How I use Clomiphene in Individuals with PCOS (Poly Cystic Ovarian Syndrome)
Either clomiphene or letrozole step-up protocol saves time
Ms. Smith comes to discuss pregnancy. She took birth control pills since teenager for cycle control. She had irregular periods since she stopped the pills 12 months ago. Her TSH and prolactin are normal.
I explained that the irregular menstruation was due to unpredictable or few ovulations, which reduced her chance of pregnancy. Clomiphene can make her ovulate more predictably, make her menstruation more predictable, and increase her chance of pregnancy. I explained how I do it.
Baseline ultrasound (cycle day 1-5)
This is a “safety check,” making sure there is no cyst more than 15 mm in the ovary. This is typically performed on or before cycle day 5; cycle day 1 is the day of full flow).
“Fertility Pills” (cycle days 5-9)
I use either clomiphene or letrozole, starting at 50 mg daily or 2.5 mg daily, respectively.
“Monitoring” ultrasound (cycle day 12)
This ultrasound is to check the response of the ovary. The size of the lead follicle determines what the next step is.
The lead follicle is 18 mm or more (up to 22 mm): the egg is mature. This is the time to use the trigger shot if it is planned.
The lead follicle is > = 12 mm or more: there is response and, usually, the follicles have momentum to grow to mature sizes (18 mm and above). I will see her in two days. By then I expect the follicle to be > = 15 mm (and she be managed per routine). If that is not the case, I will increase the dose and see her in 5 days.
The lead follicle is < = 11 mm, I increase the dose by 50 mg daily for 5 days and she returns in 7 days and be managed based on the size of the follicle.
Luteal progesterone (9 days after the day of trigger)
This test confirms ovulation if the serum progesterone is > = 3 ng/mL. In typical clomiphene or letrozole cycles, the serum progesterone is > 20 ng/mL on this day. If a blood test cannot be performed or patient requests, I prescribe Prometrium 50 mg nightly by mouth or vaginally to be started 3-4 days after trigger (or 1-2 days after expected ovulation).
Pregnancy test (16 days after the day of trigger)
Either blood test or urine test will work. If it is positive, serial blood tests are performed to monitor the trend of increase (or the health of the pregnancy).
Special considerations
Typical clomiphene or letrozole cycle lengths are 28 - 30 days. Some patients may have cycle length longer than 32 days after taking clomiphene. In this case, I increase the clomiphene or letrozole daily dose by 50 mg or 2.5 mg, respectively. This will “tighten” the cycle length to 28 - 30 days.
I do not necessarily wait for menstruation or withdrawal bleeding to begin clomiphene or letrozole - any day is cycle day 5 (or 3) in patients with PCOS. I do make sure that her pregnancy test is negative and her progesterone level indicates no recent ovulation.