Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

High omega-3:omega-6 fatty acid ratios in culture medium reduce endometrial-cell survival in combined endometrial gland and stromal cell cultures from women with and without endometriosis

OBJECTIVE: To study the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) on in vitro proliferation of endometrial cells and their production of the cytokine interleukin-8 (IL-8). DESIGN: In vitro study. SETTING: Obstetrics and gynecology department, University of Aberdeen. PATIENT(S): Women attending an infertility clinic. INTERVENTION(S): In vitro cell cultures using culture mediums supplemented with normal and high ratios of omega-3 PUFA and omega-6 PUFA. MAIN OUTCOME MEASURE(S): In vitro survival and production of IL-8 by dispersed endometrial cells. RESULT(S): In vitro survival of endometrial cells from women with and without endometriosis was significantly reduced in the presence of high omega-3:omega-6 PUFA ratios compared with cells incubated in the absence of fatty acids, in balanced omega-3:omega-6 PUFA ratios, and in high omega-6:omega-3 PUFA ratios. Endometrial cells from women with endometriosis secreted higher concentrations of IL-8, especially in the presence of high omega-3:omega-6 PUFA ratios. CONCLUSION(S): omega-3 PUFA may have a suppressive effect on the in vitro survival of endometrial cells and omega-3 PUFA be useful in the management of endometriosis by reducing the inflammatory response and modulating cytokine function.     

Do Lunar Phases Affect Conception Rates in Assisted Reproduction?

Objectives: To assess the effect of the phases of the moon on pregnancy rates in humans following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment.Design: Retrospective, observational study.Setting: Reproductive Medicine Unit, Liverpool Womens Hospital.Patient: Complete data for all women undergoing assisted conception procedures over a period of 13 years (1995–2002).Intervention: Assisted conception procedures-IVF and ICSI.Main outcome measures: Biochemical pregnancy that is positive pregnancy test result following embryo transfer.Results: There was no significant effect of any lunar phase on the incidence of biochemical pregnancy (p-value 0.71). Age of the woman significantly affects the chances of pregnancy, (OR 0.95, 95% CI 0.91, 0.998, and p-value 0.04). The chances of pregnancy rises significantly with increase in the number of embryos replaced from 1 to 2 (OR 2.97, CI 1.36, 6.48, and p-value 0.01).Conclusion: Pregnancy rates in humans, following assisted conception, appears to be independent of the effect of the lunar phase during which embryo transfer is carried out.     

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasoundat the time of embryo transfer to guide replacement, improvedpregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study andpower calculation suggested that at least 2000 embryo transferswere required to demonstrate a difference of 5%, for a testwith 80% power and Type 1 error 0.05. Randomization, data entryand analysis were arranged independently. Randomization wasstratified for age and fresh/frozen embryo transfer. Analysiswas by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birthrates between the two groups. The clinical pregnancy rate forultrasound-guided embryo transfer was 22% and for non-ultrasound-guidedembryo transfer was 23% (odds ratio: 0.96; 95% confidence interval:0.79–1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transferimproved clinical pregnancy rates and live birth rates in assistedconception. We used an appropriately powered RCT design. Wedid not demonstrate a difference. This outcome is at odds withthe UKs National Institute of Clinical Excellence recommendationsfor fertility treatment (Fertility Assessment and Treatmentfor People with Fertility Problems. London, UK: RCOG Press,2004, 112.) which used a meta-analysis of four smaller trials(range 362–800 patients, totalling 2051 embryo transfers)to conclude that ultrasound should be offered. We suggest thatthe current Cochrane review should be updated with data fromour trial and recommend that consideration is given to accountingfor heterogeneity between the included trials.     

Duration of luteal support after IVF is important,so why is there no consistency in practice? The results of a dynamic survey of practice in the United Kingdom

Luteal support is considered as an essential component of IVF treatment following ovarian stimulation and embryo transfer. Several studies have consistently demonstrated a benefit of luteal support compared with no treatment and whilst a number of preparations are available, no product has been demonstrated as superior. There is an emerging body of evidence which suggests that extension of luteal support beyond biochemical pregnancy does not confer a benefit in terms of successful pregnancy outcome. We performed two surveys separated by 5 years of practice evolution, with the latter reporting on the use of luteal support in all IVF clinics in the UK. All clinics reported utilising luteal support with the majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there was no consensus on the optimal duration of luteal support. Whilst 24% of clinics withdrew luteal support at biochemical confirmation of pregnancy, 40% continued treatment until 12 weeks gestation. Several clinics even extended luteal support beyond 12 weeks gestation. We observed no difference in practice based on the size of the IVF unit or treatment funding source. Although there was some change in practice between surveys in many clinics, there was no uniformity in the direction of change.     

Cystic fibrosis screening in assisted reproduction

PURPOSE OF REVIEW: The purpose of this review is to discuss the incidence of cystic fibrosis in the general population, in ethnically diverse populations and specifically in couples needing assisted reproduction caused by male factor subfertility. We review the current understanding of risks for reproductive couples and discuss ideal screening strategies. RECENT FINDINGS: In ethnically diverse populations, a large difference in clinical sensitivity and birth prevalence exists between the broad racial/ethnic groups examined. Extensive data clearly demonstrate the cost-effectiveness of cystic fibrosis screening. Testing for cystic fibrosis gene mutations is reliable and, with a 26-mutation panel, nearly 90% of possible severe mutations can be detected. To halve the incidence of cystic fibrosis in the community, by offering genetic testing of the fetus if both partners are carrier positive, may also be possible. SUMMARY: Recent guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for cystic fibrosis carrier status for purposes of genetic counselling. In ethnically diverse populations, ethnic-specific mutations should be included in the mutation panels.     

Effect of interleukin-8 (IL-8), anti-IL-8, and IL-12 on endometrial cell survival in combined endometrial gland and stromal cell cultures derived from women with and without endometriosis.

OBJECTIVE: To study the affects of interleukin-8 (IL-8), anti-IL-8, and IL-12 on in vitro proliferation of endometrial cells. DESIGN: An in vitro study. SETTING: Department of Obstetrics and Gynecology, University of Aberdeen, UK. PATIENT(S): Women attending a fertility clinic. INTERVENTION(S): In vitro cell cultures using culture media supplemented with IL-8 (100 ng/mL, 200 ng/mL, and 500 ng/mL), IL-12 (1 ng/mL, 5 ng/mL, and 25 ng/mL), and anti-IL-8 (0.1 microg/mL, 1 microg/mL, 10 microg/mL). MAIN OUTCOME MEASURE(S): In vitro survival of dispersed endometrial cells (combined epithelial and glandular) at 5 and 9 days of culture. RESULT(S): There was a dose-dependent stimulatory effect of IL-8 on survival of cells. From women with and without endometriosis, IL-12 at 1 ng/mL significantly inhibited the survival of endometrial cells from women without endometriosis as compared with cells from women with endometriosis. At 1 microg/mL, anti-IL-8 significantly inhibited the survival of endometrial cells from women with endometriosis compared with cells from women without endometriosis on day 5 of culture. CONCLUSION(S): Our findings confirm the stimulatory effects of IL-8 and its possible role in the pathogenesis of endometriosis. The effects of IL-12 and anti-IL-8 on endometrial cell survival varied according to the disease state and the concentration of the cytokines. Future in vitro studies on the role of anti-IL-8 and IL-12 should aim to use a greater range of concentrations and a higher density of endometrial cells in cultures supplemented with monocytes.