformin twice daily for 3 months. In group 2, 15 women received 4 mg of rosiglitazone for 3 months. In both groups, body mass index, menstrual pattern, and plasma total Hcy, insulin, glucose and lipid metabolism parameters were recorded at baseline and at 3 months. RESULTS: Hcy levels increased from 8.93+/-0.49 to 11.26+/-0.86 micromol/l (P = 0.002) and from 10.70+/-0.86 to 12.36+/-0.81 micromol/l (P = 0.01) in the metformin and rosiglitazone groups, respectively. Apolipoprotein (Apo) A1 levels increased from 127.10+/-6.85 to 145.7+/-7.18 mg/dl (P = 0.018) in the metformin group. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) and Apo B levels decreased in the metformin group, but the change was not significant. Total-C levels decreased from 161.15+/-8.94 to 150.23+/-8.73 mg/dl (P = 0.026), HDL-C decreased from 43.13+/-2.65 to 39.15+/-2.52 mg/dl (P = 0.005) and LDL-C levels decreased from 93.83+/-6.06 to 80.7+/-2.30 mg/dl (P = 0.021) in the rosiglitazone group. CONCLUSION: Treatment with insulin sensitizers in women with PCOS may lead to increases in Hcy levels.

Intima-media thickness of the carotid arteries is related to serum osteoprotegerin levels in healthy postmenopausal women.

Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and also plays a role in vascular calcification. The objective of this study was to evaluate the relationship between serum OPG levels, and carotid artery intima-media thickness (IMT) and carotid plaque formation in healthy postmenopausal women. We recruited 68 healthy postmenopausal women for the study. Carotid plaque presence and IMT were evaluated by high resolution B-mode ultrasound. IMT was positively correlated with presence of plaque, age, menopause age and OPG, and inversely correlated with Apolipoprotein A1 (Apo A1). Serum OPG level was positively correlated with IMT (r = 0.366; p < 0.003) and age (r = 0.324; p < 0.008), and negatively correlated with Apo A1 (r = -0.481; p < 0.0001). We did not observe any significant relation between plaque occurrence and levels of serum OPG. In regression analysis OPG (p < 0.02) and menopause age (p < 0.05) were independent risk factors for IMT, and age (p < 0.05) and IMT (p < 0.05) were independent risk factors for plaque formation. Although the role of OPG in the vascular biology is poorly understood, our results suggest that elevated levels of serum OPG is associated with IMT and may play a role in the pathogenesis of atherosclerotic disease.

Spontaneous regression and reaccumulation of pleural effusion in a fetus. A case report.

Isolated pleural effusion is rare and occurs when varying degrees of fluid surround the fetal lung without concomitant hydrops. The effusion may regress spontaneously, remain stable in size, or progress to involve both sides of the chest causing fetal hydrops. This may result in pulmonary hypoplasia and fetal or neonatal demise. In this article, we report a case in which spontaneous resolution of an isolated right-sided fetal pleural effusion occurred at 23 weeks of gestation and reappeared bilaterally at 34 weeks. Serial ultrasonographic evaluation of the fetus should be continued even if a spontaneous resolution of a preexisting pleural effusion has occurred.

Elevated plasma homocysteine levels in gestational diabetes mellitus.

OBJECTIVE: This prospective study investigated the occurrence of hyperhomocysteinemia in a population of patients with gestational diabetes. The aim was to determine whether elevated plasma homocysteine is associated with gestational diabetes in Turkish women. STUDY DESIGN: This prospective controlled study was conducted in the Department of Obstetrics and Gynecology of the Baskent University Faculty of Medicine between April 2002 and June 2003, and involved 304 Turkish women with uncomplicated pregnancies who were at 24-28 weeks gestation. The women in the study were assigned to one of three groups according to the results of the 50-g glucose screening and the oral glucose tolerance test (OGTT): group 1 comprised women who had normal glucose levels (< or = 135 mg/dL) after the 50-g challenge; group 2 comprised women with abnormal screening test results (> 135 mg/dL) but normal OGTT results; and group 3 comprised patients with gestational diabetes mellitus (GDM) according to the OGTT. Levels of fasting glucose, homocysteine, vitamin B(12) and folic acid, total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol levels were measured in the three groups. Levels of insulin sensitivity were calculated using the homeostasis model assessment (HOMA) formula. RESULTS: The mean level of homocysteine in group 1 was significantly lower than the levels in groups 2 and 3 (p < 0.001) The mean triglyceride and VLDL levels in group 3 were significantly higher than the corresponding levels in group 1 (p < 0.05 for both). There were no significant differences among the groups with respect to levels of total cholesterol, vitamin B(12), folic acid, creatinine, fasting glucose or insulin. The mean HOMA value in group 3 was significantly higher than that in group 1 (p < 0.05). Only the blood glucose level after the 50-g glucose screening [p = 0.000, 95% confidence interval (CI) 0.009-0.027] had a significant correlation with homocysteine levels. CONCLUSION: In this prospective study of Turkish women, we found that patients with gestational diabetes and women with abnormal screening test results (> 135 mg/dL) but normal OGTT results have higher homocysteine levels than normal pregnant women. This increased level seems to be related to an abnormal 50-g test but not to insulin resistance. Further investigations are needed to follow up for these patients in the postpartum period and later in their life.

Effects of lumbar disc surgery on bone mineral density in women with lumbar disc disease.

This prospective study evaluated 60 reproductive-age and postmenopausal women with lumbar disc disease to demonstrate the short-term effects of lumbar disc surgery on bone mineral density (BMD). Lumbar BMD was measured preoperatively and 3 months postoperatively by dual-energy X-ray absorptiometry (DEXA). Surgery was performed at only one level (L3-L4) and consisted of partial hemilaminectomy, discectomy, and, if necessary, partial facetectomy. Before surgery, 50% of the patients had osteopenia, and 31.7% had osteoporosis. After surgery, BMD decreased 5.5% in L3 vertebrae (P=.07), 14% in L4 vertebrae (P=.003), and 4.6% in L1-L4 (P=.039). Six of 11 patients with normal BMD before surgery became osteopenic postoperatively; 9 of 30 women with osteopenia fulfilled criteria for osteoporosis after surgery. Reproductive-age and postmenopausal women undergoing surgery for lumbar disc disease are at risk of bone loss and should be spared an extensive procedure, which can further increase the amount of bone lost. All women for whom a surgical intervention is planned should be evaluated by DEXA preoperatively and postoperatively.

Moclobemide in the treatment of hot flashes in postmenopausal women.

This randomized, prospective, double-blind study evaluated the efficacy and tolerability of moclobemide, a reversible, selective inhibitor of monoamine oxidase-A, in reducing the frequency and severity of hot flashes. Thirty postmenopausal women were enrolled, and 28 were allocated to 5 weeks of treatment with moclobemide 150 mg (group 1, n = 10), moclobemide 300 mg (group 2, n = 11), or placebo (group 3, n = 9). Data on hot flashes were recorded in a daily diary. Mean reductions in the hot flash severity score were 24.4% in the placebo group, 69.8% in group 1, and 35.0% in group 2. This large difference suggests that the beneficial effects were not due to a placebo effect. Moclobemide may be a new nonhormonal option for reducing the incidence, severity, and duration of hot flashes in postmenopausal women who do not wish to take estrogen or have contraindications to its use.