Endocrine Disorders Associated with Recurrent Miscarriage: Insights and Management

　For expectant mothers worldwide, pregnancy is a journey filled with hope, but certain endocrine disorders can heighten the risk of miscarriage. These conditions disrupt hormonal balance and reproductive health, requiring targeted clinical and lifestyle interventions. Below, we explore six endocrine disorders linked to recurrent pregnancy loss and evidence-based strategies to mitigate risks.

​I. Endocrine Disorders Linked to Miscarriage
　　​Hypothyroidism
　　Hypothyroidism reduces metabolic efficiency, leading to fatigue, weight gain, and dry skin. During early pregnancy, the fetus relies entirely on maternal thyroid hormones. Insufficient thyroid function increases miscarriage risk due to impaired fetal development. Proper thyroid hormone replacement therapy is critical for maintaining pregnancy.
　　​Hyperprolactinemia
　　Elevated prolactin levels disrupt gonadotropin-releasing hormone (GnRH) pulses, suppressing ovulation and corpus luteum function. This hormonal imbalance compromises progesterone production, essential for sustaining early pregnancy. Medications like dopamine agonists (e.g., cabergoline) can normalize prolactin levels and improve outcomes.
　　​Diabetes Mellitus
　　Poor glycemic control in diabetes is associated with miscarriage, fetal malformations, and placental dysfunction. Insulin resistance and chronic hyperglycemia induce oxidative stress and inflammation, damaging embryonic cells. Preconception glycemic optimization—through insulin therapy or oral hypoglycemics—is vital to reduce risks.
　　​Polycystic Ovary Syndrome (PCOS)
　　PCOS, marked by hyperandrogenism and insulin resistance, contributes to recurrent miscarriage through multiple mechanisms:
　　​Obesity and insulin resistance impair endometrial receptivity and promote hypercoagulability.
　　​Elevated plasminogen activator inhibitor-1 (PAI-1) increases thrombosis risk, disrupting placental blood flow.
　　​Hyperandrogenism alters follicular development and ovarian function.
　　Treatments include metformin (to improve insulin sensitivity), ovulation induction, and assisted reproductive technologies (ART) like IVF.
　　​Luteal Phase Defect (LPD)
　　LPD involves inadequate progesterone secretion post-ovulation, leading to poor endometrial thickening and implantation failure. It is common in women with irregular cycles or diminished ovarian reserve. Progesterone supplementation during the luteal phase can stabilize the endometrium and support early pregnancy.
　　​Endometriosis
　　Endometriosis triggers progesterone resistance and chronic inflammation, reducing endometrial receptivity. Pelvic adhesions and tubal blockages further elevate miscarriage risks. Studies show no significant increase in miscarriage rates with IVF in endometriosis patients, but surgical excision of lesions or ART may improve outcomes.
　　​II. Management Strategies
　　​A. Clinical Interventions
　　​Hypothyroidism: Levothyroxine to maintain TSH levels ≤2.5 mIU/L.
　　​Hyperprolactinemia: Dopamine agonists to normalize prolactin and restore ovulation.
　　​Diabetes: Tight glycemic control using insulin or metformin; continuous glucose monitoring.
　　​PCOS: Combined approach of metformin, lifestyle modification, and ART for refractory cases.
　　​LPD: Vaginal progesterone suppositories or oral dydrogesterone post-ovulation.
　　​Endometriosis: Laparoscopic surgery for severe cases; ART for tubal or ovarian involvement.
　　​B. Lifestyle Adjustments
　　​Diet and Weight Management
　　Avoid refined sugars and saturated fats; prioritize fiber, antioxidants, and omega-3 fatty acids.
　　Weight loss (if overweight) improves insulin sensitivity and androgen levels in PCOS.
　　​Stress Reduction
　　Mindfulness, yoga, or cognitive-behavioral therapy to lower cortisol levels and stabilize hormones.
　　​Exercise
　　150 minutes/week of moderate activity (e.g., brisk walking) enhances insulin sensitivity and metabolic health.
　　​Sleep Hygiene
　　7–8 hours of sleep nightly to regulate leptin and ghrelin, supporting hormonal balance.
　　​Conclusion
　　Endocrine disorders pose significant challenges to pregnancy, but multidisciplinary care—combining hormonal therapies, ART, and lifestyle changes—can mitigate risks. Early diagnosis, personalized treatment plans, and patient education are key to improving outcomes. For conditions like PCOS and endometriosis, emerging therapies such as GDF9-targeted interventions and immunomodulators offer hope for future advancements.