When to Consider Moving On To Injectable Fertility Meds

This post was reviewed for medical accuracy by Rosalie Gunson, a Certified Registered Nurse Practitioner specializing in fertility care.

The first fertility medication many women try is either Clomid or letrozole (with or without IUI). If that doesn’t work, they try injectables with IUI. If that doesn’t work, they consider IVF.

But how do you know how many times you should try the same protocol before moving on?

Obviously, moving on from oral fertility meds to injectables is a decision you should make with your doctor. There is no rule of thumb that applies in every couple’s situation.

But statistically, if you’re going to get pregnant with Clomid, it will probably happen within 3 cycles. Trying more than 6 cycles of Clomid is not recommended.

When Clomid (or Letrozole) Isn’t Working

How will you know that Clomid or letrozole isn’t working and you should try injectables? Again, everyone is different, but here are two common reasons for moving on:

  1. You didn’t respond well to the medication.
    This usually means that you didn’t produce mature follicles in an appropriate timeframe, or you experienced bad side effects.

    Many doctors have a definite preference for either Clomid or letrozole, based on their experience with other patients. But if you started with Clomid and you’re didn’t respond well to that, you may want to give letrozole a try (or vice versa).

  2. You responded well, but you tried it for 3-6 cycles and you are not pregnant.
    Even if you did ovulate each time, repeating the same protocol over and over may not work. The chances of oral fertility meds leading to a successful pregnancy after 6 failed cycles are very low.

For information about Femara and Letrozole, see my post Are Letrozole and Femara the Same Thing? My post What is a Combo Infertility Cycle? has some good info about taking oral meds and injectable meds in the same fertility cycle.

Why Injectables Sometimes Work Better

Compared with oral meds (Clomid and letrozole), injectable meds are more expensive and carry a higher risk of multiples. (For more on the chances of twins or more, check out the post Will Clomid Make You Have Twins?) So why might injections work when pills didn’t?

Injectable meds (Gonal-F, Follistim, Menopur, etc.) are just plain stronger. Assuming that you have a decent ovarian reserve, it’s pretty unlikely that you would fail to produce any good follicles with injectable meds.

There is also some evidence that injectables help to improve egg quality. (Note that many of these medications need to be kept cold. For tips on storing and traveling with injections, see Why Are So Many Fertility Medications Refrigerated?)

If you do end up moving to IVF, you will likely be given some of the same injectable medications as you would for a TI/ IUI cycle (along with many others).

If you have already tried Follistim, Gonal-F, etc. before doing IVF, you’ll have an idea how your body will respond, and some practice giving yourself shots.

Why Moving to Injectables Usually Means Adding IUI

It’s common to do cycles with Clomid or letrozole with just timed intercourse — in other words, without an IUI. That’s often the first step when there’s no obvious medical reason why an IUI would be necessary.

Keep in mind that there may be a reason IUI would be useful that you’re not aware of. For example, some women have low-quality cervical mucus, and the sperm basically gets stuck before it can reach the egg.

The good news is that an IUI would bypass this problem. The bad news is that if you didn’t know you have poor cervical mucus, you might waste a lot of time and effort on timed-intercourse cycles before you even try an IUI.

When you do a cycle with injectable gonadotropins (like Gonal-F or Follistim), though, your doctor will probably encourage you to add an IUI.

One reason is that the cost of the IUI itself is low compared to the cost of the injectable medications, so you might as well maximize the chance that the investment will be worth it. (Wondering how much IUIs generally run? Check out my post How Much Does an IUI Cost Without Insurance?)

Another reason is that injections are often seen as the last stop before IVF. IVF is much more invasive and expensive (per cycle), so many couples want to exhaust all other options before they contemplate going that route.

When Going Straight to IVF Makes Sense

Some couples don’t even bother with pills and IUIs and jump right to IVF. In some circumstances, IVF is the only practical method for achieving pregnancy. A few examples include:

  • Blocked fallopian tubes
  • Severe endometriosis
  • Serious male-factor fertility problems
  • Use of donor eggs
  • Use of your own eggs that were previously frozen (for example, to preserve fertility after cancer treatment)
  • Surrogacy

All things being equal, IVF has a much higher success rate than IUI does. Given the statistics, some women who would be good candidates for IUI decide to skip right to IVF rather than risk wasting time, money, and emotional energy on multiple failed IUIs.

This is especially true for older women who can afford IVF and want a baby as soon as possible. IUI isn’t recommended at all for women over 40, because it’s so unlikely to succeed.

Note that some health insurance plans require couples to demonstrate that they have tried the simpler (cheaper) options before they will pay for more involved methods such as IVF. This is frustrating, since there are fertility problems that only IVF has a chance of addressing.

Also, these rules sometimes force women in same-sex relationships to pretend they have been “trying” for a period of time before fertility treatment will be covered. That’s just silly!

Other plans don’t cover infertility treatment at all, so couples pay out-of-pocket no matter what approach they choose. Your insurance coverage, or lack thereof, will probably play some role in your decision-making.

For more information on navigating the health insurance maze, check out my post Insurance Coverage for Infertility Treatment: 8 Things to Know.

IVF for Genetic Screening

Some people choose IVF because they have a family history of serious genetic diseases. Genetic screening can be done before the embryo is transferred, helping to ensure that they have a healthy baby.

Sometimes the genetic screening for IVF brings to light a genetic problem that the couple didn’t know they had, and this condition explains why all other methods failed. Not everyone is up for such an exhausting and expensive learning process, but it may be worth it in the end.

A friend of mine had been given the unhelpful diagnosis of unexplained infertility. After 5 failed rounds of IVF, they did genetic testing. It turned out that her husband had a chromosomal abnormality that nobody knew about. Due to this problem, most of their embryos had a condition that was incompatible with life. No wonder she hadn’t gotten pregnant!

The IVF team identified the problem and screened the embryos for it. She got pregnant with a healthy baby boy that cycle, which was lucky IVF cycle #6.

While genetic problems can make it harder to conceive, they can also lead to recurrent miscarriage. Doing IVF with genetic screening would ensure that that the only embryos transferred were genetically healthy and therefore more likely to develop into a healthy, full-term baby. For more, see TTC a Rainbow Baby: Overcoming Recurrent Pregnancy Loss.

My Experience With Follistim After Letrozole

We were in the “Let’s try everything short of IVF” camp, partly because we didn’t have any other identified fertility issues besides PCOS and partly because our health insurance at the time would not have covered IVF.

Here is the progression of my medicated cycles:

Cycle 1: Letrozole
Cycle 2: Letrozole
Cycle 3: Letrozole
Cycle 4: Letrozole + IUI
Cycle 5: Letrozole +IUI
Cycle 6: Follistim + IUI
Cycle 7: Follistim + IUI (BFP)

We switched from taking letrozole on CD 5-9 to CD 3-7 to see if that would make a difference. In the last two cycles we added estrogen in the first half of the cycle and progesterone in the second half. I also did trigger shots in every cycle.

I responded well to the letrozole, producing at least one follicle in the 18mm to 20mm range by the time I triggered. But I didn’t get pregnant until I switched to Follistim. I never tried Clomid, because my doctor preferred letrozole in general (especially for women with PCOS).

Also, some scans showed that my uterine lining got thinner rather than thicker in the first half of the cycle (hence the estrogen support). Clomid has been known to cause thin linings, and I definitely didn’t need that!

For more info on the importance of a good endometrial lining, check out my post Can You Get Pregnant With a 5 mm Endometrial Lining?

In the end, I’m obviously happy I moved on to injectables! I guess it’s possible that a 6th or 7th letrozole cycle would have worked, but to be honest, all the BFNs were getting depressing. Starting a different medication brings a little bit of optimism, and you need that positive energy when you’re in the trenches of infertility.

For some suggestions to keep your spirits up, check out 8 Tips for Staying Sane During Infertility/ IVF.

Conclusion

Moving from one treatment protocol to another is an individual decision. But hopefully this post has given you a sense of why some couples decide to try injections after several rounds of pills, or skip both in favor of IVF.


This post was last updated in May 2020.