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Determining The Course
While IUI may seem less intensive than treatments like IVF, it is more intensive than alternatives like oral medications on their own or timed intercourse. The steps involved in an IUI cycle, and the timeline of that cycle, are largely determined by two decisions: which (if any) drugs to use, and whether or not monitoring is done.
Natural Cycle: No Drugs
A natural IUI cycle is when the woman takes no drugs -- she will grow a follicle and ovulate naturally. Here, the goal of IUI is simply to get sperm to the right place at the right time.
In this case, if no monitoring is done, a woman will simply call her doctor when she sees an LH surge on her home ovulation predictor kit (OPK), and she’ll likely come in the next day for insemination.
If she is doing monitoring, a patient might come in to her clinic on day 3 of her cycle (the third day of bleeding) to ensure that she is at her “baseline”. This means that no follicles (the fluid filled sacs that contain an egg) are growing, and she has a “thin uterine lining” (the part of the womb that grows each month in preparation for a possible pregnancy). This ultrasound sets the schedule for the cycle.
If a patient is confirmed to be at her “baseline,” she is typically instructed to come back about 3 - 4 days before ovulation is expected (to account for the rare cycle in which ovulation occurs early). From that point, the goal is to wait for the “dominant” (largest) follicle to be ready for ovulation.
The IUI is scheduled according to one of two scenarios:
Using A Trigger Shot: When the follicle is at least 20mm and the uterine lining is at least 7mm, a medication (known as a “trigger shot”) can be given to trigger ovulation. This medication is an injection with a small needle in the abdomen. The IUI is scheduled 36 hours after the trigger medication is injected.
Awaiting Natural Ovulation: Blood work or urine-based ovulation predictor kits (OPKs) can predict when a woman will naturally ovulate. In this case, the IUI occurs either later that day or the next morning.
IUI With Clomid or Letrozole
Anovulatory Patients: Can start medication at any time. The only exception to this rule is if a patient’s uterine lining is noted to be abnormally thick at baseline (>10mm), because this might indicate a problem with the uterus. In this case, a 7 to 10 day course of progesterone (like provera or aygestin) can be given to cause the onset of a period and clomid or letrozole would be started thereafter.
In patients who don’t ovulate, doctors who prescribe letrozole often start with a dose of 2.5 mg. In these patients, the challenge is ovulation not developing follicles—hence the goal is to develop only one follicle (known as “monofollicular growth”) rather than push to develop many. However, if patients aren’t responding to this lower dose, doctors are often ready to raise the dose.
Unexplained Patients: Can start medication on day 3 or 5 of the cycle. If the patient is having her treatment cycle monitored, she will come in on day 3 for bloodwork and an ultrasound. On ultrasound, the doctor will be checking to make sure that no follicles have already started the process of growing (because once one follicle is already growing, it is unlikely that others will also start growing in response to clomid or letrozole). The doctor will also look at estrogen levels through blood work to confirm this.
Once the patient has started taking clomid or letrozole, they continue for 5 days, and 4 days thereafter the woman may return to the office for monitoring and blood work. During this time the doctor will observe if any follicles are growing and record how big they are (reflecting the egg’s maturity).
Thereafter the doctor will either:
Increase dosing if no follicles are growing or switch to gonadotropins if no follicles are growing and the patient has reached the maximum dose for clomid (200 mg) or letrozole (7.5 mg)
Continue waiting if the cycle looks promising. Patients may return the next day for insemination if the follicles are large (18mm) or in 2 - 3 days if follicle growth is slower
Cancel the cycle, if too many (4 or more) follicles are growing quickly
If letrozole or clomid haven’t worked in causing ovulation, patients are considered “resistant” to these medications—some strategies for helping ovulation along in these patients include adding medications such as dexamethasone or metformin to the treatment regimen.
IUI With Gonadotropins
The patient comes in on day 3 of her cycle for blood work and ultrasound to make sure that all of the follicles are resting (none have started down the developmental path toward ovulation) and that the lining of the uterus is thin (which means the lining is ready to start growing in preparation for a possible pregnancy).
She will begin the injectable medications later that night. She will continue the same dose of medication for 4 nights and then come back to the office for an ultrasound and bloodwork to monitor her progress. On ultrasound, the doctor will look to see how many follicles have “woken up” and begun growing.
The doctor will also look at the estrogen levels (follicles emit estrogen) to get a sense for the woman’s response to the gonadotropins. Specifically, the doctor is looking for the rate of estrogen growth to inform what to do. In this case, the doctor has three choices:
Keep the dose the same: Things are progressing like they should
Increase the dose: Estrogen levels are not climbing and follicles are not growing
Decrease the dose: Estrogen levels are rising too fast (e.g. tripling) or too many follicles (4 or more) are growing
The response will also dictate when the next visit will be. A patient with no response can safely return in 2 to 3 days. A patient with a vigorous response will probably be back every day.
When to Trigger
The ultimate goal is to have 2 or 3 follicles reach approximately 18mm in diameter. Once that is the case and once the lining is appropriately thick (>7mm), a patient is instructed to take the “trigger” medication.
The “trigger shot” prompts mature eggs to be released in 36-40 hours. The alternative, awaiting a “natural surge,” is not a reasonable option with gonadotropins. This is because smaller, immature follicles are still growing and if there is a delay in natural surge, they may catch-up in size to the larger, mature follicles. Upon release, the woman may now have 4 or more eggs available for fertilization, which can dangerously increase her risk of a high-order multiple pregnancy.
Insemination Day
Generally speaking, on the day of treatment patients should keep in mind:
Most patients tolerate the insemination itself well and consider it far less painful than their experience with an HSG or saline sonogram
Patients are normally allowed to resume their routine, or return to work, the same day
How long patients lay in bed after the insemination does not impact outcomes
Patients should not be alarmed if they experience “leakage,” as this is relatively common and most likely a discharge of cervical mucus (which at this stage is at its most prolific)
Spotting is also common and not an indication that something has gone awry. This occurs because the cervix is especially sensitive
If you experience cramping, it’s preferable to take tylenol instead of advil. Follicles produce prostaglandins and advil works by reducing production of prostaglandins, so it’s important to avoid Advil around time when pregnancy might occur or thereafter
Pro Tips
The degree to which an IUI cycle is demanding depends on the decision of which (if any) drugs are taken and whether the cycle is accompanied by monitoring
Natural cycles do not require monitoring, but if monitoring is done, a woman comes in on cycle day 3 for a baseline ultrasound, returns back 4 days before ovulation is expected, and can either be “triggered” when the largest follicle is around or above 20mm in diameter or ovulate naturally. She’ll be inseminated around 36 hours after a trigger shot. If she’s ovulating naturally and checking with a home prediction kit, she’ll likely come in the morning after her positive test result for insemination
For cycles using clomid or letrozole, patients start medication depending upon whether they are able to ovulate. If a woman doesn't ovulate on her own, she can start medications at any time after documentation of a negative pregnancy test. If a woman does have a regular cycle, she can start medications on either day 3 or day 5 following the start of bleeding
Clomid or letrozole is taken for 5 days, then stopped for 3 to 4 days. Starting around cycle day 10, patients who are being monitored will be seen to chart progress -- if there’s no progress, drugs will be either switched or re-started with an increased dosage, and if there’s too many large follicles (4 or more) a cycle will be canceled. In some patients (e.g. those with PCOS), doctors may be comfortable waiting until day 16 or 18 to gauge response. Patients can receive a “trigger shot” and around 36 hours later undergo insemination, or ovulate naturally and come in for insemination the morning after a positive result on a home OPK
For cycles using gonadotropins, monitoring is required. Injections begin on cycle day 3, and drugs are injected for 4 nights. Around cycle day 7, the patient returns for monitoring and, depending upon response, she will continue to return until her largest follicle grows to around or above 18 to 20mm in diameter, whereupon she will give herself a “trigger shot” and return for insemination around 36 hours later. If more than 4 follicles are growing, the cycle will likely be canceled due to concerns of a high-order multiple pregnancy
Patients are often able to resume daily routine the same day as their IUI
Women should not necessarily be alarmed by “leakage,” “spotting” or cramping following IUI, though cramping should not be treated with Advil (Tylenol is preferable)