Is the bleeding that occurred on day 16 onwards after letrozole (aromatase inhibitor) induction, ovulation on day 12, and spotting on day 14, a withdrawal bleed or a typical menstrual period in a patient undergoing fertility treatment?

Bleeding After Letrozole-Induced Ovulation: Likely Early Menses

The bleeding that started on day 16 (4 days post-ovulation) most likely represents early menstruation due to luteal phase insufficiency, not a normal menstrual period, and requires immediate pregnancy testing followed by luteal phase support if pregnancy is confirmed.

Immediate Diagnostic Steps

Obtain serum hCG immediately before attributing this bleeding to any other cause, as early pregnancy-related bleeding (implantation bleeding or threatened miscarriage) can occur at this exact timeframe and must be ruled out first 1.

• If hCG is positive, perform transvaginal ultrasound to confirm intrauterine pregnancy location and rule out ectopic pregnancy, which occurs ipsilateral to the corpus luteum in 70-80% of cases 1
• The timing (day 14-16, or 2-4 days post-ovulation on day 12) is too early for normal menstruation, which typically occurs 12-16 days after ovulation 1

Understanding the Clinical Picture

The bleeding pattern you describe suggests luteal phase defect:

• Ovulation on day 12 with spotting starting just 2 days later (day 14) indicates inadequate corpus luteum function 1
• Progression to full bleeding by day 16 (only 4 days post-ovulation) is abnormally early for menstruation
• Normal luteal phase lasts 12-16 days; bleeding at 4 days post-ovulation represents premature luteal failure

Why This Matters for Letrozole Cycles

Letrozole is a potent aromatase inhibitor that induces ovulation by temporarily suppressing estrogen, which increases FSH release 2, 3. However:

• Letrozole does not provide luteal phase support 2
• The rapid follicular development induced by letrozole may result in a corpus luteum with inadequate progesterone production
• This is not a normal menstrual period but rather breakthrough bleeding from insufficient luteal support 1

Management Algorithm

If hCG is negative:

• This represents anovulatory bleeding or luteal phase defect, not true menses
• Add progesterone supplementation (micronized progesterone 200 mg vaginally twice daily or 100-200 mg orally) starting 3 days after ovulation in subsequent cycles 4
• Consider this cycle day 1 for timing purposes of next treatment cycle

If hCG is positive:

• Continue or initiate progesterone supplementation immediately to support early pregnancy 4
• Serial hCG monitoring every 48 hours to confirm appropriate rise
• Transvaginal ultrasound at 5-6 weeks gestational age to confirm intrauterine pregnancy 1

Common Pitfall to Avoid

Do not assume this is normal menstruation simply because bleeding occurred. The timing is pathologically early (4 days post-ovulation vs. expected 12-16 days), and treating this as "day 1" of a new cycle without pregnancy testing could result in:

• Missed early pregnancy diagnosis
• Inappropriate medication exposure if pregnant
• Failure to provide necessary luteal support if pregnancy is present 1