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.

A Mobile App Lifestyle Intervention to Improve Healthy Nutrition in Women Before and During Early Pregnancy: Single-Center Randomized Controlled Trial.

BACKGROUND: Unhealthy nutrition contributes to the worldwide rising prevalence of noncommunicable diseases. As most adverse reproductive outcomes originate during the periconception period, effective interventions targeting this period are needed. Therefore, we developed the lifestyle intervention Smarter Pregnancy to empower women to adapt a healthy diet prior to conception and during early pregnancy and performed a randomized controlled trial. OBJECTIVE: The objectives of this trial were to investigate compliance and effectiveness in women using the Smarter Pregnancy program. METHODS: Women aged between 18 and 45 years who were contemplating pregnancy or <13 weeks pregnant and their male partners living in the urban area of Rotterdam, the Netherlands, were eligible for participation. After baseline screening, the intervention group received personal online coaching based on identified inadequate intakes of vegetables, fruits, and folic acid supplements. The sum of these risk factors was used as a dietary risk score (DRS), ranging from 0 (healthy) to 9 (unhealthy). The control group did not receive coaching. We applied an intention-to-treat principle and used a multivariable linear regression model to evaluate the change in DRS after 24 weeks. Compliance was defined as the percentage of women who completed the screening questionnaire at 24 weeks. RESULTS: Of women recruited, 81.2% (177/218) completed the program (intervention: 91/218, 83.5%; control: 86/218, 78.9%; P=.95). After 24 weeks, the reduction in DRS of women in the intervention group was significantly larger than in the control group (ß=.75, 95% CI 0.18-1.34). This reduction was mainly due to increased vegetable intake (ß=.55, 95% CI 0.25-0.86). CONCLUSIONS: The high compliance and the larger improvements in nutritional behaviors, especially vegetable intake, in women in the intervention group emphasizes the effectiveness of empowering women by using the lifestyle change intervention Smarter Pregnancy. TRIAL REGISTRATION: Netherlands Trial Register: NL3927; https://www.trialregister.nl/trial/3927. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12884-017-1228-5.

Neighborhood Deprivation and the Effectiveness of Mobile Health Coaching to Improve Periconceptional Nutrition and Lifestyle in Women: Survey in a Large Urban Municipality in the Netherlands.

BACKGROUND: In 2011, we launched the Smarter Pregnancy mobile health (mHealth) coaching program, which has shown to effectively improve inadequate nutrition and lifestyle behaviors in women before and during pregnancy. It is known that in deprived neighborhoods, risk factors for adverse pregnancy outcomes like inadequate nutrition and lifestyle behaviors accumulate. However, it has not yet been investigated whether the Smarter Pregnancy program is equally effective in women living in deprived neighborhoods. OBJECTIVE: This paper aimed to study the associations between neighborhood deprivation and improvement of inadequate nutrition and lifestyle behaviors of women who were either contemplating pregnancy or already pregnant and subscribed to the Smarter Pregnancy program. METHODS: We performed an additional analysis on data from women who used the Smarter Pregnancy program from 2011 to 2016. The program comprised 24 weeks of coaching on 5 nutrition and lifestyle behaviors, of which adequate intakes or lifestyle behaviors were defined as an intake of 200 grams or above of vegetables, 2 pieces of fruit, daily folic acid supplement use of 400 µg per day, and no smoking or alcohol consumption. Neighborhood deprivation was determined according to the status scores of the Netherlands Institute for Social Research. Logistic regression analyses and generalized estimating equation models were used to assess the associations between the neighborhood status score (NSS) and the improvement of inadequate nutrition and lifestyle behaviors, taking into account the behaviors at baseline. We adjusted the analyses for maternal age, body mass index, geographic origin, pregnancy status, and participation as a couple. RESULTS: Of the 2554 women included, 521 participated with their male partner. Overall, daily vegetable intake was most frequently inadequate at the start of the program (77.72, 1985/2554). Women with a higher NSS (ie, nondeprived neighborhood) smoked less often (adjusted odds ratio [OR] 0.85; 95% CI 0.77-0.93), consumed alcohol more often (adjusted OR 1.14, 95% CI 1.04-1.24), and were less likely to complete the 24 weeks of coaching (OR 0.91, 95% CI 0.88-0.95) compared with women who lived in a neighborhood with a low NSS (ie, deprived). In the total group, the relative improvement of inadequate nutrition and lifestyle behaviors after 24 weeks of coaching was between 26% and 64%. NSS was negatively associated with this improvement, indicating that women with a higher NSS were less likely to improve inadequate nutrition and lifestyle behaviors, especially vegetable intake (adjusted OR 0.89, 95% CI 0.82-0.97). CONCLUSIONS: The Smarter Pregnancy mHealth coaching program empowers women to improve inadequate nutrition and lifestyle behaviors. Unexpectedly, the program seemed more effective in women living in deprived neighborhoods. It is important to unravel differences in needs and behaviors of specific target groups to further tailor the mHealth program on the basis of demographic characteristics like neighborhood deprivation.

Maternal Lifestyle Impairs Embryonic Growth: The Rotterdam Periconception Cohort.

Previously, embryonic growth has been assumed to be uniform, but in recent years, it has become more clear that genetic and environmental factors may influence the intrauterine environment and therefore embryonic growth trajectories as well as pregnancy course and outcome. The objective of this study was to investigate associations between modifiable maternal nutrition and lifestyle factors during the periconception period and embryonic growth. We established a prospective cohort including 342 women less than 13 weeks pregnant. At enrollment, women filled out a questionnaire regarding demographic and medical data and a validated food frequency questionnaire. Participants received multiple 3-dimensional ultrasound examinations up until the 12th week of pregnancy, and crown-rump length (CRL) and embryonic volume (EV) were measured offline using V-Scope Virtual Reality software (version 1.0.0) in a Barco I-Space. Associations between maternal periconception vegetable and fruit intake, folic acid supplement use, smoking, and alcohol consumption and embryonic growth measurements were assessed by linear mixed models adjusted for potential confounders. No or postconception initiation of folic acid supplement use was significantly associated with a 0.76 mm (-7.8%) and 1.63 mm (-3.7%) smaller CRL and a 0.01 cm3 (-19.5%) and 0.86 cm3 (-12.2%) smaller EV at 7+0 and 11+0 weeks of gestation, respectively. Smoking, alcohol consumption, and inadequate fruit and vegetable intake showed weaker associations with embryonic growth parameters. These results emphasize the influence of periconceptional maternal folic acid supplement use on embryonic growth. Results regarding maternal nutrition and lifestyle factors also suggest an association with embryonic growth, but this has to be confirmed in a larger study.

Opportunities of mHealth in Preconception Care: Preferences and Experiences of Patients and Health Care Providers and Other Involved Professionals.

BACKGROUND: The importance of the preconception period and preconception care (PCC) are broadly acknowledged and the potential benefits regarding health promotion have been studied extensively. PCC provides the opportunity to identify, prevent, and treat modifiable and nonmodifiable risk factors to optimize the health of couples trying to become pregnant. The prevalence of modifiable and nonmodifiable risk factors in these couples is high, but the uptake of PCC remains low. OBJECTIVE: The aim of this study is to identify the preferences and experiences of women and men (patients) trying to become pregnant and of health care providers and other involved professionals regarding mobile health (mHealth), in particular the coaching platform Smarter Pregnancy, and its potential role in PCC. METHODS: Patients who participated in the Smarter Pregnancy randomized controlled trial (RCT) and health care providers and professionals also involved in PCC were invited to participate in a qualitative study. The barriers, benefits, and opportunities of big data collection by mHealth were discussed in focus group sessions, prompted with statements regarding PCC. RESULTS: We composed five focus groups, consisting of 27 patients in total (23 women and 4 men), who participated in the RCT, and nine health care providers and other professionals. Of the patients, 67% (18/27) were familiar with the concept of PCC, but only 15% (4/27) received any form of PCC. A majority of 56% (combined percentages of statements 1 [n=18], 2 [n=11], and 3 [n=16]) of the patients believed in the benefit of receiving PCC, and all agreed that men should be involved in PCC as well. Patients did not have a problem using anonymized data obtained from mHealth tools for scientific purposes. Patients and health care providers and other professionals both acknowledged the lack of awareness regarding the importance of PCC and stated that mHealth provides several opportunities to support clinical PCC. CONCLUSIONS: Our findings substantiate previous studies addressing the low uptake of PCC due to unawareness or lack of perception of its relevance by couples who are trying to become pregnant. The positive judgment and experiences with mHealth, in particular Smarter Pregnancy, will stimulate future research and further development of effective and cost-effective personalized mHealth apps for patients, health care providers, and other professionals as an add-on to clinical PCC.

Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance.

Periconceptional nutrition and lifestyle are essential in pathogenesis and prevention of most reproductive failures, pregnancy outcome and future health. We aimed to investigate whether personalized mobile health (mHealth) coaching empowers couples contemplating pregnancy to increase healthy behaviour and chances of pregnancy. A survey was conducted among 1053 women and 332 male partners who received individual coaching using the mHealth programme 'Smarter Pregnancy' to change poor nutrition and lifestyle for 26 weeks, depending on pregnancy state and gender. Poor behaviours were translated into a total risk score (TRS) and Poisson regression analysis was performed to estimate associations with the chance of pregnancy adjusted for fertility status, age and baseline body mass index expressed as adjusted hazard ratio (aHR) and 95% confidence interval (95% CI). A lower (a)HR suggests a higher chance of achieving pregnancy. A higher TRS was significantly associated with a lower chance of pregnancy in all women (aHR 0.79, 95% CI 0.72-0.85) and (a)HR was lowest in women whose male partner participated (aHR 0.75, 95% CI 0.61-0.91). This survey shows that empowerment of couples in changing poor nutrition and lifestyle using personalized mHealth coaching is associated with an enhanced pregnancy chance in both infertile and fertile couples.

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).

Impact of an mHealth Platform for Pregnancy on Nutrition and Lifestyle of the Reproductive Population: A Survey.

BACKGROUND: Poor nutrition and lifestyle behaviors exert detrimental effects on reproduction and health during the life course. Therefore, lifestyle interventions during the periconceptional period can improve fertility, pregnancy outcome, and health of subsequent generations. OBJECTIVE: This survey investigates the compliance, usability, and initial effectiveness of the Web-based mHealth platform, Smarter Pregnancy. METHODS: A free subscription to the mHealth platform, Smarter Pregnancy, was provided to couples contemplating pregnancy (n=1275) or already pregnant (n=603). After baseline identification of inadequate nutrition and lifestyle behaviors, a personal online coaching program of 6 months was generated. Using multiple imputation and the generalized estimating equation model with independent correlations, we estimated the changes from inadequate to adequate nutrition and lifestyle behaviors over time. Subgroup analyses were performed for (1) overweight and obese women (body mass index [BMI] ≥25 kg/m(2)), (2) pregnant women at the start of the program, and (3) couples. RESULTS: A 64.86% (1218/1878) compliance rate was observed and 54.7% (range 39.2-73.4%) of participants rated the program usability as positive or very positive. Adequate nutrition and lifestyle behaviors at baseline were 21.57% (405/1878) for vegetable intake, 52.61% (988/1878) for fruit intake, 85.44% (1303/1525) for folic acid use, 86.79% (1630/1878) for no tobacco use, and 64.43% (1210/1878) for no alcohol consumption. After 6 months of coaching, these lifestyle behaviors improved by 26.3% (95% CI 23.0-29.9) for vegetable intake, 38.4% (95% CI 34.5-42.5) for fruit intake, 56.3% (95% CI 48.8-63.6) for folic acid use, 35.1% (95% CI 29.1-41.6) for no tobacco use, and 41.9% (95% CI 35.2-48.9) for no alcohol consumption. The program showed the strongest effectiveness for participating couples. CONCLUSIONS: This novel Web-based mHealth platform shows high compliance and usability, and users demonstrate improvements in nutrition and lifestyle behaviors. The next step will be further validation in randomized controlled trials and implementation.

Identification of quiescent, stem-like cells in the distal female reproductive tract.

In fertile women, the endometrium undergoes regular cycles of tissue build-up and regression. It is likely that uterine stem cells are involved in this remarkable turn over. The main goal of our current investigations was to identify slow-cycling (quiescent) endometrial stem cells by means of a pulse-chase approach to selectively earmark, prospectively isolate, and characterize label-retaining cells (LRCs). To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP) in a Tet-inducible fashion were administered doxycycline (pulse) which was thereafter withdrawn from the drinking water (chase). Over time, dividing cells progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP expression. We evaluated H2B-GFP retaining cells at different chase time points and identified long-term (LT; >12 weeks) LRCs. The LT-LRCs are negative for estrogen receptor-α and express low levels of progesterone receptors. LRCs sorted by FACS are able to form spheroids capable of self-renewal and differentiation. Upon serum stimulation spheroid cells are induced to differentiate and form glandular structures which express markers of mature mullerian epithelial cells. Overall, the results indicate that quiescent cells located in the distal oviduct have stem-like properties and can differentiate into distinct cell lineages specific of endometrium, proximal and distal oviduct. Future lineage-tracing studies will elucidate the role played by these cells in homeostasis, tissue injury and cancer of the female reproductive tract in the mouse and eventually in man.