How to manage ovulation induction in a patient with primary infertility and elevated Thyroid-Stimulating Hormone (TSH) level of 8?

Management of Ovulation Induction in Primary Infertility with TSH Level of 8

Before proceeding with ovulation induction, you must first correct the hypothyroidism by initiating levothyroxine therapy and achieving a TSH level below 2.5 mIU/L, as this is essential for successful ovulation induction and optimal pregnancy outcomes. 1, 2, 3

Step 1: Initiate Thyroid Hormone Replacement Immediately

• Start levothyroxine at 1.6 mcg/kg/day for newly diagnosed hypothyroidism (TSH ≥10 mIU/L), or 1.0 mcg/kg/day if TSH is between 4.5-10 mIU/L 4
• The target TSH for women planning conception is <2.5 mIU/L, not the standard 0.5-4.5 range used for general hypothyroidism 2, 3
• Recheck TSH every 6-8 weeks after starting therapy or after any dose adjustment until target is achieved 4

Critical Evidence Supporting Pre-Treatment Thyroid Optimization

Research demonstrates that adequate circulating thyroid hormone levels are essential for successful ovulation induction—when serum T3 levels were <80 ng/dL, clomiphene therapy failed to induce ovulation, but ovulation rates increased as T3 levels normalized 1. Furthermore, thyroxine therapy significantly reduced the infertility period from 5.2 ± 1.8 years to 0.5 ± 0.8 years in hypothyroid women, with 54% achieving pregnancy within 6 months of achieving optimal TSH levels 2.

Step 2: Monitor Thyroid Function During Ovulation Induction

Once TSH is optimized below 2.5 mIU/L, you can proceed with ovulation induction, but thyroid monitoring becomes critical during this process.

• Controlled ovarian hyperstimulation causes deterioration of thyroid function due to elevated estrogen levels increasing thyroxine-binding globulin, which reduces free T4 availability 5, 3
• Check TSH at the start of each ovulation induction cycle, as even euthyroid patients on stable levothyroxine can develop acute biochemical hypothyroidism during stimulation 5
• Women with thyroid autoimmunity are at particularly high risk for TSH elevation during controlled ovarian hyperstimulation and require closer monitoring 3

Practical Monitoring Protocol

• Measure TSH before starting each stimulation cycle 3
• If TSH rises above 2.5 mIU/L during stimulation, increase levothyroxine dose by 12.5-25 mcg daily 4
• Recheck TSH 2-4 weeks after any dose adjustment during active treatment 4

Step 3: Choose Appropriate Ovulation Induction Protocol

Start with clomiphene citrate as first-line therapy once thyroid function is optimized, as it has the best evidence for efficacy and safety. 6, 7

• Clomiphene citrate induces ovulation in approximately 80% of women with ovulatory dysfunction, with 50% of those achieving pregnancy 6
• Begin with the lowest effective dose (typically 50 mg daily for 5 days) to minimize risks of ovarian hyperstimulation 6, 8
• However, clomiphene combined with thyroid hormone replacement is superior to clomiphene alone for treating luteal phase defects in patients with subclinical hypothyroidism 1

If Clomiphene Fails

• Progress to low-dose gonadotropin therapy rather than high-dose protocols, as this induces monofollicular development with lower risk of ovarian hyperstimulation syndrome 6, 7
• Continue levothyroxine throughout gonadotropin stimulation, as hypothyroid patients who conceived after gonadotropin stimulation required similar thyroid dose increases (32.4%) as those conceiving spontaneously (30.6%) 9

Step 4: Adjust Levothyroxine Dose Upon Pregnancy Confirmation

If pregnancy is achieved, immediately increase levothyroxine dose by 25-30% and recheck TSH within 4 weeks. 4, 9

• Thyroid hormone requirements increase during pregnancy, and early adjustment prevents maternal hypothyroidism that could harm fetal neurodevelopment 4
• Monitor TSH every 4 weeks during the first trimester, then at minimum once per trimester 4
• Maintain TSH within trimester-specific reference ranges throughout pregnancy 4

Critical Pitfalls to Avoid

• Never proceed with ovulation induction while TSH remains at 8 mIU/L—this significantly reduces success rates and increases risk of luteal phase defects 1, 2
• Do not assume stable thyroid function during ovulation induction; the high estrogen levels from controlled ovarian hyperstimulation will increase levothyroxine requirements even in previously stable patients 5, 3
• Avoid using clomiphene citrate as monotherapy in hypothyroid patients without concurrent thyroid hormone optimization, as this leads to poor corpus luteum function and inadequate progesterone secretion 1
• Be aware that ovarian hyperstimulation syndrome risk is increased in patients with underlying thyroid dysfunction, making low-dose protocols particularly important 8