Dataset Information

Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study.

ABSTRACT: Objective: We investigated whether lifestyle affects assisted reproduction technology (ART) outcomes.

Design: Cohort study.

Setting: Italian fertility unit.

Participants: From September 2014 to December 2016, women from couples presenting for evaluation and eligible for ART were invited to participate. Information on alcohol intake, current smoking and leisure physical activity (PA) during the year before the interview was collected, using a structured questionnaire. We considered the ART outcomes of the cycle immediately following the interview.

Primary and secondary outcome measures: The primary outcome measure was cumulative pregnancy rate per retrieval. Secondary measures were number of retrieved oocytes, embryo transfer and live birth.

Results: In 492 women undergoing an ART cycle, 427 (86.8%) underwent embryo transfer, 157 (31.9%) had at least one clinical pregnancy and 121 (24.6%) had live birth. The cumulative pregnancy rate per retrieval was 33.3% (95% CI 28.5% to 38.7%). In women in the third tertile of alcohol intake, adjusted relative risk was 0.97 (95% CI 0.87 to 1.08), 0.90 (95% CI 0.62 to 1.30) and 0.89 (95% CI 0.57 to 1.37) for embryo transfer, clinical pregnancy and live birth, respectively. The corresponding figures in women currently smoking more than 5 cigarettes/day were 1.00 (95% CI 0.88 to 1.16), 0.94 (95% CI 0.60 to 1.48) and 1.14 (95% CI 0.68 to 1.90), and in women with PA ?5?hours/week were 0.93 (95% CI 0.79 to 1.08), 0.44 (95% CI 0.22 to 0.90) and 0.48 (95% CI 0.22 to 1.05), respectively.

Conclusion: There were no significant differences in in vitro fertilisation outcomes among women who used alcohol or tobacco in the year prior to treatment. Conservatively, all women should be advised to limit substance abuse. Moreover, our study suggested that maintaining a moderate, but not high, level of PA could be beneficial.

SUBMITTER: Ricci E

PROVIDER: S-EPMC7692844 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study.

Ricci Elena E Noli Stefania S Ferrari Stefania S La Vecchia Irene I De Cosmi Valentina V Castiglioni Marta M Somigliana Edgardo E Agostoni Carlo C Cipriani Sonia S Mauri Paola Agnese PA Parazzini Fabio F

BMJ open 20201126 11

<h4>Objective</h4>We investigated whether lifestyle affects assisted reproduction technology (ART) outcomes.<h4>Design</h4>Cohort study.<h4>Setting</h4>Italian fertility unit.<h4>Participants</h4>From September 2014 to December 2016, women from couples presenting for evaluation and eligible for ART were invited to participate. Information on alcohol intake, current smoking and leisure physical activity (PA) during the year before the interview was collected, using a structured questionnaire. We ...[more]

PMID: 33243794

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Project description:STUDY QUESTION: Could clinically-relevant moderate and/or high dose maternal folic acid supplementation prevent aberrant developmental and epigenetic outcomes associated with assisted reproductive technologies (ART)? SUMMARY ANSWER: Our results demonstrate dose-dependent and sex-specific effects of folic acid supplementation in ART and provide evidence that moderate dose supplements may be optimal for both sexes. WHAT IS KNOWN ALREADY: Children conceived using ART are at an increased risk for growth and genomic imprinting disorders, often associated with DNA methylation defects. Folic acid supplementation is recommended during pregnancy to prevent adverse offspring outcomes; however, the effects of folic acid supplementation in ART remain unclear. STUDY DESIGN, SIZE, DURATION: Outbred female mice were fed 3 folic-acid supplemented diets, control (rodent daily recommended intake or DRI; CD), moderate (4-fold DRI; 4FASD) or high (10-fold DRI; 10FASD) dose, for six weeks prior to ART and throughout gestation. Mouse ART involved a combination of superovulation, in vitro fertilization, embryo culture and embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: Upon collection of midgestation embryos and placentas (n=74-99 embryos/group), all embryos were assessed for developmental delay and gross morphological abnormalities. Embryos and placentas were also examined at the epigenetic level. We assessed methylation at four imprinted genes (Snrpn, Kcnq1ot1, Peg1, and H19) in matched midgestation embryos and placentas (n=31-32/group) using bisulfite pyrosequencing. In addition, we examined genome-wide DNA methylation patterns in midgestation placentas (n=6 normal placentas per sex/group) and embryos (n=6 normal female embryos/group; n=3 delayed female embryos/group) using reduced representation bisulfite sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: Moderate, but not high dose supplementation, was associated with a decrease in the proportion of developmentally delayed embryos. Although moderate dose folic acid supplementation reduced DNA methylation variance at certain imprinted genes in embryonic and placental tissues, high dose supplementation exacerbated the negative effects of ART at imprinted loci. Furthermore, folic acid supplements resolved female-biased aberrant imprinted gene methylation. Supplementation was more effective at correcting ART-induced genome-wide methylation defects in male versus female placentas; however, folic acid supplementation also led to additional methylation perturbations which were far more pronounced in males. LIMITATIONS, REASONS FOR CAUTION: Although the combination of mouse ARTs utilized in this study consisted of techniques commonly used in human fertility clinics, there may be species differences. Therefore, human studies, designed to determine the optimal levels of folic acid supplementation for ART pregnancies, and taking into account fetal sex, are warranted. WIDER IMPLICATIONS OF THE FINDINGS: Taken together, our findings support moderation in the dose of folic acid supplements taken during ART.

Project description:Study questionIs pre-treatment alcohol and caffeine intake associated with infertility treatment outcomes among women undergoing ART?Summary answerLow to moderate alcohol and caffeine intakes in the year prior to infertility treatment were not related to ART outcomes.What is known alreadyAlcohol and caffeine intake have been found to be associated with infertility in some studies. Nevertheless, data on their relation with outcomes of infertility treatments are scarce and inconsistent.Study design, size, durationWe included 300 women (493 ART cycles) from the Environment and Reproductive Health Study, an ongoing cohort study (2006-2016).Participants/materials, setting, methodsPre-treatment intakes of alcohol and caffeine were assessed retrospectively using a validated food frequency questionnaire. Intermediate and clinical endpoints of ART were abstracted from electronic medical records. Generalized linear mixed models with random intercepts to account for multiple ART cycles per woman were used to evaluate the association with ART outcomes adjusting for age, BMI, smoking status, infertility diagnosis, protocol type, race, dietary patterns, and calories, vitamin B12 and folate intake.Main results and the role of chanceMedian (range) pre-treatment alcohol and caffeine intakes were 5.6 (0.0-85.8) g/day and 124.9 (0.3-642.2) mg/day, respectively. The adjusted percentage of initiated cycles resulting in live birth (95% CI) for women in increasing categories of pre-treatment alcohol intake was 34% (20, 52%) for non-consumers, 46% (36, 57%) for 0.1-6 g/day, 41% (29, 53%) for 6.1-12 g/day, 42% (31, 55%) for 12.1-24 g/day, and 41% (22, 63%) for >24 g/day (P, trend = 0.87). The adjusted percentage of cycles resulting in live birth (95% CI) for women in increasing categories of caffeine intake was 46% (36-57%) for <50 mg/day, 44% (29, 60%) for 50.1-100 mg/day, 42% (31, 53%) for 100.1-200 mg/day, 40% (28, 53%) for 200.1-300 mg/day and 40% (21, 63%) for >300 mg/day (P, trend = 0.34). When specific types of alcoholic and caffeinated beverages were evaluated, no relations with ART treatment outcomes were observed.Limitations, reasons for cautionResidual confounding by other diet and lifestyle factors cannot be ruled out owing to the observational nature of this study. It is also unclear how generalizable these results are to women who are conceiving without the assistance of ART.Wider implications of the findingsOur results provide reassurance that low to moderate intakes of alcohol (e.g. ?12 g/day) and caffeine (e.g. <200 mg/day) in the year prior to infertility treatment initiation do not have an adverse effect on intermediate or clinical outcomes of ART.Study funding/competing interest(s)The authors are supported by National Institutes of Health (NIH) grants ES022955, R01ES009718, R01ES000002, P30DK46200 and L50-HD085359. No conflicts of interest to declare.Trial registration numberNCT00011713.

Project description:BACKGROUND:There is growing acceptance that nutrition may be related to fertility and specifically to assisted reproductive technologies success in women; however, there is still no specific dietary guidance. OBJECTIVE:The objective of the study was to evaluate the relationship between pretreatment adherence to various dietary patterns and outcomes of assisted reproductive technologies. STUDY DESIGN:We followed up 357 women enrolled in the prospective Environment and Reproductive Health (EARTH) study, who underwent 608 assisted reproductive technologies cycles (2007-2017). Using a validated food frequency questionnaire completed prior to treatment, we assessed adherence to the Mediterranean diet, the alternate Healthy Eating Index 2010, the Fertility Diet (developed based on risk factors for anovulatory infertility), and a profertility diet we developed based on factors previously related to assisted reproductive technologies outcomes (higher intake of supplemental folic acid, vitamin B12, vitamin D, low- rather than high-pesticide residue produce, whole grains, dairy, soy foods, and seafood rather than other meats). RESULTS:Higher adherence to the alternate Healthy Eating Index 2010 and Fertility Diet was not related to live birth following assisted reproductive technologies. Women in the second through the fourth quartiles of Mediterranean diet adherence had significantly higher probability of live birth (0.44, 95% confidence interval, 0.39-0.49) compared with women in the first quartile (0.31, 95% confidence interval, 0.25-0.39); however, there was no additional benefit of adherence to the Mediterranean diet above the second quartile. Increased adherence to the profertility diet was linearly associated with assisted reproductive technologies outcomes. The adjusted odds (95% confidence interval) of implantation, clinical pregnancy, and live birth were higher by 47% (21%, 77%), 43% (19%, 72%), and 53% (26%, 85%), respectively, per SD increase. The adjusted difference in the proportion of cycles resulting in live birth for women in the fourth vs first quartile of adherence to the profertility diet was 0.28 (95% confidence interval, 0.16-0.38). While the profertility diet was not related to estradiol levels, oocyte counts, or endometrial thickness, it was inversely associated with clinical pregnancy loss (odds ratio, 0.69, 95% confidence interval, 0.53-0.90 per SD increase). CONCLUSION:Higher pretreatment adherence to the profertility diet was associated with an increased probability of live birth among women undergoing assisted reproductive technologies. Commonly recommended dietary advice such as adhering to the Mediterranean diet may not provide the most appropriate guidance for women undergoing infertility treatment in the United States.

Project description:Study questionCould clinically-relevant moderate and/or high dose maternal folic acid supplementation prevent aberrant developmental and epigenetic outcomes associated with assisted reproductive technologies (ART)?Summary answerOur results demonstrate dose-dependent and sex-specific effects of folic acid supplementation in ART and provide evidence that moderate dose supplements may be optimal for both sexes.What is known alreadyChildren conceived using ART are at an increased risk for growth and genomic imprinting disorders, often associated with DNA methylation defects. Folic acid supplementation is recommended during pregnancy to prevent adverse offspring outcomes; however, the effects of folic acid supplementation in ART remain unclear.Study design, size, durationOutbred female mice were fed three folic acid-supplemented diets, control (rodent daily recommended intake or DRI; CD), moderate (4-fold DRI; 4FASD) or high (10-fold DRI; 10FASD) dose, for six weeks prior to ART and throughout gestation. Mouse ART involved a combination of superovulation, in vitro fertilisation, embryo culture and embryo transfer.Participants/materials, setting, methodsMidgestation embryos and placentas (n = 74-99/group) were collected; embryos were assessed for developmental delay and gross morphological abnormalities and embryos and placentas were examined for epigenetic defects. We assessed methylation at four imprinted genes (Snrpn, Kcnq1ot1, Peg1 and H19) in matched midgestation embryos and placentas (n = 31-32/group) using bisulfite pyrosequencing. In addition, we examined genome-wide DNA methylation patterns in placentas (n = 6 normal placentas per sex/group) and embryos (n = 6 normal female embryos/group; n = 3 delayed female embryos/group) using reduced representation bisulfite sequencing (RRBS).Main results and the role of chanceModerate, but not high dose supplementation, was associated with a decrease in the proportion of developmentally delayed embryos. Although moderate dose folic acid supplementation reduced DNA methylation variance at certain imprinted genes in embryonic and placental tissues, high dose supplementation exacerbated the negative effects of ART at imprinted loci. Furthermore, folic acid supplements resolved female-biased aberrant imprinted gene methylation. Supplementation was more effective at correcting ART-induced genome-wide methylation defects in male versus female placentas; however, folic acid supplementation also led to additional methylation perturbations which were more pronounced in males.Large-scale dataThe RRBS data from this study have been submitted to the NCBI Gene Expression Omnibus under the accession number GSE123143.Limitations reasons for cautionAlthough the combination of mouse ART utilised in this study consisted of techniques commonly used in human fertility clinics, there may be species differences. Therefore, human studies, designed to determine the optimal levels of folic acid supplementation for ART pregnancies, and taking into account foetal sex, are warranted.Wider implications of the findingsTaken together, our findings support moderation in the dose of folic acid supplements taken during ART.Study funding/competing interest(s)This work was funded by the Canadian Institutes of Health Research (FDN-148425). The authors declare no conflict of interest.

Dataset Information

Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study.

Publications

Pretreatment maternal lifestyle and outcomes of assisted reproduction: an Italian cohort study.

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