Can a patient with a history of infertility, currently taking letrozole (an aromatase inhibitor), still be pregnant despite experiencing spotting from day 14 to 16 of her menstrual cycle, followed by bleeding on days 17 and 18?

Pregnancy Remains Possible Despite Mid-Cycle Bleeding

Yes, pregnancy is still possible in this patient taking letrozole for infertility despite spotting on days 14-16 and bleeding on days 17-18 of her menstrual cycle. The timing of this bleeding coincides with potential implantation bleeding or breakthrough bleeding related to hormonal fluctuations during ovulation induction, neither of which excludes pregnancy 1.

Why Pregnancy Remains Possible

Timing of Ovulation and Fertile Window

• Letrozole induces ovulation typically around days 14-16 in a standard cycle, which aligns precisely with when this patient experienced spotting 2, 3
• The fertile window extends 5 days before ovulation through 1 day after, meaning conception could have occurred from approximately days 9-17 of her cycle 4
• Sperm remain viable for up to 5 days in the female genital tract, so intercourse before the bleeding episodes could still result in fertilization 4

Mid-Cycle Bleeding Does Not Rule Out Pregnancy

• Implantation bleeding occurs in 15-25% of early pregnancies, typically 6-12 days after ovulation (days 14-18 in a standard cycle), matching this patient's timeline 1
• Spotting during days 14-16 could represent ovulatory bleeding from the estrogen surge and subsequent drop that occurs with follicle rupture 1
• Letrozole-induced hormonal fluctuations can cause breakthrough bleeding that does not indicate treatment failure or absence of conception 2, 3

Clinical Approach to This Patient

Immediate Assessment

• Rule out pregnancy as the underlying cause of the bleeding, as this is specifically recommended when evaluating unscheduled bleeding in women of reproductive age 1
• Obtain a serum beta-hCG level now (approximately 2 weeks after the bleeding episodes if presenting later) or wait until expected menses is missed 1
• A urine pregnancy test has limitations this early but can be considered based on clinical judgment, though a negative result does not definitively exclude pregnancy 1

Key Diagnostic Considerations

• Pregnancy should be the first consideration when evaluating mid-cycle bleeding in a woman actively trying to conceive with ovulation induction 1
• Consider other causes only after pregnancy is ruled out: cervical pathology, endometrial polyps, infection, or medication interactions 1
• The bleeding pattern (light spotting progressing to heavier bleeding over 5 days) is consistent with either implantation or early pregnancy bleeding 1

Evidence Supporting Continued Pregnancy Potential

Letrozole and Pregnancy Outcomes

• Letrozole achieves live birth rates of 27-35% per cycle in women with PCOS-related infertility, significantly higher than clomiphene citrate 2
• The drug has no adverse effects on endometrial receptivity, unlike clomiphene, making implantation more likely even with irregular bleeding 3, 5
• Congenital malformation rates with letrozole (2.15%) are not increased compared to natural conception or other fertility treatments, so pregnancy should not be discouraged 6

Critical Timing Factors

• For women with shorter cycles or early ovulation (which letrozole can induce), the fertile window shifts earlier, potentially to days 6-11 4
• A dominant follicle of 19mm indicates imminent ovulation within 24-36 hours, so bleeding occurring days 14-18 could be post-ovulatory 4
• Intercourse timing around days 10-16 would optimally cover the ovulation period for conception 4

Common Pitfalls to Avoid

• Do not assume bleeding equals menstruation in a woman undergoing ovulation induction—pregnancy must be actively excluded 1
• Do not discontinue letrozole prematurely based on mid-cycle bleeding alone, as this is a common side effect that does not indicate treatment failure 2, 3
• Do not rely solely on urine pregnancy testing in the immediate post-ovulation period, as sensitivity is limited before implantation is complete 1
• Avoid delaying pregnancy testing until a full missed period if the patient is anxious—serum beta-hCG can detect pregnancy as early as 8-10 days post-ovulation 1

Recommended Management Algorithm

1. If presenting within days of the bleeding: Counsel that pregnancy remains possible and schedule serum beta-hCG testing for 2 weeks after ovulation (approximately day 28 of cycle) 1

2. If presenting after missed menses: Obtain immediate serum beta-hCG testing 1

3. If beta-hCG is positive: Proceed with early pregnancy management and ultrasound confirmation at 6-7 weeks 2, 6

4. If beta-hCG is negative and menses has not occurred: Repeat testing in 3-5 days or when menses is 1 week late 1

5. If pregnancy is excluded: Evaluate for other causes of mid-cycle bleeding (infection, structural abnormalities, hormonal imbalance) and continue letrozole treatment in subsequent cycles 1