What is the likely cause of bleeding on days 14 and 15 in a 34-year-old female with a history of letrozole (letrozole is a non-steroidal competitive inhibitor of the aromatase enzyme, generic name) induction, who had a corpus luteum on day 12, and had sexual contact around the time of ovulation?

Likely Cause of Bleeding on Days 14-15 After Letrozole Ovulation Induction

The bleeding on days 14 and 15 most likely represents implantation bleeding or early pregnancy-related spotting, given the timing 2-3 days after ovulation (corpus luteum on day 12) and sexual contact at the time of ovulation. However, this brief episode could also represent breakthrough bleeding from hormonal fluctuations following letrozole-induced ovulation.

Clinical Context and Timing

The clinical timeline is critical here:

• Day 12: Ultrasound showed corpus luteum (indicating ovulation had occurred or was imminent) and sexual contact occurred 1, 2
• Days 14-15: Brief bleeding episode (2 days only) with no further bleeding
• Timing: This places bleeding approximately 2-3 days post-ovulation

Most Likely Diagnosis: Implantation Bleeding

Implantation bleeding typically occurs 6-12 days after conception (or 8-14 days after ovulation), making days 14-15 consistent with this diagnosis if conception occurred on day 12. 3 The characteristics that support this include:

• Brief duration (only 2 days) 3
• Self-limited (no further bleeding) 3
• Timing coincides with expected implantation window 3

Alternative Explanation: Post-Ovulatory Hormonal Bleeding

Letrozole works by suppressing estrogen production through aromatase inhibition, and the subsequent rapid rise in estrogen after ovulation can cause endometrial instability 4. This mechanism could explain:

• Breakthrough bleeding from hormonal fluctuations as estrogen levels normalize post-ovulation 2, 5
• Luteal phase spotting which is generally benign 6

Critical Next Steps

Obtain a serum beta-hCG level approximately 14 days after the day 12 ovulation (around day 26 of cycle) to confirm or exclude pregnancy. 3 This is essential because:

• If positive, the bleeding was likely implantation-related and pregnancy is established 3
• If negative, the bleeding represented benign hormonal fluctuation 6

What to Rule Out (Lower Probability but Important)

While less likely given the clinical presentation, consider:

• Early pregnancy complications: Threatened abortion would typically present with more persistent bleeding and requires ultrasound confirmation of intrauterine pregnancy with fetal cardiac activity 3
• Ectopic pregnancy: Must be excluded if beta-hCG is positive, as 7-20% of pregnancies of unknown location are ectopic 3

Common Pitfalls to Avoid

• Do not perform digital pelvic examination before ultrasound if bleeding increases, as this could precipitate hemorrhage if placenta previa develops later in pregnancy 3, 7
• Do not assume the bleeding is pathologic without further evaluation, as brief spotting 2-3 days post-ovulation is often benign 6
• Do not delay pregnancy testing if menses do not occur within expected timeframe (typically 14 days post-ovulation) 6

Monitoring Instructions

Advise the patient to:

• Track any recurrent bleeding: Note color (pink/brown vs. bright red), volume, and presence of clots 7
• Watch for warning signs: Severe abdominal pain, lightheadedness, soaking through pads, or passage of tissue 3, 7
• Obtain pregnancy test if menses does not occur by expected date (approximately day 26-28 of cycle) 6, 3
• Return immediately if bleeding resumes with increased volume or is accompanied by severe pain 3, 7