Testing Female Fertility After Cancer

Our recent blog on the reproductive options for cancer survivors who do not receive fertility preservation raised some interesting questions. As mentioned in the post, while there is no definitive way to determine if anyone is fertile prior to attempting to conceive, some medical testing can give a good indication of future reproductive potential. Dr. Jennifer Hirshfeld-Cytron, recently discussed these tests with us and said, “what a woman does if she had cancer is the same as if she is over age 40,” and wants to learn about her fertility. A variety of hormonal tests are available that may give such clues for women, often as indicators of the ovarian reserve, the potential of an ovary to produce eggs capable of fertilization.

Two hormone tests, for follicle-stimulating hormone (FSH) and estrogen, are often initially performed to determine reproductive potential in women. FSH is a hormone that stimulates the growth of follicles in the ovary and, when measured the third day after a woman begins her menstrual flow, can indicate potential fertility. Most fertile women have FSH levels below 10 mIU/ml at Day 3, although exact clinical determinations can vary. Menopausal women and cancer survivors who have lost reproductive ability may have elevated FSH levels at this time. Estradiol, the primary type of estrogen in women, is also low at Day 3 in most fertile women.

Another important hormone, inhibin B, can be measured to indicate fertility. Inhibin B is produced by antral follicles, small follicles that require FSH to survive. Interestingly, as small antral follicles grow, they produce inhibin B, which then inhibits FSH production. Three days after menstruation begins, inhibin B is normally elevated but these tests are harder to interpret and, therefore, used less regularly than FSH and estrogen.

The two gold-standard measurements for ovarian reserve test anti-Müllerian hormone (AMH) levels and a woman’s antral follicle count. While AMH testing has been in existence for years, research resulted in its increased utility during recent years. AMH is a less variable hormone that  increases during puberty and remains constant until menopause. Granulosa cells, specialized “nurse cells” within follicles, produce AMH that also remains relatively stable across the menstrual cycle. Thus, this test can be used at any point in the menstrual cycle and even when a woman is taking hormonal birth control.

An additional reproductive test for cancer survivors interested in preserving their fertility is a count of their antral follicles at the beginning of the menstrual cycle. These follicles can be viewed near the surface of the ovary with an ultrasound. It is important to note that these counts are good indicators of the number of eggs that may be retrieved through hormonal stimulation during in vitro fertilization procedures, rather than the spontaneous pregnancies that may be an option for cancer survivors.

Future research will determine if these tests can be tailored to cancer survivors. One effect of cancer treatment can be temporary or permanent infertility begining during therapy that continues for months, years, or forever. Clarisa Gracia MD, an Oncofertility Consortium investigator, examines how fertility measurements change during and after active cancer treatment. Potentially, such measurements could provide personalized treatment to women that would destroy their cancers and, simultaneously, allow them to retain reproductive ability.