Nick A. Bersinger

Semen quality of male smokers and nonsmokers in infertile couples

OBJECTIVE To investigate the effect of cigarette smoking on main sperm variables. DESIGN Cohort study. SETTING Men attending the andrology laboratory in the context of infertility investigation in the couple. PATIENT(S) Eight hundred thirty-nine smokers and 1,266 non-smokers were enrolled; 655 smokers and 1,131 nonsmokers fulfilled the inclusion criteria and were compared. Standard clinical analysis of semen. RESULT(S) Cigarette smoking was associated with a significant decrease in sperm density (-15.3%), total sperm count (-17.5%), total number of motile sperm (-16.6%), and citrate concentration (-22.4%). The percentage of normal forms was significantly reduced in smokers, and sperm vitality, ejaculate volume, and fructose concentration were slightly but nonsignificantly affected. CONCLUSION(S) Cigarette smoking is associated with reduced semen quality.

Second- and third-trimester serum levels of placental proteins in preeclampsia and small-for-gestational age pregnancies

Background:  Poor placentation may perpetuate preeclampsia, but the presence of a major placental pathology has been questioned in cases of preeclampsia where the newborn has an appropriate birthweight for gestational age. On the other hand, poor placentation is also observed in the absence of preeclampsia, in pregnancies with small‐for‐gestational‐age (SGA) fetuses. In late gestation, maternal serum levels of placental protein hormones are changed in both preeclampsia and SGA, but no longitudinal preonset studies are available for pregnancy‐associated plasma protein A (PAPP‐A), pregnancy‐specific β1‐glycoprotein (SP1) or human placental lactogen (HPL).

First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia

OBJECTIVE The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. STUDY DESIGN First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. RESULTS sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. CONCLUSION sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia.

Anti-Müllerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection

OBJECTIVE To evaluate anti-Müllerian hormone (AMH) as a marker of reproductive outcome after IVF/intracytoplasmic sperm injection (ICSI). DESIGN Longitudinal study. SETTING University hospital. PATIENT(S) Two hundred seventy-six consecutive women undergoing IVF/ICSI. INTERVENTION(S) Ovarian stimulation, oocyte retrieval, IVF, ICSI, embryo transfer, AMH, and inhibin B determinations in serum and follicular fluid (FF). MAIN OUTCOME MEASURE(S) The AMH and inhibin B concentrations in 276 matched FF/serum pairs have been determined. Different outcome groups have been compared and set in relation to the oocyte count, morphological parameters, and steroid hormone levels. RESULT(S) The concentrations of AMH and inhibin B in both serum and FF were significantly higher in the group of women who became pregnant in the corresponding treatment cycle than in those who did not conceive. Positive correlations were observed between serum inhibin B concentrations and embryo morphology (r = 0.126, 95% confidence interval 0.026-0.284). Serum and FF AMH or inhibin B correlated positively with the oocyte count and negatively with the pretreatment cycle day 3 FSH level and the total administered gonadotropin dose. CONCLUSION(S) The AMH and inhibin B levels on the day of oocyte retrieval are correlated to reproductive outcome.

Inflammation and nerve fiber interaction in endometriotic pain

Endometriosis is an extremely prevalent estrogen-dependent condition characterized by the growth of ectopic endometrial tissue outside the uterine cavity, and is often presented with severe pain. Although the relationship between lesion and pain remains unclear, nerve fibers found in close proximity to endometriotic lesions may be related to pain. Also, women with endometriosis pain develop central sensitization. Endometriosis creates an inflammatory environment and recent research is beginning to elucidate the role of inflammation in stimulating peripheral nerve sensitization. In this review, we discuss endometriosis-associated inflammation, peripheral nerve fibers, and assess their potential mechanism of interaction. We propose that an interaction between lesions and nerve fibers, mediated by inflammation, may be important in endometriosis-associated pain.

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis.

Endometriosis affects 10–20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-α (TNF-α), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-α and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-α and glycodelin when compared with the other patients (no or moderate pain). TNF-α and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.

Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations.

OBJECTIVE To assess the relationship between endometriotic lesions with associated nerve fibers with both pain and peritoneal fluid (PF) cytokine concentrations based on lesion location. DESIGN An observational study. SETTING University hospital. PATIENT(S) Premenopausal women undergoing laparoscopy. INTERVENTION(S) The pain experienced by patients was recorded before surgery and ectopic endometrial tissue excised and matching PF collected during laparoscopy. Immunohistochemistry was performed on endometriotic tissue sections to identify nerve fibers and PF cytokine concentrations determined. MAIN OUTCOME MEASURE(S) The pain experienced by women with endometriosis, the lesion locations, and the prevalence and proximity of nerve fibers to endometriotic lesions, as well as the PF concentrations of multiple cytokines. RESULT(S) Lesions from the rectovaginal septum were significantly more likely to be associated with a nerve fiber and report more menstrual pain than lesions from other regions. The PF glycodelin concentrations were also significantly higher in samples with an endometriotic-associated nerve. In peritoneal endometriotic lesions significantly more menstrual pain was reported when endometriotic lesions were associated with nerve fibers, although no difference was observed between the cytokine concentrations. Ovarian endometriotic lesions were rarely associated with nerve fibers. CONCLUSION(S) The presence of endometriosis-associated nerve fibers appear to be related to both the pain experienced by women with endometriosis and the concentration of PF cytokines; however, this association varies with the lesion location.

First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels

Background/Aim: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). Method: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. Results: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. Conclusions: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predicitive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy ‘miracle’ serum marker for PE risk assessment seems unlikely in the near future.

Increased ENA-78 in the follicular fluid of patients with endometriosis

Background. It is known that endometriosis is an inflammatory disease and those patients seem to have lower pregnancy rates. The aim of the study was to investigate the concentrations of chemokines and proinflammatory cytokines in the follicular fluid of patients with and without endometriosis. Methods. Follicular aspiration, recovering follicular fluid during assisted reproductive treatment, follicular fluid storage and analysis of chemokines and proinflammatory cytokines were carried out. Tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, interleukin‐8, interleukin‐15, leukemia inhibitory factor, epithelial neutrophil‐activating peptide 78, regulated upon activation, normal T‐cell expressed and secreted, and growth‐regulated oncogene‐α were analyzed in the follicular fluid and compared between women with (n=47) and without endometriosis (n=279). Results. The above cytokines were detected in the follicular fluid samples. Epithelial neutrophil‐activating peptide 78 levels were significantly higher in follicular fluid from endometriosis patients than from controls (p=0.008). Increases (to twice the control level) were also observed for tumor necrosis factor‐α and for interleukin‐6. Conclusions. Increased follicular fluid levels of epithelial neutrophil‐activating peptide 78, tumor necrosis factor‐α and interleukin‐6 indicate that these cytokines may influence oocyte quality and fecundability of women with endometriosis by deteriorating the microenvironment in the human follicle.

Adiponectin as a marker of success in intracytoplasmic sperm injection/embryo transfer cycles

Adiponectin (Acrp30) is an adipose tissue-derived protein whose serum concentrations, in contrast to leptin, are reported to be negatively correlated to body mass. In spite of the comparatively high circulating adiponectin concentrations, this protein has not been studied in the context of assisted reproduction to date. The aim of this preliminary project was thus to examine the potential of adiponectin to serve as a marker for fertility. We compared adiponectin levels in serum before and after controlled ovarian hyperstimulation, as well as in follicular fluid (FF), between two groups: those with successful outcome (clinical pregnancies) and those with implantation failure. In the former, adiponectin concentrations were higher than in the negative outcome group; this difference was statistically significant (p < 0.05) in serum on the day of oocyte pick-up (OPU) as well as two or three days before OPU, but not in FF or in serum at the beginning of the stimulation phase. This finding adds a new perspective to the suggested but still controversial reduction in FF leptin concentrations in the positive outcome group, and may become a useful tool for early prediction of success of in vitro fertilization treatment for a given patient.