Background: The Maternal‐Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health.Methods: Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post‐delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the study's Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow‐up studies.Results: Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada.Conclusions: The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

What is the effect of maternal exposure to perfluorooctane sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) on female fecundity? Increasing concentrations of PFOA or PFHxS in maternal plasma were associated with reduced fecundability and infertility. Perfluorinated chemicals (PFCs) are a group of synthetic compounds used in industrial production. There is a concern about the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although some recent studies suggest that increasing concentrations of PFCs may decrease fecundity, divergence in the methodological approaches used to evaluate this association have prevented firm conclusions being reached. The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. A questionnaire was administered and medical chart data and biospecimens were collected from participants. After excluding women who withdrew, those for whom data were incomplete, those whose pregnancies followed birth control failure, and accounting for male fertility, 1743 participants remained. TTP was defined as the number of months of unprotected intercourse needed to become pregnant in the current pregnancy, as self-reported in the first trimester of pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first trimester were considered as a surrogate of preconception exposure. Fecundability odds ratios (FORs) were estimated using Cox proportional hazard models for discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The odds of infertility (TTP > 12 months or infertility treatment in the index pregnancy) were estimated using logistic regression. Each chemical concentration (ng/ml) was log-transformed and divided by its SD. The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42 (95% confidence interval (CI) 0.40–0.45), 0.81 (95% CI 0.79–0.83) and 0.90 (95% CI 0.89–0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61–1.71), 4.59 (95% CI 4.46–4.72) and 1.01 (95% CI 0.97–1.05), respectively. After adjustment for potential confounders, PFOA and PFHxS were associated with a 11 and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83–0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86–0.97; P = 0.002 for PFHxS), while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91–1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11–1.53; P = 0.001) and by 27% per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09–1.48; P = 0.003), while no significant association was observed for PFOS (OR = 1.14; 95% CI 0.98–1.34; P = 0.09). Women with the highest concentrations of PFCs might have been excluded from the study if there is a causal association with infertility. The MIREC study did not assess concentrations of PFCs in males, semen quality, menstrual cycle characteristics or intercourse frequency. Our results add to the evidence that exposure to PFOA and PFHxS, even at lower levels than previously reported, may reduce fecundability. The MIREC study is supported by the Chemicals Management Plan of Health Canada, the Canadian Institutes for Health Research (CIHR, grant no. MOP – 81285) and the Ontario Ministry of the Environment. M.P.V. was supported by a CIHR Fellowship Award, and a CIHR-Quebec Training Network in Perinatal Research (QTNPR) Ph.D. scholarship. W.D.F. is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.

Background: Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).Methods: We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.Results: Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60–1.80; I² = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20–1.50; I² = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00–6.51; I² = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58–1.92; I² = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33–1.53; I² = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).Conclusions: Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

To assess the potential effect of bisphenol A (BPA), triclosan (TCS), and phthalates on women's fecundity, as measured by time to pregnancy (TTP). Pregnancy-based retrospective TTP study. Not applicable. A total of 2,001 women during the first trimester of pregnancy recruited between 2008 and 2011 (the Maternal-Infant Research on Environmental Chemicals (MIREC) Study), with 1,742 women included in the BPA analysis, 1,699 in the TCS analysis, and 1,597 in the phthalates analysis. None. Fecundability odds ratios (FORs) estimated using the Cox model modified for discrete time data. The BPA concentrations were not statistically significantly associated with diminished fecundity either in crude or adjusted models. Women in the highest quartile of TCS (>72 ng/mL) had evidence of decreased fecundity (FOR 0.84; 95% confidence interval, 0.72-0.97) compared with the three lower quartiles as the reference group. Exposure to phthalates was suggestive of a shorter TTP, as indicated by FORs greater than 1, although the 95% confidence interval always included 1. Elevated TCS exposure may be associated with diminished fecundity. BPA and phthalates showed no negative impact; on the contrary, some phthalates might be associated with a shorter time to pregnancy. A major limitation of the study was that only one measurement of exposure was available for each woman after conception. Further research is necessary to test these findings.

What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme? Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle. Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies. This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis. IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs. The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles. The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates. Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth. M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.

Objective: The aim of this study was to evaluate the association between categories of age at natural menopause (ANM) and gait speed (slowness) and grip strength (weakness), common measures of physical functioning in older women. Methods: We analyzed data from the Canadian Longitudinal Study on Aging, which included participants from seven cities across Canada collected in 2012. The sample was restricted to women who reported to have entered menopause (N = 9,920). Women who had a hysterectomy before menopause were excluded since the age at which this surgical procedure was performed was not available. ANM was categorized into five groups: less than 40 (premature), 40 to 44 (early), 45 to 49, 50 to 54, and more than 54. We conducted linear regressions to assess the association between ANM and gait speed (m/s) and grip strength (kg) adjusting for participant age, education, body mass index, smoking, use of hormone therapy, height, and province of residence. Results: Mean ANM was 49.8 (95% confidence interval [CI]: 49.7-50.0), with 3.8% of women having a premature menopause; the average gait speed was 0.98 m/s (standard deviation: 0.22), the average grip strength was 26.6 kg (standard deviation: 6.39). Compared to women with ANM of 50 to 54, women with premature menopause had 0.054 m/s (95% CI −0.083, −0.026) lower gait speed when adjusting for age and study site. In the fully adjusted model, the association was attenuated, 0.032 m/s (95% CI −0.060, −0.004). ANM was not associated with grip strength. Conclusion: Our study suggests that premature menopause (<40 years) may be associated with lower gait speed (slowness) among Canadian women. No association was observed between ANM and grip strength. Future studies should include a life course approach to evaluate whether social and biological pathways modify the association between age at menopause and physical function in populations from different contexts.