Adherence to reporting guidelines in observational studies concerning exposure to persistent organic pollutants and effects on semen parameters.

STUDY QUESTION: Are studies on semen quality in men exposed to persistent pesticides reported according to the 'strengthening the reporting of observational studies in epidemiology' (STROBE) recommendations and the guidelines for the appraisal of semen quality studies (SEMQUA)? SUMMARY ANSWER: Most studies of the impact of pesticides on semen quality do not follow the STROBE and SEMQUA guidelines, thus adherence is low, especially in methodological aspects. WHAT IS KNOWN ALREADY: Much of the controversy about reduced semen quality in recent decades arises from a lack of standardization in the methodology applied, despite the existence of several validated instruments for evaluating the quality of reporting. Indeed, SEMQUA was purpose-designed for the particular characteristics of semen quality studies. STUDY DESIGN, SIZE, DURATION: A structured literature search identified eligible articles reporting on persistent pesticides and human semen quality, published in English before 1 September 2012. Opinion articles and reviews were excluded. We assessed the adherence to reporting guidelines of the articles, using and comparing the STROBE statement and the SEMQUA guidelines, in both cases with indicators relevant to observational studies of semen quality. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive bibliographic search in various electronic literature databases using the key words 'sperm' and 'pesticide' obtained 1179 papers, of which 46 were valid for our purposes. The papers examined occupational (26) and environmental exposure (20). Two of the present authors independently piloted the data extraction form for this review. The articles were then evaluated by two researchers using the STROBE and SEMQUA checklists. MAIN RESULTS AND THE ROLE OF CHANGE: Although no significant differences were found between the overall degree of compliance with STROBE and SEMQUA (47.0 ± 18.5% versus 43.1 ± 11.6%), there were significant differences when only methodological aspects were considered (48.4 ± 21.0% versus 39.5 ± 17.4%; P < 0.001). We observed an increase over time in the degree of compliance, for SEMQUA (r = 0.61 and P < 0.001) and STROBE (r = 0.45 and P < 0.01). The papers that reported a negative effect of exposure to persistent pesticides on sperm concentration presented a lower level of compliance to SEMQUA (42.1 ± 18.3% versus 57.6 ± 14.2%; P < 0.01) and STROBE (40.2 ± 10.3% versus 49.5 ± 11.6%; P < 0.05) than those which recorded no such influence. The year of publication and the observed effect on sperm concentration were the only candidate variables included in the model of stepwise multiple regression model for the 'degree of compliance' variables of SEMQUA and STROBE. LIMITATIONS, REASONS FOR CAUTION: Other characteristics of reporting quality, such as legibility, were not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: The low degree of compliance observed is consistent with that observed in other studies of reproductive medicine and highlights the need to improve the design of studies of semen quality. SEMQUA proved to be a more specific tool than STROBE for the field of semen quality. Editors, reviewers and authors should be aware of SEMQUA and apply it when assessing papers on semen quality. STUDY FUNDING/COMPETING INTEREST(S): No research funding was received and none of the authors have any conflict of interests.

Improving patient safety by detecting obstetric care-related adverse events: application of a new screening guide.

PURPOSE: Determining the magnitude and importance of patient safety-related incidents and the effectiveness of measures to improve patient safety (PS) are high-priority goals in efforts to improve the quality of obstetric care. The aim of this study was to evaluate the usefulness of the MRF1-OBST screening guide in detecting adverse events in women who received obstetric care. METHODS: This retrospective cohort study included 244 women who were hospitalized for delivery. All medical records were reviewed with the MRF1-OBST screening guide to identify adverse events and incidents. This tool is a modified form of the MRF1 screening guide regularly used in epidemiological studies of PS, to which we added items developed specifically for obstetric care. We calculated the positive predictive value and compared the ability of the MRF1 and MRF1-OBST guides to detect incidents related to PS in Obstetrics. RESULTS: The MRF1-OBST guide did not identify any additional complications during hospitalization or incidents related to PS that were not also identified by the MRF1 guide. CONCLUSIONS: The MRF1-OBST guide did not improve the detection of obstetric AE. The modified version of the guide required more work to use as a screening aid than the original MRF1 instrument. Efforts to improve the detection of incidents related to PS in obstetrics require complementary tools to be developed for information analysis.

Genetic testing of sperm donors for cystic fibrosis and spinal muscular atrophy: evaluation of clinical utility.

OBJECTIVE: To evaluate the clinical utility of genetic testing for cystic fibrosis (CF) and spinal muscular atrophy (SMA) in sperm donors. STUDY DESIGN: We studied the results of the genetic tests for CF and SMA applied to 372 sperm donor candidates. The CF carrier screening test analysed 32 mutations on the CFTR gene. Regarding SMA, the carrier test studied possible deletions of SMN1/2 by Multiplex Ligation-dependent Probe Amplification (MLPA) methodology. RESULTS: The carrier frequency obtained was greater for SMA than for CF. After adjusting the results obtained for the sensitivity of the tests, and taking into account the prevalence of female carriers in our population, the probability of transmission of the disease to the child from a donor with a negative genetic test was about five times lower in the case of SMA than in CF, although this difference was not statistically significant. The number of donors needed to screen (NNS) to avoid the occurrence of a child being affected by CF and SMA in our population was similar in both cases (1591 vs. 1536). CONCLUSIONS: This study demonstrates the need to include SMA among the diseases for which genetic screening is performed in the process of sperm donor selection. We believe that testing donors for SMA is as important and as useful as doing so for CF.

Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA).

STUDY QUESTION: Is there a need for a specific guide addressing studies of seminal quality? SUMMARY ANSWER: The proposed guidelines for the appraisal of SEMinal QUAlity studies (SEMQUA) reflect the need for improvement in methodology and research on semen quality. WHAT IS KNOWN ALREADY: From an examination of other instruments used to assess the quality of diagnostic studies, there was no guideline on studies of seminal quality. STUDY DESIGN, SIZE AND DURATION: Through systematic bibliographic search, potential items were identified and grouped into four blocks: participants, analytical methods, statistical methods and results. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our findings were presented to a panel of experts who were asked to identify opportunities for improvement. Then, a checklist was designed containing the questions generated by the items that summarize the essential points that need to be considered for the successful outcome of a SEMQUA. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen items were identified, from which 19 questions, grouped into four blocks, were generated to constitute the final checklist. An explanation for the inclusion of each item was provided and some examples found in the bibliographic search were cited. LIMITATIONS AND REASONS FOR CAUTION: We consider that not all items are equally applicable to all study designs, and so the hypothetical results are not comparable. For that reason, a score would not be fair to critically appraise a study. This checklist is presented as an instrument for appraising SEMQUAs and therefore remains open to constructive criticism. It will be further developed in the future, in parallel with the continuing evolution of SEMQUAs. WIDER IMPLICATIONS OF THE FINDINGS: The final configuration of the SEMQUA is in the form of a checklist, and includes the items generally considered to be essential for the proper development of a SEMQUA. The final checklist produced has various areas of application; for example, it would be useful for designing and constructing a SEMQUA, for reviewing a paper on the question, for educational purposes or as an instrument for appraising the quality of research articles in this field. STUDY FUNDING/COMPETING INTEREST(S): None.

Acceptable variability in external quality assessment programmes for basic semen analysis.

BACKGROUND: External quality assessment is essential in modern andrology laboratories. To assess the proficiency of laboratories participating in an external quality assessment programme (EQAP), limits for acceptable variability must be determined. Limits currently specified largely depend on criteria set by the organizers of individual EQAP schemes. The objective of this study was to evaluate the different criteria described in ISO 13528: 2005 for calculating acceptable variability in EQAP when applied to basic semen analysis parameters. METHODS AND RESULTS: The data used in this study were the means and standard deviations obtained for independent samples from two EQAPs, one national (Spanish) and one international (European). The acceptable variability according to ISO 13528: 2005 was calculated using four types of criteria: (i) ± 3 standard deviations of the results of all participating laboratories; (ii) ± 3 standard deviations of the results of expert laboratories; (iii) quality specifications based on biological variability, state-of-the-art and clinicians' opinions and (iv) the same quality specifications adjusted for the uncertainty of the assigned value. The first two strategies resulted in very wide ranges of acceptable variability. Conversely, the strategy based only on quality specifications resulted in very narrow ranges. For the fourth strategy, acceptable ranges were intermediate between the results produced with the other strategies. The third and fourth strategies did not produce observable differences in acceptable ranges when the model used for calculating the specifications of analytical quality was changed. CONCLUSIONS: It is essential that EQAPs for semen parameters should determine the ranges for acceptable variability in results. Moreover, these ranges must be clinically useful, i.e. the variability should have a minimal negative impact on clinical decisions. The exact definition of 'expert laboratory' is more important than the model chosen for estimating analytical quality specifications in an EQAP for semen parameters in basic semen analysis.

Maternal glucose tolerance status influences the risk of macrosomia in male but not in female fetuses.

OBJECTIVE: To elucidate whether the risk of macrosomia, large for gestational age (LGA) and small for gestational age (SGA) is influenced by maternal body mass index and glucose tolerance differently in male and female fetuses. METHODS: A population study was conducted in 16 general hospitals from the Spanish National Health Service that included 9270 consecutive women with singleton pregnancies and without a former diagnosis of diabetes mellitus who delivered 4793 male and 4477 female newborns. Logistic regression analyses were performed to predict the effect of body mass index (BMI) category and glucose tolerance on macrosomia, large for gestational age newborns (LGA) and small for gestational age newborns (SGA) Separate analyses according to foetal sex were carried out for each outcome. The results were adjusted for maternal age, gestational age and pregnancy-induced hypertension. RESULTS: There were significant differences between males and females in the percentage of infants who had macrosomia, LGA or SGA. Maternal BMI category was positively associated with the risk of macrosomia and LGA in both male and female newborns. In addition, there was a negative association between maternal BMI and SGA that only reached significance in males. In contrast, gestational diabetes was only a predictor of macrosomia exclusively in male fetuses (OR 1.67, 95% CI 1.12 to 2.49) CONCLUSIONS: There is sexual dimorphism in the risk of abnormal birth weight attributed to maternal glucose tolerance status. A closer surveillance of foetal growth might be warranted in pregnant women with abnormal glucose tolerance carrying a male fetus.

Body mass index has a greater impact on pregnancy outcomes than gestational hyperglycaemia.

AIMS/HYPOTHESIS: We evaluated diabetes-related pregnancy outcomes in a cohort of Spanish women in relation to their glucose tolerance status, prepregnancy BMI and other predictive variables. METHODS: The present paper is part of a prospective study to evaluate the impact of American Diabetes Association (2000) criteria in the Spanish population. A total of 9,270 pregnant women were studied and categorised as follows according to prepregnancy BMI quartiles and glucose tolerance status: (1) negative screenees; (2) false-positive screenees; (3) gestational diabetes mellitus (GDM) according to American Diabetes Association criteria only; and (4) GDM according to National Diabetes Data Group criteria (NDDG). We evaluated fetal macrosomia, Caesarean section and seven secondary outcomes as diabetes-related pregnancy outcomes. The population-attributable and population-prevented fractions of predictor variables were calculated after binary logistic regression analysis with multiple predictors. RESULTS: Both prepregnancy BMI and abnormal glucose tolerance categories were independent predictors of pregnancy outcomes. The upper quartile of BMI accounted for 23% of macrosomia, 9.4% of Caesarean section, 50% of pregnancy-induced hypertension and 17.6% of large-for-gestational-age newborns. In contrast, NDDG GDM accounted for 3.8% of macrosomia, 9.1% of pregnancy-induced hypertension and 3.4% of preterm births. CONCLUSIONS/INTERPRETATION: In terms of population impact, prepregnancy maternal BMI exhibits a much stronger influence than abnormal blood glucose tolerance on macrosomia, Caesarean section, pregnancy-induced hypertension and large-for-gestational-age newborns.

Potential impact of American Diabetes Association (2000) criteria for diagnosis of gestational diabetes mellitus in Spain.

AIMS/HYPOTHESIS: This study was carried out to determine the impact of American Diabetes Association (ADA) 2000 criteria for the diagnosis of gestational diabetes mellitus (GDM) in the Spanish population. METHODS: Pregnant women were assigned to one of four categories: negative screenees, false-positive screenees, ADA-only-GDM (untreated) and GDM according to National Diabetes Data Group (NDDG) criteria (treated). Fetal macrosomia and Caesarean section were defined as primary outcomes, with seven additional secondary outcomes. RESULTS: Of 9,270 pregnant women screened for GDM, 819 (8.8%) met NDDG criteria. If the threshold for defining GDM had been lowered to ADA criteria, an additional 2.8% of women would have been defined as having the condition (relative increase of 31.8%). Maternal characteristics of women with ADA-only-GDM were between those of false-positive screenees and women with NDDG-GDM. The risk of diabetes-associated complications was slightly elevated in the individuals who would have been classified as abnormal only after the adoption of ADA criteria. In addition, the ADA-only-GDM contribution to morbidity was lower than that of other variables, especially BMI. CONCLUSIONS/INTERPRETATION: Use of the ADA criteria to identify GDM would result in a 31.8% increase in prevalence compared with NDDG criteria. However, as the contribution of these additionally diagnosed cases to adverse GDM outcomes is not substantial, a change in diagnostic criteria is not warranted in our setting.

Successful pregnancy in a woman with acromegaly treated with somatostatin analog (octreotide) prior to surgical resection.

A 27-year-old woman with a GH-secreting pituitary macroadenoma was treated with continuous s.c. infusion of octreotide prior to surgical resection. Subsequently, she was found to be 6 months pregnant. Fetal echographs were normal, the newborn had no malformation, and postnatal development was normal.

Influence of obstetric and perinatal care on perinatal mortality.

OBJECTIVE: Cases of perinatal death attributed to suboptimal perinatal care between 1979 and 1992 inclusive at a large, tertiary care center are reviewed. STUDY DESIGN: The study compared two periods: 1979-1985 and 1986-1992. The perinatal morbidity-mortality committee analyzed patient records for the mothers and neonates, delivery room records, the results of fetal autopsy, and histological sections of the placenta. RESULTS: In the first period, 21.5% of the deaths were found to have received suboptimal care; this figure declined 13.5% in the second period (P < 0.05). During the second period, antenatal, intranatal and postnatal care improved, as shown by the lower suboptimal care rate for antepartum (15.8% versus 9.8%; P < 0.05), intrapartum (49.2% versus 22.1%; P < 0.001) and postpartum death (19.9% versus 8.1%; P < 0.001). During both periods, fetal death during pregnancy made up the largest proportion of deaths attributed to suboptimal care, with 44 cases (43.1%) during 1979-1985, and 36 cases (64.3%) during 1986-1992 (P < 0.01). Of these cases, fetuses with intrauterine growth retardation were the most frequent recipients of suboptimal care (20 cases (45.5%) during the first period; 18 cases (50%) during the second period). CONCLUSION: Despite better prenatal care, the highest suboptimal care rate was due to suboptimal care during pregnancy, when some high risk situations were overlooked by the obstetrician.

Intracystic lipidic profile in fibrocystic breast disease.

This study was designed to investigate the lipidic profile of fibrocystic breast disease. The study entailed measuring total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and triglyceride levels in the serum of 50 women with fibrocystic breast disease without macrocysts, and in the serum and breast cyst fluid of 60 women with fibrocystic breast disease and macrocysts. The relationships between the lipids analyzed in the cyst fluid and intracystic estradiol, progesterone, dehydroepiandrosterone sulfate, testosterone and 17 alpha-hydroxyprogesterone were studied. No differences were found for serum lipid levels between the two groups of patients. The levels of total cholesterol and HDL-C were found to be significantly higher, and the levels of triglycerides and VLDL-C significantly lower in breast cyst fluid compared to serum. In cysts with high potassium concentrations, we found a higher concentration of cholesterol and HDL-C and a lower concentration of LDL-C than in cysts with a potassium/sodium ratio < 3. No significant differences were found in cystic levels of triglycerides and VLDL-C. Multiple regression analysis showed that the only intracystic variable, which was, in part, positively responsible for the hormone levels measured, was HDL-C. These data suggest that local steroidogenesis in fibrocystic breast disease uses HDL-C as the substrate.

Strict glycemic control in women with pregestational insulin-dependent diabetes mellitus.

OBJECTIVE: To determine the efficacy of strict glycemic control in women with pregestational insulin-dependent diabetes mellitus (IDDM). METHODS: The records of 62 pregnant women with pregestational IDDM who had attended the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Virgen de las Nieves General Hospital, Granada, Spain, between 1982 and 1992, were reviewed. The women had received several daily doses of a mixture of rapid action (regular) and intermediate action insulin with the aim of keeping preprandial glucose levels lower than 95 mg/dl and postprandial glucose levels lower than 120 mg/dl. Perinatal outcomes were compared with those of a control group consisting of 96 randomly selected, normal, pregnant women who gave birth at approximately the same time. RESULTS: Mean glycemic profile in the first assay at an insulin dose of 33.1 +/- 15.9 IU/day was 153.7 +/- 52.3 mg/dl and the HbA1c was 7.7 +/- 2.3%. In the last assay before delivery patients received an insulin dose of 68.2 +/- 30.7 IU/day and had a mean glycemic profile of 94.4 +/- 18.1 mg/dl and an HbA1c of 5.9 +/- 1.4% (P < 0.001 for all parameters). The perinatal mortality of newborn infants of the diabetic mothers was 48 per 1000, and 11.3 per 1000 had some congenital malformations. CONCLUSIONS: Our results verify that strict glycemic control decreases the elevated perinatal mortality normally suffered by IDDM patients. However, if it is to reduce the number of congenital malformations, it must be initiated before the early gestational stages.

Reactive sacroiliitis as late sequela after severe pelvic inflammatory disease verified by laparoscopy or laparotomy.

OBJECTIVE: To investigate the frequency of lumbosacral pains and sacroiliitis as late sequela of severe pelvic inflammatory disease (PID) confirmed by laparoscopy or laparotomy. DESIGN: The sacroiliac joints were examined radiographically and scintigraphically to search for signs of reactive sacroiliitis. SETTING: Department of Obstetrics and Gynecology, Hospital General Virgen de las Nieves, Granada, Spain. PATIENTS: Thirty-five out of 70 women admitted with severe clinical symptoms of PID during a five-year period. PID was confirmed by laparoscopy or laparotomy. MEASUREMENTS: The sacroiliac joints were examined radiographically, and bone scintigraphic studies of the pelvic girdle were performed with 99technetium labelled pyrophosphate. RESULTS: Twenty out of 35 patients reported lumbosacral pain. The bone scintigraphic findings were positive for sacroiliitis in 18 out of 33 patients (54.6%), and the radiographic findings were positive in 11 women (33.3%). CONCLUSIONS: Patients with previous severe clinical PID complaining of lumbosacral pains may be offered a bone scintigraphy, a sensitive procedure using low-dose radiation, to search for early signs of reactive sacroiliitis.

Serum CA-125 in the diagnosis of acute pelvic inflammatory disease.

OBJECTIVES: To determine the efficiency of different tumor markers (CA-125, carcinoembryonic antigen, CA-15.3, CA-19.9) and insulin-like growth factor I (IGF-I) measurements as a screening procedure for acute pelvic inflammatory disease (PID). METHODS: Peripheral blood samples were obtained at the time of laparoscopy from three groups of women: (1) 50 women who underwent laparoscopic tubal ligation and had no evidence of PID (control group); (2) 20 women admitted because of suspected PID, but at laparoscopy or laparotomy had no signs of PID; (3) 20 patients who underwent acute PID diagnosed by laparoscopy. Serum levels of: CA-125, carcinoembryonic antigen, CA-15.3 and CA-19.9, and plasma IGF-I, were measured by radioimmunoassay. RESULTS: No differences were observed in the levels of CA-15.3, CA-19.9, carcinoembryonic antigen and IGF-I between the three groups studied. Serum levels of CA-125 were significantly higher in patients who had PID. Analysis of receiver operating characteristic curves showed that only CA-125 was useful in diagnosis of acute PID. The cut-off level was 43.7 U/ml for CA-125. CONCLUSIONS: Measurement of serum CA-125 concentrations is recommended as a useful test for acute PID in patients undergoing laparoscopy for pelvic pain.

Diagnosis of pelvic inflammatory disease with 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes and pelvic radionuclide scintigraphy.

In a prospective study, we assessed the performance of pelvic radionuclide scintigraphy after the injection of 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes as a noninvasive tool for the differential diagnosis of pelvic inflammatory disease (PID). The results of radionuclide scintigraphy in 20 women with PID confirmed laparoscopically were compared with the findings in 20 others hospitalized for suspected PID but with PID ruled out later by laparoscopy. The proportion of radionuclide scintigraphic findings demonstrating increased uptake in the genital region, compatible with an inflammatory process, was significantly larger (P < .001) in patients with PID (95%) than in those without PID (15%). The sensitivity of the technique was 95% and specificity was 85%; in all, 90% of the patients were correctly classified. We conclude that radionuclide scintigraphy preceded by the injection of 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes can detect PID in a high proportion of patients.

Distribution of free amino acids in human preovulatory follicles.

The purpose of the present study was to investigate the possible role of intrafollicular amino acids in the human ovarian follicle. Follicular fluid (FF) and oocytes were obtained from 12 women for in vitro fertilization. Follicular development was induced with clomiphene citrate and human menopausal gonadotropin. Thirty-six FF samples, free of visible blood contamination and containing mature oocytes were used to measure free amino acids, steroids and gonadotropins. The FF were divided into three groups: (1) follicles yielding oocytes that were unfertilized (n = 12); (B) follicles containing oocytes that were fertilized and cleaved to less than four cells (n = 12); (C) follicles yielding oocytes that were fertilized and cleaved to four or more cells (n = 12). The concentrations of histidine, phenylalanine and asparagine in FF were significantly greater than those in plasma at the time of follicle aspiration. However, amino acid concentrations in FF did not differ significantly between the three groups studied. No significant relationships were found between intrafollicular levels of amino acids and those of LH, FSH, estradiol, progesterone and testosterone. These results suggest that intrafollicular amino acids are not involved in the regulation of human preovulatory follicle.

Sex differences in serum hormone levels in umbilical vein blood.

OBJECTIVE: To determine the serum levels of FSH, LH, PRL, estradiol, progesterone and testosterone in umbilical vein blood in a group of normal neonates. METHOD: Umbilical vein blood was obtained for serum analyses from 52 newborns (25 females and 27 males) in the Maternity of the Hospital Regional Virgen de las Nieves, Granada (Spain) and means were compared with Student's t-test. RESULT: Mean values of prolactin, estradiol and progesterone were similar in both sexes. The levels of gonadotropins in umbilical vein blood found were significantly higher in newborn males than in females (P < 0.001 for LH, P < 0.007 for FSH). Testosterone levels were higher in male neonates than in females (P < 0.004). CONCLUSION: Our data reflect the dynamic state of male fetal endocrinological status in comparison to female fetuses, and strongly suggest that the mechanisms of hormonal regulation differ in the two sexes.

Mononuclear cell subpopulations in human follicular fluid from stimulated cycles.

The study of lymphocyte subsets from human follicular fluid (FF) provides an opportunity to evaluate immunological features of the ovary. We investigated the mononuclear cell subsets in FF and peripheral blood obtained at the time of laparoscopy from ten in vitro fertilization (IVF) patients. Midcycle nonpregnant peripheral blood was used as the control. A marked increase in the proportion of monocytes (CD14+) was observed in FF. Although FF was enriched with CD8+ lymphocytes, a decrease in the proportion of CD4+ lymphocytes was observed. "Memory" T cells in FF, identified by the CD4+ CD45R- phenotype, predominated over "naive" T cells (CD4+ CD45R+) at a ratio of 2:1, which differs from the ratio yielded by control blood samples (1:1). The percentage of activated T cells (CD3+ HLA-DR+ cell) increased significantly in FF. When lymphocyte subsets were studied in the peripheral blood of IVF patients, changes similar to but less significant than those in FF were found. These data support the concept that lymphocytes play an important role in ovarian physiology.