Avi Harlev

Cigarette Smoking and Semen Quality: A New Meta-analysis Examining the Effect of the 2010 World Health Organization Laboratory Methods for the Examination of Human Semen

OBJECTIVE Approximately 37% of men of reproductive age smoke cigarettes, with Europe having the highest tobacco use among all the World Health Organization (WHO) regions. Toxins from tobacco smoking can potentially affect sperm development and function, with a negative effect on semen parameters. Given the high prevalence of smoking and recent changes in the WHO laboratory methods for the examination of human semen, the role of this exposure in face of new WHO methods needs to be clarified. EVIDENCE ACQUISITION We conducted a systematic review, followed by a meta-analysis, to determine whether cigarette smoking affects human semen parameters. PubMed, Saint Josephs University Discover, and Google Scholar were used to identify relevant studies published after release of the latest WHO methods for laboratory evaluation of human semen. Participants were from fertility/urologic clinics and andrology laboratories. The outcome measures were semen volume, sperm concentration, motility, and morphology, the parameters usually used in clinical settings to assess fertility. EVIDENCE SYNTHESIS Twenty studies with 5865 participants were included in the meta-analysis. Exposure to cigarette smoking was associated with reduced sperm count (mean difference [MD]: -9.72×106/ml; 95% confidence interval [CI], -13.32 to -6.12), motility (MD: -3.48%; 95% CI, -5.53 to -1.44), and morphology (MD: -1.37%; 95% CI, -2.63 to -0.11). Subgroup analyses indicated that effect size was higher in infertile men than in the general population and in moderate/heavy smokers than in mild smokers. The overall effect size on semen volume, sperm count, and motility remained similar when 2010 and earlier WHO manuals were used for semen analysis but was lower with regard to sperm morphology. CONCLUSIONS Our results suggest that cigarette smoking has an overall negative effect on semen parameters. The latest WHO laboratory methods for the examination of human semen had a minimal impact on the magnitude of effect size, thus confirming the observed negative effect of smoking on conventional semen parameters. PATIENT SUMMARY A new systematic review and meta-analysis comprising 5865 men shows that cigarette smoking is associated with reduced sperm count and motility. Deterioration of semen quality is more pronounced in moderate and heavy smokers.

New insights on glucose pathophysiology in gestational diabetes and insulin resistance.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition of GDM does not preclude the possibility that unrecognized glucose intolerance may have existed before the pregnancy, and the definition applies whether insulin, oral antidiabetic agents, or dietary modification is used for treatment. Approximately 7% of all pregnancies in the United States are complicated by gestational diabetes resulting in more than 200,000 cases annually, but the prevalence ranges from 1% to 14% of all pregnancies depending on the population studied and the diagnostic tests used. Despite the better detection of GDM and recognition of its adverse consequences for mother and baby in many countries, there is still no consensus regarding GDM pathophysiology; as a result, diagnosis and treatment of GDM remain controversial. A better understanding of obesity along with new studies in GDM has identified the intra-abdominal metabolically active adipose tissue as a major factor in the pathophysiology of GDM. This review examines recent research regarding the link between obesity and glucose intolerance and highlights studies in the areas of genetics, glucose transport, and adipokines.

Smoking and Male Infertility: An Evidence-Based Review.

Many studies have reported that the contents of cigarette smoke negatively affect sperm parameters, seminal plasma, and various other fertility factors. Nevertheless, the actual effect of smoking on male fertility is not clear. The effect of smoking on semen parameters is based on the well-established biological finding that smoking increases the presence of reactive oxygen species, thereby resulting in oxidative stress (OS). OS has devastating effects on sperm parameters, such as viability and morphology, and impairs sperm function, hence reducing male fertility. However, not all studies have come to the same conclusions. This review sheds light upon the arguable association between smoking and male fertility and also assesses the impact of non-smoking routes of tobacco consumption on male infertility. It also highlights the evidence that links smoking with male infertility, including newly emerging genetic and epigenetic data, and discusses the clinical implications thereof.

Bibliometrics: tracking research impact by selecting the appropriate metrics

Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist′s profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact.

Effect of varicocele on semen characteristics according to the new 2010 World Health Organization criteria: a systematic review and meta-analysis.

This study investigated the effects of varicocele on semen parameters in infertile men based on the new 2010 World Health Organization laboratory manual for the examination of human semen. Semen analysis results (volume, sperm count, motility, and morphology) were the primary outcomes. An electronic search to collect the data was conducted using the Medline/PubMed, SJU discover, and Google Scholar databases. We searched articles published from 2010 to August 2015, i.e., after the publication of the 2010 WHO manual. We included only those studies that reported the actual semen parameters of adult infertile men diagnosed with clinical varicocele and contained a control group of either fertile men or normozoospermic men who were not diagnosed with varicocele. Ten studies were included in the meta-analysis, involving 1232 men. Varicocele was associated with reduced sperm count (mean difference: −44.48 × 10 [6] ml−1 ; 95% CI: −61.45, −27.51 × 10 [6] ml−1 ; P < 0.001), motility (mean difference: −26.67%; 95% CI: −34.27, −19.08; P < 0.001), and morphology (mean difference: −19.68%; 95% CI: −29.28, −10.07; P < 0.001) but not semen volume (mean difference: −0.23 ml; 95% CI: −0.64, 0.17). Subgroup analyses indicated that the magnitude of effect was influenced by control subtype but not WHO laboratory manual edition used for semen assessment. We conclude that varicocele is a significant risk factor that negatively affects semen quality, but the observed pooled effect size on semen parameters does not seem to be affected by the WHO laboratory manual edition. Given most of the studies published after 2010 still utilized the 1999 manual for semen analysis, further research is required to fully understand the clinical implication of the 2010 WHO laboratory manual on the association between varicocele and semen parameters.

Targeting oxidative stress to treat endometriosis

Introduction: Endometriosis affects 10% of women of reproductive age. It is defined as the presence of implanted active endometrial tissue outside the uterine cavity. The exact pathophysiology of endometriosis is still uncertain, although several optional etiological theories have been suggested. Being so common, a novel treatment for endometriosis is widely quested. Recent studies addressing the pathological characteristics of endometriosis have revealed a vicious cycle in which oxidative stress (OS) is generated, which in turn facilitates the implantation of the ectopic endometrium. At the same time, the generation of high amounts of reactive oxygen species further triggers a state of OS. Areas covered: The author examined the evidence associating OS and endometriosis. After establishing an association, a search for antioxidant agents that were investigated specifically on endometriosis patients are described including Vitamins C and E, melatonin, resveratrol, xanthohumol and epigallocatechin-3-gallate. A significant effect of all the reviewed antioxidants on endometriosis is reported. Expert opinion: Aiming for the reduction of OS as the treatment goal for endometriosis looks promising. However, since most of the studies are either in vitro or are animal based, further studies on human subjects are deemed necessary to elucidate the impact of OS reduction on patients with endometriosis.

Risk factors for early postpartum hemorrhage (PPH) in the first vaginal delivery, and obstetrical outcomes in subsequent pregnancy

Abstract Objective: To investigate risk factors for postpartum hemorrhage (PPH) in vaginal deliveries and the influence of previous PPH on the subsequent pregnancy. Study design: A retrospective cohort study including first singleton deliveries between the years 1988 and 2012 was performed comparing deliveries with and without PPH. In addition, perinatal outcomes of the subsequent pregnancy were evaluated. Multivariable analysis was performed to control for confounders. Results: PPH complicated 0.8% of all first vaginal deliveries. Significant risk factors for PPH in vaginal delivery, using a multiple logistic regression model, were: post-term pregnancy, fertility treatments, hypertensive disorders, labor dystocia during the 2nd, and perineal tears grade 2 and 3, respectively. Previous PPH was found to be an independent risk factor for PPH in the subsequent pregnancy. Moreover, previous PPH was found to be a significant risk factor for cesarean section (CS) deliver, to complicate delivery with revision of uterus cavity, anemia, and to require blood transfusion. Conclusion: Previous PPH poses a risk for recurrent PPH in subsequent delivery and an increased risk for CS. As PPH remains one of the major causes of maternal morbidity, this study strengthens the need for a comprehensive evaluation of prior PPH as a major risk factor for PPH recurrence.

Reproductive outcomes following uterine septum resection

Abstract Objective: To determine the reproductive outcome following hysteroscopic septum resection in women with a septated uterus and a history of spontaneous miscarriages or premature deliveries. Study design: A retrospective, cohort study investigating reproductive outcomes following septum resection was conducted. Patients who had no other apparent cause for spontaneous miscarriage or preterm delivery were included in the study. Reproductive outcomes were compared between pregnancies prior to and after the septum resection. Multiple pregnancies were excluded. Results: Twenty-eight patients met the inclusion criteria with a total of 85 pregnancies, 45 prior and 40 after septectomy. The mean gestational age increased from 33.73 ± 6.27 (weeks) prior to the resection to 38.47 ± 1.71 (weeks) after it (p < 0.05). The mean birth weight increased from 2520 ± 764.4 (g) to 3202.6 ± 630.2 (g) after the resection. Spontaneous miscarriage rate dropped from 63.6% to 12.5%. Multivariate analysis models showed uterine septectomy to be independently associated with increased gestational age at delivery (β = 0.606, Adjusted R2 = 0.328, CI 10.647–20.612, p < 0.01), increased birth weight (β = 0.424, Adjusted R2 = 0.129, CI 202.097–1210.287, p < 0.01) and with lower risk for preterm delivery (OR = 0.073, CI 0.16–0.327, p < 0.01). Conclusion: Hysetroscopic resection of a uterine septum improves reproductive outcomes in women with a septated uterus and a history of spontaneous miscarriages or premature deliveries.

Is antenatal depression associated with adverse obstetric and perinatal outcomes

Abstract Objective: To examine whether a pre-gestational diagnosis of depression is a risk factor for adverse obstetric and neonatal outcome. Study design: A retrospective cohort study investigating maternal characteristics, obstetrical and perinatal outcomes in singleton pregnancies of women with and without a diagnosis of depression was conducted. A pre-gestational diagnosis of depression was made by a psychiatrist or family physician and was recorded in the patients’ chart. Multiple logistic regression models were used to control for possible confounders. Results: During the study period, 256 312 deliveries occurred. Of which, 221 women (0.1%) had a pre-gestational diagnosis of depression. When examining obstetric outcomes, women with a diagnosis of depression were older (32.05 ± 5.772 versus 28.56 ± 5.851) and smokers (7.2% versus 1.1%), had a higher rate of preterm deliveries (37.99 ± 2.989 versus 39.02 ± 2.249) and cesarean sections (CS; 28.5% versus 13.6%) in comparison to the control group. When examining neonatal outcomes, neonates of women diagnosed with depression had a lower birth mean weight (3.038.47 ± 649.6 versus 3183.44 ± 551.8) and increased rates of perinatal mortality (3.2% versus 1.3%). Using a multiple logistic regression model, with perinatal mortality as the outcome variable to control for cofounders such as maternal age, preterm birth, chronic hypertension and gestational diabetes mellitus, a diagnosis of depression was not found to be an independent risk factor for perinatal mortality. Another multiple logistic regression model found advanced maternal age, smoking, preterm birth and labor induction to be associated with a diagnosis of depression. Conclusion: Pregnant women diagnosed with depression are at an increased risk for preterm birth, low birth weight, and CSs. However, it was not associated with increased rates of perinatal mortality.

An initial miscarriage is associated with adverse pregnancy outcomes in the following pregnancy

OBJECTIVE The objective of the study was to determine whether 1 previous miscarriage is associated with an increased rate of adverse pregnancy outcomes in the following pregnancy. STUDY DESIGN Second pregnancies of women with and without a miscarriage in their initial pregnancy were compared. Multivariable logistic regression models were constructed to control for confounders. RESULTS Of 35,125 singleton deliveries in the second pregnancy, 5777 (16.4%) were of patients with an initial miscarriage. Multivariable analysis showed a significant association between a previous miscarriage and the following adverse pregnancy outcomes including premature rupture of membranes (odds ratio [OR], 2.22; 95% confidence interval [CI], 2.01-2.44), preterm delivery (OR, 1.34; 95% CI, 1.21-1.48), intrauterine growth restriction (OR, 1.24; 95% CI, 1.04-1.47), hypertensive disorders (OR 1.41; 95% CI 1.07-1.85), preeclampsia (OR, 1.63; 95% CI, 1.22-2.18), and cesarean delivery (OR, 1.59; 95% CI, 1.46-1.73). Perinatal mortality was significantly higher among women with an initial miscarriage (1.6% vs 1.0%; P < .001). CONCLUSION An initial miscarriage is independently associated with adverse pregnancy outcomes.