While advances in treatment have certainly made parenthood an option for many, there are still risks to consider, says Dr. Lynn Savoie, Clinical Associate Professor in the departments of Medicine and Oncology at the University of Calgary. From stopping medication to monitoring for relapse, careful planning and medical guidance are key to ensuring a safe and healthy pregnancy. We asked Dr. Savoie what people living with CML need to know about starting a family.
How does CML and its treatments affect fertility?
There are two parts to that: There’s fertility, which is the ability to procreate, but there’s also the possible effects on the fetus. As far as we know, there is no fertility impairment from CML, or from the medication (TKIs or interferon). The concerns are to the fetus, to the unborn child.
With male CML patients, there are no issues to fathering a child. With women, there are enough reports of an increase in birth defects in women who have taken a TKI while pregnant to suggest it is possibly teratogenic (a substance that negatively affects a fetus during pregnancy). This means that women should not take them in their first and possibly second trimester. There’s no specific defect that comes to mind with TKIs. It’s not like how thalidomide caused a very recognizable syndrome. It’s nothing like that. There are just more issues than average with children born to women who are taking TKIs.
Can women who are taking medication for CML conceive and carry a child to term?
It is possible. It absolutely has happened but it isn’t recommended. There have been issues in enough women that you’re rolling the dice a bit.
So, you would recommend that women stop taking their medication prior to getting pregnant?
Absolutely. For the best possible outcome, we ask our patients let us know when they are thinking of having a family. I usually recommend that they wait until their disease is as well controlled as it can possibly be before they try to get pregnant. If it’s unexpected, we ask that they let us know as quickly as possible so that plans can be made.
What are some of the risks of stopping medication for pregnancy?
The risks are that the patient will lose whatever response state they’re in. So, if a patient has only recently been diagnosed and only recently started on drug and has not achieved an undetectable disease state, if they stop a TKI, the leukemia could start to creep back.
If you’re undetectable and stop drug, there’s probably a 50 to 60% chance the leukemia will come back, just as in all the treatment-free remission (TFR) trials, right? It’s no different. So, the better the response, the more likely it is that it won’t come back. If it does start to come back while pregnant, it also depends: If you’re undetectable and it starts to come back in month four, five or six of pregnancy that’s different than if it starts to climb straight away in month one or two. If it comes back and is untreated, the concern is that it could progress to a more advanced phase.
What do you do in that situation? If a pregnant patient’s cancer appears to be returning?
Prior to getting pregnant, we recommend that patients stop drug for a month or two. Once they’ve stopped (and also during pregnancy) we monitor their molecular response with monthly PCRs, like we do with patients who are trying TFR. Then we look at the rate of rise and where we’re at in the pregnancy.
For sure, during the first three months, you wouldn’t want a woman to be taking a TKI; in the second trimester, it might be safe; in the third trimester, it is safe. So, if there’s an increase in the third trimester and it’s just starting to go up, maybe you wait. If it’s clearly going up in the third trimester, you could probably come back in with your TKI to get them back into response. If it’s in the first trimester, maybe even the second — this would be a discussion — the other option would be to use interferon.
Is that the case with all the current treatments for CML?
Yes, for the six drugs (the five traditional TKIs plus Asciminib), we would recommend all of those be stopped. If someone’s on interferon, which I don’t think many people are these days unless they have to be, that is safe in pregnancy. If we can get away without using anything, I think that’s best. There are better preparations of interferon than there were 30 years ago — people don’t feel quite as unwell on it now — but it does have some side effects that would not be pleasant on top of being pregnant.
Are there cases where pregnancy is just not advisable for CML patients?
Not really. Not for a CML patient who is responding well and has the normal life expectancy that we expect a CML patient to have. In very rare instances, where you’re dealing with patients who have never really responded well to the medication and — irrespective of pregnancy — you’re worried they could progress to blast crisis or accelerated phase, you would be very worried about those women. Not because of the effect of the pregnancy and the CML, but rather what happens if you’re pregnant and you progress quickly? If you’re six months pregnant and you go into blast crisis, it can be challenging to treat. You would need real chemotherapy and that’s a risk to the fetus.
For patients who want to preserve their eggs, when should that be done?
Ideally, it wouldn’t be done while they’re on treatment. Same with IVF, which would include sperm. There’s no great data to say you should wait six weeks, eight weeks or 10 weeks, but a few months might be advised. Having said that, you can safely get pregnant while on medication, so it probably doesn’t have an effect on the egg per se, the effect is on the fetus that’s developing, as we’ve said.
Would the procedure be the same as for any woman who is interested in IVF or freezing eggs?
In terms of the process of IVF or egg retrieval, it would all be exactly the same as a normal woman, absolutely, with just the caveat of monitoring that CML. Again, we would only recommend doing that when you’ve had a good response and can come off drug. Ideally, it would only be for maybe three months, not the nine months of a pregnancy, right? So, it’s less risky but we would only recommend doing it when you’re in really good control.
One of my young patients has met the criteria for TFR for a long time, but we decided not to do it until she was ready to have a baby. Now, she’s like, ‘Well, I’m over 30 and I don’t have a partner, so I’m going to freeze my eggs.” We’re doing her TFR at the same time. She came off drug for the egg harvest and she’s going to stay off because, so far, her disease control has been good.
What are some of the emotional challenges you’ve seen CML patients face on their fertility journey?
Treatment-free remission at any time is very stressful — you’re coming off drug and worrying if the leukemia is going to come back. Then you add in the emotional roller coaster of pregnancy and worries about your unborn child and it really compounds everything. We are lucky in Alberta that our patients can see their test results in real time, so they can see that PCR and track it themselves, which is reassuring. All my patients who are in TFR, pregnant or not, they go get that blood drawn and it takes two or three weeks to get those results and that’s very stressful, waiting to see if this is the month the disease is coming back. Then, a month or so later, they’ve got to go do it all again. That’s very stressful for patients. I reassure them that if anything goes wrong, I will call them. We usually have scheduled appointments, but if I get a result back five days before their scheduled appointment and it’s clearly going in the wrong direction, I won’t make them wait, if I can.
Do you have any advice on how patients can manage some of the anxiety surrounding fertility and family planning? Do you recommend counselling?
Definitely. At my cancer centre we have cancer counselors, if you will, who help people deal with their diagnosis and whatever loss that means for them. They also talk to their partners. I know a lot of our patients find having counselors who know a little about cancer is more helpful than a general counselor in the community, but I think any counselor is helpful if the patient can have a good relationship with them.
Because the patients we’re talking about fall into the window of what’s called AYA (adolescents and young adults), which is a group people are interested in, there are support groups that address their issues. So, it’s acknowledged that having cancer in that AYA defined group (typically age 15 to around 40) is very different than a 70-year-old having cancer. There are AYA supports in many cancer centres that we will also refer to because they deal specifically with that population. So, they have their own counselors as well.
Do the complexities surrounding CML and fertility affect the number of children a patient might be able to have?
It might limit the number. Patients might choose not to put themselves at risk for their own health, their future and their ability to be there as a parent to their already existing children (if they have them). Some patients probably choose to have fewer children and some decide not to go down that road at all.
Are there any concerns that some of the genetic issues associated with CML might be passed on to a child?
We reassure them that this is not hereditary. They should not avoid having children because they might pass it on.
Are there generally any issues with the delivery itself?
No, with respects to the mother, the delivery would be exactly the same.
What about surrogacy? Is that a route that many CML patients consider?
I’ve not seen it, but it could be an option for someone who did harvest their eggs or did a cycle of IVF and their disease was never really well controlled and they didn’t want to take that risk. I’ve not encountered that personally but I’m sure it has happened.
For those not interested in starting a family, are there any issues related to birth control that patients should know about?
It is absolutely as effective, that’s not a concern, but there are a few things to know. When people have active cancer — any cancer — there is an increased risk of blood clots early on. That’s something to keep in mind because hormonal birth controls can also increase your risk of blood clots. So, the risk of pulmonary emboli (blood clots that travel to the lungs) could be a bit higher in cancer patients. Some of the hormonal birth controls can cause problems with the liver, which some TKIs can also do.
Sometimes, when you have two medications that can cause something like that, you don’t know which one is causing what and maybe the two together are worse than each separately. So, we monitor the liver very closely. Most of the time, these are very low risk things but they are things that would cross our minds. Most women can be on birth control and TKIs and it is just as effective.