Severe Maternal and Neonatal Morbidity Among Gestational Carriers : A Cohort Study.

BACKGROUND: Use of a gestational ("surrogate") carrier is increasingly common. Risk for maternal and neonatal adversity is largely unknown in this birthing population. OBJECTIVE: To determine the risk for severe maternal morbidity (SMM) and severe neonatal morbidity (SNM) in gestational carriers. DESIGN: Population-based cohort study. SETTING: All of Ontario, Canada. PARTICIPANTS: All singleton births at more than 20 weeks' gestation, from 2012 to 2021. MEASUREMENTS: Exposure was type of conception, namely, gestational carriage (main exposure), unassisted conception (comparison group 1), and in vitro fertilization (IVF) (comparison group 2). Main composite outcomes were SMM and SNM. Modified Poisson regression models generated weighted relative risks (wRRs) using propensity score-based overlap weighting. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, preterm birth, and postpartum hemorrhage. RESULTS: Of all eligible singleton births, 846 124 (97.6%) were by unassisted conception, 16 087 (1.8%) by IVF, and 806 (0.1%) by gestational carriage. Respective risks for SMM were 2.3%, 4.3%, and 7.8%. The wRRs were 3.30 (95% CI, 2.59 to 4.20) comparing gestational carriage with unassisted conception and 1.86 (CI, 1.36 to 2.55) comparing gestational carriage with IVF. Respective risks for SNM were 5.9%, 8.9%, and 6.6%, generating wRRs of 1.20 (CI, 0.92 to 1.55) for gestational carriage versus unassisted conception and 0.81 (CI, 0.61 to 1.08) for gestational carriage versus IVF. Hypertensive disorders, postpartum hemorrhage, and preterm birth at less than 37 weeks were also significantly higher contrasting gestational carriers to either comparison group. LIMITATION: Absence of information about indications for choosing a gestational carrier, and oocyte or sperm donor source. CONCLUSION: Among singleton births of more than 20 weeks' gestation, a higher risk for SMM and adverse pregnancy outcomes was seen among gestational carriers compared with women who conceived with and without assistance. Although gestational carriage was associated with preterm birth, there was less clear evidence of severe neonatal morbidity. Potential mechanisms for higher maternal morbidity among gestational carriers require elucidation, alongside developing special care plans for gestational carriers. PRIMARY FUNDING SOURCE: The Canadian Institutes of Health Research.

Pregnancy Outcomes in Survivors of Adolescent and Young Adult Breast Cancer: A Population-Based Cohort Study.

OBJECTIVES: To evaluate the association between adolescent and young adult (AYA) breast cancer (BC) and the adverse pregnancy outcomes of preterm birth, small for gestational age birth, cesarean delivery, and preeclampsia, and the effect of fertility treatment on this association. METHODS: Population-based cohort study with universal coverage health data for Ontario, Canada. BC was identified from the Ontario Cancer Registry. All births >220 weeks gestation between April 2006 to March 2018 were included. Modified Poisson regression generated risk ratios between AYA BC and adverse pregnancy outcomes, adjusted for maternal characteristics. Models were stratified by fertility treatment. RESULTS: Among 1 189 980 deliveries, 474 mothers had AYA BC history (exposed), while 1 189 506 had no cancer history (unexposed). AYA BC was associated with cesarean delivery (adjusted risk ratio [aRR] 1.26; 95% CI 1.14-1.39). There was no association between AYA BC and other adverse outcomes. Modelling cesarean delivery subtypes, AYA BC was associated with increased risk of planned (aRR 1.27; 95% CI 1.08-1.49) and unplanned cesarean delivery (aRR 1.41; 95% CI 1.20-1.66). An increased risk of cesarean delivery in exposed persisted among singleton pregnancies (aRR 1.27; 95% CI 1.15-1.41), but not in models stratified by mode of conception (fertility treatment: aRR 1.07; 95% CI 0.84-1.36; unassisted conception: aRR 1.30; 95% CI 1.16-1.46). CONCLUSIONS: A history of AYA BC did not confer an elevated risk of adverse pregnancy outcomes, except for planned and unplanned cesarean delivery. The risk of adverse pregnancy outcomes does not appear to be an indication for delayed pregnancy after AYA BC diagnosis.

The contributions of fertility during adolescence to disability across the life-course: hypothesized causal pathways, research gaps, and future directions.

CONTEXT: Robust associations have been identified between fertility during adolescence and the disablement process, including pathologies, impairments, functional limitations and disability. Limited theoretical or empirical research considers how and why such relationships exist generally or with the individual associated components of disablement. OBJECTIVE: To consolidate and critically evaluate literature to describe testable, theory-based hypotheses to guide future research on the mechanisms by which fertility during adolescence contributes to disablement. METHODS: Targeted literature review of research from diverse global settings contextualised in two well-accepted theoretical frameworks in life-course epidemiology: the cumulative risk model and the critical period approach. RESULTS: Five hypothesised causal pathways linking adolescent fertility to disablement in later life are described: 1) Causal relationship initiated by fertility during adolescence; 2) Common cause(s) for both, such as adverse childhood experiences; 3) Contributing cause(s) to adolescent fertility; 4) Interaction between adolescent fertility and other risk factors; and 5) Critical period effects unique to adolescence. Most research on the topic is on pathologies versus functional limitations and disability. CONCLUSION: We highlight promising research avenues to inform future research and interventions on adolescent fertility and the disablement process. This work provides theoretical clarity, identifies research gaps, and offers hypotheses-testing opportunities for future research.

Endometriosis, Severe Maternal Morbidity, and the Effect of Infertility: Population-Based Cohort Study.

This population-based cohort evaluated the association between endometriosis and severe maternal morbidity (SMM), and the mediating effect of infertility and fertility treatment. Included were all singleton deliveries in Ontario between 2006 and 2014. Modified Poisson regression generated adjusted relative risks. Mediation analysis estimated the direct effect of endometriosis and indirect effect through infertility and mode of conception. 787 449 deliveries were included (19 099, 2.4% with endometriosis). SMM occurred in 29.0 per 1000 deliveries among women with endometriosis, in contrast to 18.2 per 1000 deliveries among those without endometriosis-corresponding to an adjusted relative risk of SMM of 1.43 (95% CI 1.31-1.56). Mediation analysis demonstrated that the effect of endometriosis on SMM was independent of infertility or fertility treatment. We conclude that SMM in women with endometriosis appears to be due to the disease itself and not to infertility or related treatments.

The varying estimation of infertility in Ethiopia: the need for a comprehensive definition.

BACKGROUND: Infertility is a marginalized sexual and reproductive health issue in low-resource settings. Globally, millions are affected by infertility, but the lack of a universal definition makes it difficult to estimate the prevalence of infertility at the population level. Estimating the prevalence of infertility may inform targeted and accessible intervention, especially for a resource-limited country like Ethiopia. This study aims to estimate the prevalence of female infertility in Ethiopia using the Demographic and Health Survey (DHS) through two approaches: (i) the demographic approach and (ii) the current duration approach. METHODS: Data from 15,683 women were obtained through the 2016 Ethiopian DHS. The demographic approach estimates infertility among women who had been married/in a union for at least five years, had never used contraceptives, and had a fertility desire. The current duration approach includes women at risk of pregnancy at the time of the survey and determines their current length of time-at-risk of pregnancy at 12, 24, and 36 months. Logistic regression analysis estimated the prevalence of infertility and factors associated using the demographic approach. Parametric survival analysis estimated the prevalence of infertility using the current duration approach. All estimates used sampling weights to account for the DHS sampling design. STATA 14 and R were used to perform the statistical analysis. RESULTS: Using the demographic definition, the prevalence of infertility was 7.6% (95% CI 6.6-8.8). When stratified as primary and secondary infertility, the prevalence was 1.4% (95% CI 1.0-1.9) and 8.7% (95% CI 7.5-10.1), respectively. Using the current duration approach definition, the prevalence of overall infertility was 24.1% (95% CI 18.8-34.0) at 12-months, 13.4% (95% CI 10.1-18.6) at 24-months, and 8.8% (95% CI 6.5-12.3) at 36-months. CONCLUSION: The demographic definition of infertility resulted in a lower estimate of infertility. The current duration approach definition could be more appropriate for the early detection and management of infertility in Ethiopia. The findings also highlight the need for a comprehensive definition of and emphasis on infertility. Future population-based surveys should incorporate direct questions related to infertility to facilitate epidemiological surveillance.

Addressing the Rehabilitation Needs of Women Experiencing Infertility in Ethiopia: Time for Action.

The psychological, social, and financial disabilities caused by infertility are significant for women, particularly those living in low- and middle-income countries such as Ethiopia. Although rehabilitation can be an important form of support for such women, infertility is frequently overlooked as a disability or potential target of rehabilitation interventions. This study aimed to determine what rehabilitation-related services and supports are available for women experiencing infertility in Ethiopia. We used an Interpretive Description design. We purposefully selected fourteen rehabilitation, medical, and policy service providers from diverse institutions across three geographical locations. We used semi-structured questions during our in-person and telephone interviews. The data were analyzed using reflexive thematic analysis with the assistance of NVivo. We identified five main themes, including (a) policies related to infertility, (b) the concept that disabilities are physically visible fails to recognize infertility, (c) the need for rehabilitation services for women with infertility, (d) the importance of wellness services for women experiencing infertility, and (e) the role of religion in rehabilitation services. In conclusion, it is essential to strengthen the policies around infertility, incorporate rehabilitation services in fertility care, and view infertility as a disabling condition for women who experience it in Ethiopia.

Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

Menopause hormone therapy and physical performance: The Canadian Longitudinal Study on Aging.

OBJECTIVE: To examine the association between menopause hormone therapy (MHT) and physical performance among women from the Canadian Longitudinal Study on Aging. STUDY DESIGN: Cross-sectional study of 12,506 postmenopausal Canadian women. MAIN OUTCOME MEASURES: Grip strength (kg), gait speed (m/s), timed up and go (s), chair rise (s), and balance (s) were assessed following standard procedures. The association between MHT and physical performance was evaluated using linear regression models adjusted for age, education, study site, smoking, alcohol consumption, body mass index, diabetes, hypertension, and hysterectomy. Sensitivity analyses were conducted according to age at study visit (<65 vs. ≥65 years), body mass index (<25 kg/m2 vs. ≥25 kg/m2), physical activity level (less vs. more active), duration and type of MHT, and time of starting MHT after menopause. RESULTS: Compared with those who never used MHT, prior or current use was associated with better performance on the timed up and go test (ß: -0.19; 95%CI: -0.28; -0.11) and faster gait speed (ß = 0.01, 95%CI = 0.00; 0.02). No association was found for grip strength, balance, and chair rise. Results did not change by body mass index, physical activity, or duration of MHT use. When stratified by age at study visit, the effect remained significant only in among those aged 65 years or more. Starting MHT <5 years after menopause was associated with better physical performance. CONCLUSIONS: MHT was associated with better physical performance in gait speed and timed up and go tests. The cross-sectional design of the study limits causal interpretation. Prospective studies are needed to confirm our results.

Assessing preconception exposure to environmental chemicals and fecundity: Strategies, challenges, and research priorities.

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.