Fertility Preservation for Oncology Patients: Insights from Dr. Sokalska 

Dr. Anna Sokalska, MD, PhD, is a Clinical Assistant Professor in Obstetrics & Gynecology, specializing in Reproductive Endocrinology and Infertility. With a clinical focus on fertility preservation, IVF, and reproductive endocrinology, Dr. Sokalska is board-certified in both Obstetrics and Gynecology (2017) and Reproductive Endocrinology and Infertility (2021) by the American Board of Obstetrics and Gynecology. She completed a fellowship in REI at the Hospital of the University of Pennsylvania (2019) and a residency in Obstetrics and Gynecology (2016). Dr. Sokalska received her medical degree from Poznan University of Medical Sciences in Poland (1999). 

LEVY Health

What are the available fertility preservation techniques for oncology patients, and how do you decide which is best for each individual?

Dr. Sokalska

We have four main methods of fertility preservation for patients planning to undergo gonadotoxic treatment, with oocyte cryopreservation (“egg freezing”) and embryo cryopreservation (“embryo freezing”) being the gold standards. Egg freezing may be a good option for single women who are not interested in using a sperm donor or are not in a stable relationship. It gives them reproductive freedom. Embryo banking is better for couples who strongly desire to have children together.

The third method is ovarian tissue cryopreservation, which is the number one choice for prepubertal patients or those who need to start chemotherapy immediately. It involves surgically removing ovarian tissue, freezing it, and reimplanting it later. This method was experimental until December 2019, when ASRM removed the experimental label. However, it has lower success rates due to so-called reperfusion injury and loss of a significant number of oocytes in the transplanted ovarian cortex. Approximately 200 children have been born worldwide from this method. This method is not recommended for patients with cancers that may metastasize to the ovaries or involve the ovaries directly, such as ovarian cancer, or hematologic malignancies (like leukemia).
The fourth method is ovarian suppression. The literature on the protective effects of GnRH analogs and ovarian suppression is conflicting, with some studies suggesting GnRH analogs may offer potential protection only for breast cancer patients specifically. The weakness of many studies evaluating the effectiveness of the protective function of GnRH analogs is using the return of menstruation as the primary outcome and a surrogate marker of fertility.

LEVY Health

How does each type of cancer treatment affect fertility, and what measures can be taken to mitigate these effects?

Dr. Sokalska

Chemotherapy affects ovarian reserve, with alkylating agents (e.g., cyclophosphamide) being the most gonadotoxic. The extent of damage to the ovarian tissue is dose-dependent, with higher dosages being more harmful. The Cyclophosphamide Equivalent Dose (CED) calculation may help to predict infertility risk based on the type and dose of chemotherapeutic agents. The CED ranges estimating the risk as minimal, high, or extremely high are different for prepubertal and postpubertal patients. Radiation’s impact depends on the radiation field, radiation type and dose, with pelvic radiation being the most harmful to the ovaries. Even low doses, like 2 Gy, can cause the loss of half of the follicles. The uterus is less sensitive, and irreversible damage was observed with radiation dose 45 Gy. If high pelvic radiation is planned and eggs or embryos are being frozen, discussing the potential for a future gestational carrier and completing FDA testing should be considered.
Radiation of the intracranial structures, particularly the pituitary gland and hypothalamus, can affect FSH and LH production, but this may be overcome by administering gonadotropins during an IVF cycle.
Fertility preservation should be done optimally before starting treatment. Another method to mitigate the gonadotoxic effects of radiation is ovarian transposition. Unfortunately, moving the ovaries outside the radiation field, above the pelvic brim, is not always 100% effective due to failure of the surgical transposition or scattered radiation.
Early referral to a reproductive endocrinologist is crucial, as fertility preservation can be completed in 2-2.5 weeks, often before oncology treatment begins. Oncologists should not hesitate to refer patients to Reproductive Endocrinologists (REIs) promptly. Time is of the essence.

LEVY Health

What are the costs of fertility preservation and how often are these procedures covered by insurance?

Dr. Sokalska

Coverage varies by insurance plan and state, with some states mandating fertility preservation for patients at risk of infertility due to gonadotoxic treatment, while others provide partial or no coverage.

• Seventeen states currently have complete coverage.
• California has partial coverage, with some insurance plans obligated to cover fertility preservation for patients undergoing gonadotoxic treatments due to California Senate Bill 600.
• Medi-Cal patients in California often pay out of pocket

Stanford offers a 50% discount for self-pay cancer patients. There are available programs like Heart Beat and LIVESTRONG sponsoring medications for IVF cycle for qualifying patients.
More work is needed to improve coverage and access to fertility preservation, and I’m hoping that the landscape will change over time in California and other states.

LEVY Health

How do you coordinate fertility preservation plans between reproductive endocrinologists and oncologists?

Dr. Sokalska

As the director of Stanford’s fertility preservation program, I have dedicated time to see cancer patients within 24-48 hours of referral. Over time, I’ve established relationships and collaboration with oncology divisions within Stanford and outside cancer centers to facilitate an efficient workflow.
Providing outreach and having an established system is key to connecting oncologists and reproductive endocrinologists. It takes time to build these relationships and create a smooth referral process. However, we are likely still missing patients from community hospitals and those far away from academic institutions, as there is no easy way for them to be referred to our program. Patients may have to find our contact information online and reach out themselves, which creates extra obstacles and delays potential fertility preservation procedures.
I collaborate closely with oncologists to communicate treatment plans, understand timelines, discuss potential risks and expectations. Easy and efficient communication is essential.
Being readily available and having a dedicated Oncofertility Nurse Practitioner (Robyn Service, NP) significantly helps decrease stress for patients during this extremely challenging time.
We also follow up with patients who did not have a chance to proceed with fertility preservation before gonadotoxic treatment. They still may have a chance to preserve fertility after cancer treatment, while undergoing surveillance, or if they are not yet ready to build a family.

LEVY Health

What options are available for using preserved gametes or embryos after cancer treatment, and what are their success rates?

Dr. Sokalska

The success rates for using preserved eggs or embryos are comparable with elective fertility preservation. For patients who cannot carry a pregnancy, like those with advanced stages of cancer requiring lifelong therapy, a gestational carrier is an alternative.

LEVY Health

How do you address fertility preservation in young patients or those with genetic predispositions to cancer?

Dr. Sokalska

Genetic testing is widely offered to cancer patients. If a gene is identified, the patient will have (in majority of the cases) an option to test embryos for the disordered gene and select an unaffected embryo for transfer.

LEVY Health

Which methods are there to predict how much ovarian reserve will be affected by treatment, and how likely a pregnancy is after recovery?

Dr. Sokalska

Several factors are helpful to estimate the impact of the treatment on fertility potential after gonadotoxic treatment. These are: patient age at the time of the diagnosis, puberty status (prepubertal vs. postpubertal), initial ovarian reserve, type of the treatment, and dose calculated based on Cyclophosphamide Equivalent Dose (CED). Having a CED below 4 indicates minimal risk, 4-8 significantly increased risk, and over 8 very high risk of infertility.
If prolonged treatment is planned, the natural decline of fertility due to aging should also be considered. A perfect example is patients diagnosed with breast cancer. After initial chemotherapy or chemoradiation, they may receive adjuvant hormonal treatment for several consecutive years. Based on the results of the POSITIVE trial published in May 2023, in the early stages, hormone-positive breast cancer patients, oncologists are comfortable with hormonal treatment interruption (usually after 2 years of completed hormonal therapy) to attempt pregnancy. However, this delay means a 38-year-old at the time of diagnosis would be 40 when trying to conceive. The decline in oocyte quality and chance of having euploid embryos may be significantly lower. Thorough counseling on scenarios and options is crucial.

LEVY Health

Thank you so much for sharing your insights and experiences Dr. Sokalska!