Fertility Preservation for Cancer Patients
Tailoring Treatment for a Cancer Diagnosis
Video Lesson
Experts you'll learn from
Director, Reproductive Survivorship Program
University of California San Diego Health
Professor of Obstetrics and Gynecology, University of New South Wales
Director of Reproductive Medicine, The Royal Hospital for Women
Written Lesson
Overview of Treatment Approaches
As we discussed earlier in the risk section, often fertility doctors need to make exceptions to their standard way of doing things to accommodate cancer patients. Our goal in this section is to summarize what those might be to catalyze a more nuanced discussion with your doctor.
In most cases, the objective is to adjust the process to help patients complete the fertility treatment process as quickly (but successfully) as possible to shorten the delay in receiving cancer care. This is often a function of two concepts:
- Shortening the delay to begin taking drugs and
- Shortening the amount of time on drugs in the lead up to the retrieval
In addition, doctors often need to make adjustments to mitigate the risk of exacerbating the cancer (e.g. heightened estrogen levels which can abet some cancers) or its byproducts (e.g. blood clotting challenges.)
The Basics on Fertility Drugs & Protocols
Gonadotropin is the injectable hormone used to encourage the ovaries to grow a large number of follicles to produce a large number of eggs. While gonadotropin is the critical drug in most every fertility treatment “protocol” (the assortment of drugs used in treatment), it’s not the only drug. Often two other types of drugs are needed to accompany gonadotropin: those that block eggs from “maturing” and being ovulated before they can be retrieved, and those that help trigger the eggs to mature so they can be retrieved. As you can see in our summary below, there are multiple drugs that can perform these two functions — the one that’s chosen dictates the protocol strategy. In some cases, a combination of both types of triggers may be used.
The Long Agonist & Antagonist Protocols
Historically, doctors have used a protocol called the "Agonist" or "Long Agonist" protocol which required patients to take an "agonist" to prevent eggs from maturing before they can be retrieved. As you can see below, the duration for suppression was long and began weeks before gonadotropin was initiated.
An alternative is the "antagonist" protocol where drugs called “antagonists” are used while overlapping with gonadotropin use. This approach stands to shorten the length of time the patient is taking drugs and provides an alternative to patients who are too many days into their cycle to likely begin taking suppression drugs.
While there are no large studies comparing the protocols against one another in cancer patients, the rates of success for fertility patients doing IVF tend to be comparable.
Progestin Primed Ovarian Stimulation (PPOS)
Another alternative is to consider a Progestin Primed Ovarian Stimulation (PPOS) approach. As you can see in the data below from China, in a small number of patients with endometrial cancer, the PPOS approach yielded superior pregnancy rates and comparable rates of recurrence versus standard approaches.
Random Start Protocol & Shortening the Delay to Start Drugs
Often the multi-week process of being on fertility drugs (to grow as many follicles and eggs as possible) is tied to a person’s menstrual cycle. This was true in the last examples we gave where both protocols were anchored and timed to the start of a patient’s menstrual cycle. Depending upon when a patient presents themselves to the clinic, this could result in hardly any delay or possibly a delay as long as a few weeks. If there’s likely to be a delay, doctors have the ability to use a “random start” protocol which, as the name implies, allows patients to start taking medications with hardly any delay, regardless of where they are in their menstrual cycle.
Below is data from a small study that’s largely reassuring: cancer patients on a “random start” protocol recorded similar rates of success (in this case, the number of eggs retrieved given their starting blood work). While the “random start” protocol required they be on fertility drugs another day-or-so longer, that was likely far superseded by the time saved in starting treatment without delay.
Unmedicated Cycles, Tamoxifen, Letrozole, and FSH Dosing for Estrogen-Sensitive Cancers
Gonadotropins tend to raise a person’s estrogen levels, which can be problematic for patients who have been given an “estrogen sensitive” (e.g. some forms of breast cancer) cancer diagnosis.
To avoid the risk associated with gonadotropins, some patients opt for an “unmedicated cycle” (no gonadotropins) and, while cancer recurrence rates remain low, the outcomes from these cycles tend to be disappointing (0.6 embryos created per retrieval in one single center study).
In recent years, doctors have had success allowing patients to do IVF with gonadotropins while coupling the regimen with tamoxifen, or better yet, letrozole. Below are the studies that have given doctors more confidence in these approaches, specifically amongst patients with certain forms of breast cancer.
When clinicians added a drug called tamoxifen (a drug that reduces estrogen’s impact) to an IVF cycle that included gonadotropins, breast cancer recurrence rates remained low but the fertility treatment outcomes improved, as you can see below. The study was small but encouraging.
Next, the same group of investigators decided to look at how including a drug called letrozole might impact results. While letrozole has the effect of helping to minimize estrogen levels, it also indirectly prompts the body to produce the same hormone as found in gonadotropin, possibly enhancing the results of the cycle. The results, shown below, showed adding letrozole to an IVF protocol may improve the results compared to adding tamoxifen to an IVF protocol, all the while holding down estrogen levels. While the study was not designed for rigorous follow-up, investigators noticed a higher percentage of cancer recurrence occurred in the tamoxifen group than in the letrozole group.
Now that we’ve covered whether it may be feasible for patients to take gonadotropin, a following question might be how the dose impacts rates of success? In breast cancer patients, investigators noted patients given a dose of 150 IUIs per day performed as well, and in some cases better, than those given a larger dose. Since terms like “low dose” or “minimal stimulation” tend to be discussed without a lot of specifics, we’d remind you this “lower dose” group was still taking 150 IUs per day.
Blood Clotting Considerations
Cancer patients may have challenges that relate to their blood’s ability to coagulate and so it’s important your doctor perform a platelet count and coagulation panel before starting treatment.
Some patients with a cancer diagnosis may be more likely to have their blood coagulate too easily. To combat this, some doctors may consider having a patient take Low Molecular Weight Heparin during their stimulation period and take it again briefly after their egg retrieval. As always, it’s critical not to take these drugs, or any other, without your doctor prescribing them.
On the other hand, other cancer patients (e.g. those with a blood, bone marrow or liver cancer diagnosis) may not have their blood coagulate quickly enough. This might present an issue during the egg retrieval and require doctors to be prepared for a platelet or plasma transfusion. Again, testing before treatment begins can be important.