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STUDY QUESTION Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? SUMMARY ANSWER Amongst 17 POPs detected in over 20% of serum samples, only p,p′-DDE was significantly associated with an increased risk of DOR, and β-hexachlorocyclohexane (β-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. WHAT IS KNOWN ALREADY Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. STUDY DESIGN, SIZE, DURATION Our study included 138 cases and 151 controls from the AROPE case–control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) <7, and controls were women with AMH levels between 1.1 and 5 ng/ml and AFC ≥ 7, without genital malformations and with a menstrual cycle length between 26 and 35 days. A total of 43 POPs (including 15 organochlorine pesticides, 17 polychlorinated biphenyls, and 9 polybromodiphenylethers) were measured in the serum at inclusion into the study. We conducted logistic regression adjusted for potential confounders using a directed acyclic graph to study the effect of each POP on DOR as single exposures, and used Bayesian kernel machine regression (BKMR) to measure the mixture effect of POPs on DOR. MAIN RESULTS AND THE ROLE OF CHANCE Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p′-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10–1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74–2.87, and OR 1.72, 95% CI 0.88–3.37, respectively). β-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when β-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44–0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21–0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42–1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. LIMITATIONS, REASONS FOR CAUTION Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. WIDER IMPLICATIONS OF THE FINDINGS This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p′-DDE and estrogenic properties of β-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: Is there a relationship between maternal occupational exposure to endocrine-disrupting chemicals (EDCs) during pregnancy and the semen quality of their sons?Summary Answer: Our results suggest an association between maternal occupational exposure to potential EDCs, especially to pesticides, phthalates and heavy metals, and a decrease in several semen parameters.What Is Known Already: Sexual differentiation, development and proper functioning of the reproductive system are largely dependent on steroid hormones. Although there is some animal evidence, studies on maternal exposure to EDCs during pregnancy and its effect on the semen quality of sons are scarce and none have focused on maternal occupational exposure.Study Design, Size, Duration: A cross-sectional study aiming to evaluate semen quality was carried out among Swiss conscripts aged 18 to 22 years between 2005 and 2017.Participants/materials, Setting, Methods: Conscript and parent questionnaires were completed prior to the collection of a semen sample. Semen parameters were categorised according to the guidelines of the World Health Organization (WHO). Data on maternal employment during pregnancy were provided by the parent questionnaire. Maternal occupational exposure to potential EDC categories was defined using a job-exposure matrix (JEM). Logistic regressions were used to analyse the relationship between maternal occupational exposure to EDCs and each semen parameter adjusted for potential confounding factors. Results are presented using odds ratios and 95% confidence intervals.Main Results and the Role Of Chance: In total, 1,737 conscripts provided a conscript and parent questionnaire, as well as a semen sample; among these 1,045 of their mothers worked during pregnancy. Our study suggests an association between occupational exposure of mothers during pregnancy to potential EDCs and low semen volume and total sperm count, particularly for exposure to pesticides (OR 2.07, 95% CI 1.11-3.86 and OR 2.14, 95% CI 1.05-4.35), phthalates (OR 1.92, 95% CI 1.10-3.37 and OR 1.89, 95% CI 1.01-3.55), and heavy metals (OR 2.02, 95% CI 1.14-3.60 and OR 2.29, 95% CI 1.21-4.35). Maternal occupational exposure to heavy metals was additionally associated with a low sperm concentration (OR 1.89, 95% CI 1.06-3.37).Limitations, Reasons For Caution: Several limitations should be noted, such as the indirect method for maternal occupational exposure assessment during the pregnancy (JEM) and the cross-sectional design of the study.Wider Implications Of the Findings: Our observations reinforce the need to inform pregnant women of potential hazards during pregnancy that could impair their child's fertility. Additional studies are needed to confirm the involvement of EDCs.Study Funding/competing Interest(s): This work was supported by the Swiss Centre for Applied Human Toxicology: SCAHT and the 'Fondation privée des Hôpitaux Universitaires de Genève'. The collection of human biological material used for this study was supported by the FABER Foundation, the Swiss National Science Foundation (SNSF): NFP 50 'Endocrine Disruptors: Relevance to Humans, Animals and Ecosystems', the Medical Services of the Swiss Army (DDPS) and Medisupport. The authors declare they have no competing financial interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Sperm counts have been steadily decreasing over the past five decades with regional differences in the Western world. The reasons behind these trends are complex, but numerous insights indicate that environmental and lifestyle factors are important players. Objective: To evaluate semen quality and male reproductive health in Switzerland. Materials and methods: A nationwide cross‐sectional study was conducted on 2523 young men coming from all regions of Switzerland, recruited during military conscription. Semen volume, sperm concentration, motility, and morphology were analyzed. Anatomy of the genital area and testicular volume was recorded. Testicular cancer incidence rates in the general population were retrieved from Swiss regional registries. Results: Median sperm concentration adjusted for period of sexual abstinence was 48 million/mL. Comparing with the 5th percentile of the WHO reference values for fertile men, 17% of men had sperm concentration below 15 million/mL, 25% had less than 40% motile spermatozoa, and 43% had less than 4% normal forms. Disparities in semen quality among geographic regions, urbanization rates, and linguistic areas were limited. A larger proportion of men with poor semen quality had been exposed in utero to maternal smoking. Furthermore, testicular cancer incidence rates in the Swiss general population increased significantly between 1980 and 2014. Discussion: For the first time, a systematic sampling among young men has confirmed that semen quality is affected on a national level. The median sperm concentration measured is among the lowest observed in Europe. No specific geographical differences could be identified. Further studies are needed to determine to what extent the fertility of Swiss men is compromised and to evaluate the impact of environmental and lifestyle factors. Conclusion: A significant proportion of Swiss young men display suboptimal semen quality with only 38% having sperm concentration, motility, and morphology values that met WHO semen reference criteria. [ABSTRACT FROM AUTHOR]

There appears to be an incompressible high rate of preterm births among populations of African origin irrespective of their geographic location. The objective of this study was to assess the risk factors for preterm birth in a French Caribbean population of African descent, offered medical care comparable to that on the French mainland, but presenting a higher rate of preterm birth. The study was based on a birth cohort at maternity hospitals in Guadeloupe (French West Indies) including 911 singleton pregnancies enrolled during their third trimester check-up visits. Associations between risk factors and the risk of preterm delivery (spontaneous and induced) were assessed using a multivariate Cox model. In addition, prevalences of sociodemographic and medical factors in Guadeloupe were compared with those on the French mainland. 144 women (15.8 %) delivered preterm, medically induced in 52 %. Women delivering preterm were more often over 35 years old (37 %), single (54 %), and had higher prevalence of prior preterm birth (20 %), prior miscarriage (37 %), lupus (3 %), asthma (14 %), gestational hypertension (26 %), gestational diabetes (13 %) and urinary tract infection (24 %) than women with term births. In the whole cohort, these risk factors were also more frequent than in mainland France. Our results suggest highly prevalent medical risk factors for preterm births in Guadeloupe. This observation combined with specific social risk factors (older maternal age, single living) less frequent on the French mainland probably explains a large part of a higher prevalence of preterm births in this population despite similar medical provision. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there evidence at the population level of associations between different male genital disorders, outside Scandinavian countries? SUMMARY ANSWER At an international scale, there is evidence for a number of correlations between rates of four male reproductive disorders (hypospadias, cryptorchidism, testicular cancer and low sperm concentration). WHAT IS KNOWN ALREADY Some associations between these outcomes have been shown in studies focusing on individuals and mainly in Nordic European countries. These associations, together with histological evidence of a dysgenesis pattern in testicular tissue specimens, have generated the concept of the existence of a ‘testicular dysgenesis syndrome’ originating in utero. STUDY DESIGN, SIZE, DURATION This is a geographical correlation study using cancer, malformations rates and sperm quality data collected between the years 1998 and 2005. PARTICIPANTS/MATERIALS, SETTING, METHODS Incidence rates of testicular cancer were extracted from International Agency for Research on Cancer registries and Globocan, while cryptorchidism and hypospadias prevalence rates were obtained from EUROCAT and International Clearinghouse for Birth Defects Surveillance and Research registries. Sperm concentration data were extracted from recent studies using standardized methodology. A total of 39 registries and 9 sperm studies were selected. Non-parametric Spearman correlation tests were used to test the association between these four disorders. Correlations were computed for all registries together, for registries with high-quality matching coverage only and by continents. Sensitivity analyses were also conducted using data from prospective clinical studies to take into account potential bias related mainly to ascertainment of malformation rates. MAIN RESULTS AND THE ROLE OF CHANCE We found positive correlations between testicular cancer and hypospadias (r = 0.32, P = 0.05) and between hypospadias and cryptorchidism (r = 0.70, P = 0.008). Stronger correlations were observed when using registries with high-quality matching coverage. Among these registries, differences between Europe and the rest of the world appeared (the positive correlation between testicular cancer and cryptorchidism was stronger outside Europe, r = 0.83, P = 0.01 compared with 0.40, P = 0.60 for European registries). A negative correlation between testicular cancer and sperm concentration was observed (r = −0.88, P = 0.002). These correlations support our initial hypothesis but remain only suggestive due to the intrinsic limitations in the study design (i.e. geographical correlation study) and do not allow causal inference. LIMITATIONS, REASONS FOR CAUTION Differences in the ascertainment of malformations rates (definition, length of follow-up) make the international comparison difficult. The small number of registries for some conditions (cryptorchidism) or of studies (for sperm quality) and the absence of information about major risk factors such as ethnicity and socioeconomic status in the registries are also limitations. WIDER IMPLICATIONS OF THE FINDINGS Our findings are in agreement with results of studies focusing on individuals and suggest that shared risk factors are present in the populations studied. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by Inserm (Institut National de la Santé et de la Recherche Médicale), the University of Rennes 1, EHESP (School of Public Health) and the Post-Grenelle 189 Program of INERIS (Institut National de l'Environnement industriel et des Risques). No competing interests were declared. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to assess whether HIV infection is associated with a higher risk of invasive cervical cancer (ICC). Methods We conducted a region-wide, population-based observational cohort study of 1232 HIV-infected women over the age of 15 years in Guadeloupe, a French Caribbean archipelago, during the period 1999-2006. The observed numbers of incident cases of cervical intraepithelial neoplasia (CIN) and ICC were compared with the expected numbers of cases based on the incidence rates for the general population, and the standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. Results The incidence rate of CIN was higher in the HIV-infected women than in the general population for all grades (SIR 10.1, 95% CI 6.8-14.6 for CIN grade 1; SIR 9.9, 95% CI 6.1-15.3 for CIN grade 2; and SIR 5.2, 95% CI 3.4-7.7 for CIN grade 3). However, no increase in the risk of ICC was observed (SIR 1.7, 95% CI 0.3-4.9). Conclusions Despite an increase in the occurrence of cervical cancer precursors, no increase in the risk of cervical cancer was found in a population of HIV-infected women who receive treatment for their infection and have access to ICC prevention services. [ABSTRACT FROM AUTHOR]

Objectives To describe urine levels of metabolites of glycol ethers and chlorinated solvents in a sample of pregnant women from the general population, to study their occupational and non-occupational determinants and to compare them with the results of indirect assessment methods of solvent exposure. Methods A sample of 451 pregnant women was randomly selected from a general population cohort. At inclusion, the women in this sample completed a self-administered questionnaire about their social and medical characteristics, occupation and exposure to different products at work and in non-occupational activities. Occupational exposure to solvents was assessed from the woman's self-report and from a job-exposure matrix. Eight alkoxycarboxylic acids and trichloroacetic acid and trichloroethanol were measured with chromatography in urine samples collected at inclusion. Associations between metabolite levels and job titles, exposure to products used at work, and solvent exposure were studied. Results The different glycol ether metabolites were detected in 5.3%-96.4% of the urine samples, trichloroacetic acid in 6.4% and trichloroethanol in 5.5%. Nurses had butoxyacetic acid and phenoxyacetic acid in their urine most often, whereas methoxyethoxyacetic acid was the most frequent among nursing aides. Among cleaners, ethoxyacetic acid and ethoxyethoxyacetic acid were the most frequent. The occupation of hairdresser was associated with urinary excretion of ethoxyacetic acid, ethoxyethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid. Among the women classified as exposed to solvents, the agents identified most often were ethoxyacetic acid, ethoxy-ethoxyacetic acid, butoxyacetic acid, phenoxyacetic acid, trichloroacetic acid and trichloroethanol. Ethoxyethoxyacetic acid was the only metabolite associated with non-occupational exposure. Conclusions Metabolites of glycol ethers and chlorinated solvents were present at low levels in the urine of pregnant women. Most metabolites were associated with occupational exposure. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether there was a relation between male exposure to pesticides and the amount of time needed to conceive (time to pregnancy) for farmers and agricultural workers in France and Denmark. The authors used retrospective studies to compare the time to pregnancy of couples in which the man was exposed to pesticides during the year before the birth of their youngest child with that of couples in which the man was not exposed. In 1995 and 1996, the authors studied 362 French rural workers (142 exposed to pesticides and 220 not exposed), 449 Danish farmers (326 conventional farmers exposed to pesticides and 123 nonexposed organic farmers), and 121 Danish greenhouse workers exposed to pesticides. The fecundability ratio for exposure to pesticides (Cox model, before and after adjustment for confounding factors) did not differ from 1 in any of the three populations. In France, the adjusted fecundability ratio was 1.17 (95% confidence interval (CI) 0.89-1.55) for exposed and nonexposed agricultural workers. In Denmark, it was 1.09 (95% CI 0.82-1.43) for exposed and nonexposed farmers and 0.83 (95% CI 0.69-1.18) for greenhouse workers and nonexposed farmers. Thus, this study found no relation between fertility (time to pregnancy) and male exposure to pesticides. Am J Epidemiol 1999; 150: 157–63. [ABSTRACT FROM PUBLISHER]

Objectives: Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether-based solvents have pronounced adverse effects on sperm production and male fertility in laboratory animals. The authors investigated the effects of past and current exposure to glycol ether-containing products on semen quality and reproductive hormones among men employed by the Paris Municipality. Methods: Between 2000 and 2001 the authors recruited 109 men who gave semen, blood and urine samples and underwent an andrological examination. Information on lifestyle, occupation, exposure and medical history was obtained by interview. According to their job and chemical products used during the period 1990-2000, men were classified as either occupationally exposed or non-exposed. Current exposure levels to glycol ethers at the time of the study were evaluated by biological monitoring of six urinary metabolites. Results: Previous exposure to glycol ethers was associated with an increased risk for sperm concentration, for rapid progressive motility and for morphologically normal sperm below the World Health Organization semen reference values. No effect of previous glycol ether exposure on hormones levels was observed. By contrast, current glycol ether exposure levels were low and not correlated with either seminal quality or hormone levels. Conclusions: This study suggests that most glycol ethers currently used do not impact on human semen characteristics. Those that were more prevalent from the 1960s until recently may have long lasting negative effects on human semen quality. [ABSTRACT FROM AUTHOR]

Background: An increasing number of reports suggest that chemical and physical agents in the environment, introduced and spread by human activity, may affect male fertility in humans. We investigated the relationships between exposure to environmental agents and seminal characteristics, and the concentrations of reproductive hormones in the serum of men seeking infertility treatment.Methods: We studied 225 male partners from consecutively recruited couples, who had their first infertility consultation between 1995 and 1998, in the Litoral Sur region of Argentina, one of the most productive farming regions in the world.Results: A multivariate logistic regression model showed that exposure to pesticides and solvents is significantly associated with sperm threshold values well below the limit for male fertility. We also found that men exposed to pesticides had higher serum oestradiol concentrations, and that men exposed to solvents had lower LH concentrations than non-exposed men. All of these effects were greater in men with primary infertility than in men with secondary infertility.Conclusion: We have shown that environmental factors contribute to the severity of infertility, and that this may worsen the effects of pre-existing genetic or medical risk factors. [ABSTRACT FROM AUTHOR]

We investigated infertility risk factors by conducting a population-based case-control study in the military population of the French town of Brest. Sixty couples who had sought medical advice for infertility of more than 12 months duration (cases) were compared with 165 couples who had had a child (controls). All the men in these couples had been employed by the military. The infertility risk factors studied were male and female medical factors, occupational and environmental exposures. We obtained age-adjusted odds ratios of 7.4 [95% confidence interval (CI): 1.4--39.5] for testis surgery, and 13.0 for varicocele (95% CI: 1.4--120.3) in men. In logistic regression, the age-adjusted odds ratio for men who had worked in a nuclear submarine was found to be 2.0 (95% CI: 1.0--3.7), and that for heat exposure was 4.5 (95% CI: 1.9--10.6). One limitation of this study is the lack of exposure measurements, especially for potential exposure to nuclear radiation (type of reactor used in nuclear-powered submarines, inability to obtain personal dosimeters worn by military personnel working in nuclear submarines). In conclusion, this study suggests that in this military population, having worked as a submariner in a nuclear-powered submarine, and having worked in very hot conditions, should be considered as risk factors for infertility. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether there was a relation between male exposure to pesticides and the amount of time needed to conceive (time to pregnancy) for farmers and agricultural workers in France and Denmark. The authors used retrospective studies to compare the time to pregnancy of couples in which the man was exposed to pesticides during the year before the birth of their youngest child with that of couples in which the man was not exposed. In 1995 and 1996, the authors studied 362 French rural workers (142 exposed to pesticides and 220 not exposed), 449 Danish farmers (326 conventional farmers exposed to pesticides and 123 non-exposed organic farmers), and 121 Danish greenhouse workers exposed to pesticides. The fecundability ratio for exposure to pesticides (Cox model, before and after adjustment for confounding factors) did not differ from 1 in any of the three populations. In France, the adjusted fecundability ratio was 1.17 (95% confidence interval (Cl) 0.89-1.55) for exposed and non-exposed agricultural workers. In Denmark, it was 1.09 (95% Cl 0.82-1.43) for exposed and non-exposed farmers and 0.83 (95% Cl 0.69-1.18) for greenhouse workers and non-exposed farmers. Thus, this study found no relation between fertility (time to pregnancy) and male exposure to pesticides. [ABSTRACT FROM AUTHOR]

In humans, as in most mammals, spermatogenesis is temperature dependent. This temperature dependence has been clearly demonstrated by several experimental studies showing that artificial increases in scrotum or testicle temperature in fertile men reduce both sperm output and quality. Our knowledge of the effects of occupational heat exposure on male fertility comes mostly from a small number of epidemiological studies. We conducted an extensive review of these published reports, focusing on methodology and design (retrospective or prospective; reference group; number of subjects) and principal results (using several indicators such as the time taken to obtain a pregnancy or sperm characteristics). We concluded that occupational heat exposure is a significant risk factor for male infertility, affecting sperm morphology and resulting in delayed conception. The limits and biases involved in this type of research are also discussed. [ABSTRACT FROM AUTHOR]

Lactoferrin is a non-enzymatic secretory protein of human pancreas and is specifically increased in pancreatic juice of patients with chronic pancreatitis. Duodenal contents being easier to obtain than pure pancreatic juice, the possibility of using lactoferrin measurement in duodenal juice as a diagnosis test for chronic pancreatitis was explored. Forty-eight patients were studied. Duodenal juice was obtained devoid of salivary contamination by a special double lumen tube. Under these conditions lactoferrin secretion (concentration and output) is increased in patients with chronic pancreatitis. When expressed as the ratio of lactoferrin to lipase units, there was no overlap between chronic pancreatitis and other pancreatic disease or controls. The simplicity and the reproducibility of the technique on a material as readily available as duodenal juice confirms the diagnostic value of lactoferrin measurement in the assessment of patients with suspected pancreatic disease. [ABSTRACT FROM PUBLISHER]

This article discusses various issues related to occupational exposure to glycol ethers and ovarian function. The article makes specific reference to the article "Prolonged Menstrual Cycles in Female Workers Exposed to Ethylene Glycol Ethers in the Semiconductor Manufacturing Industry," by G.Y. Hsieh, J.D. Wang, T.J. Cheng, and P.C. Chen. The glycol ether compounds are grouped into two main classes: ethylene glycol ethers (EGEs) and propylene glycol ethers. Short chain EGES, more specifically, ethylene glycol methyl ether, ethylene glycol ethyl ether, and their acetates, were first shown to affect testicular function, and more precisely, spermatocytes in the pachytene stage, dose dependently in all species tested, resulting in reduced fertility. The wives of male production workers in the semiconductor industry, that is, those exposed to glycol ethers, show a slightly longer average time to pregnancy compared to non-production workers. The reproductive toxicity of these compounds among females has been the object of much less study. Studies of women's reproductive health in relation to environmental or occupational exposures have rarely looked at menstrual cycle characteristics or ovarian function, probably because of the specific difficulties associated with this evaluation.

Background: There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations.Methods: A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans.Results: No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats.Conclusion: Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors. [ABSTRACT FROM AUTHOR]