The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis.

BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CONCLUSIONS: Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.

Current understanding of hypothalamic amenorrhoea.

Hypothalamic amenorrhoea (HA) accounts for approximately 30% of cases of secondary amenorrhoea in women of reproductive age. It is caused by deficient secretion of hypothalamic gonadotrophin-releasing hormone, which in turn leads to failure of pituitary gonadotrophin and gonadal steroid release. Functional HA (FHA) is defined as HA occurring in the absence of a structural lesion and is predominantly caused by significant weight loss, intense exercise or stress. Treatment of FHA is crucial in avoiding the long-term health consequences on fertility and bone health, in addition to reducing psychological morbidity. This article summarises our understanding of the mechanisms underlying FHA, the evidence base for its clinical management and emerging therapies.

Negative histology with surgically treated tubal ectopic pregnancies - A retrospective cohort study.

OBJECTIVE: To determine the outcome of histological examinations of surgical specimens obtained from treatment of tubal ectopic pregnancy and to correlate with clinical findings, pre-operative ultrasound scans and the type of surgery. STUDY DESIGN: A retrospective cohort study of 941 women diagnosed with a tubal ectopic pregnancy in the Early Pregnancy Unit and having surgical treatment at King's College Hospital, London. Clinical and ultrasound data had been entered contemporaneously on our electronic early pregnancy database and hospital clinical records over an 11year period from 2004 to 2014. Demographic data, clinical history, ultrasound scan parameters, type of surgical management and histological diagnosis were recorded. The primary outcome measure was the presence or absence of chorionic villi in the surgical specimen. Data were analysed using Mann Whitney U test for non-parametric data, relative risk for categorical data and binomial logistic regression. RESULTS: A surgical specimen was obtained in 925 cases. Of these, 881/925 (95.2%) were positive for the presence of chorionic villi on histological examination. Patients with negative histology had a lower median gestational age, smaller ectopic pregnancies and lower serum human chorionic gonadotrophin levels. The relative risk of negative histology was significantly higher with a solid ectopic pregnancy on ultrasound (RR1.91, 95% CI 1.07-3.4) and with conservative surgery (RR 3.68, 95% CI 1.25-10.77). The relative risk was significantly lower with the presence of embryonic cardiac activity (RR 0.12, 95% CI 0.02-0.85). Only the serum hCG level was a significant predictor of negative histology on logistic regression analysis (p=0.048). In 39/44 women with negative histology, the human chorionic gonadotrophin level declined after surgery with no further intervention. Five of the 44 required a second surgical procedure as the ectopic pregnancy had been missed at the initial surgery and did not resolve. CONCLUSION: There is lack of histological confirmation of sonographically diagnosed and surgically confirmed ectopic pregnancies in approximately 5% of cases, making this a relatively common finding following surgical treatment of tubal ectopic pregnancy. Clinicians should be aware of this when counselling women with tubal ectopic pregnancies about to undergo surgery, include this risk in the consent process and plan post-surgical follow up with this in mind.

The impact of self-hypnosis and Johrei on lymphocyte subpopulations at exam time: a controlled study.

In a prospective randomised controlled trial, 48 students were randomly assigned to stress reduction training before exams with self-hypnosis, Johrei or a mock neurofeedback relaxation control. Peripheral blood lymphocyte subpopulations and self-reported stress (Perceived Stress Scale) were measured before training and 1-2 months later as exams approached. Absolute number and percentages of CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocytes, CD3(-)CD56(+) Natural Killer cells (NK cells) and NK cell cytotoxic activity was measured from venous blood. Stressed participants showed small but significant declines in both CD3(-)CD56(+) NK cell percentages and NK cell cytotoxic activity levels while CD3(+)CD4(+) T cell percentages increased, changes supported by correlations with perceived stress. The effects of stress were moderated in those who learned Johrei at exam time; 11/12 showed increases in CD3(-)CD56(+) NK cell percentages with decreased percentages of CD3(+)CD4(+) T cells, effects not seen in the relaxation control group. Stress was also buffered in those who learned and practised self-hypnosis in whom CD3(-)CD56(+) NK cell and CD3(+)CD4(+) T cell levels were maintained, and whose CD3(+)CD8(+) T cell percentages, shown previously to decline with exams, increased. The results compliment beneficial effects on mood of self-hypnosis and Johrei. The results are in keeping with beneficial influences of self-hypnosis and provide the first evidence of the suggestive value of the Japanese Johrei procedure for stress reduction, which clearly warrants further investigation.