Drinking water nitrate and risk of pregnancy loss: a nationwide cohort study.

BACKGROUND: Nitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss. METHODS: We conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996-2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables. RESULTS: No consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges. CONCLUSION: No association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

Healthcare Use in the Five Years Before a First Infertility Diagnosis: A Danish Register-Based Case-Control Study in the CROSS-TRACKS Cohort.

Purpose: Infertility may affect somatic and mental health later in life. Nevertheless, health status before diagnosed infertility is sparsely studied in women. We aimed to describe healthcare use in primary and secondary care before a first infertility diagnosis and compare use between cases and controls. Materials and Methods: The case-control study was based on register data and used incidence density sampling. From the CROSS-TRACKS Cohort, we included women residing in the Horsens area in Denmark in 2012-2018 (n = 54,175). Eligible women were aged 18-40 years, nulliparous, and living in heterosexual relationships. Cases were women with a first infertility diagnosis in the Danish National Patient Registry (index date). Five controls were matched on age, birth year, and calendar time. Through linkage to Danish national health registries, we identified general practitioner (GP) attendance, paraclinical examinations, hospital contacts, diagnoses, and redeemed prescriptions. Healthcare use from one year to five years before index date was compared with conditional logistic regression. Results: We identified 711 cases and 3555 controls. At one year before index date, cases consulted their GP (odds ratio (OR) = 5.2, 95% confidence interval (CI): 3.2, 8.3) and visited hospital (OR = 1.2, 95% CI: 1.0, 1.4) and redeemed prescriptions (OR = 2.3 95% CI: 1.9, 2.7) more often compared to controls. Cases more often had blood and hemoglobin tests performed, redeemed more drugs related to genitourinary and hormonal diseases, and were more often diagnosed with endocrine and genitourinary diseases in the year before a first infertility diagnosis compared to controls. Cases and controls had comparable healthcare use from five years to one year before a first infertility diagnosis. Conclusion: Cases and controls had similar healthcare use from five years to one year before a first infertility diagnosis. However, cases had a higher healthcare use in the year preceding a first infertility diagnosis compared to controls.

Nitrate in Drinking Water and Time to Pregnancy or Medically Assisted Reproduction in Women and Men: A Nationwide Cohort Study in the Danish National Birth Cohort.

Purpose: No studies have investigated if drinking water nitrate affects human fecundity. Experimental studies point at detrimental effects on fetal development and on female and male reproduction. This cohort study aimed to explore if female and male preconception and long-term exposure to nitrate in drinking water was associated with fecundability measured as time to pregnancy (TTP) or use of medically assisted reproduction (MAR) treatment. Methods: The study population consisted of pregnant women recruited in their first trimester in 1996-2002 to the Danish National Birth Cohort. Preconception drinking-water nitrate exposure was estimated for the pregnant women (89,109 pregnancies), and long-term drinking water nitrate exposure was estimated from adolescence to conception for the pregnant women (77,474 pregnancies) and their male partners (62,000 pregnancies) by linkage to the national drinking water quality-monitoring database Jupiter. Difference in risk of TTP >12 months or use of MAR treatment between five exposure categories and log-transformed continuous models of preconception and long-term nitrate in drinking water were estimated. Binominal regression models for risk ratios (RR) were adjusted for age, occupation, education, population density, and lifestyle factors. Results: Nitrate in drinking water (median preconception exposure: 1.9 mg/L; median long-term exposure: 3.3 mg/L) was not associated with TTP >12 months or use of MAR treatment, neither in the categorical nor in the continuous models. Conclusion: We found no association between preconception or long-term exposure to drinking water nitrate and fecundability.

Female cigarette smoking and successful fertility treatment: A Danish cohort study.

INTRODUCTION: Despite smoking being a well-established risk factor for adverse pregnancy and neonatal outcomes, a substantial proportion of women of reproductive age smoke. Previously, meta-analyses have indicated a significantly negative impact of female smoking on outcomes of assisted reproduction, yet most of the included studies have several, essential methodological limitations. We aimed to investigate whether female cigarette smoking may affect the chance of achieving a clinical pregnancy and live birth among women and couples receiving medically assisted reproduction treatment. MATERIAL AND METHODS: A cohort study with longitudinally and repeatedly collected exposure information from 1 January 2010 to 31 August 2015, including data on 1708 women and potential partners initiating either intrauterine insemination, in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) or frozen embryo transfer treatment cycles at the public Fertility Clinic, Aarhus University Hospital, Denmark. Smoking was assessed from self-reported questionnaires completed before treatment. Outcomes were a clinical pregnancy and a live birth. Information on these was obtained from the Danish national health registries, allowing complete follow-up. To evaluate associations between female occasional/daily cigarette smoking and successful medically assisted reproduction treatments, a modified Poisson regression with robust standard errors was used. RESULTS: Female occasional/daily cigarette smoking was not associated with the chance of achieving a clinical pregnancy or a live birth in all intrauterine insemination or IVF/ICSI treatment cycles. When compared with nonsmokers, the adjusted relative risk for obtaining a live birth for those reporting smoking was 1.22 (0.70-2.12) among women initiating 1456 intrauterine insemination treatment cycles. Among women initiating 2788 IVF/ICSI treatment cycles, those reporting occasional/daily smoking had a relative risk for obtaining a live birth of 1.15 (0.82-1.60) when compared with nonsmokers. CONCLUSIONS: Occasionally/daily cigarette smoking women had similar chance of achieving a clinical pregnancy or a live birth as the nonsmokers when receiving medically assisted reproduction treatments. However, tobacco use before and during pregnancy remains a major cause of reduced fertility as well as maternal, fetal, and infant morbidity and mortality, and should strongly be discouraged.

Impact of female daily coffee consumption on successful fertility treatment: a Danish cohort study.

OBJECTIVE: To investigate whether female coffee consumption affects the chance of achieving a clinical pregnancy and a live birth among women and couples receiving medically assisted reproduction (MAR) treatment. DESIGN: Cohort study with prospectively collected exposure data. SETTING: Public fertility clinic. PATIENT(S): A total of 1,708 women and potential partners undergoing fertility treatment, contributing with 1,511 intrauterine insemination (IUI) cycles, 2,870 in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, and 1,355 frozen embryo transfer cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth in consecutive treatment cycles in the Danish national health registries, enabling complete follow-up, and estimation of the cumulative chance of live birth for three consecutive treatment cycles. RESULT(S): Among women receiving IVF or ICSI treatment, coffee consumption did not seem to affect the chance of achieving a clinical pregnancy and a live birth. Women treated with IUI who had a daily coffee consumption of 1-5 cups were more likely to achieve a clinical pregnancy (adjusted relative risk 1.49; 95% confidence interval, 1.05-2.11) and live birth (adjusted relative risk 1.53; 95% confidence interval, 1.06-2.21) compared with the reference group of coffee abstainers. CONCLUSION(S): Women consuming 1-5 cups versus none had a 1.5-fold higher probability of achieving a pregnancy or a live birth when receiving IUI. No associations were found, however, between women's daily coffee consumption and achieving a pregnancy or a live birth from IVF/ICSI.

Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis.

OBJECTIVE: The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility (ie, time to pregnancy [TTP] and spontaneous abortion [SAB]) and among women in fertility treatment (ie, clinical pregnancy rate or live birth rate). DESIGN: This study was a systematic review and dose-response meta-analysis including data from case-control and cohort studies. METHODS: An extensive literature search was conducted in MEDLINE and Embase, with no time and language restrictions. Also, reference lists were searched manually. Two independent reviewers assessed the manuscript quality using the Newcastle-Ottawa Scale (NOS). A two-stage dose-response meta-analysis was applied to assess a potential association between coffee/caffeine consumption and the outcomes: TTP, SAB, clinical pregnancy, and live birth. Heterogeneity between studies was assessed using Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's regression test. RESULTS: The pooled results showed that coffee/caffeine consumption is associated with a significantly increased risk of SAB for 300 mg caffeine/day (relative risk [RR]: 1.37, 95% confidence interval [95% CI]: 1.19; 1.57) and for 600 mg caffeine/day (RR: 2.32, 95% CI: 1.62; 3.31). No association was found between coffee/caffeine consumption and outcomes of fertility treatment (based on two studies). No clear association was found between exposure to coffee/caffeine and natural fertility as measured by fecundability odds ratio (based on three studies) or waiting TTP (based on two studies). CONCLUSION: Results from this meta-analysis support the growing evidence of an association between coffee/caffeine intake and the risk of SAB. However, viewing the reproductive capacity in a broader perspective, there seems to be little, if any, association between coffee/caffeine consumption and fecundity. In general, results from this study are supportive of a precautionary principle advised by health organizations such as European Food Safety Authority (EFSA) and World Health Organization (WHO), although the advised limit of a maximum of two to three cups of coffee/200-300 mg caffeine per day may be too high.

[Uterine artery pseudoaneurysm is a rare delayed complication after caesarean section].

Uterine artery pseudoaneurysm is a rare complication after caesarean section and may be the cause of acute and potentially life-threatening secondary post-partum haemorrhage. In this case report, we present the clinical presentation and management of a case of uterine artery pseudoaneurysm manifesting as delayed post-partum bleeding after caesarean section. The case report emphasizes the importance of performing Doppler-flow when diagnosing the existence of a uterine artery pseudoaneurysm ultrasonically.

[Concurrent achalasia and severe obesity].

Achalasia is a rare oesophageal motility disorder which classically is not associated with obesity. We present the case of a 50-year-old woman who underwent gastric bypass and afterwards was diagnosed with achalasia. Following, she was treated successfully with peroral endoscopic myotomy (POEM). A thorough medical history revealed that symptoms of achalasia had been present for 25 years and were the cause of inappropriate eating habits and consequently morbid obesity. This case story illustrates the importance of being aware of simultaneous occurrence of achalasia and morbid obesity. Furthermore, it demonstrates that POEM is safe and effective for symptomatic relief of achalasia after previous gastric bypass.

[The diagnostic value of human chorionic gonadotrophin ratio compared to single measurements of S-human chorionic gonadotrophin on the outcome of pregnancy of unknown location].

Pregnancy of unknown location is defined by a positive pregnancy test, without visualizing of the intrauterine or extrauterine pregnancy by transvaginal sonography. We present the advantages of using human chorionic gonadotrophin (hCG) ratio instead of single measurements of S-hCG for predicting the outcomes of pregnancies of unknown location.