Ali Salmassi

Combined Surgical and Hormone Therapy for Endometriosis is the Most Effective Treatment: Prospective, Randomized, Controlled Trial

STUDY OBJECTIVE To evaluate 3 therapy strategies: hormone therapy, surgery, and combined treatment. DESIGN Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING University-based teaching hospital. PATIENTS Four hundred fifty patients with genital endometriosis, aged 18 to 44 years, before first laparoscopy. INTERVENTIONS Patients were randomly assigned to 1 of 3 treatment groups: hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focussed on the endometriosis stage, recurrence of symptoms, and pregnancy rate. MEASUREMENTS AND MAIN RESULTS All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of ≥50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. CONCLUSION In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group.

Circulating level of macrophage colony-stimulating factor can be predictive for human in vitro fertilization outcome

OBJECTIVE To evaluate the level of macrophage colony-stimulating factor (M-CSF) in serum in response to ovarian stimulation (group 1) in low-response (n = 26), moderate-response (n = 40), and high-response (n = 29) patients and to compare its changes (n = 23, group 2) throughout the menstrual cycle between pregnant and nonpregnant patients. DESIGN Randomized controlled trial. SETTING University IVF program. PATIENT(S) Ninety-five women undergoing IVF. INTERVENTION(S) Serum and FF collection from 95 women. MAIN OUTCOME MEASURE(S) The M-CSF concentration was determined by ELISA. RESULT(S) The M-CSF levels in FF were higher than in serum. The M-CSF levels in serum increased from low-, through moderate-, to high-response patients; pregnancy rates were 11.5%, 22.5%, and 51.7%, respectively. Levels of M-CSF in serum increased throughout stimulation until the day of oocyte retrieval and decreased until ET. During the postretrieval days, from the day of ET, through implantation, to the day of confirmation of pregnancy, the M-CSF levels of those patients who became pregnant (n = 13) increased significantly and reached their highest level. After implantation the M-CSF level decreased slightly and reached a plateau during gestation. CONCLUSION(S) Macrophage colony-stimulating factor is involved in follicle development and ovulation and could be an additional predictor for IVF outcome.

Identification of the M-CSF Receptor in Endometriosis by Immunohistochemistry and RT-PCR

Problem:  The aim of this paper is to provide further evidence that the dystopic proliferation of endometriotic epithelia is caused by the stimulation of peritoneal macrophages. It is essential to show that endometriotic epithelial cells express the macrophage colony‐stimulating factor receptor (M‐CSFR) which binds the M‐CSF produced by the peritoneal macrophages.

Circulating concentration of stem cell factor in serum of stimulated IVF patients

Stem cell factor (SCF) plays a major role in haematopoiesis and spermatogenesis, and possibly female fertility. This study investigated the role of changes in SCF concentrations in 74 assisted conception patients. In group 1 (n=74) SCF concentration was assessed in serum and follicular fluid (FF) on the day of follicular puncture (FP) and compared in serum and FF in response to ovarian stimulation between low (n=25), moderate (n=26) and high (n=14) responders. In group 2 (n=30) serum for SCF assessment was collected throughout the menstrual cycle until gestation. SCF concentration related to the number of follicles in serum and in FF decreased from low to moderate and high responders (P<0.001); pregnancy rates were 20.0%, 34.6% and 50.1%, respectively (P=0.05). SCF in serum increased from stimulation days 6-8 to 9-11 and peaked on the day of human chorionic gonadotrophin injection (P=0.03). The SCF concentrations dropped slightly on the day of FP, increased significantly to the day of pregnancy confirmation and reached highest concentration (P=0.02) during gestation. SCF is involved in follicle development and may be a predictor of IVF outcome.

The Role of Interleukin-18 in Serum and Follicular Fluid during In Vitro Fertilization and Intracytoplasmic Sperm Injection.

Cytokines are key modulators of the immune system and play an important role in the ovarian cycle. IL-18 levels in serum and follicular fluid were analyzed in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. The cohort study group consisted of 90 women, who were undergoing IVF or ICSI. The body mass index (BMI) was determined in all patients; IL-18 levels were measured in follicular fluid and serum. IL-18 levels in serum were significantly higher than those in follicular fluid. The median level in serum was 162.75 (80.21) pg/mL and that in follicular fluid, 138.24 (91.78) pg/mL. Women undergoing IVF treatment had lower IL-18 levels in serum (median, 151.19 (90.73) pg/mL) than those treated with ICSI (median, 163.57 (89.97) pg/mL). The correlation between IL-18 levels in serum and BMI was statistically significant, as well as the correlation between IL-18 levels in follicular fluid and ovarian stimulation response (p = 0.003). IL-18 was correlated with the response to ovarian stimulation and was the reason for successful pregnancy after IVF or ICSI treatment. Among other cytokines, IL-18 appears to be a promising prognostic marker of success in reproductive treatment and should be evaluated as such in further prospective studies.

Apoptosis Resistance in Endometriosis

INTRODUCTION In a cytological analysis of endometriotic lesions neither granulocytes nor cytotoxic T-cells appear in an appreciable number. Based on this observation we aimed to know, whether programmed cell death plays an essential role in the destruction of dystopic endometrium. Disturbances of the physiological mechanisms of apoptosis, a persistence of endometrial tissue could explain the disease. Another aspect of this consideration is the proliferation competence of the dystopic mucous membrane. METHODS Endometriotic lesions of 15 patients were examined through a combined measurement of apoptosis activity with the TUNEL technique (terminal deoxyribosyltransferase mediated dUTP Nick End Labeling) and the proliferation activity (with the help of the Ki-67-Antigens using the monoclonal antibody Ki-S5). RESULTS Twelve out of 15 women studied showed a positive apoptotic activity of 3-47% with a proliferation activity of 2-25% of epithelial cells. Therefore we concluded that the persistence of dystopic endometrium requires proliferative epithelial cells from middle to lower endometrial layers. CONCLUSION A dystopia misalignment of the epithelia of the upper layers of the functionalism can be rapidly eliminated by apoptotic procedures.

Distended jugular lymphatic sacs in fetuses with increased nuchal translucency: correlation with first-trimester findings in aberrant karyotypes

Abstract Objective: We investigated the prognostic relevance of ultrasound visibility of distendend jugular lymphatic sacs (JLS) in fetuses with aberrant karyotypes in First-trimester-screening. Furthermore we tried to differentiate between increased nuchal translucency (NT) and cystic hygroma colli. Methods: We performed a retrospective single center study in 1874 patients presenting for First-trimester-screening between 2009 and 2013. All fetuses with an abnormal risk calculation and NT > 2.5 mm (95th percentile) were reviewed for ultrasound visibility of JLS. A group of 30 fetuses with normal risk calculation served as control. Karyotyping was performed by chorionic-villi-sampling or amniocentesis, respectively. Results: In a total of 2030 fetuses 70 (3.44%) with pathologic first-trimester-screening results showed either aberrant karyotypes or severe ultrasound pathologies. Main aberrant karyotypes were trisomy 21 (25), trisomy 18 (16), trisomy 13(six), Monosomy X (four), 47, XYY or 47, XXX (three) and Noonan’ syndrome (two). Distended JLS were visible in 47% of all cases. Statistical anaylsis found a significant correlation between NT and JLS size for the fetuses with trisomies 21, 18 and 13 (r = 0.53, p < 0.002). Cystic hygroma colli was present in all Turner and Noonan syndromes. Conclusions: Distended JLS have a strong correlation with abnormal karyotypes and increased nuchal translucency. Karyotyping should be offered in these cases.