Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos?
PGT-A is associated with a greater ...probability of live birth among women 35 years old and older who are undergoing IVF.
Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected.
We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis.
Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards.
Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A.
We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles.
Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A.
No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest.
N/A.
Infertility affects up to 15% of couples. In vitro fertilization (IVF) treatment has modest success rates and some factors associated with infertility and poor treatment outcomes are not modifiable. ...Several studies have assessed the association between female dietary patterns, a modifiable factor, and IVF outcomes with conflicting results. We performed a systematic literature review to identify female dietary patterns associated with IVF outcomes, evaluate the body of evidence for potential sources of heterogeneity and methodological challenges, and offer suggestions to minimize heterogeneity and bias in future studies.
We performed systematic literature searches in EMBASE, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials for studies with a publication date up to March 2020. We excluded studies limited to women who were overweight or diagnosed with PCOS. We included studies that evaluated the outcome of pregnancy or live birth. We conducted an initial bias assessment using the SIGN 50 Methodology Checklist 3.
We reviewed 3280 titles and/or titles and abstracts. Seven prospective cohort studies investigating nine dietary patterns fit the inclusion criteria. Higher adherence to the Mediterranean diet, a 'profertility' diet, or a Dutch 'preconception' diet was associated with pregnancy or live birth after IVF treatment in at least one study. However, causation cannot be assumed. Studies were potentially hindered by methodological challenges (misclassification of the exposure, left truncation, and lack of comprehensive control for confounding) with an associated risk of bias. Studies of the Mediterranean diet were highly heterogenous in findings, study population, and methods. Remaining dietary patterns have only been examined in single and relatively small studies.
Future studies with rigorous and more uniform methodologies are needed to assess the association between female dietary patterns and IVF outcomes. At the clinical level, findings from this review do not support recommending any single dietary pattern for the purpose of improving pregnancy or live birth rates in women undergoing IVF treatment.
Regular consumption of fish is generally recommended by authorities because fish is an important source of essential nutrients. However, the presence of potentially toxic contaminants in fish has ...raised many concerns about the food's safety for human health. In the present study, we used a validated semi-quantitative food frequency questionnaire to assess the dietary habits of a representative sample of 719 individuals (319 males and 400 females) aged 18–87 years residing in Northern Italy. We estimated weekly dietary intakes of Arsenic (As) and Mercury (Hg), and we compared them with safety standards set by the European Food Safety Authority. In this population, fish was the main contributor to As and Hg intake. The highest levels of As were in sardine, sole/flounder and cephalopods, and of Hg in the biggest, predatory fish. About the other foods, cereals were the second contributor to the intake of these elements, especially rice for As and bread for Hg, and high levels of As and Hg were also found in mushrooms, coffee and wine. Average weekly intake of both contaminants was below recommended safety limits.
•We assessed arsenic and mercury contamination levels in foods composing dietary habits of Northern Italy community.•Sardine and sole species showed higher concentration of arsenic, while swordfish and tuna of mercury.•Estimated dietary intake of both trace elements were below the EFSA recommended tolerable intake.
Selenium is a trace element of both nutritional and toxicological interest, depending on its dose and chemical form. Diet is the primary source of exposure for most individuals. We sought to ...investigate the influence of food intake on serum levels of selenium species.
Among fifty subjects randomly selected from a Northern Italian population, we assessed dietary habits using a validated semi-quantitative food frequency questionnaire. We also measured circulating levels of selenium species in serum using high pressure liquid chromatography associated with inductively-coupled plasma dynamic reaction cell mass spectrometer.
Circulating levels of inorganic selenium, the most toxic selenium species, were positively associated with intake of fish, legumes and dry fruits, and inversely associated with intake of dairy products and mushrooms. Concerning the organic selenium species, selenoproteinP-bound selenium was inversely associated with intake of fish, fresh fruits, vegetables, and legumes, while selenocysteine-bound selenium positively associated with intake of fresh fruit, potato, legume and mushroom. In the present study, intakes of different foods were correlated with different types of selenium species. These results have important public health implications when assessing the nutritional and toxicological potential of diet composition with reference to selenium exposure.
•Selenium species concentrations in serum shows different correlation pattern with food intake.•Inorganic selenium positively correlates with intake of fish, legumes and dry fruits, and negatively with dairy products.•Organic Se-Cys positively correlates with intake of cereals, eggs, vegetables and fresh fruits, and negatively with sweets.
•Phthalates widely detected among a cohort of reproductive-aged Black women.•Biomarkers generally showed weak-to-moderate inverse associations with UL incidence.•Inverse associations stronger among ...women with BMI ≥ 30 kg/m2 for specific phthalates.•Little evidence of effect of the phthalate biomarkers mixture on UL incidence.
Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies.
We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence.
We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23–35 years who were recruited during 2010–2012. We quantified fourteen phthalates and two phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate ΣDEHP and potency-weighted sum of anti-androgenic WΣAA biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence.
Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m2. HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08).
In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly.
Abstract
Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an ...internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21–45 year residing in the United States or Canada during December 2020–September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.
To evaluate the association between adiposity, physical activity (PA), and fecundability.
Prospective cohort study.
Not applicable.
A total of 2,062 female pregnancy planners from the United States ...and Canada who were enrolled during the preconception period.
None.
Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using proportional probabilities models that adjusted for potential confounders.
Relative to body mass index (BMI) 18.5-24 kg/m(2), FRs for BMI <18.5, 25-29, 30-34, 35-39, 40-44, and ≥45 kg/m(2) were 1.05 (95% CI 0.76-1.46), 1.01 (95% CI 0.89-1.15), 0.98 (95% CI 0.82-1.18), 0.78 (95% CI 0.60-1.02), 0.61 (95% CI 0.42-0.88), and 0.42 (95% CI 0.23-0.76), respectively. Reduced fecundability was observed among women with the largest waist-to-hip ratios (≥0.85 vs. <0.75; FR = 0.87, 95% CI 0.74-1.01) and waist circumferences (≥36 vs. <26 inches ≥90 vs. <66 cm; FR = 0.80, 95% CI 0.59-1.01). Tendency to gain weight in the chest/shoulders (FR = 0.63, 95% CI 0.36-1.08) and waist/stomach (FR = 0.90, 95% CI 0.79-1.02), relative to hips/thighs, was associated with lower fecundability. Moderate PA was associated with increased fecundability (≥5 vs. <1 h/wk; FR = 1.26, 95% CI 0.96-1.65), but there was no dose-response relation. Among overweight/obese women (BMI ≥25 kg/m(2)), fecundability was 27% higher for vigorous PA of ≥5 versus <1 h/wk (95% CI 1.02-1.57).
Various measures of overall and central adiposity were associated with decreased fertility among pregnancy planners. Vigorous PA was associated with improved fertility among overweight and obese women only; moderate PA was associated with improved fertility among all women.
Selenium, a trace element to which humans are exposed mainly through diet, has been involved in the etiology of human cancer. We investigated the long-term effects of selenium exposure on cancer ...incidence using data from a natural experiment in Northern Italy. During the 1970s–1980s, in a part of the Italian municipality of Reggio Emilia, residents were inadvertently exposed to unusually high levels of inorganic hexavalent selenium (selenate) through drinking water. We followed the exposed residents for 28years, generating data on incidence (when available) and mortality rates for selected cancer sites; the remaining municipal residents comprised the unexposed (reference) group. We observed no substantial difference in overall cancer incidence comparing exposed and unexposed cohorts. We detected, however, a higher incidence of cancer at some sites, and for a few of them, namely cancers of the buccal cavity and pharynx, melanoma, urinary tract and lymphoid tissue, the excess incidence was particularly evident in the first period of follow-up but decreased over time. Overall, these results suggest that consumption of water with levels of selenium in its inorganic hexavalent form close to the European standard, 10μg/L, may have unfavourable effects on cancer incidence.
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•Chronic exposure to inorganic selenium via drinking water may be unsafe to the human.•Long-term exposure to inorganic selenium may increase cancer risk.•Selenium exposure increased melanoma and oropharyngeal, urinary and lymphoid cancer risk.•The EU drinking water selenium standard of 10μg/L should be reassessed.
Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen ...species. 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity.
The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population.
We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017–2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine.
Among 137 participants aged 30–60 years, median urinary selenium and 8-oxodG concentrations were 22.02 μg/L and 3.21 μg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 μg/L and 78.7 μg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females.
Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.
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•Overall selenium was not associated with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG).•Selected selenium species were associated with the biomarker of oxidative stress.•Effect modification by sex was encountered.•Selenomethionine-bound selenium was strongly associated with 8-oxodG.
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