Calligonum comosum (Escanbil) extract exerts anti-angiogenic, anti-proliferative and anti-inflammatory effects on endometriotic lesions.

ETHNOPHARMACOLOGICAL RELEVANCE: Calligonum comosum is a desert plant that is applied in traditional folkloric medicine for the treatment of abnormally heavy or prolonged menstruation and menstrual cramps. Moreover, it has been suggested for the treatment of infertility-causing conditions. Its bioactive chemical constituents inhibit multiple processes, such as angiogenesis, inflammation and invasive tissue growth, which may be beneficial in the therapy of endometriosis. AIM OF THE STUDY: We investigated the effects of Calligonum comosum on the development of endometriotic lesions. MATERIALS AND METHODS: We evaluated the anti-angiogenic activity of Calligonum comosum ethyl acetate fraction (CCEAF) in different in vitro angiogenesis assays. Moreover, we surgically induced endometriotic lesions in BALB/c mice, which received 50 mg/kg Calligonum comosum total extract (CCTE) or vehicle (control) over 4 weeks. The growth, cyst formation, vascularization and immune cell infiltration of the lesions were assessed with high-resolution ultrasound imaging, caliper measurements, histology and immunohistochemistry. RESULTS: CCEAF doses of up to 10 µg/mL did not impair the viability of human dermal microvascular endothelial cells (HDMEC), but dose-dependently suppressed their migration, tube formation and sprouting, indicating a substantial anti-angiogenic effect of CCEAF. Furthermore, CCTE significantly inhibited the growth and cyst formation of developing murine endometriotic lesions when compared to vehicle-treated controls. This was associated with a reduced vascularization, cell proliferation and immune cell infiltration. CONCLUSIONS: Our findings show that Calligonum comosum targets multiple, fundamental processes in the pathogenesis of endometriosis, which may be beneficial for the treatment of this common gynecological disorder.

Effect of the estrus cycle stage on the establishment of murine endometriosis lesions.

BACKGROUND: Establishment of a standardized animal endometriosis model is necessary for evaluation of new drug effects and for explaining different ethological aspects of this disease. For this purpose, we need a model which has more similarity to human endometriosis. OBJECTIVE: Our objective was to establish an autologous endometriosis mouse model based on endogenous estrogen level and analyze the influence of estrus cycle on the maintenance of endometriotic lesions. MATERIALS AND METHODS: In this experimental study, endometriotic lesions were induced in 52 female NMRI mice by suturing uterine tissue samples to the abdominal wall. The transplantation was either performed at proestrus/estrus or at metestrus/diestrus cycles. Urine-soaked beddings from males and also male vasectomized mice were transferred to the cages to synchronize and maintenance of estrus cycle in female mice. The mice were sacrificed after different transplantation periods (2, 4, 6 or 8 wk). The lesions size, macroscopic growth, model success rate, histological and immune-histochemical analyses were assessed at the end. RESULTS: From a total of 200 tissue samples sutured into the peritoneal cavity, 83 endometriotic lesions were confirmed by histopathology (41.5%). Model success rate for proestrus/estrus mice was 60.7% vs. 79.2% for metestrus/diestrus mice. The endometriotic lesions had similar growth in both groups. Number of caspase-3, Ki67-positive cells and CD31-positive micro vessels were also similar in endometriotic lesions of two groups. CONCLUSION: If we maintain the endogenous estrogen levels in mice, we can induce endometriosis mouse model in both proestrus/estrus and metestrus/diestrus cycle without any significant difference.

The effect of valeric on anxiety severity in women undergoing hysterosalpingography.

AIM & SCOPE: Hysterosalpingography (HSG) is the radiographic evaluation of the uterine cavity and fallopian tubes, which is generally assumed as a stressful and painful procedure. This study aims to determine effect of oral Valeric capsules on anxiety severity in women under Hysterosalpingography. METHOD & EXAMINATION: This study, as a double-blind clinical trial, was conducted on 64 infertile women undergoing hysterosalpingography, who referred to radiology ward at Comprehensive Women's hospital. To measure anxiety, visual analog anxiety scale was used 90 minutes before starting procedure, individuals in intervention group (n=32) received a single dose (1,500 mg) of 3 Valeric capsules, together with routine prophylaxy, where routine prophylaxis contains Mefenamic acid 250mg capsules in 30 minutes before procedure, and the same capsules were prescribed to placebo group (n=32) with the same instruction. Anxiety severity before and once 90 minutes after intervention in both groups were measured and compared. RESULTS: There was no difference on anxiety severity before intervention in both groups (p=0.26), and the groups were homogeneous; after intervention, a significant difference on anxiety severity was reported in both groups (p<0/0001), and anxiety score in intervention group compared to placebo reduced statistically. CONCLUSION: Present study indicated that Valeric was effective on reducing anxiety in women undergoing hysterosalpingography.

Impact of the endometrioma on ovarian response and pregnancy rate in in vitro fertilization cycles.

BACKGROUND: Our objective was to evaluate the effect of ovarian endometrioma on ovarian stimulation outcomes in in vitro fertilization cycles (IVF). MATERIALS AND METHODS: In this prospective cohort study, we followed 103 patients who underwent intra-cytoplasmic sperm injection (ICSI) procedures over a 24-months period. The study group consisted of 47 infertile women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm. The control group consisting of 57 patients with mild male factor infertility was candidate for ICSI treatment during the same time period as the study groups. Both groups were compared for number of oocytes retrieved, grades of oocytes, as well as embryo quantity and quality. RESULTS: Our results showed similar follicle numbers, good embryo grades (A or B) and pregnancy rates in the compared groups. However, patients with endometrioma had higher gonadotropin consumption than the control group. The mean number of retrieved oocytes in patients with endometrioma was significantly lower than control group (6.6 ± 3.74 vs. 10.4 ± 5.25) (p<0.001). In addition, patients with endometrioma had significantly lower numbers of metaphase II (MII) oocytes (5 ± 3.21) than controls (8.2 ± 5.4) (p<0.001). In patients with unilateral endometrioma, there were no significant differences in main outcome measures between normal and involved ovaries in the patients with endometrioma. CONCLUSION: Patients with ovarian endometrioma had poor outcome. They showed poor ovarian response with lower total numbers of retrieved oocytes and lower MII oocytes during the stimulation phase; however, it does not affect the total number of embryos transferred per patient, quality of embryos, and pregnancy rate per patient.

Women's health bridges and barriers: a qualitative study.

The authors aimed to understand the social bridges and social barriers to women's health in Iran. We used a qualitative content analysis method and interviewed 22 women. The participants identified appropriate employment, physical exercise, and cultural and educational development as social bridges to women's health. Social barriers to women's health included gender inequalities, burden of responsibility, and financial difficulties. Based on the results of this study, we suggest an interdisciplinary approach to plan social-based health programs in order to improve women's health outcomes in the developing countries such as Iran.

Comparison of easy and difficult embryo transfer outcomes in in vitro fertilization cycles.

BACKGROUND: The aim of this study was to compare the effects of easy and difficult embryo transfers (ET) on implantation and pregnancy rates. MATERIALS AND METHODS: In this prospective study, we analyzed the results of 706 ET procedures over a 12-month period. An easy ET was defined as a transfer that occurred without the use of force or other instrumentation. A difficult ET was defined as the use of force for catheter placement, and/or the use of additional instruments, and/or manipulation. Pregnancy rate was compared between patients with easy or difficult ETs. RESULTS: There was a significantly higher implantation rate in the easy group (21.7%) compared to the difficult group (12.1%, p<0.05).The easy group had a higher pregnancy rate (38.1%) compared to patients who had difficult ETs (21.4%; p<0.05). CONCLUSION: Any uterine manipulation during ET adversely affects in vitro fertilization (IVF). Precaution should be taken to identify possibly difficult ET cases in advance.

Hysteroscopic findings in patients with a history of two implantation failures following in vitro fertilization.

BACKGROUND: This study was designed to evaluate the incidence of uterine pathologies in infertile women with a history of two implantation failures after in vitro fertilization (IVF) and estimate the effect of hysteroscopic correction on achieving a pregnancy in these patients. MATERIALS AND METHODS: The retrospective study population included 238 infertile women attended the outpatient infertility clinic between November 2007 and December 2008. Patients with at least two previous IVF failures were eligible for this study. All patients had normal findings on hysterosalpingography performed prior their first attempt for IVF. Standard transvaginal ultrasonography and diagnostic hysteroscopy were performed in patients before the subsequent IVF attempt. RESULTS: Out of 238 patients with previous IVF failure who underwent hysteroscopic evaluation, 158 patients (66.4%) showed normal uterine cavity. Abnormal cavity was found in 80 patients (33.6%). We found polyp as the most common abnormality (19.7%) in the patients with previous history of IVF failure. The pregnancy rate was similar between IVF failure patients who treated by hysteroscopy for a detected uterine abnormality (24.6%) and similar patients with normal uterine cavity (21.2%) in hysteroscopic examinations. CONCLUSION: The intrauterine lesions diagnosed by hysteroscopy in patients with previous IVF failure ranges from 0.8%-19.7%. Correction of abnormalities such as myoma and polyp showed good outcome, similar to that achieved in patients with a normal hysteroscopy.

Improvement in pregnancy rate by removal of cervical discharge prior to embryo transfer in ICSI cycles: a randomised clinical trial.

AIMS: The present study aimed to evaluate the effect of removing cervical discharge prior to embryo transfer (ET) on pregnancy rates. METHODS: Five hundred and thirty women who were candidates for fresh ET in intracytoplasmic sperm injection (ICSI) cycles were randomly allocated to intervention or control groups. In the intervention group, the cervical canal was cleansed using sterile cotton swabs prior to ET. The control group had routine ET. Multiple logistic regression analysis was used to estimate the adjusted effect of removing the cervical discharge on pregnancy rates. RESULTS: There was a significant difference in pregnancy rates between the two groups. The clinical pregnancy rate was 104/265 (39.2%) in the intervention group compared with 60/265 (22.6%) in the control group (P<0.001). The intervention group also had a higher implantation rate (20.5%) compared with the control group (12.2%; P<0.001). Additionally, the live birth rate in the intervention group (33.6%) was significantly higher than in the control group (17.4%; P<0.001). The logistic regression analysis indicated that the odds ratio of pregnancy in the intervention group was 2.297 (95% CI, 1.552-3.399) compared with the control group. CONCLUSIONS: Removal of cervical discharge prior to ET may have a significant effect on the rate of implantation, pregnancy and live birth.

The effect of low dose human chorionic gonadotropin on follicular response and oocyte maturation in PCOS patients undergoing IVF cycles: a randomized clinical trial of efficacy and safety.

PURPOSE: To compare the efficacy of two regimens of low dose human chorionic gonadotropin (hCG) on follicular response and oocyte maturation in women with polycystic ovarian syndrome (PCOS). METHODS: Ninety women with PCOS who underwent assisted reproduction were eligible for this controlled, prospective, randomized study. Our trial was performed at Royan Institute Reproductive Research Center over a 24-month period. Ovarian stimulation in all groups was initiated with recombinant FSH, 150 IU daily. The dose and duration of FSH treatment were adjusted by monitoring follicular development with ultrasound and estradiol levels. Patients were randomized using a block randomization technique which assigned them to three groups: group A (control group) continued r-FSH until oocyte retrieval. In group B, r-FSH was reduced to 75 IU once the lead follicle reached 14 mm in mean diameter and low dose hCG (100 IU/day) was initiated. In group C, r-FSH was discontinued and low dose hCG (200 IU/day) was begun when the lead follicle reached 14 mm in mean diameter. The main outcome measure was follicular response and oocyte maturation. RESULTS: As compared to the FSH only group, groups which were given low dose hCG had lower gonadotropin consumption and fewer immature oocytes than the control group. No women in the low dose hCG groups developed severe ovarian hyper-stimulation syndrome. Fertilization, implantation and pregnancy rates were similar in the three groups. CONCLUSIONS: A combination of FSH and low dose hCG improved oocyte maturity and preserved outcomes with improved safety and lowered cost.

Appropriate timing of uterine cavity length measurement positively affects assisted reproduction cycle outcome.

An appropriate and easy embryo transfer has a direct impact on pregnancy rates. Proper evaluation of the uterocervical axis and uterine depth are necessary for suitable embryo transfer. The aim of this study was to assess the appropriate time for cervical axis evaluation and uterine measurement. A total of 124 patients undergoing IVF treatment were included in the study. They were divided equally into two groups. In group I (62 women), uterine cavity depth was measured and the uterocervical axis was determined on day 2 or 3 of the menstrual cycle, and in group II (62 women) at the time of oocyte retrieval. There was a statistically significant difference in clinical pregnancy rates between the two groups (P = 0.006). Thirty-four women became pregnant in group I (64.2%) versus 19 women in group II (35.8%). In conclusion, uterine cavity measurement is necessary for suitable embryo transfer. It seems that the time of measurement significantly affects clinical pregnancy rate in IVF cycles. The best time for uterine measurement is on day 2 or 3 of menstruation.

Hysteroscopic polypectomy without cycle cancellation in IVF cycles.

Endometrial polyps destroy the endometrial texture and play an important role in implantation failure. There is no consensus about the management of patients diagnosed with endometrial polyp in IVF cycles. In this study, nine patients who underwent assisted reproduction treatment cycles were diagnosed with endometrial polyps less than 1.5 cm by transvaginal ultrasonography. Eight patients were treated by long protocol and one patient was the recipient of an egg donation cycle. In all patients, polyp resection was performed through hysteroscopic polypectomy. Polypectomy was done during ovarian stimulation in the standard treatment cycles, and during hormone replacement therapy in the recipient of the egg donation cycle. The interval between polyp resection and embryo transfer was 2-16 days. Four patients achieved pregnancy (two twins, two singletons), four patients were unsuccessful, and one pregnancy was a blighted ovum. All of the successful pregnancies are still ongoing. There is a dilemma regarding the management of patients diagnosed with endometrial polyps in assisted reproduction treatment cycles. If polypectomy before embryo transfer in an IVF cycle is proven to be safe, then embryos will be transferred without cycle cancellation. This study included nine patients; further studies with more patients are required to confirm these findings.