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      Now that nivolumab is approved in the adjuvant setting, and more than likely BRAF/MEK is also likely to follow, how has/will this change your practice in terms of recommendations regarding family planning for appropriate patients?

      I feel we have entered unchartered territory……


        I would completely agree. Just recently had a patient who recurred in the lymph nodes underwent surgical resection and now will start adjuvant nivolumab. Had to have a very difficult discussion about discontinuation of breast feeding as well as future fertility as she really would like to have more children. Not a conversation that came easily.

        I believe in the patients for whom this is applicable this will be an important discussion upfront and included in the pretreatment teaching as with any other expected side effect.

        Great question!


          This is a very relevant issue, especially in the adjuvant setting. This came up for us recently when a 34 year old woman with Stage IV melanoma resected to NED (no evidence of disease) was going to start adjuvant ipilimumab. She was recently married and asked about having children. In discussion with her PCP, she was referred to a fertility specialist who felt immunotherapy itself would not impact her ovarian reserve, but her advancing age could as she awaits completion of therapy and then more time to ensure she does not recur. For that reason, embryo cryopreservation could be considered. One of our concerns was that development of hypophysitis from I/O therapy may make in vitro fertilization difficult, but that was not felt to be a major concern as gonadroptropins would be used in this setting.

          Here is another related question – what are your recommendations about pregnancy for females with a history of Stage III or Stage IV melanoma resected to NED?


            This is such a challenging issue. We had a patient on adjuvant ipi who developed hypophysitis. She has been off treatment for almost a year, and she would now like to conceive. This is definitely unchartered territory for us, her OB and her Reproductive Endocrinologist. Beyond the hypophysitis, we know that the immune system plays a pivotal role in pregnancy and that there are checkpoints involved (PD-1/PDL-1 being one of them) to prevent the mom’s immune system from attacking the fetus. If a patient is having a durable response to immunotherapy, is the mom’s immune system, in that case, going to be too upregulated to sustain a pregnancy?…….There are certainly lots of unknowns in this realm.


              Given the unknowns with regard to fertility issues and ICIs and targeted therapies; we have been counseling patients about the possibility of sperm/egg harvesting. I have to be honest and say this is a little unsettling to tell patients we “just don’t know”. Sperm banking, technically is relatively low tech; however, egg retrieval is a bigger deal (admittedly I know next to nothing about it). The ramifications of this recommendation, I imagine, could be significant (emotionally, physically) not to mention the costs! As alluded to above, this tends to pertain to the adjuvant setting primarily. In the metastatic setting; that conversation is entirely different.

              Couple questions:
              1) Does anyone know if insurance will cover costs for fertility (male or female) counseling for patients in the adjuvant setting. Since this is not “antineoplastic chemotherapy” I would fear it would not be covered at all.

              #2) Does anyone know of a fertility specialist at their institution (or anywhere else) that may be willing to act as a resource? It would be great to have some experts weight in on this.

              #3) What is the responsibility of Pharma in these situations? Can they release data about any post-Rx pregnancy complications or infertility issues s/p Rx on ICI or targeted therapy (post marketing data I would suspect) or data from expanded access trials.

              I would appreciate any insight anyone has to offer. These situations are challenging; and I feel like a fish out of water.


                Great questions and very relevant right now with increased adjuvant options. Unfortunately, I am not well versed in this topic, but I will share what I know.

                I believe that it will depend on a patient’s insurance whether the cost of fertility counseling is covered. I recently had a patient in this situation; the cost of counseling was covered, but not the fertility preservation (egg harvesting or IVF). And it is incredibly expensive (one patient told me $10-20,000).

                We have referred patients to a nearby IVF center for counseling. However, it would be really helpful to identify a resource within the institution.

                The idea of asking Pharma about their experiences is a good one. It sounds like we should contact our reps and inquire about post marketing data. We have to start somewhere to learn about this very important issue!



                  Insurance coverage for IVF and fertility treatment in general varies by state and by insurance plans. There are certain states that are “baby states,” and fertility coverage is mandated. These include Mass and IL (that I know of). I know that some larger West Coast companies that are progressive are providing fertility coverage for employees as well. Unfortunately, insurance plans usually don’t differentiate between needing fertility preservation for cancer or for general infertility – a plan has fertility benefits, or it doesn’t. It’s sad, as an egg retrieval for egg harvesting is tens of thousands of dollars (usually $20K plus). The meds alone are $5K plus. Sperm banking, on the other hand, is relatively cheap….several hundred dollars plus storage fees that are probably around several hundred per year. Another caveat is that a patient (female) has to have enough time before treatment to go through the stimulation/egg harvesting process. It’s easier for males, as sperm banking is usually a one-day affair.

                  There is an OncoFertility Consortium that I believe is run out of Northwestern. One reproductive endocrinologist that I know of that specializes in treating cancer patients/fertility preservation is Dr. Laxmi Kondapalli at Colorado Center for Reproductive Medicine. There might be a few others across the country, but it is a very small group, for sure. There is a definite need for more of them as we diagnose and treat (and hopefully cure) patients that are younger and younger.

                  As for the responsibility of pharma…..I don’t know, but I would think that they are required to report any relevant info in the post-marketing setting.


                    Thanks Mollie, for that wealth of info.!!

                    Clearly cost is inhibitory for many (or most). I’m sure with time, this will become a greater issue prompting more and more attention being directed at exploring this issue.


                    I am hoping that OncoEndocrinology will become a specialty such as oncodermatology has in response to the oncology patient community needs. I suspect the development of a specialty will take some time, but the long term endocrine effects are across the cancer spectrum now.
                    Fertility preservation and long term planning as noted above can vary state to state and insurance plan to plan, sometimes at great personal cost. We will only find out more by doing research and following this population of patients.


                      Yes! It’s certainly something that needs more advocacy, particularly as more and more young patients are diagnosed with cancer and hopefully cured from cancer. Not to mention the fact that more women are delaying childbearing, so the odds that a woman will be diagnosed with cancer before having children increases with that in mind.

                      I know that when we’ve referred patients to fertility clinics, they do expedite getting these patients in for consultation. However, it’s one more piece of the puzzle to make the circumstances even more complicated and overwhelming, not to mention being cost prohibitive for many.

                      And, the fact that so few fertility specialists actually specialize in the Oncology patient creates another barrier. We know that many ancillary providers are not familiar with newer oncolytics (IO, for example), so it’s possible that many fertility experts are not either. It’s scary to think about that, especially with an IO patient who has completed therapy in the adjuvant setting, for example. Just what could the long-term ramifications on carrying a pregnancy be? We all have a lot to learn.

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