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

• Low-carbohydrate diet group (Dietary supplement), also known as Intensive Intervention 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.
• Health Education Group (Behavioral): 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.

Primary outcomes

• Weight [Regular data collection between baseline and 12 weeks of weight loss intervention]: kilogram (kg)

Secondary outcomes

• Semen parameter- Sperm concentration [Collected at baseline and until 12 weeks after weight loss intervention]: Concentration (in million sperm cells/ml)
• Semen parameter- Sperm motility [Collected at baseline and until 12 weeks after weight loss intervention]: Sperm motility (%)
• Semen parameter- Sperm morphology [Collected at baseline and until 12 weeks after weight loss intervention]: Morphology (%)
• Semen parameter- Sperm DNA fragmentation index (DFI) [Collected at baseline and until 12 weeks after weight loss intervention]: DFI (%)
• Semen parameter- Sperm progressive motility (PR) [Collected at baseline and until 12 weeks after weight loss intervention]: PR(%)
• Semen parameter- Non-progressive motility (NP) [Collected at baseline and until 12 weeks after weight loss intervention]: NP(%)
• Semen parameter- Immotility (IM) [Collected at baseline and until 12 weeks after weight loss intervention]: IM(%)
• body mass index (BMI) [Regular data collection between baseline and 12 weeks of weight loss intervention]: Calculated ad weight (kg)/height(m)\^2
• Waist circumference [Regular data collection between baseline and 12 weeks of weight loss intervention]: Centimetre(cm)
• Hip circumference [Regular data collection between baseline and 12 weeks of weight loss intervention]: Centimetre(cm)
• Lean mass [Collected at baseline and until 12 weeks after weight loss intervention]: (g), Assessed by an Anthropometric Analyzer
• Fat mass [Collected at baseline and until 12 weeks after weight loss intervention]: (g), Assessed by an Anthropometric Analyzer
• Abdominal fat [Collected at baseline and until 12 weeks after weight loss intervention]: (g), Assessed by an Anthropometric Analyzer
• Visceral fat [Collected at baseline and until 12 weeks after weight loss intervention]: (g), Assessed by an Anthropometric Analyzer
• Blood pressure [Regular data collection between baseline and 12 weeks of weight loss intervention]: mmHg
• Heart rate [Regular data collection between baseline and 12 weeks of weight loss intervention]: beats per minute
• Lipid profile-triglycerides [Collected at baseline and until 12 weeks after weight loss intervention]
• Lipid profile-LDL [Collected at baseline and until 12 weeks after weight loss intervention]: low-density lipoprotein
• Lipid profile-HDL [Collected at baseline and until 12 weeks after weight loss intervention]: high-density lipoprotein
• Lipid profile-VLDL [Collected at baseline and until 12 weeks after weight loss intervention]: very-low-density lipoprotein
• Lipid profile-total cholesterol [Collected at baseline and until 12 weeks after weight loss intervention]
• Glucose metabolism-fasting glucose [Collected at baseline and until 12 weeks after weight loss intervention]
• Glucose metabolism-OGTT [Collected at baseline and until 12 weeks after weight loss intervention]: Oral Glucose Tolerance Test
• Glucose metabolism-insulin [Collected at baseline and until 12 weeks after weight loss intervention]
• Sex hormones [Collected at baseline and until 12 weeks after weight loss intervention]: Samples will be analyzed for total testosterone, free testosterone, luteinizing hormone(LH), follicle-stimulating hormone(FSH), pituitary prolactin(PRL) and anti-müllerian hormone(AMH)

Other outcomes

• Adult background [Collected prior baseline]: Demographic information and medical background
• Questionnaire - Adult physical activity [Collected at baseline and until 12 weeks after weight loss intervention]: Physical activity will be assessed by the International Physical Activity Questionnaire (IPAQ)
• Questionnaire - Quality of life [Collected at baseline and until 12 weeks after weight loss intervention]: Quality of life will be assessed by the validated tool, Short form-36 (SF-36).
• Questionnaire - Psychological condition [Collected at baseline and until 12 weeks after weight loss intervention]: Psychological condition will be assessed by the validated tool, Depression-Anxiety-Stress Scale (DASS-21)
• Questionnaire - Sleep [Collected at baseline and until 12 weeks after weight loss intervention]: Sleep will be assessed by the validated tool, Pittsburgh sleep quality index questionnaire (PSQI).
• Spouse's reproductive outcome - Methods of Fertilization [through study completion, an average of 6 months]: 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
• Spouse's reproductive outcome - Time to pregnancy [through study completion, an average of 6 months]: Duration of time to conception defined from time point allowed to conceive to registration of pregnancy.
• Spouse's reproductive outcome - Length of gestational age [Assessed at birth of offspring]: gestational weeks
• Spouse's reproductive outcome - Medication use [Collected from initiation of labor until completed birth of offspring]: Medication use during labor
• Spouse's reproductive outcome - Delivery mode [Collected at birth of offspring]: Delivery mode (rupture of membranes or premature contractions, vaginal, cesarean section, instrumental delivery, miscarriage and stillbirth)
• Spouse's reproductive outcome - Pregnancy complications [through study completion, an average of 18 months]: 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).
• Spouse's reproductive outcome - Obstetrics complications [Collected at birth of offspring]: Obstetrics complications (e.g. preterm prelabour rupture of the membranes, shoulder dystocia, birth trauma (perinatal rupture), postpartum hemorrhage, maternal infections, maternal hospitalization)
• Fetal and offspring - Apgar score [Collected at birth of offspring]: Apgar score (0-10). The higher the score, the better health condition of the offspring
• Fetal and offspring - body weight [through study completion, an average of 18 months]: Fetal body weight will be measured with ultrasound during pregnancy and offspring body weight will be measured using an electronic scale.
• Fetal and offspring - Birth defects/abnormalities [Collected at birth of offspring]
• Fetal and offspring - Cognitive development of offspring [Collected at 6, 12 and 18 months after birth.]: Offspring cognitive development will be assessed by a Habituation and Free Play Test.
• Labs - Semen epigenetics marks [Collected at baseline and until 12 weeks after weight loss intervention]: Epigenetic profile based on array-measurements. Analysed for methylation changes.
• Labs - Adult Epigenetics [Collected at baseline and until 12 weeks after weight loss intervention]: 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.

Sex: Male, ages: 22 Years to 40 Years

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 ART 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.