SAT-148 - Successful Conception Following Tirzepatide Therapy in Long-Standing Unexplained Infertility

Background: Obesity and metabolic syndrome are established contributors to impaired reproductive outcomes. GLP-1 and the dual GLP-1/GIP receptor agonists promote weight loss and improve fertility by modulating the hypothalamic-pituitary-gonadal axis. Data on fertility outcomes following their use in women with obesity and metabolic dysfunction remain scarce.

Case: A 30-year-old woman with hypothyroidism, benign thyroid nodules, and 6 years of infertility was referred to the endocrinology clinic for weight gain. She had failed three intrauterine insemination cycles and two in vitro fertilization cycles. Initial BMI was 28 kg/m². Thyroid studies showed TSH 5 mIU/L and free T4 1.2 ng/dL. Desiccated thyroid was changed to levothyroxine 125 mcg daily; TSH improved to 2.2 mIU/L at 3 months. Despite lifestyle measures, thyroid optimization, and a phentermine trial, BMI increased to 31 kg/m². Labs suggested insulin resistance and dyslipidemia: fasting glucose 130 mg/dL, insulin 17 µIU/mL, HbA1c 5.2%, total cholesterol 270 mg/dL, LDL 189 mg/dL, triglycerides 216 mg/dL, and HDL 56 mg/dL. Metformin was started but soon discontinued due to gastrointestinal intolerance. She was then started on Tirzepatide, 2.5 mg weekly, titrated to 5 mg. Comprehensive hormonal workup (FSH, LH, prolactin, estradiol, progesterone, testosterone, DHEAS, aldosterone, cortisol) was normal. Menstrual cycles were regular (30–35 days) and prior pelvic ultrasound and hysterosalpingography were normal. After six months of therapy, she lost 31 lb (BMI 27 kg/m²) with improved insulin resistance. Thyroid function remained well controlled. One month later, she conceived spontaneously. Tirzepatide was discontinued immediately upon confirmation of pregnancy. The pregnancy resulted in a full-term live birth.

Conclusion: This case provides a clinical correlate to emerging preclinical and observational data that suggests GLP-1 receptor agonist therapy may improve spontaneous and assisted pregnancy rates and obstetric outcomes, even when matched for BMI or comparable weight loss. The patient's successful outcome after years of failed interventions highlights the critical role of metabolic optimization in restoring fertility, particularly in non-PCOS patients. Additionally, the temporal association and the patient's unique profile invite consideration of improved insulin sensitivity, reduced inflammation, or direct gonadal action as additional mechanisms for improved fertility.

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