The effects of bariatric surgery on periconception maternal health: a systematic review and meta-analysis.

BACKGROUND: Worldwide, the prevalence of obesity in women of reproductive age is increasing. Bariatric surgery is currently viewed as the most effective, long-term solution for this problem. Preconception bariatric surgery can reduce the prevalence of obesity-related subfertility and adverse maternal, pregnancy and birth outcomes. Maternal health during the periconception period is crucial for optimal gametogenesis and for embryonic and fetal development which also affects health in the later lives of both mother and offspring. Although preconception bariatric surgery improves several pregnancy outcomes, it can also increase the prevalence of pregnancy complications due to excessive and rapid weight loss. This can lead to iatrogenic malnutrition with vitamin deficiencies and derangements in metabolic and endocrine homeostasis. Thus, bariatric surgery can greatly influence periconception maternal health with consequences for reproduction, pregnancy and health in later life. However, its influence on periconception maternal health itself has never been reviewed systematically. OBJECTIVE AND RATIONALE: The aim of this review was to investigate associations between bariatric surgery and determinants of periconception maternal health such as endocrine changes, fertility, vitamin status, irregular menstrual cycles, miscarriages and congenital malformations. SEARCH METHODS: Medline, Embase, PubMed, Web of Science, Google Scholar and the Cochrane databases were used for the literature search until 1 November 2020. The search strategy terms included, among others, bariatric surgery, hormones, fertility, malformations, miscarriages and vitamin status. We searched for human studies that were written in English. Abstracts, reviews, meta-analyses and conference papers were excluded. The ErasmusAGE score was used to assess the quality of the included studies. OUTCOMES: A total of 51 articles were analysed. The mean quality score was 5 (range 2-8). After bariatric surgery, hormonal axes normalized and menstrual cycle regularity was restored, resulting in increased fertility. Overall, there were no short-term risks for reproductive outcomes such as the increased risk of miscarriages or congenital malformations. However, the risk of vitamin deficiencies was generally increased after bariatric surgery. A meta-analysis of 20 studies showed a significant decrease in infertility (risk difference (RD) -0.24, 95% confidence interval (CI) -0.42, -0.05) and menstrual cycle irregularities (RD -0.24, 95% CI -0.34, -0.15) with no difference in rates of miscarriage (RD 0.00, 95% CI -0.09, 0.10) and congenital malformations (RD 0.01, 95% CI -0.02, 0.03). WIDER IMPLICATIONS: The current systematic review and meta-analysis show associations between bariatric surgery and periconception maternal health and underlines the need for providing and personalizing preconception care for women after bariatric surgery. We recommend preconception care including the recommendation of postponing pregnancy until weight loss has stabilized, irrespective of the surgery-to-pregnancy interval, and until vitamin status is normalized. Therefore, regular monitoring of vitamin status and vitamin supplementation to restore deficiencies is recommended. Furthermore, this systematic review emphasizes the need for a long-term follow-up research of these women from the periconception period onwards as well as their pregnancies and offspring, to further improve care and outcomes of these mothers and children.

First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial.

OBJECTIVE: To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing in vitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI). DESIGN: Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March 2017. SETTING: IVF clinics. PATIENT(S): A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners. INTERVENTIONS(S): Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period. MAIN OUTCOME MEASURE(S): Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program. RESULT(S): Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors. CONCLUSION(S): The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome. NETHERLANDS TRIAL REGISTER NUMBER: NTR4150.

The use of the mHealth program Smarter Pregnancy in preconception care: rationale, study design and data collection of a randomized controlled trial.

BACKGROUND: Unhealthy nutrition and lifestyle contribute to the worldwide rising prevalence of non-communicable diseases. This also accounts for the reproductive population, in which unhealthy behavior affects fertility and pregnancy outcome. Maternal smoking, alcohol consumption and inadequate folic acid supplement use are strongly associated with fetal complications as small for gestational age, premature birth and congenital malformations. In the Netherlands 83% of the perinatal mortality rate is due to these complications and is relatively high compared to other European countries. In order to reduce this prevalence rate, preconception care should be focused on the promotion of health of prospective parents by identification and intervention on modifiable nutrition and lifestyle risk factors. We developed the personal mHealth program 'Smarter Pregnancy' (Dutch version available on: https://www.slimmerzwanger.nl ) to provide individual coaching and information to improve nutrition and lifestyle during the preconception period in order to improve health of the reproductive population and subsequent generations. METHODS: Women between 18 and 45 years of age, and trying to conceive are eligible for inclusion in a randomized controlled trial. Participants are allocated either to a general population cohort or a subfertile (IVF/ICSI) population cohort. The intervention group receives personal online coaching based on the identified nutrition and lifestyle risk factors at baseline. Coaching comprises recipes, incentives, additional questions including feedback and text and e-mail messages, with a maximum of three per week. The control group only receives one recipe per week to maintain adherence to the program and prevent drop out. Screening questionnaires are send in both groups at 6, 12, 18, and 24 weeks of the program to monitor the change in the identified risk factors. DISCUSSION: We expect to demonstrate that the mHealth program 'Smarter Pregnancy' can effectively improve nutrition and lifestyle in couples contemplating pregnancy. By the identification and improvement of modifiable nutrition and lifestyle risk factors on a large scale, both reproductive and pregnancy outcomes can be improved and subsequent perinatal morbidity and mortality rates are expected to be reduced. The current use and rapid development of mHealth applications offers new opportunities to reach and educate large populations, which can facilitate the implementation of preconception care. TRIAL REGISTRATION: Dutch trial register: NTR4150 . (Registered 19th August 2013).

Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.

AIMS/HYPOTHESIS: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. METHODS: We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. RESULTS: During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. CONCLUSIONS/INTERPRETATION: DHEA serum levels might be an independent marker of type 2 diabetes.

Preconception folic acid use influences the follicle fluid proteome.

BACKGROUND: The investigation of the human follicle fluid proteome has gained much interest in the search of new markers as predictors for in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatment outcome. Follicular fluid folate, as substrate of one carbon (1-C) metabolism, affects follicular metabolism and oocyte and embryo quality. From this background, we aim to identify a folate-related follicle fluid proteome that associates with IVF/ICSI treatment outcome. METHODS: In a nested case-control study embedded in a periconception cohort, we performed qualitative and quantitative proteomic analyses using nanoflow LC-MS/MS and TMT labelling in 30 monofollicular fluid samples from women undergoing IVF/ICSI treatment of which 15 used and 15 did not use a folic acid supplement. The protein data are analysed using scaffold proteome Software and differential abundances are expressed as Log2-fold change. Blood samples were obtained before and after treatment for determination of biomarkers of 1-C metabolism and estradiol. RESULTS: We identified 227 uniquely expressed proteins in follicular fluid. In folic acid supplement users compared to nonusers, we established a lower abundance of C-reactive protein (-2.03; P = < 0.01) and higher abundances of apolipoproteins from high-density lipoprotein (HDL), most notably A-I (+1.28; P = < 0.01) and C-I (+1.11; P = 0.016). CONCLUSION: Preconception folic acid supplement use is associated with suppression of the inflammatory pathway and upregulation of the HDL pathway in human follicular fluid, being a preferential source of cholesterol for steroid hormone synthesis. Studies are needed on the tissue specificity and on the beneficial effects of embryo quality and IVF/ICSI treatment outcome of the proteome of these pathways.

Increased preconception omega-3 polyunsaturated fatty acid intake improves embryo morphology.

The association between preconception dietary intake of the polyunsaturated fatty acids (LC-PUFAs) omega-6 and omega-3 and the E(2) levels and IVF/intracytoplasmic sperm injection (ICSI) outcome were investigated in women in a prospective study. It revealed that high intakes of omega-3 LC-PUFA alpha-linolenic acid increase baseline E(2), high intakes of eicosapentaenoic acid and docosahexaenoic acid reduce E(2) response and the number of follicles after ovarian stimulation, and total omega-3 intake, in particular alpha-linolenic acid and docosahexaenoic acid, improve embryo morphology.

IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid.

BACKGROUND: Maternal hyperhomocysteinemia is detrimental for reproduction, but the effects on embryo quality are unknown. The aim of this study was to investigate whether biomarkers of the homocysteine pathway are associated with in vitro fertilization (IVF) outcome. METHODS: In a prospective study, we investigated biomarkers of the homocysteine pathway for associations with embryo quality and biochemical pregnancy in women undergoing IVF or intracytoplasmic sperm injection treatment (n = 181). In the treatment cycle, blood and monofollicular fluid samples were collected for determination of folate, cobalamin and total homocysteine (tHcy) concentrations. RESULTS: Of all the women in the study, 67% used folic acid supplements. In blood, a significant correlation was established between high cobalamin and better embryo quality [standardized adjusted regression coefficient: -0.17, 95% confidence interval (CI): -0.30, -0.01]. In monofollicular fluid of non-supplemented women, high cobalamin correlated with better embryo quality (estimate: -0.87; 95% CI: -1.68, -0.06), whereas high tHcy resulted in poor embryo quality (estimate: 1.01; 95% CI: 0.08, 1.95). However, in monofollicular fluid of supplemented women, high tHcy correlated with better embryo quality (estimate: -0.58; 95% CI: -1.12, -0.04). In the total group, a 2-fold increase of monofollicular fluid folate corresponded with a 3.3 times higher chance (95% CI: 1.09, 9.71) of achieving pregnancy. CONCLUSIONS: An optimal homocysteine pathway in follicular fluid is associated with a better embryo quality and chance of pregnancy.