Preserving Fertility in Patients With Lymphoma

Richard Anderson, PhD

Lymphoma treatments can drastically affect fertility and should actively be worked into treatment considerations for many patients, according to experts.

According to Richard Anderson, PhD, the Elsie Inglis professor of Clinical Reproductive Science and deputy director at the Centre for Reproductive Health and The University of Edinburgh, some lymphoma treatments can lead to infertility or difficulty conceiving, such as radiotherapy. Cytotoxic therapies are designed to kill growing cells, including the growing follicles in the ovaries. This can result in the loss of menstruation and potentially fertility all together. 

Fertility planning should be an essential part of the treatment discussion, according to Anderson. Steps can be taken to help preserve fertility, such as freezing eggs prior to the start of therapy.

In an interview with Targeted Oncology^TM, Anderson discussed how fertility is impacted by many lymphoma treatments, and what can be done to help preserve fertility in patients prior to treatment.

TARGETED ONCOLOGY™: Can you give an overview of how lymphoma treatments impact fertility?

ANDERSON: So, many chemotherapy treatments, damage female reproduction. The essence of it is that women are born with all the eggs they're ever going to have. They're all formed in fetal life. And so, you have this nonrenewable pool of primordial follicles, the non-growing follicles within the ovary, and over the course of reproductive life, they're progressively activated until ultimately, at the time of the menopause, there aren't any left. So, a lot of cytotoxic therapies will, by definition, are designed to kill growing cells, so that's particularly the growing follicles of the ovary. That will result in amenorrhea, loss of periods, and potential loss of fertility in women during treatment and a period of time afterwards. But the key thing is what's going on to the primordial follicle pool, because that will determine what potential there is for recovery, and how long that woman may have until her ultimate loss of fertility and menopause. The problem that we have in reproduction is that this primordial follicle pool is essentially invisible. You can only count those follicles by actually taking the ovary out and slicing it up, looking at it through a microscope in a lab, you can't do it clinically. The only tools we've got are things like having periods or not, or biochemically, things that reflect the growing follicle pool in the ovary. They are of course interrelated, but they don't directly tell us the number of eggs that that woman has at any time before, during or after treatments.

What treatments specifically impact fertility?

The main treatments that impact fertility in women are high doses of the alkylating agents. That's very relevant to the type regimens that are widely used for virgins, non-Hodgkin lymphoma. And of course, radiotherapy and actually that is perhaps one of the really bad news things for female fertility, because we're not only talking about the ovary. The uterus is also compromised by radiotherapy and that can be directed to the pelvis, to the to the uterus itself, or particularly in children, it can be scattered therapy from lower abdominal radiotherapy. This is one of the key issues that we face.

How should family planning be worked into treatment decisions?

It's now recognized as being an essential part of discussing treatment plans with patients, as to what might be the risks to them, and that for many young women are risks to fertility is going to be high on their list of serious concerns, and of course, young men as well. So, that is all part of the conversation that needs to be brought in with patients. It may be that the treatment plan is clear the situation clinically is such that this is the treatment that needs to be given. But, if that is the case, then the implications for fertility, it's essential for the patient to be aware of that, and therefore have the potential to do something about it in that short interval before treatment starts.

What tools do clinicians have to basically help a young patient preserve some of their fertility during and after treatment?

So, in terms of preserving fertility, storing sperm, freezing sperm has been around for a long time. But one of the problems for that, and it does very much relate to patients with lymphoma, is that often spermatogenesis is already markedly impaired before treatment even starts. A lot of guys coming along to store sperm will find that their sperm count is already very low. And of course, they may be unwell in themselves, that may preclude or may compromise, being able to store a specimen. For women we've had embryo freezing as part of an IVF procedure for a long time. But I guess now probably for a dozen years or so, egg freezing using vitrification, so ultra-fast freezing of eggs, has become the norm and has revolutionized the success with that. Because with slow cryopreservation techniques, eggs just didn't survive that. But with vitrification, a frozen egg is almost as good as a fresh egg, which has really been revolutionary to the whole field of reproduction.

I would like to touch on the use of GnRH agonists to help preserve fertility. The evidence that that is an effective form of maintaining fertility, perhaps it comes from breast cancer. There have been some large, well-designed, well-conducted studies in women with breast cancer that showed that this approach does reduce the risks of premature ovarian insufficiency. In lymphoma, that is not the case the data do not exist to support that this is an effective treatment. So, there have been trials, it hasn't been shown that they're effective. The reason for that is isn't clear at the moment. It may be because of the wide range of treatments that are used for lymphoma, from very toxic to not very toxic, and perhaps you need a sort of a sweet spot of a degree of toxicity but not too much for that GnRH agonist approach to actually be able to have some fertility-preserving efficacy there. And it's also important, I think, to remember that these excellent studies in breast cancer, there outcome was premature ovarian insufficiency. It wasn't fertility. So, although some of them did have a little bit of fertility data, it wasn't the primary outcome of the study.