What is the cause of vaginal bleeding on day 14 in a female of reproductive age undergoing fertility treatment with letrozole (5mg) from day 3 to day 7?

Vaginal Bleeding on Day 14 After Letrozole: Most Likely Ovulation-Related

The bleeding you're experiencing on day 14 is most likely mid-cycle ovulation bleeding, which is a common and benign occurrence during letrozole-induced ovulation cycles and does not indicate treatment failure or reduced fertility. 1

What This Bleeding Represents

Mid-cycle bleeding during ovulation induction is a normal physiological response that occurs when estrogen levels fluctuate around the time of follicle rupture and ovulation. 1 This typically happens precisely when you would expect ovulation—around day 14 of your cycle after taking letrozole from days 3-7. 2, 3

• Letrozole works by temporarily blocking estrogen production, which stimulates follicle development. 2
• When the medication effect wears off (around days 10-14), estrogen levels rise and then drop sharply at ovulation, which can cause breakthrough bleeding. 2
• This bleeding is generally not harmful and does not compromise your fertility outcomes. 1

Critical First Step: Rule Out Pregnancy

Before assuming this is simple ovulation bleeding, you must perform a pregnancy test if there's any possibility of conception from a previous cycle. 1 This is the single most important exclusion, as implantation bleeding can also occur around day 14 if you conceived in a prior cycle. 1

When to Investigate Further

Consider underlying gynecological problems if: 1

• The bleeding is unusually heavy (soaking through pads hourly)
• You have severe pelvic pain beyond typical ovulation discomfort
• You have fever or foul-smelling discharge (suggesting infection like chlamydia or gonorrhea) 1
• This represents a completely new bleeding pattern different from your usual cycles 1

If any of these red flags are present, evaluation for pathologic uterine conditions (polyps, fibroids) or sexually transmitted infections is warranted before attributing the bleeding to letrozole alone. 1

Treatment Options

If Bleeding is Bothersome

For light spotting or bleeding that concerns you, NSAIDs are the first-line treatment: 1

• Mefenamic acid 500 mg three times daily for 5-7 days during bleeding 1
• Alternative: Naproxen 440-550 mg every 12 hours with food 1
• Alternative: Ibuprofen 600-800 mg every 6-8 hours with food 1

Non-Pharmacological Measures

• Heat therapy applied to abdomen or back can reduce cramping discomfort 1
• Acupressure on specific points may provide additional pain relief 1

If No Concerning Features Are Present

Reassurance and observation are entirely appropriate. 1 The bleeding typically resolves spontaneously within a few days and does not require any intervention. 1

Critical Pitfalls to Avoid

Do not assume this bleeding means letrozole has failed or is ineffective. 1 Letrozole has excellent safety and efficacy profiles for ovulation induction, with ovulation rates of 89-90% and pregnancy rates of 21-26% per cycle at the 5 mg dose you're taking. 3, 4

Do not discontinue letrozole prematurely in future cycles without proper counseling about expected bleeding patterns. 1 This is a common and benign side effect that many women experience. 1

Do not perform unscheduled cervical cancer screening based solely on this bleeding episode if you're up to date with routine screening. 1

Do not overlook pregnancy testing, especially if your bleeding pattern changed abruptly from your usual cycles. 1

When to Escalate Care

If bleeding persists beyond 7 days despite NSAID treatment and you find it unacceptable, consider referral to a reproductive endocrinologist to discuss alternative fertility treatment approaches. 1 However, this should not be done hastily, as isolated mid-cycle bleeding does not indicate a need to change your current letrozole protocol. 1

Bottom Line

This day 14 bleeding is almost certainly ovulation-related breakthrough bleeding, which is expected and harmless during letrozole cycles. 1 After confirming you're not pregnant, simple reassurance is often all that's needed. 1 If the bleeding bothers you, short-term NSAIDs are safe and effective. 1 Continue your letrozole as prescribed in future cycles—this bleeding does not indicate treatment failure. 1, 2