After trying to conceive with Clomid or letrozole, for many patients the next step is to try intrauterine insemination. Intrauterine insemination (IUI), sometimes referred to as “artificial insemination”, is the process of placing sperm in a woman’s uterus. This procedure delivers sperm past the vagina and cervix, both potential barriers for sperm, and into the uterus near the fallopian tubes, thereby raising the chances sperm will fertilize a woman’s egg.

While IUI is less intensive than options like IVF (which we’ll cover momentarily), IUI can still require a fair amount of time at a doctor’s office, and the costs can add up. For example, in the United States, the cost of an IUI cycle can range from $500 to $4,000 (in China, prices tend to hover around 3,000 yuan) and depends on which, if any, medications are taken in the lead-up to the insemination (more on that in a moment).

We have an incredibly detailed course on IUI here, that we suggest you look at if this becomes an option you want to consider.

However, these success rates are highly dependent on age. As you can see from a handful of studies below, IUI success rates decrease with age regardless of geography. To be certain, some clinics will see higher rates of success than what's quoted below, but even in those centers, rates of success decline with age. We should note, this chart is not meant to draw comparisons of rates of success between regions.

Yet, even for a woman under the age of 35 with no infertility diagnosis, the odds are likely that any given IUI will not work. This can be a devastating surprise and so it’s important to get familiar with the odds of success for IUI.

Given the single-cycle failure rate for IUI, it’s common for women or couples to try multiple inseminations in back-to-back months.

IUI Medication Options

IUI success rates and costs vary depending on which, if any, medications are used leading up to an insemination.

The chart below incorporates study data from China and shows the correlation of increasingly intensive drugs and higher success rates, but also higher risks (in the form of multiple gestation pregnancies — which can be dangerous both to the mother and child). In some studies (though not reflected in the chart below), if a woman conceived with IUI-plus-gonadotropin, there was a 30% chance she would carry twins without a dramatic overall improvement in live birth outcome. Many doctors would consider this a poor risk versus reward decision.

Furthermore, although the data may suggest that in Clomid cycles the risk of multiples is higher than with gonadotropins—although both risks are relatively low in absolute terms—this discrepancy arises due to the notably low dosage of gonadotropin administered. It's critical to note that the higher doses typically utilized in stimulation protocols significantly elevate the potential for a heightened twin rate.

Unmedicated or "Natural" IUI

There’s the option to do a “natural” IUI cycle, and use no drugs at all, in which case you’ll merely do monitoring to understand when ovulation is likely and have the insemination performed just before ovulation.

The best candidates for this option are women with “regular cycles”, meaning they have no ovulatory disorders. That said, there is no proven benefit in doing this for patients with “unexplained infertility” and where no medical challenge has been identified.

On the other hand, doctors are often very open to the idea of an unmedicated IUI cycle for unpartnered cis-gender female patients, same-sex female couples, or any other circumstance where there’s no fertility concern about the person being inseminated and to-date access to high quality sperm has been the sole challenge.

In the data above, these natural cycles had the lowest chances of working, but also the lowest risk of resulting in a multiple gestation pregnancy like twins, triplets, or more. The available evidence indicates that IUI success rates plateau after 3-6 cycles. Therefore, it is not advisable to undergo additional cycles beyond that point.

Clomid or Letrozole

The next level up are the medications most commonly used with IUI. These are oral medications like Clomid (clomiphene) or letrozole (which also goes under the brand name Femara). These medications are fairly easy to take, inexpensive, and they do boost success rates per cycle into the low teens.

However, the chances that a resulting pregnancy is a multiple gestation pregnancy also rise.

Finally, taking these medications will probably step up the logistics involved in a cycle, because it’s more likely that your doctor will have you come in for monitoring appointments to ensure the medications are working properly—this is more time consuming and also adds some cost.

Generally speaking, many doctors are comfortable performing an IUI with these drugs: they feel the improved odds of success compensate for the increased (but still “tolerable”) risk, cost, and inconvenience.

Gonadotropins

Finally, the most intensive medications are gonadotropins—these are injections that are expensive (around $2,000 per cycle in some countries like the U.S. and far less in most other regions).

They variably increase success rates over letrozole (Femara) or Clomid depending upon the patient type. It's less common that they are recommended for IUI, because they are often more costly and many studies (including the one below published in the New England Journal of Medicine) reflect they drive up the risk of a multiple gestation delivery.

Many of the newsworthy stories of high-order multiple pregnancies you may have read about were the result of combining gonadotropins and IUI. A serious discussion about risks should happen between the patient and doctor before pushing ahead with IUI in conjunction with gonadotropins.

What Is IVF & Who Benefits?

IVF, or in vitro fertilization, is a more intensive and expensive treatment option than IUI—it requires that eggs are surgically removed from the ovaries, that those eggs are inseminated with sperm in a laboratory, and that a resulting embryo is placed in a woman’s uterus with the hopes that it implants and leads to a healthy baby.

A hopeful parent might strongly consider IVF if:

• They are mostly focused on getting pregnant as fast as possible. However, some patients require multiple IVF cycles to deliver.

• IUI has not previously worked in the first 3–5 or so attempts.

• A woman has a medical condition (like blocked fallopian tubes) that renders IUI ineffective.

• A male partner suffers from “male factor infertility” and upon semen analysis, produces a “total motile count” (number of moving sperm) below 5-10 million.

• A hopeful parent or couple plans to have multiple children, across multiple pregnancies. IVF allows patients to create and freeze multiple embryos for future use.

• A woman has already frozen her eggs, and thus, completed the most expensive and intensive portion of the IVF process.

• A hopeful parent has a known genetic condition and wants to minimize the risk of transmission to their future children.

• Hopeful parent(s) have suffered through multiple pregnancy losses due to genetic abnormalities.

• Fertility preservation was necessary in the face of a cancer diagnosis.

• Sex selection is desired and it is legal in their jurisdiction.

• There is a need for a gestational carrier.

IVF Success Rates

IVF success rates tend to correlate closely with female age, regardless of geography, as you can see below. This chart is not meant to draw comparisons of success rates between regions or territories, as that would require far more data.

When British investigators looked at historical data, they noted more than half of women under age 40 deliver a child after three IVF cycles, whereas for women over the age of 40, rates of IVF success tend to be much lower.

As you’ll see below, when “donor eggs” are incorporated into the process, success rates climb quickly.

The same is also true in circumstances where a male partner has an underlying fertility issue and “donor sperm” is provided.

If a female partner has difficulty conceiving or carrying with embryos that appear to be of good quality, having a gestational carrier or surrogate also dramatically raises the odds of success.

The Process of IVF

As we mentioned, IVF is practiced differently in many parts of the world, but generally speaking there are a handful of basic steps (and decisions) involved. We’ll summarize those below, but if you want the full set of details, head to our comprehensive guide to IVF here.

Ovarian Stimulation

A woman is usually given injectable hormones to make her ovaries develop as many eggs as they can (say, 8–20) instead of the usual 1–2 that would be matured each month. This continues for an average of 10 days until a “trigger shot” is taken to start the ovulation process where eggs become mature.

In some countries, like Japan, many doctors and patients prefer to substitute out high levels of injectable hormones for lower doses or less-potent oral medications. For most (but not all) patients, this tends to lower success rates. For a closer analysis, see our lesson on IVF "protocols" here.

Egg Retrieval

Eggs are surgically retrieved from the ovaries, and typically, anesthesia is used during the procedure. A doctor usually uses a vaginal ultrasound to guide a needle that suctions out each egg.

Growing Embryos

Over the next 3–7 days, a fertility clinic’s laboratory will take all of the collected, mature eggs and try to grow them into healthy embryos.

First, they fertilize the eggs with sperm either by surrounding an egg with sperm in a petri dish, or using ICSI, a micro-procedure where a single sperm is injected into an egg.

Then the laboratory will try to grow the embryos into either Day 3 “cleavage stage” embryos or heartier Day 5, 6, or 7 “blastocyst stage” embryos. Growing embryos to “blastocyst stage” is challenging, and depending upon the region, it can be more common (e.g. United States, Singapore) or less common (e.g. China, Europe) to find clinics able or prepared to do so.

Optional Genetic Screening

Once embryos have reached the blastocyst stage, there is an option to remove a few cells and have them sent out for genetic testing, sometimes referred to as PGT-A, PGT, or PGS screening. This testing can either test for a single genetic disorder that runs in your family history or testing can predict if an embryo is likely or unlikely to lead to a healthy pregnancy.

As you can see, implantation rates per embryo transfer are higher with PGT-A-tested and approved embryos than they are with untested embryos and are less likely to lead to a miscarriage.

That said, experts disagree on the utility of PGT-A screening, unless a patient is looking to do testing to screen out embryos for a specific genetic disorder. We go into more detail on the topic to help you make your decision in our dedicated course here.

Option to Freeze

After developing embryos, whether or not genetic screening has been done, more clinics and patients are using the option to freeze all of their embryos. Then embryos will be transferred later on.

As you’ll see, according to limited data from the United States, when people of East Asian heritage opt to freeze their embryos and wait (a month or so) to transfer, the odds of IVF success may improve.

Transfer

An embryo will be transferred into the uterus with the hopes that it “implants” and leads to a healthy pregnancy. The safest option is to transfer one embryo at a time. That said, some societies deem it acceptable to contemplate transferring multiple embryos per transfer under special circumstances. Here’s an example of the American Society of Reproductive Medicine’s recommendations on setting limits on the number of embryos to be transferred during any given transfer. When patients transfer more than one embryo per transfer, the risks they'll conceive with twins or triplets rise (most dramatically for younger women). As you can see in the data below, multiple gestation pregnancies raise the risk to both the person carrying the pregnancy and to the offspring. For this reason, in many regions (e.g. Sweden, Japan, Beijing) transferring multiple embryos during a single transfer is discouraged or outright illegal.

Option to Freeze Any Additional Embryos

Any embryos of reasonable quality that were not transferred will be frozen and can be used later, either in the event that the first transfer doesn’t work, or if it does work, for more children in the future.

Thinking of IVF as a Funnel

In some senses, you can think of IVF like a funnel. Unfortunately, not every developed ovarian follicle will contain a mature egg, and not every mature egg will lead to a healthy embryo or a baby. At each stage throughout the process, you’ll lose something. That’s why the goal is to have a high number of eggs to start off with. Below is a sample summary of this funnel.

Costs of IVF

IVF prices vary dramatically by region and whether a local government or insurer covers some of the cost. In regions where patients pay for IVF “out of pocket,” costs can range dramatically. In Japan, IVF typically costs around ¥300,000 (~$3,000), while in China, the prices tend to be somewhat higher (~30,000 yuan or ~$5,000), and in some areas in China, costs are comprable to the U.S. where prices can easily reach $20,000 or more.

It’s common for patients to pay significantly more for treatment than the figures quoted by a fertility clinic. Often these quoted prices exclude the prices for required drugs (which can be meaningful) or “add-ons” (e.g. ICSI or embryo testing) the clinic may later insist upon.

To showcase in an American context how drugs and add-ons can change the total cost for each cycle, below is a chart of what patients pay in a handful of U.S. cities.

Insurance

In the U.S., it’s rare to have IVF covered by an employer’s insurance plan, and even if coverage exists, a woman or couple may be asked to try a progression of timed intercourse, oral medication, and IUIs before receiving coverage for IVF.

Generally speaking, IVF costs and coverage vary. In many countries, a woman or couple will be asked to try multiple (less expensive) IUIs before IVF can be covered. Even if IVF is covered, certain aspects of the process (e.g. drugs, fertilization techniques, tests, ability to transfer multiple embryos at once) may not be. Finally, in many countries where IVF is covered, there can be lengthy delays to receive treatment, and oftentimes, a cap on female age, often 40–45, whereafter treatment won’t be covered.

We think there are a handful of criteria in determining whether one should start with IUI or IVF. We elucidate the factors below, though of course, prioritizing those factors is a personal choice.