An Intervention Model for the Prevention of Infertility in Healthy Young Men Living in Highly Polluted Areas
An Intervention Model for the Prevention of Infertility in Healthy Young Men Living in Highly Polluted Areas
We planned a randomized controlled trial (RCT) with the main aim to evaluate the effects of lifestyle changes on semen quality in healthy young men living in polluted areas in Italy. Secondary aims are to assess: a) the association between semen quality and biomarkers of early damage or inflammation; b) the associations between biomarkers of exposure to heavy metals and semen quality and biomarkers of early damage or inflammation; c) the associations between diet and physical activity and semen quality and biomarkers of early damage or inflammation; d) the effects of lifestyle changes on the blood and semen levels of heavy metals.
The RCT includes 450 young men living in one of the following three polluted areas:
Inclusion criteria are: a) healthy males aged 18- 22 years; b) residents in the area since at least 5 years; c) non smokers; d) non alcohol or drug users; e) normo-weight (18.5< BMI<24.99); f) no occupationally exposed to fertility toxics; g) not affected by chronic diseases. Subjects will be randomly assigned to an intervention or control group. The intervention group will follow a nutritional pathway and receive suggestions on practice of physical activity for 4 months, under the guide of some nutritionists, who will establish individualized diets for each subject. The control group will receive only a booklet including the dietary recommendations by the Italian National Institute for Research on Food and Nutrition. All subjects will undergo urologic examination, measurement of weight, height and abdominal circumference, an interview on demographic data, lifestyle variables, dietary habits, adherence to Mediterranean diet and physical activity, and will provide blood and semen samples in fasting conditions, at the enrollment (baseline), at the end of the intervention phase (after 4 months) and at the end of follow-up (after 8 months).
Laboratory analyses include the following:
Human semen quality is affected by genetic, metabolic, lifestyle and environmental factors. It is a sensitive marker of the general health status of an individual and a predictor of disease occurrence and mortality. Some studies suggested that a diet rich in anti-oxidant compounds and regular physical activity could improve semen quality. We planned a randomized controlled trial (RCT) with the main aim to evaluate the effects of lifestyle changes on semen quality in healthy young men living in three polluted areas in North, Centre and South Italy. Secondary aims are to assess: a) the association between semen quality and biomarkers of early damage or inflammation (prostate-specific antigen, RedOx status, epigenetic changes); b) the associations between biomarkers of exposure to toxic agents (heavy metals) and semen quality and biomarkers of early damage or inflammation; c) the associations between diet and physical activity and semen quality and biomarkers of early damage or inflammation; d) the effects of lifestyle changes on the blood and semen levels of heavy metals.
This RCT includes 450 healthy young men, aged 18-22 years, living in one of the following three polluted areas:
According to a 1:1 randomization plan, the young men will be assigned to an intervention or control group.
The subjects will be enrolled among high school and university students, after a 20 minute meeting with students in each class, during a lesson, and in the presence of the teacher, for explaining the study design and inviting them to participate. After a short self-administered screening questionnaire for excluding subject not suitable to the research, the potential candidates are invited to undergo a urologic visit, in a Urology and Fertility Unit, including a clinical examination and spermiogram analysis. In the same time, participant undergo a fasting blood sample for the analysis of common parameters (glycemia, cholesterolemia, ecc.), and measures of height, weight and abdominal circumference by trained dieticians. Then each dietician evaluated each participant's dietary habits and physical activity using the European Prospective Investigation into Cancer (EPIC) and nutrition questionnaire, the PREvención con DIeta MEDiterránea (PREDIMED), and the International Physical Activity Questionnaire (IPAQ).
Each urological visit, blood and semen sampling will be repeated with the same methodology in both intervention and control groups, at time 0 (baseline, enrollment), after 4 months (end of the intervention) and after 8 months (end of follow-up).
The intervention for changing lifestyle in the experimental group has been planned on the basis of previous experience of educational intervention in nutritional epidemiology. It should be noted that the Mediterranean diet is the focus of the intervention and that the aim of the intervention is not to loss weight but to increase the amount of anti-oxidants and anti-inflammatory dietary compounds. It is well known that also motivated subjects have difficulties in changing dietary habits. Therefore the change will be based on the following points: personalized diet (according to taste and practical reasons), progressive change (one objective a time), frequent contacts with dieticians (weekly contacts in the first month). The subjects are also invited to share dieticians' indications with their parents and especially the person who usually cooks at home. The dietician intervention has been planned with the help of Dr. Stefania Ubaldi, President of the European Lifestyle Medicine Organization (ELMO), Geneva.
The subjects included in the control group will receive only a booklet with present recommendations for Mediterranean diet at the enrollment (baseline), and will further contact only after 4 and 8 months.
Blood and semen samples will be collected and stored at -80° according to a standard protocol up to the time of laboratory analysis. Laboratory analyses include the following:
Differences of means and proportions of all variables between the intervention and control group and the associations between diet, physical activity and sperm and blood parameters will be assessed using common statistical tests for comparisons of means and proportions as a first step. Multivariable models, including multi-factor analysis of variance, multiple regression and multiple logistic regression, will then be used for assessing the associations when taking account of possible confounders. All the statistical tests are two-sided with p=0.05 as the threshold for refusal of the null hypothesis.
The two Urology and Fertility Units: a) Unità Operativa Complessa di Urologia, Ospedale S. Francesco d'Assisi di Oliveto Citra (SA), Azienda Sanitaria Locale (ASL) Salerno and b) the Unit of Hygiene, epidemiology and biostatistics and Unit of Urology of the University of Brescia will provide routine hematological parameters (whole blood count, glycemia, cholesterolemia, etc.) and semen quality parameters, according to the 2010 WHO criteria.
Each recruitment unit will collect and treat the biological samples, which will be sent to the laboratories for the specific analysis:
The data management and statistical analysis will be performed by the Unit of Hygiene, epidemiology and biostatistics of the University of Brescia.
Inclusion Criteria:
Exclusion Criteria: