Fertility Preservation in Women with Cancer

Clinical Update

Discover the latest advancements in fertility preservation for women with cancer at Tree of Life Fertility Center, where innovative medical solutions support future family planning.

Cancer survival rates have increased over the past 20 years thanks to advances in cancer treatment. The 5-year relative survival rate for all cancers combined is more than 83 percent in women aged 15 to 44. For children aged 0 to 14, the overall 5-year relative survival rate is more than 81 percent in the United States. The survival rate for Hodgkin’s disease in the pediatric population is more than 95 percent. Long-term relative survival rates are greatest among women aged 20 to 29 years when compared to other age groups.In the United States, 4 percent to 5 percent (55,000/year) of newly diagnosed cancer patients are under age 35. Five percent to 7 percent (11,000/year) of patients diagnosed with invasive breast cancer are under age 40. In addition, there are approximately 450,000 cancer survivors who are of reproductive age. Infertility due to cancer therapy can cause significant psychological stress and directly influence the quality of life of cancer survivors. At least 75 percent of young women, without children at the time of cancer diagnosis, desire to have children in the future. Among adolescent girls diagnosed with cancer, 80 percent of them are interested in fertility preservation. In addition, cancer survivors prefer to have their own biological children. Therefore, fertility preservation is one of the most important issues in women diagnosed with cancer, as aggressive cancer treatment can cause premature ovarian insufficiency (POI). Most women of reproductive age wish to preserve fertility, but either: 1) fail to receive adequate information about fertility preservation or 2) fail to be referred to fertility specialists when appropriate.

Infertility Problems. Portrait Of Upset Young Indian Couple Looking At Negative Pregnancy Test While Sitting Together On Couch At Home, Caring Eastern Husband Comforting Depressed Wife, Free Space

Currently available fertility preservation strategies for females include:

Gonadotropin-releasing hormone agonists (GnRHa)
Cryopreservation of mature oocytes (eggs) or embryos
In Vitro Maturation followed by cryopreservation of mature oocytes
Cryopreservation of ovarian tissue

Embryo/Oocyte cryopreservation (with controlled ovarian stimulation)

Embryo and mature oocyte cryopreservation are well established technologies for fertility preservation in cancer patients. Embryo cryopreservation has shown positive results for approximately 40 years. The current live birth rate per transfer is around 50 percent in women younger than 35 years of age. The success rates with oocyte cryopreservation have significantly improved since past 10 years. Current live birth rates from a series of cryopreserved oocytes are comparable to those in cryopreserved embryo transfer cycles—especially if those cryopreserved oocytes have undergone vitrification (a freezing method that requires a high concentration of cryoprotectants along with an extremely high cooling rate).As the process of embryo cryopreservation takes two weeks or more, it may not be applicable to patients who require immediate cancer treatment. In addition, this process is not practical for patients without partners or who do not want to use donor sperm. Furthermore, gonadotropins (the main medication for ovarian stimulation) increase peak estradiol levels, which may be contraindicated in patients with breast cancer—especially those with ER+ status.Oocyte cryopreservation is a valuable and practical strategy for fertility preservation regardless of the marital status. Especially, it is ideal for women who do not have a partner and do not want to use donor sperm. It also can be a suitable option for women who do not want to create embryos for storage. This procedure requires controlled ovarian stimulation (COS) and egg retrieval—the same process required for embryo cryopreservation. Oocyte cryopreservation, however, does not require in vitro fertilization, and can avoid ethical and religious issues.

Molecule of DNA forming inside the test tube equipment.3d rendering,conceptual image.

In vitro maturation followed by cryopreservation of mature oocytes

To date, immature oocytes (GV stage) do not survive well after cryopreservation, therefore, in vitro maturation (IVM) of GV stage oocytes to mature (MII stage) oocytes followed by vitrification of those matured oocytes appears to be more practical (although it requires expertise). The advantages of retrieving immature oocytes without COS include no delay of cancer treatment and no increase in serum hormone levels (safe for hormone dependent cancer).

Ovarian tissue cryopreservation

Ovarian tissue cryopreservation is the only option for: 1) pre-pubertal girls 2) patients who cannot delay cancer treatment or 3) patients who are unwilling to undergo COS. Patient age is crucial as the chances of restoration of ovarian function and fertility are closely correlated to the number of follicles in the ovarian tissue (which declines with age). In general, it is not recommended to cryopreserve ovarian tissue if the patient is older than age 38. Another crucial factor for the success of ovarian tissue cryopreservation is the expertise of the laboratory.

The main advantages of ovarian tissue cryopreservation are:

1) It can permanently store abundant amounts of immature oocytes for future use2) It can restore fertility as well as endocrine function after ovarian tissue transplantation3) It does not delay cancer treatment4) It does not increase serum hormone levels

For ovarian tissue cryopreservation, one whole ovary (or a portion of it) is harvested using laparoscopic surgery under general anesthesia. It takes approximately one hour to complete surgery. As this is an invasive procedure, surgical complications can occur. Most times, cancer therapy can be resumed two to four days after surgery. The harvested ovary is processed into thin sections of ovarian cortical tissue before cryopreservation. Cryopreserved ovarian tissue (usually with slow freezing method) is then stored in liquid nitrogen until use.When the patient is ready to have a child, she may need another surgery to transplant frozen-thawed ovarian tissue back to her own body. To date, more than 200 viable babies were born worldwide after ovarian tissue transplantationAlthough rare, ovarian tissue can harbor cancer cells—especially in cases of hematologic malignancy, such as leukemia. Awareness and recognition of the risks of reintroduction of cancer cells are crucial for the safety of ovarian tissue transplantation. To date, hundreds of ovarian transplantations have been successfully performed in women with no documented cases of cancer cell reintroduction. Cases include women with various cancers, such as breast cancer, cervical cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and Ewing sarcoma. Despite these results, safety concerns for this procedure will remain until highly reliable screening methods to detect minimal residual disease in ovarian tissue are developed.

Female embryologist works with biomaterial for cryopreservation

Things to remember

1) Most women of reproductive age desire to preserve fertility in order to have a family in the future2) It is important to address fertility issues when counseling the patient, preferably immediately after cancer diagnosis3) In general, there is not much time between the time of cancer diagnosis and treatment. If fertility preservation is desired, it is recommended to refer the patient to a fertility specialist once a cancer diagnosis is made (without delay)4) Strategies for fertility preservation should be carried out based on each individual patient case, taking into account diagnosis, treatment, age, marital status, etc.S. Samuel Kim, MD

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