Navigating Fertility After Cancer

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As a patient navigator at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Kristin Smith guides newly diagnosed cancer patients through a hopeful process – preserving their future  ability to have children in the face of life-saving, fertility-threatening treatments. We spoke with Smith about her unique position, what fertility preservation options are currently available for women, and the exciting prospects that lie ahead.

Kristin Smith (photo by Huge Galdones of Galdones Photography)Kristin Smith (photo by Huge Galdones of Galdones Photography)How do you start developing a fertility preservation plan for a patient?
When I meet with someone, we talk about her cancer, the treatment she will likely get, and how damaging it might be to her fertility. And by that I mean how damaging it will be to her ovarian reserve, or the amount of eggs in [her] ovaries.

Men have somewhat of an advantage, because they’re constantly producing sperm. As a female, we’re born with all of the eggs we’re ever going to have, and we have no way to make new eggs. A female’s fertility is dependent on how many eggs she has in her ovaries and the quality of those eggs. Generally, a female is in her peak fertility in her late teens to early 20s. As a female ages, the ovarian reserve naturally declines until the female becomes naturally infertile, [in her] late 40s to early 50s.

Specific types of chemotherapy and radiation treatments can destroy the ovarian follicles (ovarian follicles mature and support an egg until ovulation) and predispose a female to premature menopause and infertility. Another way to think of it is that chemotherapy or radiation can take you from having the ovaries of, say, a twenty-nine-year-old and make you have the ovaries of a forty-two-year-old. Each treatment is going to affect a patient differently, and [this] depends on many factors. It’s important for each patient to have a tailored approach to fertility preservation so her best interests are kept in mind.

What options are currently available?

There are three options a woman has to remove her eggs from her body before she receives treatment that will negatively impact her fertility.

[First], she can do egg or embryo freezing. These are fairly similar in terms of [what] goes into it up front. We time the start of it with her menstrual cycle. The female will inject herself with fertility medications, which tell her ovaries to recruit and mature multiple eggs instead of one egg. It could be anywhere between five to twenty eggs. As she’s maturing these eggs, a reproductive endocrinologist (REI) is continuously monitoring her with trans-vaginal ultrasounds and blood work to measure estrogen levels. This monitoring ensures that the patient is safely stimulating her ovaries. When she gets to a specific point in the stimulation, the REI will perform an egg retrieval in an outpatient setting.

We put her into a conscious sedation, and use that same trans-vaginal ultrasound to visualize her ovaries. While you’re looking at the ovary, you can see the follicles. The physician will take a needle, which is run through a needle guide on top of the ultrasound, to literally poke a hole in the back wall of the vagina, into the ovary, and then into the follicle.  The REI uses it to suck out all of the liquid and the egg from each and every follicle that he or she can see.

Once our embryology lab gets these eggs, they can do one of two things. First, they can just freeze the eggs. Or, they can mix the eggs with sperm, create embryos (in vitro fertilization), and then freeze the embryos. Embryo freezing is something that’s been done at Northwestern for 20+ years – it’s something that we’re very comfortable with. We have great success rates with it.

Egg freezing is relatively new, and the American Society of Reproductive Medicine (ASRM) has stipulated that egg freezing still be considered experimental. The reason that it’s more difficult is because an egg is a little more delicate than an embryo. An egg is one cell, it’s full of water, and during some freezing procedures, if they’re not done correctly, ice crystals can form within the egg and destroy it. We use a process here at Northwestern called vitrification, which is a flash-freezing process, and it has higher success rates of subsequent thaw and fertilization compared to a slow freeze, which is how most centers cryopreserve embryos.

The downside to embryo freezing is that you need sperm. For a lot of patients who are young adults, they just haven’t decided on whom they’re going to pick to be the father of their future children.
We’ve had quite a few patients do both egg and embryo banking. If a patient is partnered with someone and they aren’t married yet, but they still would like to create embryos, we ensure that [they see] a lawyer to draft a legal contract so that both parties are protected, should anything happen to that relationship.

The biggest drawback to egg and embryo freezing is the time it takes to undergo this process. Often times, it takes two to three weeks for a patient to go through a stimulation and retrieval. Sometimes this time window isn’t an option for a patient who needs to begin treatment immediately.

Are there options for patients who don’t have this time window?
The other option is ovarian tissue freezing. Here at Northwestern, we’ve had around 25 cases of tissue freezing. A good example of a patient who would undergo [this procedure] is someone who has just been diagnosed with a type of very aggressive cancer and the chemotherapy they’re going to get will most likely deplete their ovarian reserve. Oftentimes, alkylating chemotherapy is used to treat aggressive cancer. “Alkylating” refers to a specific class of chemotherapy that works directly on the DNA of a cell to prevent cellular division. When DNA is altered like this, the cell cannot multiply, and this can often affect gonadal cells in humans. When we’re looking at different chemotherapeutic agents, there are certain ones that are more benign than others, and for us the alkylating agents are kind of the “big bad.”

For ovarian tissue freezing, an entire ovary is surgically removed from a patient. This surgery is done as an outpatient procedure, and is usually done laparoscopically. Once the ovary is removed, scientists in a lab remove the outer edge of the ovary, the cortex. The cortex is where all of the primordial follicles – the very young and immature follicles – are located. Scientists cut the outer edge into cortical strips and then freeze those strips. The hope is that, in the future when the female is ready to attempt a pregnancy, you could take a portion of those strips, thaw them, sew them back together to look almost like a quilt, and then transplant that tissue back into the vascular bed where the ovary used to sit.

To date, there have been over a dozen documented pregnancies resulting from this type of technology (at other facilities, not at Northwestern). However, we don’t know the denominator to those successes, so we can’t put a number on how often this type of procedure results in a live birth.

For some patients, like a leukemia patient, you wouldn’t be able to do this because ovarian tissue is leukocyte rich, and there’s a chance you could reseed that patient with her cancer. So there’s only a small handful of patients for whom that transplant of tissue would be something her physician would be comfortable with.

Are there other options being researched at Northwestern?

Teresa Woodruff’s lab (chief of the Division of Fertility Preservation) is working on in vitro maturation. We take one of those cortical strips, thaw it, and isolate a primordial follicle. That follicle gets put into a 3D alginate (a gelatinous substance extracted from the walls of some types of algae) system, so that the egg can grow and mature within that 3D alginate sphere. The hope is that we would then get a mature egg, which we could mix with sperm in vitro to create an embryo, and then transfer that embryo into the female’s uterus. That has been successful in mice. We’re working now on non-human primates, but we're not sure when we’ll be ready for humans.

You mentioned that you also work with patients and families at Children’s Hospital. What are some of the unique challenges that surround discussing fertility preservation in pediatric cases?

It is a very different discussion when you’re talking to a parent about saving their child’s life and then also talking to them about that child’s fertility in the future. It's hard enough on a parent who has a three-year-old who has just been diagnosed with cancer, and then you’re also asking to take out one of her ovaries for an experimental procedure. It’s a very delicate and difficult situation.

But, I think it’s really important that parents are at least given a consult and given the option! When I’ve met survivors of childhood cancers, there’s anger and resentment in some of these patients who were never talked to about their fertility. Imagine being a survivor of a childhood cancer, now in your late 20s or early 30s, ready to start a family, and finding out you can’t because of your cancer treatment when you were a child.  It’s a really frustrating position to be in, and we want all patients to have access to information and be able to make decisions based on that information.

There are a lot of long-term effects that go with cancer treatment. And our rates of survival are getting so much better, especially in pediatrics – most of our pediatric patients have about an 80% survival rate. That’s phenomenal, what we’re able to offer our patients now. But a lot of long-term survival issues are now coming up, whether she has premature ovarian failure, bone density issues or hormonal issues. There are issues like this that really need to be discussed and explained to patients.

The Fertility Preservation Program here is much more focused on ensuring that all of our patients get a consult, and have all of their options presented to them. It’s not necessarily that all of these patients have to go through or are appropriate candidates for fertility preservation. We just want our patients to feel informed, and feel that they’re armed to make what they feel is the best decision at the moment.

To learn more about the Fertility Preservation Program, part of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, visit their website.

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