The Impact of Lifestyle Intervention on Weight and Fertility in Obese Males

Obesity Clinical Trial

Official title:

The Impact of Lifestyle Intervention on Weight and Fertility in Obese Males

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06339840
• Other study ID #: 2024-036-01
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: March 31, 2027

Study information

• Verified date: March 2024
• Source: Third Affiliated Hospital of Zhengzhou University
• Contact: Yichun Guan, PhD
• Phone: +8613608695579
• Email: lisamayguan[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obesity, defined by WHO standards as having a body mass index (BMI) equal to or greater than 30 kg/m², affects approximately 800 million people worldwide. It is evident that obesity has become a serious public health issue, resulting in significant health burdens. Previous systematic reviews have indicated an association between obesity and male factor infertility. In populations undergoing assisted reproductive technology (ART), some studies have shown a correlation between increased male BMI and adverse ART outcomes. Furthermore, the negative effects of obesity may also be transmitted to offspring through genetic and epigenetic changes in reproductive cell DNA, increasing their risk of obesity, metabolic diseases, or other chronic conditions. Currently, there is a lack of data on the impact of weight loss in obese men on fertility, and it is unclear which nutritional pattern in lifestyle interventions can more effectively control weight, improve semen quality, and address related endocrine issues in obese men, thereby improving reproductive treatment outcomes. Based on previous literature, we hypothesize that lifestyle interventions, particularly strict low-carbohydrate diets combined with lifestyle guidance, may offer greater health benefits for obese men. These benefits include effective weight loss, improvement in semen parameters, reproductive metabolic health, quality of life related to reproductive health, and the impact on reproductive treatment outcomes. This provides a basis for non-pharmacological intervention strategies and methods for the health of obese men.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 38
• Est. completion date: March 31, 2027
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 22 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Male, aged 22-40 years.

2. BMI=30 kg/m² (defined as obesity according to WHO standards).

3. Patients who are willing and able to provide informed consent and follow all study procedures, including ongoing visits to the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University and undergoing relevant tests

4. Spouse aged 20-40 years, with menstrual regularity (menstrual cycle length of 21-35days, duration of 2-7days), with a BMI of 18.5=BMI < 25 kg/m², planning for AIH or IVF treatment at our center due to male factor infertility.

5. Not participating in any other research projects currently or in the preceding three months.

6. Willing to allow offspring conceived through the study to participate in follow-up research.

Exclusion Criteria:

1. Male reproductive urinary system abnormalities: active urinary reproductive system infections; hypogonadism; hyperprolactinemia; excessive estrogen; cryptorchidism, etc.;

2. Acute and chronic diseases that may affect fertility: chronic systemic diseases; history of systemic cytotoxic therapy or pelvic radiotherapy; other acute diseases that may affect study results;

3. Digestive system and metabolic abnormalities: acute and chronic digestive system diseases affecting digestive absorption function; history of or current eating disorders; allergies to ingredients in meal replacement products; gout, kidney stones, or gallstones; history of weight loss surgery;

4. Unhealthy lifestyle habits: meeting at least one of the following conditions: heavy alcohol consumption, daily smoking, history of drug abuse, history of substance abuse;

5. Personal factors affecting trial participation: impaired capacity to fully consent to participation in the study; major mental disorders; occupations requiring intense physical exercise; current diets that may interfere with the dietary plans of this study; exclusion of current or past use of hormones or anti-obesity drugs, or the use of other medications that affect hormone levels, carbohydrate metabolism, or appetite.

Related Conditions & MeSH terms

• Body Weight
• IVF-ET
• Male Fertility
• Obesity
• Weight Loss

Intervention

Dietary Supplement:
• Low-carbohydrate diet group
During the initial 8-week weight loss phase, participants will adopt a low-carbohydrate dietary pattern (with carbohydrate energy ratio of 20-30%, protein energy ratio of 30-40%, and fat energy ratio of 40-45%), with a caloric intake approximately 75% of their usual daily intake, but not less than 1200 kcal. Throughout the intervention period, participants will receive a daily nutritionally balanced meal replacement for 8 weeks to substitute for staple foods and control carbohydrate intake. Nutritionists will reinforce interventions by setting health goals, providing health education, implementing dietary and exercise interventions, and monitoring through a combined approach using a mobile platform. During the subsequent 4-week transition phase, participants' diets will gradually transition to a balanced dietary pattern (with carbohydrate energy ratio of 45-60%, protein energy ratio of 20-30%, and fat energy ratio of 20-25%) under the guidance of nutritionists.

Behavioral:
• Health Education Group
Upon enrollment, nutritionists will provide lifestyle guidance to patients, including personalized adjustments such as limiting total energy intake to <1600 kcal/day, adjusting macronutrient distribution to 45-55% for carbohydrates, 20-30% for fats, and 20-30% for protein. Participants are advised to accumulate at least 150 minutes of moderate-intensity aerobic exercise per week (achieving 50%-70% of maximum heart rate). At enrollment, nutritionists will educate participants on healthy lifestyle principles, train them on nutritional intervention tools, and assist in food selection for weight management planning. Throughout the intervention, nutritionists will conduct follow-ups with patients via phone or mobile platforms to monitor weekly dietary and exercise habits, weight changes, and address any participant concerns promptly.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Third Affiliated Hospital of Zhengzhou University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adult background	Demographic information and medical background	Collected prior baseline
Other	Questionnaire - Adult physical activity	Physical activity will be assessed by the International Physical Activity Questionnaire (IPAQ)	Collected at baseline and until 12 weeks after weight loss intervention
Other	Questionnaire - Quality of life	Quality of life will be assessed by the validated tool, Short form-36 (SF-36).	Collected at baseline and until 12 weeks after weight loss intervention
Other	Questionnaire - Psychological condition	Psychological condition will be assessed by the validated tool, Depression-Anxiety-Stress Scale (DASS-21)	Collected at baseline and until 12 weeks after weight loss intervention
Other	Questionnaire - Sleep	Sleep will be assessed by the validated tool, Pittsburgh sleep quality index questionnaire (PSQI).	Collected at baseline and until 12 weeks after weight loss intervention
Other	Spouse's reproductive outcome - Methods of Fertilization	The information will be collected through follow-up telephone calls or clinic registration. In the case of non-natural conception, specific assisted reproductive methods should be recorded in the registration	through study completion, an average of 6 months
Other	Spouse's reproductive outcome - Time to pregnancy	Duration of time to conception defined from time point allowed to conceive to registration of pregnancy.	through study completion, an average of 6 months
Other	Spouse's reproductive outcome - Length of gestational age	gestational weeks	Assessed at birth of offspring
Other	Spouse's reproductive outcome - Medication use	Medication use during labor	Collected from initiation of labor until completed birth of offspring
Other	Spouse's reproductive outcome - Delivery mode	Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth)	Collected at birth of offspring
Other	Spouse's reproductive outcome - Pregnancy complications	Pregnancy complications e.g. miscarriage, abortion (induced and indication for abortion), hydramnios, gestational hypertension, preeclampsia, need for maternal corticosteroid treatment for fetal lung maturation, urinary tract infection).	through study completion, an average of 18 months
Other	Spouse's reproductive outcome - Obstetrics complications	Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization)	Collected at birth of offspring
Other	Fetal and offspring - Apgar score	Apgar score (0-10). The higher the score, the better health condition of the offspring	Collected at birth of offspring
Other	Fetal and offspring - body weight	Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.	through study completion, an average of 18 months
Other	Fetal and offspring - Neonatal fat mass	Skinfold thickness measurement, millimeters (mm).	Assessed at birth (strived <24 hours, but allow <48 hours)
Other	Fetal and offspring - Birth defects/abnormalities		Collected at birth of offspring
Other	Fetal and offspring - length	Centimetre(cm)	through study completion, an average of 18 months
Other	Fetal and offspring - abdominal circumference	Centimetre(cm)	through study completion, an average of 18 months
Other	Fetal and offspring - crown circumference	Centimetre(cm)	through study completion, an average of 18 months
Other	Fetal and offspring - Glucose metabolism	Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for glucose, insulin, C-peptide and HbA1c	Collected at 6, 12 and 18 months after birth
Other	Fetal and offspring - Lipid profile	Parents will be instructed that the offspring should not have eaten two hours prior to the assessment.Samples will be analysed for triglycerides, LDL, HDL, VLDL and total cholesterol.	Collected at 6, 12 and 18 months after birth
Other	Fetal and offspring - Offspring growth factors and hormones	Parents will be instructed that the offspring should not have eaten two hours prior to the assessment. Samples will be analysed for Insulin-like Growth Factor 1 (IGF-1) and growth hormone (GH).	Collected at 6, 12 and 18 months after birth
Other	Fetal and offspring - Cognitive development of offspring	Offspring cognitive development will be assessed by a Habituation and Free Play Test.	Collected at 6, 12 and 18 months after birth.
Other	Labs - Semen epigenetics marks	Epigenetic profile based on array-measurements. Analysed for methylation changes.	Collected at baseline and until 12 weeks after weight loss intervention
Other	Labs - Adult Epigenetics	Epigenetics analyses from whole blood. Will be analysed for methylation changes. The indicators for epigenetic testing include DNA methylation levels, histone modifications, non-coding RNA expression, etc.	Collected at baseline and until 12 weeks after weight loss intervention
Other	Labs - Cord blood - epigenetics	Cord blood will be drawn immediately after birth and analysed for epigenetic profile.	Collected at birth
Other	Labs - Cord tissue	A sample of cord tissue will be collected immediately after birth and analysed for epigenetic profile.	Collected at birth
Other	Labs - Placenta	Placenta weight (gram).	Collected at birth
Other	Labs - Placenta - biopsies	Eight biopsies will be collected, four on the maternal site and four on the fetal side - one in each quadrant. The samples will be analyzed for protein expression patterns, placental markers, metabolomics, proteomics, markers of inflammation, immune markers and exosomes.	Collected at birth
Other	Labs - Offspring urine	Parents will be instructed to collect offspring's urine samples. Offspring urine will be analyzed for metabolomics	Collected at birth and at 1, 3, 6, 12 and 18 months of age
Other	Labs - Offspring feces	Parents will be instructed to collect offspring's urine samples. Offspring urine will be analyzed for metabolomics	Collected at birth and at 1, 3, 6, 12 and 18 months of age
Primary	Weight	kilogram (kg)	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Semen parameter- Sperm concentration	Concentration (in million sperm cells/ml)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Sperm motility	Sperm motility (%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Sperm morphology	Morphology (%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Sperm DNA fragmentation index (DFI)	DFI (%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Sperm progressive motility (PR)	PR(%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Non-progressive motility (NP)	NP(%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Semen parameter- Immotility (IM)	IM(%)	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	body mass index (BMI)	Calculated ad weight (kg)/height(m)^2	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Waist circumference	Centimetre(cm)	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Hip circumference	Centimetre(cm)	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Lean mass	(g), Assessed by an Anthropometric Analyzer	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Fat mass	(g), Assessed by an Anthropometric Analyzer	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Abdominal fat	(g), Assessed by an Anthropometric Analyzer	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Visceral fat	(g), Assessed by an Anthropometric Analyzer	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Blood pressure	mmHg	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Heart rate	beats per minute	Regular data collection between baseline and 12 weeks of weight loss intervention
Secondary	Lipid profile-triglycerides		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Lipid profile-LDL	low-density lipoprotein	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Lipid profile-HDL	high-density lipoprotein	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Lipid profile-VLDL	very-low-density lipoprotein	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Lipid profile-total cholesterol		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Glucose metabolism-fasting glucose		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Glucose metabolism-OGTT	Oral Glucose Tolerance Test	Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Glucose metabolism-insulin		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Glucose metabolism-C-peptide		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Glucose metabolism-HbA1c		Collected at baseline and until 12 weeks after weight loss intervention
Secondary	Sex hormones	Samples will be analyzed for total testosterone, free testosterone, luteinizing hormone(LH), follicle-stimulating hormone(FSH), pituitary prolactin(PRL) and anti-müllerian hormone(AMH)	Collected at baseline and until 12 weeks after weight loss intervention