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.

Giant hemorrhagic adrenal pseudocyst in a primiparous pregnancy: report of a case.

Adrenal cysts are rare and are usually discovered incidentally during diagnostic imaging, surgery, or autopsy. Most cystic lesions of the adrenal gland are nonfunctioning and become symptomatic when complicated by rupture, hemorrhage, or infection. A 40-year-old woman presented with a history of gradual-onset pain in her left flank region at 20 weeks' gestation. Ultrasound showed a 20-cm cystic mass in her left abdominal cavity. Pertinent laboratory tests were within normal limits. The patient underwent exploratory laparotomy, which revealed a 20 × 15-cm left adrenal cyst; thus, we performed left adrenalectomy with complete excision of the cyst. Histological examination confirmed a hemorrhagic adrenal pseudocyst. The patient had an uneventful postoperative course, and subsequent routine obstetric ultrasound examinations showed normal fetal activity and development until the pregnancy terminated with a stillbirth caused by pre-eclampsia at 34 weeks' gestation. To the best of our knowledge, this is only the 12th reported case of adrenal pseudocyst discovered during pregnancy. We analyze the clinicopathologic findings and discuss the possible association of pregnancy, with special reference to etiopathogenesis, presentation, diagnosis, and treatment.

Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment.

Our aim was to evaluate the optimal treatment strategy addressing cardiovascular risk in obese and nonobese patients with polycystic ovary syndrome (PCOS). We planned a prospective randomized clinical study. Normoandrogenemic and oligoamenorrheic women with PCOS and impaired glucose tolerance (n = 96) were enrolled in the study. Six months of treatment with metformin HCL or oral contraceptive pills (OCPs) were given to the patients. Group 1 were obese and receiving metformin. Group 2 were obese and receiving OCPs. Group 3 were nonobese and receiving metformin, and Group 4 were nonobese receiving OCPs. ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated. ADMA, homocysteine, hs-CRP and HOMA-IR were similar in obese and nonobese groups before the treatment. After 6 months of treatment, a significant decrease was observed in ADMA, homocysteine and HOMA-IR levels in Groups 1 and 3. An increase in ADMA and hs-CRP levels was observed in Groups 2 and 4. In this study, metformin treatment leads to improvement in hormonal and metabolic parameters and decreases ADMA and homocysteine levels possibly independent of BMI. However, the use of oral contraceptives in obese and nonobese patients with PCOS with impaired glucose tolerance increases ADMA and hs-CRP levels and creates an increase in the metabolic risk.

Efficacy of anti-tumor necrosis factor therapy on endometriosis in an experimental rat model.

OBJECTIVE: To show the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in an experimental model. DESIGN: A randomized, placebo-controlled, blinded study using rat endometriosis model. SETTING: Experimental research center of Ankara Education and Research Hospital. ANIMAL(S): Twenty-two Wistar female rats. INTERVENTION(S): After peritoneal implantation of endometrial tissue, rats were randomized to two equal intervention groups: control and etanercept-treated groups. After measuring implant volume, blood and peritoneal fluid samples were obtained. Vehicle treatments of 2 mL saline to rats in control and 0.4 mg/kg etanercept SC once weekly were administered in treatment group. Four weeks later, a third laparotomy was performed to remeasure implant volumes, blood, and peritoneal fluid samples. MAIN OUTCOME MEASURE(S): To compare spherical volume, peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α between groups. RESULT(S): There was 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). In etanercept-treated group, a significant difference was found between peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α (p < 0.01). CONCLUSION(S): These results indicate that etanercept was found to effectively reduce the development of endometriosis.

Abdominal and pelvic hydatid cyst obstructing the labor.

Hydatid cystic disease is a parasitic disease primarily infesting the sheep and cattle. It is a rare condition in pregnancy with an incidence of 1/20000 pregnancies. An eighteen-year-old primigravida was evaluated due to obstructed labor. Multiple abdominal and pelvic hydatid cysts were diagnosed by ultasonography and a healthy infant with birthweight of 3330 g was delivered by cesarean section. While the cysts situated on the posterior uterine wall, paraovarian region and omentum were removed totally, the hepatic cysts were only partially removed and then drained. The hydatid disease should be considered in differential diagnosis of adnexal masses obstructing the labor in pregnancy (Fig. 3, Ref. 9).

The long-term effects of progesterone-only contraceptives on endometrium and ovary in rats.

Progestin-only (p-only) contraceptives often cause breakthrough bleeding for unknown reasons. In this study, we aimed to evaluate the long-term effects of p-only contraceptives to gain a better understanding of breakthrough bleeding mechanism. Wistar rats were divided into etonorgesterel implant (Group 1, n = 25), depot medroxyprogesterone acetate injectable (Group 2, n = 25), and control groups (n = 5). Five rats each from groups 1 and 2 were examined every 10 days for up to 50 days after the medication. Uteri and ovaries were removed and prepared for immunohistochemistry and scanning electron microscopy. The tissue nitric oxide (NO) levels were determined by Griess reaction. Dynamic changes of endometrial estrogen and progesterone receptor immunoreactivity were observed in a time-dependent manner in groups 1 and 2. The number of endometrial pinopodes, which are small endometrial protrusions, increased in both groups. There was no difference between groups for the estrogen receptor in the surface epithelium of the ovary. Estrogen-alpha and progesterone receptor in follicular cells decreased in a time-dependent manner. The granulosa cells underwent atrophic and were disorganized. Decreased levels of uterine tissue NO were determined in groups 1 and 2. The effect of some p-only contraceptives make some dynamic changes in the endometrium, ovaries, steroid hormone receptors, cell morphology, and biochemical features of the tissues during their use.

Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and its relationship to clinical parameters.

OBJECTIVE: To investigate the differences in steroid receptor expression patterns between glandular and stromal portions in endometrial polyps among premenopausal and postmenopausal patients and the relationship between the receptor expression in endometrial polyps and clinical parameters. MATERIALS AND METHODS: A total of 25 postmenopausal and 25 premenopausal patients with solitary endometrial polyp detected by office hysteroscopy were involved in the study. All patients underwent hysteroscopic polypectomy under general anesthesia or spinal anesthesia. Estrogen and progesterone expression patterns were investigated in the polyps using immunohistochemistry. The mean age was 57.6 years in postmenopausal patients and 36.9 in premenopausal patients. Average gravida, body mass index (BMI), and frequency of smokers did not differ between groups. However, the patient's age and their concomitant diseases were significantly different between premenopausal and postmenopausal patients (P = 0.01). RESULTS: Comparison in postmenopausal patients showed that glandular estrogen and progesterone receptor expression were both significantly greater than stromal estrogen and progesterone receptor expression (P = 0.037 and <0.001, respectively). Proliferative phase endometrial polyps also demonstrated significantly greater expression of progesterone receptors in glandular epithelium compared with stroma (P = 0.019). However, stromal and glandular estrogen receptor expression did not differ among premenopausal patients. There was a statistically significant correlation among stromal progesterone receptor expression, plasma estrogen and FSH level (P = 0.01). A negative correlation was found between stromal progesterone receptor expression and patient's age (P = 0. 01). CONCLUSION: Estrogen and progesterone receptor expression were lower in the stromal portion of the endometrial polyp than in the glandular portion in postmenopausal patients. Stromal progesterone receptor expression was lower in older patients and there was a relation between low estrogen hormone levels and lower stromal progesterone receptor expression.

The value of vascular endothelial growth factor, pregnancy-associated plasma protein-A, and progesterone for early differentiation of ectopic pregnancies, normal intrauterine pregnancies, and spontaneous miscarriages.

OBJECTIVE: To evaluate the capacity of vascular endothelial growth factor (VEGF), pregnancy-associated plasma protein-A (PAPP-A), and progesterone (P) to discriminate ectopic pregnancies (EP) from nonectopic ones. DESIGN: Prospective, case-controlled study. SETTING: Tertiary care center. PATIENT(S): Twenty-nine women with EP, 29 women with normal intrauterine pregnancy (nIUP), and 28 women with spontaneous miscarriage, all matched for gestational age. INTERVENTION(S): Serum samples were obtained. MAIN OUTCOME MEASURE(S): Serum concentrations of VEGF, PAPP-A, and P were measured. RESULT(S): Serum VEGF concentrations did not show statistically significant differences among women with EP (median, 55.24 pg/mL; range, 0.20-179.24), spontaneous miscarriages (median, 26.24 pg/mL; range, 0.22-365.24), and nIUP (median, 43.24 pg/mL; range, 0.86-101.24). The median level of P was significantly increased in the nIUP group (20.58 ng/mL; range, 13.9-37.04) compared with the other two groups, but there was no statistically significant difference between the spontaneous miscarriage and EP groups. Like P, PAPP-A values were also significantly higher in the nIUP group than in the other two groups, but the difference between PAPP-A values in the EP and spontaneous abortion groups was statistically insignificant. CONCLUSION(S): VEGF, PAPP-A, and P cannot be used to diagnose EPs, but PAPP-A and P can at least be used to differentiate abnormal pregnancies.

A soluble molecule secreted by human blastocysts modulates regulation of HOXA10 expression in an epithelial endometrial cell line.

OBJECTIVE: To determine the existence of a soluble signal, secreted from the human blastocyst embryo, that induces HOXA10 gene expression before cell-cell contact. DESIGN: To analyze, by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), cell-free media that had contained human embryos cultured to the blastocyst stage for a soluble molecule that induces HOXA10 expression in an endometrial epithelial cell line (Ishikawa). SETTING: Assisted reproduction technology program of Yale University, New Haven, Connecticut. PATIENT(S): Patients undergoing intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) cycles. Treatment of Ishikawa cells with blastocyst-conditioned media. MAIN OUTCOME MEASURE(S): Determination of HOXA10 gene expression. RESULT(S): We demonstrate that cell-free media that had contained human embryos cultured to the blastocyst stage contain a soluble molecule that induces HOXA10 expression in an endometrial epithelial cell line (Ishikawa). We found that hCG does not induce HOXA10 in Ishikawa cells. CONCLUSION(S): Soluble molecules induce a well-characterized marker of endometrial receptivity in endometrial cells without blastocyst apposition. Additionally, HOXA10 induction can serve as a means of evaluating human embryos cultured for IVF and ET. High quality embryos may induce local endometrial receptivity before trophectoderm-endometrial contact.