What are the next steps for a female patient experiencing irregular periods and difficulty conceiving after stopping birth control, with negative pregnancy tests?

Post-Birth Control Irregular Periods and Difficulty Conceiving

If you have been trying to conceive for 12 months with irregular periods after stopping birth control and negative pregnancy tests, you need a formal infertility evaluation now, which includes hormonal testing (LH, FSH, prolactin, thyroid, progesterone), pelvic ultrasound, and semen analysis for your partner. 1

Immediate Diagnostic Workup Required

Hormonal Assessment

• Measure LH and FSH levels (average of three samples taken 20 minutes apart between cycle days 3-6 if you have any bleeding): An LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS), while FSH >35 IU/L indicates ovarian failure 2
• Check mid-luteal progesterone (approximately 7 days before expected period): Levels <6 nmol/L confirm anovulation, meaning you are not ovulating despite having some bleeding 2
• Obtain prolactin levels (morning, resting, not after a seizure): Levels >20 μg/L may indicate hyperprolactinemia, which disrupts ovulation 2
• Test thyroid function and testosterone: Testosterone >2.5 nmol/L suggests hyperandrogenism, commonly seen in PCOS 2

Structural Evaluation

• Transvaginal ultrasound is mandatory to evaluate for polycystic ovaries (>10 peripheral cysts of 2-8 mm), fibroids, polyps, or other structural abnormalities that affect fertility 2, 3
• Transvaginal approach is more sensitive than transabdominal for detecting ovarian pathology 2

Male Partner Evaluation

• Semen analysis must be obtained immediately since male factor contributes to 40-50% of infertility cases 1
• Do not delay this test—it is essential from the outset 1

Treatment Based on Findings

If Anovulation is Confirmed (Low Progesterone)

• Clomiphene citrate 50 mg daily for 5 days starting on cycle day 5 is the first-line treatment for ovulatory dysfunction after stopping birth control 4
• If no ovulation occurs after the first cycle, increase to 100 mg daily for 5 days 4
• Time intercourse for 5-10 days after completing each clomiphene course when ovulation typically occurs 4
• Most women who will ovulate do so within the first three treatment cycles 4
• Treatment beyond six total cycles (including three ovulatory cycles) is not recommended 4

If PCOS is Diagnosed

• Clomiphene remains first-line, but use the lower 50 mg dose initially due to increased risk of ovarian hyperstimulation in PCOS patients 4
• Address metabolic concerns including glucose/insulin ratio if hyperandrogenism signs are present 5

If Irregular Bleeding Persists Without Pregnancy

• For light irregular spotting: NSAIDs such as mefenamic acid 500 mg three times daily for 5 days during bleeding episodes 3
• For heavy or prolonged bleeding: Low-dose combined oral contraceptives (20-35 mcg ethinyl estradiol) for 10-20 days can achieve hemostasis 5, 3
• Rule out pregnancy, sexually transmitted infections, and pathologic uterine conditions (polyps, fibroids) before starting any bleeding treatment 5

Critical Timing Considerations

The 12-month mark is your threshold for formal infertility evaluation. 1 However, if you are over 35 years old, this evaluation should have started at 6 months, and if over 40, immediate evaluation is warranted 1. Post-birth control irregular cycles do not justify delaying this workup—irregular periods themselves indicate potential ovulatory dysfunction requiring investigation 2, 6.

Common Pitfalls to Avoid

• Do not assume irregular periods after birth control are "normal adjustment" lasting beyond 3-6 months—this may represent underlying pathology like PCOS that existed before contraception use 6
• Do not rely solely on negative home pregnancy tests to rule out pregnancy before starting fertility treatments; clinical criteria or formal testing may be needed 2
• Do not start clomiphene without confirming you are not pregnant and without pelvic examination to exclude ovarian cysts 4
• Do not continue trying without male partner evaluation—this wastes valuable time if male factor is present 1

When to Refer to Specialist

• Refer to reproductive endocrinology if: No ovulation after three cycles of clomiphene 4, complex hormonal abnormalities are found 3, or pregnancy has not occurred after three ovulatory cycles on clomiphene 4
• Refer to gynecology if: Structural abnormalities (fibroids, polyps) are identified on ultrasound 3, or if you have known conditions causing infertility 1
• Immediate referral if: You are over 40 years old 1 or have conditions known to cause infertility (severe endometriosis, premature ovarian failure) 1

Maximizing Natural Conception While Awaiting Treatment

• Have intercourse every 1-2 days starting soon after any bleeding stops to ensure coverage of the fertile window 2
• Monitor for slippery, stretchy cervical mucus indicating peak fertility 2
• Avoid smoking, alcohol, recreational drugs, and commercial vaginal lubricants as these reduce fertility 2
• Maintain healthy weight (BMI 18.5-25) as both very thin and obese states reduce fertility 2