Healthy Parents - Healthy Children. Weight Loss Before Fertility Treatment

Study Overview
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Brief Summary
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The detrimental effect of overweight and obesity on fecundity has been well documented. The investigators wish to investigate the intervention program for weight loss before fertility treatment. Subsequently to gain knowledge on the effect of overweight/obesity and weight loss on the vaginal microbiome, on DNA damage on sperm cells, on the occurrence of endocrine disruptors in the endometrium, and on the gene expression in the endometrium.

Detailed Description
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Purpose and aim of the study The Fertility Clinic at Zealand University Hospital wishes to introduce a new care concept: 'Healthy Parents - Healthy Children´ with the purpose of changing the behaviours of infertile men and women towards a healthier life style now and for future generations. The Zealand Region includes areas of significant deprivation compared to Copenhagen and has a higher prevalence of obesity and poor diet. These inequalities generate socio-demographic and long-term health challenges, decrease the chance of becoming pregnant and increase risk of life style related diseases for parents and their offspring in the long term. The waiting time before fertility treatment (12 months in the region) represents a unique window of opportunity to encourage long-term life style changes. The aforementioned reasons initiated the planned Preconception Clinic 'Healthy Parents - Healthy Children´. The Preconception Clinic utilises waiting list time to optimise parental health prior to conception. We will provide weight loss interventions aimed at helping the patients to a healthier lifestyle, an increased chance of conception and a decreased risk of life style diseases for themselves and their future offspring. Purpose of study: Patient weight loss of at least 10% at the end of intervention and at annular follow up until 5 years. Study population: Sub-fertile population referred to the Fertility Clinic Region Zealand due to infertility. Inclusion criteria: 20 women and 20 men with a BMI>30, age 18-40 years. Exclusion criteria: Inability to understand the written and oral information. Baseline and end of intervention-sampling: Blood tests (metabolic markers), blood tests for Biobank and for miRNA biomarkers Urine sample Women: Endometrial biopsy and vaginal swab for microbiome testing Men: Sperm sample Intervention: Weight reduction through life style changes in diet and exercise by the following means: Counselling with a Nutritionist Nurse on diet and exercise. Online smartphone coaching program (LifeSum-App) Motivational and adjustment dialogue and counselling with Nutritionist Nurse including anthropometric measures every month. Primary endpoint: Weight loss of at least 10%. Anticipated impact The aim of this study is to find a feasible intervention that can change adverse life styles in a preconception setting. Elements from the weight loss intervention can be incorporated to the broader community, for instance as Preconception weight loss packages in the local municipalities, aimed at optimizing health before conception in the general fertile population.

Official Title
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Healthy Parents - Healthy Children. Weight Loss Before Fertility Treatment

Conditions
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Infertility, Overweight and Obesity, Weight Loss, Vaginal Flora Imbalance, DNA Damage

Intervention / Treatment
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* Behavioral: Systematic weight loss intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI>30 Referred to The Fertility Clinic, Zealand Region Exclusion Criteria: Unable to speak and read Danish

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intervention<br>Systematic weight loss intervention | Behavioral: Systematic weight loss intervention<br>* Weight reduction through life style changes in diet and exercise by the following means: Counselling with a Nutritionist Nurse on diet and exercise Online Smartphone coaching program (Life-sum App) Motivational and adjustment dialogue and counselling with Nutritionist Nurse including anthropometric measures every month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss | The change in weight (in kilograms) from baseline to the 6 month | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the semen quality 1 | The change in the morphological semen parameters, from baseline to 6 month will be measured by using WHO recommendation for semen analysis: Sperm count (mill/ml), | 6 months | 
| Change in the semen quality 2 | The change in the morphological semen parameters, from baseline to 6 month will be measured by using WHO recommendation for semen analysis: Sperm concentration (ml) | 6 months | 
| Change in the semen quality 3 | The change in the morphological semen parameters, from baseline to 6 month will be measured by using WHO recommendation for semen analysis: Sperm motility (mill/ml) | 6 months | 
| Change in the semen quality 4 | The change in the morphological semen parameters, from baseline to 6 month will be measured by using WHO recommendation for semen analysis: Sperm morphology (percent) | 6 months | 
| Change in the DNA fragmentation index (DFI) | The change in DNA fragmentation index is measured by SPZlab using the SDI®-test | 6 months | 
| Change in the vaginal microbiome | The change in the vaginal microbiome will be investigated at Statens Serum Institute (SSI), measured by PCR | 6 months | 
| Change in the occurence of synthetic endocrine disruption chemicals (EDCs) | The change in the occurrence of synthetic endocrine disruption chemicals (EDCs) endometrium is measured by The Department of Growth and Reproduction at Rigshospitalet by using LC-MS/MS analyze | 6 month | 
| Change in MicroRNA | The change in MicroRNA will be measured froom blood samples and is is analysed by Department of Science and Environment, RUC | 6 months | 
| Change in the gene expression of gene involved in implantation | The change in the gene expression in the endometrium is analysed by Department of Science and Environment, RUC | 6 months | 
| Numbers of achieved pregnancy | Both biochemical and clinical | Gestational week 4-8 | 
| Numbers of life births | Life birth | From 9 month after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DFI, EDCs, female infertility, male infertility, life style intervention, vaginal microbiome, synthetic endocrine disrupting chemicals, DNA fragmentation index, gene expression