How to initiate letrozole for ovulation induction in a female patient with suspected Polycystic Ovary Syndrome (PCOS) phenotype D, infertility, and irregular periods who has not had a menstrual cycle in the last 70 days?

Initiating Letrozole for Ovulation Induction in PCOS Phenotype D with Prolonged Amenorrhea

For a patient with suspected PCOS phenotype D, infertility, and no menstrual periods for 70 days, initiate letrozole 5 mg daily for 5 days after inducing a withdrawal bleed with progesterone. 1, 2

Initial Assessment and Preparation

• Confirm PCOS diagnosis by evaluating for oligomenorrhea/amenorrhea, polycystic ovaries on ultrasound, and ruling out other causes of anovulation 3
• For patients with prolonged amenorrhea (>70 days), induce withdrawal bleeding with oral progesterone before starting letrozole 4
• Ensure the patient is not pregnant before initiating treatment by performing a pregnancy test 3

Letrozole Administration Protocol

• Start with letrozole 5 mg daily for 5 days beginning on day 3-5 of the induced withdrawal bleed 2, 5
• Monitor follicular development with transvaginal ultrasound starting around day 12 of the cycle 2
• When the dominant follicle reaches 18-24 mm, administer hCG trigger (if prescribed) and advise timed intercourse 24-36 hours later 2
• If no response occurs with the initial 5 mg dose, consider increasing to 7.5 mg daily in subsequent cycles 6, 5

For Patients with Letrozole Resistance

• If no ovulation occurs after standard 5-day regimen of 5 mg letrozole, consider extending treatment duration 7
• First try a 7-day regimen of 5 mg letrozole daily, which has shown to induce ovulation in approximately 70% of letrozole-resistant patients 7
• If still no response, extend to a 10-day regimen of 5 mg letrozole daily in the subsequent cycle 7
• This stepwise extended regimen has demonstrated a cumulative ovulation rate of 92.75% in previously letrozole-resistant patients 7

Monitoring and Follow-up

• Schedule ultrasound monitoring 7-9 days after completing letrozole to assess follicular development 2, 5
• Measure endometrial thickness during ultrasound monitoring (optimal thickness >7 mm) 2
• Consider mid-luteal phase progesterone level (day 21-23) to confirm ovulation 3
• If no ovulation occurs after three cycles with dose adjustments, reevaluate diagnosis and consider alternative treatments 1

Efficacy and Expectations

• Letrozole has higher ovulation rates (73.08% vs 60.78%) and pregnancy rates (21.56% vs 7.84%) compared to clomiphene citrate in PCOS patients 2
• Letrozole produces more monofollicular cycles (79.49%) compared to clomiphene (54.84%), reducing multiple pregnancy risk 2
• Live birth rates are significantly higher with letrozole compared to selective estrogen receptor modulators for ovulation induction in PCOS 1

Common Pitfalls to Avoid

• Failing to rule out pregnancy before starting letrozole 3
• Not inducing withdrawal bleeding in patients with prolonged amenorrhea, which can lead to poor response 4
• Starting with too high a dose, which doesn't improve outcomes but may increase side effects 5
• Inadequate monitoring of follicular development and endometrial thickness 2
• Not considering extended duration protocols in letrozole-resistant patients 7