Can Fat-Burning Shots Boost Fertility? Comparing Weight-Loss Injections vs. Healthy Habits for Obese Men With Low Sperm Health

Официальное название

Male Fertility Preservation: Efficacy Evaluation of GLP-1Receptor Agonist Therapy for Infertility in Obese Males - A Multicenter Clinical Randomized Controlled Trial

Обзор

Why is this study being done? Obesity can harm men's fertility by lowering sperm quality and hormone levels, making it harder to have children. Weight loss through diet and exercise helps, but it's often hard to stick with. New medicines called GLP-1 receptor agonists, like semaglutide (Ozempic) and tirzepatide (Mounjaro), help people lose weight and improve health. Early studies suggest these drugs might also boost sperm health in obese men, but more proof is needed. This study tests if these drugs can safely improve fertility in obese men who are having trouble conceiving. What will happen in this study? This is a 48-week study at several hospitals in China. About 180 men will be randomly assigned to one of three groups: Group 1: Standard lifestyle changes, like a healthy diet and exercise, guided by experts. Group 2: Weekly injections of semaglutide, starting low and increasing as tolerated. Group 3: Weekly injections of tirzepatide, starting low and increasing as tolerated. All men will have regular check-ups, including blood tests, semen analysis, and weight measurements. We will track sperm quality, hormone levels, weight loss, and whether their partners get pregnant naturally. The study includes an 8-week adjustment period, 24 weeks of treatment, and 16 weeks of follow-up. Who can join this study? Men aged 20-45 who are married, obese (BMI 28 or higher or waist size 90 cm or more), and have been trying to have a baby for at least a year without success due to low sperm count or poor sperm movement. Their female partners must be under 40 and have no major fertility issues. Men must be willing to attend visits and provide samples. People with serious health problems, recent use of similar drugs, or other causes of infertility (like genetic issues) cannot join. How long will this study last? The full study lasts 48 weeks (about 11 months), with visits every 4-8 weeks, plus monthly phone check-ins for pregnancy updates. What are the possible benefits and risks? Benefits: If the drugs work, men may lose weight, improve sperm quality, and have a better chance of their partners getting pregnant naturally. They might also feel healthier overall. Risks: Common side effects include nausea, vomiting, or diarrhea from the drugs, which usually improve over time. Rare risks include pancreas inflammation or gallbladder issues. Lifestyle changes might cause minor injuries from exercise. All side effects will be monitored closely, and participants can quit anytime. Insurance covers any study-related harm.

Вмешательства

• Препарат Semaglutide (Rybelsus®)
  Participants receive once-weekly subcutaneous injections of Semaglutide. The dose is titrated every 4 weeks: 0.25 mg (Weeks 1-4), 0.5 mg (Weeks 5-8), and maintained at 1.0 mg from Week 9 to Week 32. Injections are administered in the abdomen, thigh, or upper arm
• Препарат Tirzepatide
  Participants receive once-weekly subcutaneous injections of Tirzepatide. The dose is titrated every 4 weeks: 2.5 mg (Weeks 1-4), 5 mg (Weeks 5-8), 10 mg (Weeks 9-12), and maintained at 15 mg from Week 13 to Week 32. Injections are administered in the abdomen, thigh, or upper arm
• Поведенческое Standardized Lifestyle Intervention
  Participants receive individualized intensive lifestyle management, including a calorie-restricted Mediterranean diet (daily deficit of 500 kcal), structured aerobic and resistance exercise (150 mins/week), and behavioral coaching. Delivered through weekly face-to-face sessions for the first 12 weeks, followed by bi-weekly sessions for the remaining 20 weeks. No pharmacotherapy is administered.

Первичные конечные точки

• Change from Baseline in Sperm Concentration (million/mL) at Week 32 of Intervention [Срок оценки: Baseline and Week 32]

Вторичные конечные точки (9)

• Change from Baseline in Total Sperm Count at Week 32 [Срок оценки: Baseline and Week 32]
• Change from Baseline in Sperm Motility (Progressive + Non-progressive) at Week 32 [Срок оценки: Baseline and Week 32]
• Change from Baseline in Serum Total Testosterone Level at Week 32 [Срок оценки: Baseline and Week 32]
• Change from Baseline in Follicle-Stimulating Hormone (FSH) Level at Week 32 [Срок оценки: Baseline, Week 32]
• Change from Baseline in Luteinizing Hormone (LH) Level at Week 32 [Срок оценки: Baseline, Week 32]
• Change from Baseline in Body Mass Index (BMI) at Week 32 [Срок оценки: Baseline, Week 16, Week 32]
• Change from Baseline in Waist Circumference at Week 32 [Срок оценки: Baseline, Week 16, Week 32]
• Number of Participants Achieving Natural Pregnancy Within 48 Weeks [Срок оценки: Monthly during the study, up to Week 48]
• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [Срок оценки: From first dose until 30 days after last dose (up to Week 48+30)]

Критерии участия

Критерии включения

• (1) Married men aged 20-45 (considering childbearing age and ensuring fertility requirements), with female spouses <40 years old and no significant infertility factors.

(2) Meeting China's adult obesity criteria: BMI ≥28 kg/m² or meeting central obesity criteria (waist circumference ≥90 cm).

(3) Meeting WHO diagnostic criteria for male infertility: Failure to achieve pregnancy after ≥1 year of unprotected normal sexual activity, diagnosed as male-factor infertility after basic evaluation (e.g., oligospermia, asthenospermia, or high sperm deformity rate; excluding azoospermia), with essentially normal fertility function in the female spouse.

(4) Abnormal semen analysis: Baseline semen testing shows low sperm concentration or motility (e.g., sperm concentration <15×10⁶/mL or progressive motility <32%).

(5) Willing to undergo randomization and corresponding interventions, able to attend regular follow-ups, and provide semen and blood samples.

(6) Informed consent to participate in the study and signing of the informed consent form.

Критерии исключения

• (1) Other clear causes affecting male fertility: e.g., obstructive azoospermia, severe oligospermia (sperm concentration <5×10⁶/mL), history of bilateral cryptorchidism surgery, genetic abnormalities (chromosomal anomalies such as Klinefelter syndrome, Y-chromosome microdeletions), severe reproductive tract damage, or infection history.

(2) Spouse has significant infertility factors (e.g., bilateral tubal blockage, severe ovulation disorders) without effective treatment, which may severely impact pregnancy outcomes.

(3) Previous bariatric surgery (e.g., gastric bypass, sleeve gastrectomy) or current use of other weight-loss medications (e.g., orlistat), or weight fluctuation >5% within 3 months before enrollment.

(4) Endocrine diseases affecting reproduction or sexual function: e.g., uncontrolled diabetes (HbA1c >9%) or insulin-treated diabetes, clinically significant thyroid dysfunction, hyperprolactinemia.

(5) Severe systemic diseases: Including significant cardiovascular diseases (unstable angina, class III-IV heart failure, etc.), active liver disease (transaminases >2× upper limit of normal), severe renal impairment (eGFR <30 mL/min/1.73m²), etc., making participation in clinical trials inappropriate.

(6) History of acute pancreatitis; personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2) (GLP-1RA is contraindicated in these cases)

; or conditions unsuitable for weight-loss medications, such as severe hepatic/renal impairment or gallstones.

(7) Use of GLP-1 receptor agonist therapy within the past 6 months. (8) Received other fertility-improving treatments within the past 6 months that cannot be discontinued (e.g., gonadotropins, clomiphene, testosterone preparations, or other drugs affecting semen such as exogenous testosterone or 5-alpha-reductase inhibitors).

(9) Alcohol or drug abuse. (10) Psychiatric or cognitive disorders preventing cooperation with follow-up. (11) Any other condition deemed by the investigator to interfere with trial results or increase participant risk.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07179120 · KY2025-354

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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