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In 2022, approximately one out of six people globally experienced infertility at some point in their life. Environmental chemicals, particularly those with endocrine disrupting activity, may contribute to impaired fecundity and infertility. We review existing prospective cohort studies of environmental chemicals and fecundity, identify methodological challenges and biases, and outline future research priorities. Studies of preconception environmental chemical exposures and fecundity have occurred in US, Singapore, China and Denmark with recruitment as early as 1982-1986, as recent as 2015-2017 and sample sizes ranging from 99 to 936. Higher exposure to certain chemicals (e.g. heavy metals, perfluoroalkyl substances) was associated with longer time to pregnancy; yet the literature is scarce or nonexistent for many chemicals. Furthermore, prospective studies face challenges and potential biases related to recruiting participants prior to conception, measuring environmental chemicals during critical windows of exposure, and ascertaining when pregnancy occurred. Research priorities include expanding the scope of biomonitoring data collected during the preconception period, continuing to develop and validate analytic methods for self-sampled biospecimens in traditional and novel matrices, collecting data in male partners and investigating etiologic associations according to indicators of marginalization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time-to-pregnancy (TTP) and infertility., Design: Pregnancy-based retrospective TTP cohort study., Setting: Hospitals and clinics from ten cities across Canada., Population: A total of 1784 pregnant women., Methods: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete-time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre-pregnancy body mass index, education, income, recruitment site and plasma lipids., Main Outcome Measures: TTP was self-reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months., Results: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02-1.16); however, the association was not linear when exposure was modelled in tertiles., Conclusion: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Importance: Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors., Objective: To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association., Design, Setting, and Participants: This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks' gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023., Exposures: The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)., Main Outcome and Measures: The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity., Results: A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%., Conclusions and Relevance: In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

Infertility, irrespective of receipt of fertility treatment, is associated with an increased risk of adverse pregnancy outcomes, including cesarean section (CS) and preterm birth (PTB). These complications are associated with significant physical, mental, emotional, social, and financial costs to individuals, healthcare systems, and society at large. Although multiple pregnancy is one of the most significant contributors to the elevated CS and PTB rates in women receiving fertility treatment, singleton pregnancy is also at an increased risk of these outcomes. Single embryo transfer policies through publicly funded in vitro fertilization programs have demonstrated beneficial health outcomes and cost savings. Low-dose aspirin prophylaxis may be considered for PTB reduction in patients with infertility. Finally, upstream prevention strategies such as lifestyle modification and social policies to address the underlying needs for fertility treatment may also beneficially impact both CS and PTB rates., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the association between endometriosis and adverse pregnancy outcomes., Design: Population-based retrospective cohort study using linked universal health databases through ICES Ontario., Patient(s): All singleton pregnancies with an estimated date of confinement between October 2006 and February 2014., Intervention(s): Endometriosis was determined based on a surgical and/or medical diagnosis (defined as an in-hospital admission or surgery with a diagnosis code of International Classification of Diseases [ICD]9-617 or ICD10-N80 and/or 2 medical consults billed as ICD9-617)., Main Outcome Measure(s): The association between endometriosis and pregnancy outcomes was quantified by relative risks, derived using modified Poisson regression, and adjusted for maternal age, income quintiles, and history of fibroids (aRR). Mediation analysis was conducted to estimate direct effects of endometriosis diagnosis and indirect effects through mode of conception, namely: infertility without fertility treatment (known infertility but conceived without assistance), ovulation induction or intrauterine insemination, and in vitro fertilization or intracytoplasmic sperm injection, relative to unassisted conception., Result(s): A total of 19,099 pregnancies had an antecedent diagnosis of endometriosis, while 768,350 did not. Mean time (standard deviation) from endometriosis diagnosis to the index pregnancy was 5.6 (4.3) years. Endometriosis was associated with an increased risk of hypertensive disorders of pregnancy (aRR, 1.09; 95% confidence interval [CI], 1.02-1.16), preterm birth <37 weeks (aRR, 1.26; 95% CI, 1.20-1.33), early preterm birth <34 weeks (aRR, 1.33; 95% CI, 1.17-1.50), placenta previa (aRR, 2.07; 95% CI, 1.84-2.33), placenta abruption (aRR, 1.55; 95% CI, 1.31-1.83), other placental disorders (aRR, 1.77; 95% CI, 1.36-2.30), cesarean delivery (aRR, 1.18; 95% CI, 1.16-1.21), and stillbirth (aRR, 1.32; 95% CI, 1.09-1.59). Mediation analysis suggests that endometriosis directly affects most adverse pregnancy outcomes studied, except for stillbirth where infertility diagnosis or fertility treatment indirectly accounted for part of the increased risk., Conclusion(s): Endometriosis was associated with adverse pregnancy, independent of infertility diagnosis, or fertility treatment. Future studies should investigate the mechanisms of action and potential interventions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We conducted a population-based, retrospective, matched-cohort study to examine the impact of breast cancer diagnosis and treatment on fertility outcomes. Relative risks of infertility, childbirth, premature ovarian insufficiency (POI; age < 40) and early menopause (age < 45) were calculated using modified Poisson regression. Our primary cohort included young women (15-39) with early stage BC diagnosed 1995-2014. Five cancer-free patients were matched to each BC patient by birth year and census subdivision. The BC cohort was further divided by treatment with chemotherapy vs. no chemotherapy treatment. 3903 BC patients and 19,515 cancer-free women. BC patients treated with chemotherapy were at increased risk of infertility (RR 1.81; 95% CI 1.60-2.04), and POI (RR 6.25; 95% CI 5.15-7.58) and decreased childbirth (RR 0.85; 95% CI 0.75-0.96), compared to women without cancer. BC patients who did not receive chemotherapy were also at increased risk of infertility (RR 1.80 95% CI 1.48-2.18) and POI (RR 2.12 95% CI 1.37-3.28). All young BC survivors face an increased risk of diagnosed infertility and POI relative to women without cancer, independent of chemotherapy. These results emphasize the importance of pre-treatment fertility counselling for young women diagnosed with BC.

Objective: To study the association between mode of conception and risk of preterm birth, including, spontaneous and provider-initiated subtypes., Design: Population-based retrospective cohort study., Setting: Not applicable., Patients: All singleton livebirths and stillbirth in Ontario, Canada, 2006-2014., Intervention: The main exposure was mode of conception, namely unassisted conception, infertility without fertility treatment (i.e., known infertility but conceived without assistance), ovulation induction (OI) or intrauterine insemination (IUI), and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Modified Poisson regression generated risk ratios (RRs) and 95% confidence intervals for the association between exposure categories and preterm birth adjusted for clinically relevant covariates using a propensity score., Main Outcome Measure(s): The primary outcome was preterm birth <37 weeks, further categorized as spontaneous or provider-initiated subtypes. The secondary outcome was preterm birth <34 weeks., Results: We included 732,810 singleton births born to 649,918 mothers, of which 646,926 (88.3%) were from an unassisted conception, 68,822 (9.4%) with infertility but no fertility treatment, 9,024 (1.2%) following OI/IUI, and 8,038 (1.1%) following IVF/ICSI. Preterm birth <37 weeks occurred among 6.0% of births by unassisted conception, 7.7% with infertility without fertility treatment, 8.0% with OI/IUI, and 10.8% following IVF/ICSI. Relative to unassisted conception, the unadjusted RR of provider-initiated preterm birth was 1.30 (1.26-1.33) in women with infertility without fertility treatment, 1.36 (1.26-1.45) after OI/IUI, and 1.82 (1.70-1.93) after IVF/ICSI. The corresponding adjusted RRs (aRR) were 1.23 (1.16-1.31), 1.48 (1.29-1.69), and 2.35 (2.09-2.64). The unadjusted RR of spontaneous preterm birth was 1.22 (1.18-1.27) in women with infertility without fertility treatment, 1.22 (1.12-1.34) after OI/IUI, and 1.47 (1.35-1.60) after IVF/ICSI. The corresponding aRR were 1.15 (1.10-1.19), 1.19 (1.09-1.31), and 1.40 (1.27-1.53). For preterm birth <34 weeks, the RRs followed a similar pattern as for preterm birth <37 weeks, with the exception of women with infertility without fertility treatment (aRR 1.08; confidence interval, 0.95-1.23)., Conclusions: Infertility and receipt of fertility treatment are each associated with a higher risk of preterm birth, spontaneous and provider-initiated subtypes, even in singleton pregnancies. Strategies are needed to reduce the risk for preterm birth in these women., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception?, Summary Answer: Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment., What Is Known Already: Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear., Study Design, Size, Duration: This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006-2014. Outcomes were assessed up to June 2020., Participants/materials, Setting, Methods: Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present)., Main Results and the Role of Chance: The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4-8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16-1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01-1.17) in the OI/IUI group and 1.12 (95% CI 1.04-1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males., Limitations, Reasons for Caution: Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding., Wider Implications of the Findings: Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study., Study Funding/competing Interest(s): This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Subfertility and infertility treatment can be stressful experiences, but it is unknown whether each predisposes to postpartum mental illness. We sought to evaluate associations between subfertility or infertility treatment and postpartum mental illness., Methods: We conducted a population-based cohort study of individuals without pre-existing mental illness who gave birth in Ontario, Canada, from 2006 to 2014, stratified by fertility exposure: subfertility without infertility treatment; noninvasive infertility treatment (intrauterine insemination); invasive infertility treatment (in vitro fertilization); and no reproductive assistance. The primary outcome was mental illness occurring 365 days or sooner after birth (defined as ≥ 2 outpatient visits, an emergency department visit or a hospital admission with a mood, anxiety, psychotic, or substance use disorder, self-harm event or other mental illness). We used multivariable Poisson regression with robust error variance to assess associations between fertility exposure and postpartum mental illness., Results: The study cohort comprised 786 064 births (mean age 30.42 yr, standard deviation 5.30 yr), including 78 283 with subfertility without treatment, 9178 with noninvasive infertility treatment, 9633 with invasive infertility treatment and 688 970 without reproductive assistance. Postpartum mental illness occurred in 60.8 per 1000 births among individuals without reproductive assistance. Relative to individuals without reproductive assistance, those with subfertility had a higher adjusted relative risk of postpartum mental illness (1.14, 95% confidence interval 1.10-1.17), which was similar in noninvasive and invasive infertility treatment groups., Interpretation: Subfertility or infertility treatment conferred a slightly higher risk of postpartum mental illness compared with no reproductive assistance. Further research should elucidate whether the stress of infertility, its treatment or physician selection contributes to this association., Competing Interests: Competing interests: Simone Vigod reports receiving royalties from UpToDate for authorship of materials related to depression and pregnancy. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Though immigrant women comprise a growing portion of the Canadian population, there remains a lack of information on the rates of infertility diagnosis in this group. Our study aimed to investigate the differences in rates of infertility consults between refugee, non-refugee immigrant, and Canadian-born women. We conducted a population-based matched cohort study in women 15-45 years of age in Ontario. Immigration status was defined as refugee, non-refugee immigrant, and Canadian-born woman. Refugee and non-refugee immigrant women were matched by age and residence in the same Local Health Integration Network (LHIN) to two Canadian-born women. The cohort was followed for 2 years for occurrence of infertility consult. Proportion of infertility consults by immigration status was calculated and differences between groups were assessed using standardized differences (SD). Modified Poisson regression was used to calculate the relative risk (RR) for infertility consults by immigration status after adjusting for confounding variables. Our results showed an increased proportion of infertility consults among both refugees (4.7%) and non-refugee immigrant women (5.8%) compared to their Canadian-born matches (2.8% and 3.2%, respectively), with SD ≧ 0.1 in most stratified age groups, denoting a meaningful statistical difference. In the multivariable analysis, relative to Canadian-born women, the RR for fertility consults was increased in refugee women (RR 1.66, CI 95% 1.58-1.75), and non-refugee immigrants (RR 1.77, 95% CI 1.74-1.80). These findings may be explained by immigrant women originating from areas with higher infertility rates, or their experience of higher than average stress levels, a known risk factor for infertility., (© 2022. Society for Reproductive Investigation.)

The prevalence of maternal cardiovascular disease (CVD) has risen throughout the developed world, reflecting an increase in acquired cardiovascular risk factors, such as hypertension and diabetes, and the improved life expectancy of those living with congenital and acquired heart disease owing to advances in care. Because many cardiovascular risk factors and conditions are associated with infertility, reproductive-age individuals with CVD may increasingly seek reproductive assistance. The worldwide use of assisted reproductive technologies (ART), such as in vitro fertilisation, with or without intracytoplasmic sperm injection, or intrauterine insemination after pharmacologic ovulation induction have increased steadily over the past several decades. It is incumbent on providers who care for reproductive-age individuals with preexisting CVD or CVD risk factors to understand and appreciate the types of treatments offered and inherent risks related to infertility treatments, in order to guide their patients to making safe reproductive choices in line with their values and preferences. Infertility treatments increase the risk of complicated pregnancy, but whether these risks are compounded among individuals with preexisting CVD is less well known. In this review, we summarise current available evidence regarding short-term and long-term cardiovascular implications of ART among individuals with and without CVD, as well as treatment considerations for these individuals. Existing knowledge gaps and priority areas for further study are presented., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Caesarean section rates are higher among pregnancies conceived by assisted reproductive technology (ART) compared to spontaneous conceptions (SC), implying an increase in neonatal and maternal morbidity. We aimed to compare caesarean section rates in ART pregnancies versus SC, overall, by indication (elective versus emergent), and by type of ART treatment (in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), fresh embryo transfer, frozen embryo transfer) in a systematic review and meta-analysis., Methods: We searched Medline, EMBASE and CINAHL databases using the OVID Platform from 1993 to 2019, and the search was completed in January 2020. The eligibility criteria were cohort studies with singleton conceptions after in-vitro fertilization and/or intracytoplasmic sperm injection using autologous oocytes versus spontaneous conceptions. The study quality was assessed using the Newcastle Ottawa Scale and GRADE approach. Meta-analyses were performed using odds ratios (OR) with a 95% confidence interval (CI) using random effect models in RevMan 5.3, and I-squared (I 2 ) test > 75% was considered as high heterogeneity., Results: One thousand seven hundred fifty studies were identified from the search of which 34 met the inclusion criteria. Compared to spontaneous conceptions, IVF/ICSI pregnancies were associated with a 1.90-fold increase of odds of caesarean section (95% CI 1.76, 2.06). When stratified by indication, IVF/ICSI pregnancies were associated with a 1.91-fold increase of odds of elective caesarean section (95% CI 1.37, 2.67) and 1.38-fold increase of odds of emergent caesarean section (95% CI 1.09, 1.75). The heterogeneity of the studies was high and the GRADE assessment moderate to low, which can be explained by the observational design of the included studies., Conclusions: The odds of delivering by caesarean section are greater for ART singleton pregnancies compared to spontaneous conceptions. Preconception and pregnancy care plans should focus on minimizing the risks that may lead to emergency caesarean sections and finding strategies to understand and decrease the rate of elective caesarean sections.

Purpose: The use of assisted reproductive technology (ART) has increased in the last 2 decades and continuous surveillance is needed. This systematic review aims to assess the risk of adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestationalage [SGA] and large for gestational-age [LGA]), in singleton pregnancies conceived by fresh or frozen embryo transfer (FET) compared to spontaneous conceptions., Methods: Cohort studies were identified from MEDLINE, Embase, Cochrane Library (January 2019), and manual search. Meta-analyses were performed to estimate odds ratios (OR) using random effects models in RevMan 5.3 and I-squared (I 2 ) test > 50% was considered as high heterogeneity., Results: After 3142 titles and abstracts were screened, 1180 full-text articles were assessed, and 14 were eligible. For fresh embryo transfer, the pooled ORs were PTB 1.64 (95% CI 1.46, 1.84); I 2  = 97%; LBW 1.67 (95% CI 1.52, 1.85); I 2  = 94%; SGA 1.46 [95% CI 1.11, 1.92]; I 2  = 99%, LGA 0.88 (95% CI 0.80, 0.87); I 2  = 80%). For frozen, the pooled ORs were PTB 1.39 (95% CI 1.34, 1.44); I 2  = 0%; LBW 1.38 (95% CI 0.91, 2.09); I 2  = 98%; SGA 0.83 (95% CI 0.57, 1.19); I 2  = 0%, LGA 1.57 (95% CI 1.48, 1.68); I 2  = 22%)., Conclusions: When compared with spontaneous pregnancies, fresh, but not frozen was associated with LBW and SGA. Both fresh and frozen were associated with PTB. Frozen was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards monitoring adverse neonatal outcomes in these pregnancies.

Purpose: To assess the fertility preservation (FP) referral rates and patterns of newly diagnosed breast cancer in female adolescent and young adult (AYA) patients., Methods: Women aged 15-39 years with newly diagnosed breast cancer in Ontario from 2000 to 2017 were identified using the Ontario Cancer Registry. Exclusion criteria included prior sterilizing procedure, health insurance ineligibility, and prior infertility or cancer diagnosis. Women with a gynecology consult between cancer diagnosis and chemotherapy commencement with the billed infertility diagnostic code (ICD-9 628) were used as a surrogate for FP referral. The effect of age, parity, year of cancer diagnosis, staging, income, region, neighborhood marginalization, and rurality on referral status was investigated., Results: A total of 4452 patients aged 15-39 with newly diagnosed breast cancer met the inclusion criteria. Of these women, 178 (4.0%) were referred to a gynecologist with a billing code of infertility between cancer diagnosis and initiation of chemotherapy. Older patients, prior parity, and advanced disease were inversely correlated with referrals. Referral rates also varied regionally: patients treated in the south-east and south-west Local Health Integration Networks (LHINs) had the highest probability of referral, and patients covered by north LHINs had the lowest (central LHIN as reference). General surgeons accounted for 36.5% of all referrals, the highest percentage of all specialists. Referral rates significantly increased over time from 0.4% in 2000 to 10.7% in 2016., Conclusion: FP referral rates remain low and continue to be influenced by patient demographics and prognosis. These findings highlight the need for further interdisciplinary coordination in addressing the fertility concerns of AYA with newly diagnosed breast cancers.

Objectives: Time-to-Pregnancy (TTP) is an epidemiological tool to assess couple fecundity. The finger digit ratio (2D:4D) has been suggested as a marker of androgen exposure in utero. Maternal, paternal, or couple-mediated factors related to fecundity may also have an effect on androgen exposure during pregnancy. We aimed to investigate the association between TTP, infertility, or use of Assisted Reproductive Technologies (ART) and offspring 2D:4D., Methods: Data from 673 mother-child pairs were collected from questionnaires in the Maternal-Infant Research on Environmental Chemicals (MIREC) study across 10 cities in Canada. The mean maternal age was 33.4 years (SD 4.7), with a median gestational age of 12.1 weeks (SD 1.3), at the time of recruitment. Our study included 338 girls and 335 boys, and the mean age of the children at follow-up was 3.5 years (SD 1.0). TTP was assessed through questionnaires during the first trimester of pregnancy. Digital photographs of both hands were taken in a follow-up study to calculate the children's 2D:4D (2-5 years). anova, t tests, and multiple linear regression analyses were conducted., Results: Boys had significantly lower mean 2D:4Ds (0.936 ±0.041 in right hand, 0.936 ±0.040 in left hand) compared to girls (0.948 ±0.038 in right hand, 0.945 ±0.038 in left hand). The mean 2D:4D did not differ according to TTP, infertility, or use of ART. The only factors associated with the child's 2D:4D were the child's age and maternal 2D:4D., Conclusions: Our study does not support an association between TTP, infertility, or use of ART and children's 2D:4D., (© 2018 Wiley Periodicals, Inc.)

Objective: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time‐to‐pregnancy (TTP) and infertility. Design: Pregnancy‐based retrospective TTP cohort study. Setting: Hospitals and clinics from ten cities across Canada. Population: A total of 1784 pregnant women. Methods: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete‐time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre‐pregnancy body mass index, education, income, recruitment site and plasma lipids. Main Outcome Measures: TTP was self‐reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months. Results: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02–1.16); however, the association was not linear when exposure was modelled in tertiles. Conclusion: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP. [ABSTRACT FROM AUTHOR]

A retrospective cohort study was performed to evaluate the outcome of modified natural IVF-intracytoplasmic sperm injection {mnlVF-ICSI) cycles to compare 81 mnlVF- ICSI first cycles using ejaculated spermatozoa with 44 mnlVF-ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group (41.5 versus 36.5 years, P= 0.001). There were no significant differences in fertilization rate or cleavage rate between the ejaculated and the surgically retrieved groups; however the prevalence of embryo transfer was higher in the surgically retrieved group (65.9% versus 45.7%, P = 0.03). Only single-embryo transfer was performed. Biochemical (34.5% versus 37.8%) and clinical (31.0% versus 35.1%) pregnancy rates per embryo transfer were similar between the ejaculated and the surgically retrieved groups. The data suggest that mnlVF-ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required. [ABSTRACT FROM AUTHOR]