What is a Combo Infertility Cycle?

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

You may have heard infertility patients say they’re doing combo cycles and wondered, “Combo of what?” So I thought I’d explain what a combo cycle is and why you might consider doing one as part of your fertility treatment.

A combo cycle involves taking pills (Clomid or letrozole) and injections (Gonal-F, Follistim, or Menopur) in the same medicated fertility cycle.

Your doctor may recommend a combo cycle for a few different reasons, depending on the diagnosis. Combo cycles can be done with timed intercourse, IUI, or IVF.

Combo Cycles With Timed Intercourse or IUI

If you are doing timed intercourse and/ or an IUI, your doctor may recommend trying a combo cycle if you didn’t have a good response to Clomid or letrozole alone. (You might know letrozole as Femara, as I explain in the post Are Letrozole and Femara the Same Thing?)

A poor response means that your ovaries didn’t produce enough follicles or they didn’t grow at an appropriate rate. Generally, doctors want to see at least one follicle in the 18 mm to 20 mm range at the time you take the trigger shot.

Not producing large enough follicles to trigger is a common reason for cancelling a fertility cycle. I have a whole post on cancelled cycles here.

A combo cycle is much cheaper than an injections-only cycle, since you wouldn’t be doing more than a few days of shots. You may also need fewer internal ultrasounds, although that depends on how thoroughly you are being monitored.

(Nervous about internal ultrasounds? Check out my post Do Transvaginal Ultrasounds Hurt? for practical info.)

Here’s a typical progression for a combo cycle with TI/ IUI:

  • Every day, CD 3-7: Clomid or letrozole (pills)
  • Every day or every other day, CD 8-12: Gonal-F, Follistim, or Menopur (injections)
  • CD 12: Ultrasound to check follicle development
  • (More injections as needed until trigger)

Depending on your diagnosis, your hormone levels, and your doctor’s experience with other patients, your doctor may prefer doing an injectables-only cycle instead of a combo cycle. In an injectables-only cycle, you would start injections on CD 3 or CD 5 and continue doing them daily until you were ready to trigger. Your doctor might make adjustments to the dose based on the results of your ultrasounds.

How do these drugs work, anyway? It’s not hard to figure out that Follicle Stimulating Hormone (FSH) is a hormone that stimulates follicles. (I wish everything had such a straightforward name!) You need FSH to develop follicles and ovulate.

Clomid and letrozole stimulate FSH indirectly, by lowering your estrogen. Injections give your body FSH directly (or, in the case of Menopur, FSH + LH). That’s why injections might work for you if Clomid or letrozole alone didn’t.

Here’s where I would ordinarily say something about my experience with combo cycles… except I never did a combo cycle. I responded well to letrozole on its own, in the sense that I had one or two decent follicles each time and ovulated with the help of the Ovidrel trigger.

But I never got a positive pregnancy test. After five unsuccessful letrozole cycles (two with IUIs), I switched to injections. (For more info on these options, see When to Consider Moving to Injectable Fertility Meds.)

I’m not sure if my doctor just wasn’t a fan of combo cycles, or if she thought that they wouldn’t be helpful in my case. But I learned a lot about combo cycles for this post, so keep reading!

Combo Cycles With IVF

Combo cycles can be done with IVF, although they are less common than with TI/ IUI cycles. Your doctor might recommend a combo cycle if you’re a low responder or you have diminished ovarian reserve (DOR).

Women diagnosed with DOR have a lower number of good eggs left, so they need to make the best possible use of the ones they have.

Another option for DOR is to do IVF with donor eggs instead of your own. Although the baby would not be related to you  genetically, you would still be able to experience pregnancy and childbirth.

There isn’t a cure for DOR, and ovarian reserve naturally drops over time as menopause approaches. Younger women who are diagnosed with DOR but are not ready to become parents may choose to freeze some of their eggs, to help preserve their fertility for the future. This would involve the early steps of IVF, from stimulation through egg retrieval.

Egg freezing (officially called oocyte cryopreservation) is also used to help cancer patients retain their fertility. This part is super interesting!

Combo Cycles for Onco-Fertility Preservation

Onco-fertility is an emerging field that combines oncology with reproductive endocrinology.

While cancer researchers have made amazing breakthroughs in the last few decades, the treatment for cancer — including chemotherapy, radiation, and surgery — can still cause long-term fertility problems.

In women, these treatments can mess with menstrual cycles, and even bring on premature menopause. In addition, radiation in the pelvic area can cause permanent damage to the ovaries.

Luckily, fertility treatment has also come along way. We now have technology at our disposal that would have been science fiction 30 years ago! Doctors of different specialties are joining forces to ensure that patients can beat cancer and still go on to have the family of their dreams.

Onco-fertility preservation allows women to freeze their eggs before they go through cancer treatment. Once the cancer is in remission, they can do IVF with those eggs.

That is an especially useful option for women who didn’t have a partner at the time they got the cancer diagnosis, but want to preserve their options for the future.

Women who do have partners (or are using donor sperm) may be able to freeze embryos instead. Embryos tend to survive the freezing and thawing process better than eggs, especially for older women.

And remember, when fertility doctors say “older,” they mean over 35. I know, it’s not fair! The post Should You Do a FET if You Are Sick? has more details about this.

Sadly, some cancer treatment can damage the uterus to the point that the woman is unable to carry a baby, regardless of egg quality. And some women with ovarian cancer (or other serious medical conditions) end up needing a hysterectomy.

But even in these cases, women may be able to have biological children if they have frozen eggs or embryos available and are open to surrogacy.

The hope is that the woman responds really well to the first round of stimulation drugs and is able to freeze plenty of high-quality eggs before undergoing cancer treatment.

But beating the cancer in the first place is always the highest priority. How long they can afford to wait before beginning cancer treatment is an important discussion that patients should have with their medical team. It may not be safe to delay chemo or radiation for several months to get a successful egg retrieval.

But anyway, back to combo cycles! When women are doing a stimulation cycle for fertility preservation, doctors often have them take letrozole every day.

Some reproductive cancers — such as breast cancer — respond to elevated estrogen, so the letrozole helps to keep the estrogen level low. (Fun fact: Letrozole was originally developed as a breast cancer drug. Ovulation induction is actually an off-label use for letrozole. My post Are Letrozole and Femara the Same Thing? has more info.)

Men get cancer too, obviously, and treatment for testicular cancer can damage their fertility as well.

Luckily, collecting and freezing sperm is more pretty straightforward, at least compared to collecting eggs. Even in cases where the sperm count is extremely low, the sperm can be collected using a minor surgical procedure.

One of my friends has had two children thanks to sperm harvesting and IVF. In their case, the male-factor issue was due to thyroid disease rather than cancer. Sperm harvesting can also be done with men who had previously had a vasectomy, although the actual procedure is a bit different.

I should point out that not every type of cancer treatment causes fertility-related complications. Cancer patients and survivors should talk to their medical teams about their individual situation. They should definitely not assume they’re infertile and throw all their birth control out the window — at least not if they are trying to avoid pregnancy!

For more information about onco-fertility, check out Save My Fertility from the Oncofertility Consortium.

Conclusion

OK, I got a little carried away with that cancer info! The upshot is that doing a combination of pills and injections can be an effective way of stimulating the ovaries, especially for women who didn’t respond to Clomid or letrozole by themselves, women with diminished ovarian reserve, and women who are trying to preserve their fertility before undergoing treatment for cancer.

This post was last updated in May 2020.