Do obesity and age effect the clinicopathological features and survival outcomes in premenopausal women with endometrial cancer?

PURPOSE: The purpose of this study was to review the effect of age and body mass index (BMI) on the prognosis, demographic characteristics, and pathological features of patients diagnosed with endometrial cancer, specifically before menopause. MATERIALS AND METHODS: Patients that were diagnosed with endometrial cancer before menopause, were screened retrospectively. Between 1999 and 2011, 163 patients were identified while 40 were excluded. Patients were classified into three groups according to age (under 40 years, between 40-45 years, more than 45 years) and BMI (normal weight group, overweight group, and obese weight group). Demographical characteristics, histopathological features (Stage, grade and histology of the tumor, the presence of myometrial and/or lymphovascular invasion, history of diabetes mellitus, history of hypertension, hormonal contraception method, smoking, parity, infertility, family history, and recurrences) and survival rates were compared among the groups. RESULTS: In total, 123 patients with a mean of 65.0 months follow up were enrolled into the study. The majority of the patients had endometrioid type in all age-related subgroups. Advanced stage endometrium cancer (Stage 2 and greater) was seen more commonly in the group of patient over 45 years of age against the other age-related subgroups (27.9% vs. 8% vs. 3.3%). Ratio of myometrial invasion more than 50% and occurrence of well-differentiated tumor were seen with a similar ratio among the age-related subgroups. Ratio of nulliparity and infertility were found statistically significant in the group of patients under 45 years of age against the group of patients over 45 years of age (p = 0.001, p = 0.03). The five-year estimated disease-free survival rates of women under 40 years of, women with an age between 40-45 years, and women over the age of 45 years were calculated as 73%, 95%, and 87%, respectively (p = 0.152). Concerning the histopathological features, there were no statistical differences between weight related subgroups. Comorbid conditions (hypertension and diabetes mellitus) were found as statistically high in the obese patients' group (43.5%-25.8%). In contrast to comorbid conditions, nulliparity and infertility histories were observed more often within the normal weight group (55.6%-38.5%). Mean disease-free survival time was calculated as 155.81 months in the normal weight group; 114.691 months in the overweight group, and 144.677 months in the obese group. Five-year disease-free survival rate was calculated as 91%, 81%, and 87%, respectively (p = 0.452). CONCLUSION: Women with premenopausal cancers generally exhibit early and favorable histopathological symptoms. Although advanced stage endometrium cancer incidence was detected to be higher in the premenopausal endometrium cancer patients aged above 45 years compared to other age subgroups. A significant difference in terms of survival rates between these groups was not reached. In the same manner, the authors did not find a significant difference in survival rates among different weight subgroups of premenopausal endometrium cancer patients. As a secondary result, the authors discovered that diabetes mellitus and hypertension play a key role in patients with a BMI above 30 kg/m2 and nulliparity and infertility play a key role in patients with a BMI below 25 kg/m2 in the development of premenopausal endometrial cancer.

A deceiving disease in women for clinicians: peritoneal tuberculosis.

INTRODUCTION: Peritoneal tuberculosis (TB) is uncommon in developed countries, although there is an increase in incidence due to the patients with acquired immunodeficiency syndrome and in immigrants from countries with tuberculosis. The aim of the study was to identify characteristic features of peritoneal tuberculosis (TB), which may be useful for the clinical differential diagnosis and management of this deceiving disease. MATERIALS AND METHODS: For this retrospective study, 18 patients, who were diagnosed with peritoneal TB were identified after surgery. RESULTS: Initial presentation consisted of ascites, pelvic masses, and elevated levels of CA-125. All patients were initially misdiagnosed as ovarian carcinoma. Tissue biopsies obtained from laparoscopy or laparotomy revealed accurate diagnosis of peritoneal TB. CONCLUSION: Peritoneal TB should be included in the differential diagnosis ofascites and pelvic masses and can be accurately diagnosed by laparoscopic biopsy.

Implications of premature ovarian failure on bone turnover markers and bone mineral density.

INTRODUCTION: Premature ovarian failure (POF) is the cessation of ovarian function before the age of 40. The loss of ovarian function, whether premature or not, has an overwhelming impact on female skeletal health, leading to an increased risk of developing osteoporosis because of the lengthened time of exposure to reduced estrogen. The objective of this study was to compare the implications of premature ovarian failure on bone turnover markers and bone mineral density in patients under the age of 40. MATERIALS AND METHODS: Sixty-one patients with a diagnosis of POF were selected for this prospective study. Patients were divided into two groups according to age, patients < 30 years old (n = 30), and patients > or = 30 years old (n = 31). RESULTS: Between the two age sub-groups (< 30 and > or = 30 years old), there was a significant difference in menopause rating scale (MRS), lumbar spine t-score, N-telopeptides crosslinks (NTx), and serum bone specific alkaline phosphatase (bALP) between the two age groups (10.93 +/- 7.79 vs 17.38 +/- 8.62; -1.84 +/- 1.47 vs -1.06 +/- 0.93; 58.80 +/- 21.32 vs 41.1 +/- 11.37; 48.99 +/- 42.16 vs 23.76 +/- 10.08, respectively). CONCLUSION: It is apparent that bone mineral density (BMD) is commonly less in women with POF than normal healthy women. Therefore, measurement of BMD is warranted. At this time, it is not clear how often the tests should be carried out to evaluate BMD. Further prospective studies are required to establish guidelines. However, it seems reasonable to monitor women with POF yearly for the presence of any endocrine dysfunction and to assess BMD at periodic intervals.

The effects of subfascial wound versus epidural levo-bupivacaine infusion on postoperative pain following hysterectomy.

BACKGROUND: Local analgesia through wound catheters is used as a part of multimodal analgesia. The efficacy of continuous subfascial wound infusion compared to epidural analgesia is unknown for abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) via Pfannenstiel incision. The aim of this study was to compare the aforementioned two methods in this type of surgery for postoperative morphine consumption, acute and persistent postsurgical pain. METHODS: Fifty patients enrolled in the study were randomly allocated to receive continuous 10 mL/h levobupivacaine either via subfascial (Group S) or epidural (Group E) catheter for 48 h postoperatively. In Group S 0.25% levobupivacaine was used for the first six hours and 0.125% thereafter, whereas Group E received 0.125% levobupivacaine throughout the study period. Cumulative morphine consumption, static and dynamic pain, gastrointestinal recovery, ambulation, patient satisfaction, hospital stay, as well as pain at 2nd and 6th months were evaluated. RESULTS: Group S was superior to Group E regarding cumulative morphine consumption (16.8±7.2 mg and 28.7±10.3 mg respectively, P<0.001; mean difference -11.9 with 95% CI of the difference -17.1 to -6.7) and pain relief. Patient satisfaction was higher in Group S compared to Group E (P=0.006). Less postoperative vomiting was observed in Group S. No difference was detected in length of hospital stay and persistent postsurgical pain incidence. CONCLUSION: Wound analgesia via subfascial catheter with continuous levobupivacaine infusion decreases postoperative morphine consumption and increases patient satisfaction compared to epidural analgesia with no difference in persistent postsurgical pain following TAH-BSO via Pfannenstiel incision.

Elevated tissue levels of tumor necrosis factor-α in vulvar vestibulitis syndrome.

The purpose of this study was to compare levels of inflammatory cytokines, namely TNF-α, IL-1ß, and IL-1 receptor in women with vulvar vestibulitis syndrome (VVS) relative to levels in controls. The authors hypothesized that tissue concentrations of inflammatory cytokines would be elevated significantly in women with VVB compared to pain-free controls. The study population consisted of 15 women with strictly defined VVB in reproductive age and 13 age-matched women with no history of vulvodynia. For TNF-α, positive staining was observed in 40% of the samples from the study group and in 7.7% of the samples from the control group. The difference between the groups was statistically significant (p < 0.05). In conclusion, a limitation of the present study was the relatively small sam- ple size. However, the authors' intention was simply to propose that the local inflammation may be mediated by cytokines as TNF-α may rather than trying to single out a pathogenesis of VVS. The authors' findings of elevated TNF-α may suggest new therapeutic alternatives for VVS, as inhibiting cytokine synthesis or antagonism of the cytokine receptor.

Apoptosis through regulation of Bcl-2, Bax and Mcl-1 expressions in endometriotic cyst lesions and the endometrium of women with moderate to severe endometriosis.

The aim of the study was to evaluate apoptosis through regulation of Bcl-2, Bax and Mcl-1 proteins by comparing their expressions in endometriotic cyst lesions and the endometrium of the patients with moderate to severe endometriosis. This is a cross-sectional study of 30 women in reproductive age with a clinical or sonographic suspicion of endometrioma, who underwent laparoscopy. Bcl-2 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly reduced in the cystic endometriotic lesions (p < 0.0001). There was a significant difference in Bcl-2 expression between cystic endometriotic stromal cells and endometrial stromal cells (p < 0.0001). Bax expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the endometrium (p < 0.0001). There was a significant difference in Bax expression between cystic endometriotic stromal cells and endometrial stromal cells (p = 0.03). Mcl-1 expression was positive both in cystic endometriotic lesions and endometrium, and its expression was significantly lower in the cystic endometriotic lesions (p = 0.003). Apoptosis may play a role in the pathophysiology of endometriosis by potentially contributing to the survival of regurgitating endometrial cells in the peritoneal cavity.

Relevance of thrombophilia and impact of office hysteroscopy on recurrent in vitro fertilization failures: a case series.

The study evaluated the validity of office hysteroscopy (OH) in 51 infertile women and whether congenital or acquired thrombophilia is more prevalent in women with recurrent IVF failures.

Hemoperitoneum and acute abdomen caused by the rupture of ovarian granulosa cell tumor: a case report.

Granulosa cell tumors (GCT) constitute 70% of all ovarian sex-cord stromal tumors, which account for less than five percent of all ovarian carcinoma. The authors herein report a rare case of a ruptured GCT of the ovary in a 43-year-old female who was admitted to the emergency department with signs of acute abdomen.

Acute hemorrhage related to spontaneous rupture of an uterine fibroid: a rare case report.

The authors present smooth muscle tumors of uncertain malignant potential (STUMP) diagnosis and surgical management of a spontaneously-ruptured degenerated uterine fibroids. A 48-year-old nulliparous presented with a two-day history of abdominal pain, bloating, constipation, and menorrhagia. Within eight hours, her distress level increased. Computed tomography (CT) scanning of the abdomen showed a large, 31 x 25 cm solid-cystic lesion. An emergency laparotomy was indicated. Surgery revealed approximately 2,000 cc of blood and a 30 cm degenerated uterine fibroid with a fundal rupture, cystic, and solid components extending to the lower pole of the liver. Pathology results noted mild nuclear atypia, six mitoses per ten high-power fields (hpf) and necrosis spread that was not coagulative with a STUMP diagnosis. STUMP presents a problematic group of uterine smooth muscle tumors for any clinician. In addition, STUMP can rarely cause acute complications like a rupture. Therefore, prompt diagnosis and effective management are important.

A rare case of lymphangiomyomatosis treated with leuprolide acetate: five-years follow-up.

Lymphangiomyomatosis (LAM) is a rare and systemic disease that is characterized by the abnormal proliferation of smooth muscle-like cells in the lungs and along the axial lymphatic system. The authors herein present a rare case of LAM that was treated with long-term use of leuprolide acetate, a gonadotropin-releasing hormone analogue (GnRHa).

Relevance of anti-Müllerian hormone on in vitro fertilization outcome.

PURPOSE: The aim of this study was to investigate the relevance of serum and follicular anti-Müllerian hormone (AMH) concentrations on ovarian reserve and clinical pregnancy. MATERIALS AND METHODS: Thirty patients were prospectively included in this study. Serum AMH levels were quantitatively measured on the follicle aspiration day. Retrieving less than five oocytes was defined as poor response. Eleven days after embryo transfer, beta-human chorionic gonadotropin (beta-hCG) level in the blood was measured. Two weeks after the beta-hCG test, a clinical pregnancy was confirmed by transvaginal ultrasound (TVUS). RESULTS: There was a statistically significant correlation between serum AMH and number of retrieved oocytes (p = 0.024). There was a correlation between the number of retrieved oocytes and baseline antral follicle count (AFC), between ovarian reserve and baseline follicle-stimulating hormone (FSH), and between ovarian reserve and serum AMH (p < 0.05). Serum AMH cut-off value for the normal ovarian reserve was calculated as 0.37ng/ml (sensitivity 71.43%, specificity 66.67%, positive prediction 83.33%, negative prediction 50%). CONCLUSION: Increasing use of serum AMH will be of considerable benefit. Consequently, the observed positive correlation between serum AMH and ovarian reserve will require larger sampling to refine the role of AMH.

Evaluation of low-dose letrozole addition to ovulation induction in IVF.

PURPOSE: The aim was to investigate the impact of low-dose letrozole usage along with gonadotropin treatment in vitro fertilization (IVF) cycles in comparison to gonadotropin treatment alone. MATERIALS AND METHODS: Fifty patients were prospectively included in this randomized study and were divided into two groups. Age, demographic features, causes, and period of infertility were adjusted and matched for both groups. Group 1 included 25 patients who received gonadotropin treatment and letrozole along with gonadotropin-releasing hormone (GnRH) antagonist protocol; group 2 included 25 patients who received gonadotropin treatment along with GnRH antagonist protocol. RESULTS: Total follicle-stimulating hormone (FSH) and daily FSH doses were lower in group 1, although not statistically significant (p > 0.05). The period of ovulation induction was significantly shorter in group 2. While numbers of retrieved oocytes and transferred embryos were lower in group 1, they were not statistically significant (p > 0.05). Number of clinical pregnancies per embryo transfer, number of clinical pregnancies per cycle, and number of ongoing pregnancies (> 16 gestational weeks) were similar in both groups (p > 0.05). CONCLUSIONS: Addition of low-dose letrozole to gonadotropin treatment in GnRH antagonist protocols may result in a lower dose of gonadotropin administration. However, routine clinical practice remains questionable due to no evident positive effect on pregnancy rates.

Evaluation of embryo transfer time (day 2 vs day 3) after imposed single embryo transfer legislation: when to transfer?

To determine whether the timing of embryo transfer (day 2 or day 3) affects pregnancy outcome in IVF patients, receiving single or double embryo transfer, 380 patients were included in this retrospective study. All patients underwent GnRH antagonist protocol. When stratified by number of transferred embryos, single embryo transfer (SET) patients undergoing a day 2 embryo transfer (ET) had similar biochemical pregnancy (25% vs 20.4%; p > 0.05) and clinical pregnancy (16.6% vs 14.6%; p > 0.05) rates to SET patients that were undergoing a day 3 ET. A similar observation was again noted in double embryo transfer (DET) patients undergoing a day 2 ET, with similar biochemical pregnancy (35% vs 29.8%; p > 0.05) and clinical pregnancy (25% vs 15.5%; p > 0.05) rates to DET patients undergoing a day 3 ET. Women, despite age, number of transferred embryos and ET timing, have similar reproductive outcomes. Shortening or lengthening the duration of in vitro culture provides no obvious benefit.

Impact of the mandatory age-based single-embryo transfer legislation in Turkey on outcome of in vitro fertilization: a multicentre study.

This study in Turkey evaluated the impact of age-based mandatory single-embryo transfer (SET) legislation with the subsequent increase in frozen-thawed embryo transfer (FT-EU) on pregnancy outcome of in vitro fertilization (IVF) patients. SET, FT-FT and double-embryo transfer were used in 5632 patients after legislation, while traditional IVF and FT-FT approach was used in 6029 patients before legislation. The cumulative pregnancy rate after legislation was slightly lower (38.2%) than before legislation (42.0%) but not significantly so. The single pregnancy rate for SET and traditional IVF were similar between the 2 groups (37.8% versus 28.7%), while multiple pregnancy rates were significantly higher before than after legislation (13.7% versus 0.3%). For FT-ET, the number of cycles was significantly higher after legislation (862 versus 616). SET yielded similar results to traditional IVF. In order to reduce multiple pregnancies without significantly decreasing pregnancy rates, SET might be a successful strategy.

Impact of the mandatory age-based single-embryo transfer legislation in Turkey on outcome of in vitro fertilization:a multicentre study

This study in Turkey evaluated the impact of age-based mandatory single-embryo transfer [SET] legislation with the subsequent increase in frozen-thawed embryo transfer [FT-ET] on pregnancy outcome of in vitrofertilization [IVF] patients. SET, FT-ET and double-embryo transfer were used in 5632 patients after legislation, while traditional IVF and FT-ET approach was used in 6029 patients before legislation. The cumulative pregnancy rate after legislation was slightly lower [38.2%] than before legislation [42.0%] but not significantly so. The single pregnancy rate for SET and traditional IVF were similar between the 2 groups [37.8% versus 28.7%], while multiple pregnancy rates were significantly higher before than after legislation [13.7% versus 0.3%]. For FT-ET, the number of cycles was significantly higher after legislation [862 versus 616]. SET yielded similar results to traditional IVF. In order to reduce multiple pregnancies without significantly decreasing pregnancy rates, SET might be a successful strategy

Management of precancerous lesions prior to conception and during pregnancy: a narrative review of the literature.

Special considerations aiming at preserving reproductive function have to be implemented when treating young patients with precancerous lesions of the lower genital tract. These high-grade lesions may progress into invasive cancer if left untreated. Currently, there are limited data on the impact of vulvar and vaginal precancerous lesions on fertility and its management during pregnancy. However, management and outcomes for cervical lesions have been extensively reported. The main approach for vulvar and vaginal lesions are maintaining anatomical function and cosmetics; whereas, treatment options for cervical precancerous lesions range from observation, cryotherapy or the more aggressive conisation. Gestational age is the most important factor in determining expectant management or surgical intervention. This narrative review draws attention to the relevant aspects of precancerous lesions of the lower genital tract, the potential effects and management prior to conception and during pregnancy.

Ovarian stem cells and aging.

OBJECTIVE: To review successes to date in the field of ovarian stem cell research and discuss the evidence supporting their potential to rejuvenate the follicular pool during adult life; to present factors that may contribute to their competence; and to address the question of why menopause is an inevitable outcome of advanced age if ovarian stem cells exist. METHOD: In a review of the literature, relevant articles were identified through a PubMed literature search from inception to July 2010. RESULTS: The current concept that mammalian ovaries possess a static ovarian reserve is at odds with the experimental results discussed in this review. Ovarian stem cells are likely to be the source of germline stem cells during fetal and adult life, due to their potential to differentiate into competent oocytes given a suitable environment. CONCLUSIONS: Stem cells in different compartments share properties such as pluripotency, self-renewal, and diminished regenerative potential in old age. Our model of ovarian stem cell aging suggests that menopause is driven by an age-related decline in ovarian stem cell function rather than depletion of a non-renewable follicular reserve. Understanding how ovarian stem cells interact with their surrounding environment moves us a step closer to controlling the female biological clock when it might be clinically desirable.