Follicular fluid expression of alpha-defensins and their role in ovulation.

INTRODUCTION: Defensins are cytotoxic peptides and have a well-defined role in host defense. Human alpha defensins 1-3 (HNP1-3) are primarily produced by peripheral neutrophils and constitute about 50% of the azurphil granule protein. Studies have suggested that peripheral neutrophils and the resident neutrophils in the ovary enhance the release of IL-8 and TNF-alpha that play a role in ovulation and influence fertilisation rate and IVF outcome. The production of HNP1-3 by follicular fluid and its role in ovulation has never studied. The aim of this study was to demonstrate the presence of HNP1-3 in follicular fluid and to ascertain its correlation with fertilisation rate and IVF outcome. METHOD: Women attending the Reproductive Medicine Unit at Liverpool Women's Hospital UK, for IVF treatment were invited to participate in the study. Sixty-three patients were recruited for the study and underwent controlled ovarian stimulation and oocyte retrieval according to the unit's protocol. Fluid from the first follicle only was collected to minimise blood contamination of the sample and HNP1-3 was estimated using ELISA technique. RESULTS: HNP1-3 was detected in follicular fluid samples. The concentration did not correlate with the fertilisation rate (r=0.01). The concentrations were also not significantly different in the women who did or did not become pregnant following treatment. Subgroup analysis showed that women with endometriosis were not more likely to have higher levels of the HNP1-3 when compared with controls (male factor infertility group). CONCLUSION: This is the first study to show the expression of HNP1-3 in follicular fluid. HNP1-3 concentrations did not correlate with fertilisation rate or IVF outcome. It did not show an increased expression of HNP1-3 in fluid collected from women with endometriosis suggesting that inflammatory processes associated with endometriosis do not influence HNP1-3 concentration in the follicular fluid. Further studies to evaluate the correlation between HNP1-3 and IL-8 and TNF-alpha may clarify the role of defensins in ovulation.

The expression of human alpha and beta defensin in the endometrium and their effect on implantation.

BACKGROUND: Alpha and beta defensins have been isolated from various human tissues and form an important part of the innate immune system. Their role in implantation of the embryo has not yet been studied. This study was designed to detect both alpha and beta defensins in the mid luteal phase endometrium and investigate the correlation between the defensin expression and implantation of the embryo. METHOD AND RESULTS: An experimental study was designed to detect alpha defensin (HNP1-3) and beta defensin (HBD1) in midluteal phase endometrial samples obtained from women attending the IVF unit at the Liverpool Women's Hospital, UK. Samples were obtained at least two menstrual cycles before IVF treatment was commenced. Immunohistochemical staining was conducted to estimate defensin expression. Some endometrial stromal cells stained positive for HNP1-3 during the midluteal phase. HNP1-3 expression is significantly higher in cases presenting with female factor infertility as compared with purely male factor infertility. A significant increase was not observed in tubal factor or endometriosis when considered separately. Endometrial stromal neutrophils were shown to be the main source of endometrial HNP1-3. HBD1 was the only beta defensin detected by immunochemical staining in the midluteal phase endometrium. The intensity of staining was significantly different in the endometrial stroma, luminal and glandular epithelia. HBD1 expression is not significantly higher in female factor infertility. CONCLUSION: The study confirmed secretion of HNP1-3 by endometrial stromal neutrophils. Glandular epithelium is the main source of HBD1 expression in the human endometrium. HNP1-3 shows increased expression in female factor infertility. HBD1 expression is not higher in female factor infertility. These defensins do not appear to influence implantation.

Does repeated electro-ejaculation improve sperm quality in spinal cord injured men?

STUDY DESIGN: Retrospective analysis. OBJECTIVES: To assess the effect of repeated electro-ejaculation on the sperm quality in spinal cord injured men. SETTING: Regional Spinal Injuries Unit, Southport, UK and Hewitt Center for Reproductive Medicine, Liverpool, UK. METHOD: Retrospective, observational study of men with spinal cord injuries undergoing repeated electro-ejaculation as a part of fertility treatment. RESULT: There was no improvement in the volume, sperm concentration, motility or the total motile count in the successive antegrade and retrograde samples following repeated electro-ejaculations. CONCLUSION: Electro-ejaculation is an invasive procedure and its use should be restricted to obtaining semen sample for carrying out assisted conception procedures only.

Growing concern over the safety of using mobile phones and male fertility.

There are growing concerns about the possible hazards of electromagnetic waves emitted by mobile phones on human health. One of the biggest concerns is their possible association with increased risk of cancer and their possible effects on cellular DNA. Electromagnetic waves can inflict their results through both thermal and non-thermal effects. There are many animal studies that show that electromagnetic waves have a wide range of damaging effects on the male reproductive system and sperm parameters. However, similar studies are quite limited in humans, and the results of animal studies should be interpreted with caution when considering their application to humans. Large controlled studies are required before confirming such possible effects on male fertility.

A case of rapid deterioration in sperm quality following spinal cord injury.

STUDY DESIGN: Case report. SETTING: Northwest Regional Spinal Injuries Unit, Southport, UK and Reproductive Medicine Unit, Liverpool Women's Hospital, Liverpool, UK. CASE REPORT: A 28-year-old man suffered from paraplegia on sustaining a fall. Fertility preservation was an important aspect of his treatment and electro-ejaculation and cryopreservation of sperm was possible within days of sustaining the fall. The sperm samples obtained subsequently showed a rapid decline in quality. Frozen sperm from the first normal ejaculate obtained soon after the injury was used for assisted reproduction and has resulted in an ongoing pregnancy. CONCLUSION: This case highlights the importance of collection and freezing of seminal fluid within 2 weeks of spinal cord injury (SCI), or earlier to improve fertility outcomes in spinal cord-injured men, as the clinical stability of the patient may allow.

Cystic fibrosis mutation screening before assisted reproduction.

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians, with a reported incidence of one in 2500. In 97-98% of men with CF, a congenital bilateral absence of the vas deferens (CBAVD) blocks the transport of spermatozoa from testicular or epididymal structures to the outer genital tract, resulting in azoospermia. Abnormalities in semen parameters have also been identified in males with CF. Around 10% of obstructive azoospermia is congenital and is due to mutations the CF gene. It is therefore suggested that men who have CBAVD should be considered for CF screening prior to intracytoplasmic sperm injection (ICSI) treatment. Men with azoospermia of unknown origin should also be considered for screening. Couples requesting surgical sperm retrieval/ICSI should therefore be advised and counselled to bear an elevated risk for CF in their offspring. Counselling of these couples is vitally important in order to help them understand and cope with the diagnosis.

Lack of association of the common immunologically anomalous LH with endometriosis.

BACKGROUND: Subfertile women with endometriosis have been reported to demonstrate impaired follicular growth, ovulatory dysfunction and disturbed LH patterns. In addition, abnormal LH and/or LH receptors have been linked with endometriosis-associated infertility. Carriers of a variant of the beta-subunit of luteinizing hormone (V-LH) are largely healthy; however, differences in their gonadal function such as alterations in gonadal steroidogenesis, ovarian reserve, pubertal development and predisposition to diseases such as infertility and polycystic ovarian disease have been found. METHODS AND RESULTS: To explore the possible relationship between endometriosis and V-LH, we examined its frequency in 230 women undergoing laparoscopic surgery for the investigation of infertility. For the entire study population, 185 (80.4%) were wild type; 42 (18.3%) were heterozygous; and three (1.3%) were homozygous for V-LH. No difference was found between women with (n = 85) and without (n = 145) endometriosis concerning the frequency of the type of LH. CONCLUSION: Our results do not support the hypothesis that the variant form of LH is associated with an altered risk of endometriosis in the population tested.

New considerations for the pathogenesis of endometriosis.

OBJECTIVES: To review the available evidence regarding the immunological, epidemiological and other factors involved in the pathogenesis of endometriosis. METHODS: Literature review. RESULTS: Endometriosis remains a poorly-understood disease of unknown etiology and pathogenesis. CONCLUSIONS: There is evidence to suggest that alterations in the immune response, whether genetically transmitted or environmentally induced, predispose women to the ectopic implantation of endometrial cells transported into the peritoneal cavity by way of retrograde menstruation. This predisposition may exist because of an impaired peritoneal clearing of endometrial cells and fragments or because of pathological angiogenesis.

Concentration of interleukin-12 in the peritoneal fluid is not influenced by the presence of endometriosis, its stage or the phase of the menstrual cycle.

BACKGROUND: IL-12 is a key immunomodulatory cytokine. Its presence or concentration in peritoneal fluid is not related to the presence of endometriosis or the stage of the disease. A study was carried out to gain insight into the role of IL-12 in the development and maintenance of endometriosis in relation to menstrual cycle. METHODS: A prospective study recruiting 64 consecutive women undergoing laparoscopic surgery for benign gynecological indications. Peritoneal fluid was obtained during laparoscopy. Concentration of IL-12 was measured and correlated to the presence of endometriosis, its stage and the phase of the menstrual cycle. RESULT(S): Peritoneal fluid concentrations of IL-12 showed no correlation with the presence of endometriosis, the AFS stage of the disease or the phase of the menstrual cycle. CONCLUSION(S): IL-12 is a normal constituent of peritoneal fluid in around one third of the population tested and is not involved in the pathogenesis of endometriosis at any stage of the disease or the phase of the menstrual cycle.