Preserving fertility in female cancer patients: A snapshot of the options
ABSTRACTWith the odds of surviving cancer improving, many young women facing chemotherapy or radiotherapy may first wish to take steps to ensure that they will still be able to bear children afterward. The options depend on the type of disease, the treatment required, the age of the patient, whether she has a long-term partner, and whether cancer treatment can be delayed. This paper is an overview of current and experimental strategies for preserving fertility in female cancer patients.
KEY POINTS
- Chemotherapy and radiotherapy are toxic to the ovaries, although the damage can be attenuated in some cases.
- The standard option for preserving fertility has been oocyte retrieval after controlled ovarian stimulation, followed by in vitro fertilization and subsequent cryopreservation of the resulting embryos.
- Unfortunately, controlled ovarian stimulation takes time, may delay needed cancer therapy, and may worsen estrogen-dependent cancers. Alternatives are being explored.
- Cryopreservation of unfertilized oocytes is an option for women who do not have a partner, although oocytes are more susceptible to damage during freezing than embryos are.
In the last few decades, the survival rates have improved in many of the malignancies that affect young adults. This progress has made fertility preservation and quality of life after cancer treatment important, most of all in survivors of childhood cancers.
Men who are about to undergo cancer treatment can bank their sperm, but as yet no analogous noninvasive option is available for women. The most studied methods are often invasive and require the woman to take large doses of hormones. They may also necessitate a delay in starting cancer treatment.
Which method of fertility preservation a woman should choose depends on several factors, including the type of disease, the treatment required, the age of the patient, whether she has a long-term partner, and whether treatment can be delayed.
Chemotherapy and radiotherapy have well-known deleterious effects on female reproductive function. Many studies have shown that acute loss of growing follicles within the ovary and resultant premature ovarian failure often follow chemotherapy. This ovarian damage has long-term consequences, such as shortened reproductive life span and hormone deficiency.1
Fertility preservation requires a team effort. It should be managed by an oncology center that has built a close collaboration between oncologists, fertility specialists, psychologists, and primary care physicians to allow early discussion and to offer a full range of options to these patients.
The aim of this paper is to discuss the current options for preserving fertility in female cancer patients who have to undergo gonadotoxic cancer treatment.
FEMALE FERTILITY AND ASSESSMENT OF OVARIAN RESERVE
At birth, baby girls have about 1 million primordial ovarian follicles, which is the most they will ever have. By the time they reach menarche, this number has declined to 180,000, and at menopause only about 1,000 remain.2
Throughout a woman’s reproductive life, the number of oocytes remaining—both primordial follicles and the relatively small number of maturing, growing follicles—is called her ovarian reserve. When cancer is diagnosed, we need to assess the patient’s ovarian reserve to direct the discussion about the need for fertility preservation.
In search of markers of ovarian reserve
Fertility experts have been looking for clinical biomarkers that could give us an estimate of the number of nongrowing follicles and, consequently, of the ovarian reserve.
All methods used for the assessment of ovarian reserve actually provide an indirect determination of the remaining pool of oocytes. In clinical practice, a high blood level of follicle-stimulating hormone (FSH) on cycle day 3 (>15 mU/mL) or a low level of anti-Müllerian hormone (AMH) (<1 ng/mL) is generally associated with a low ovarian reserve.
The serum FSH level is the marker most commonly used, but it varies widely at different times in the menstrual cycle.
The FSH test is usually performed on day 3 of the menstrual cycle, when the estrogen level is expected to be low due to negative feedback. The FSH result needs to be combined with the estradiol level, especially in those patients with irregular menstruation or in cases of amenorrhea. A random FSH test is considered valid if the detected estrogen level is low. Women undergoing in vitro fertilization with a day 3 FSH lower than 15 mIU/mL are more likely to conceive than women with a higher FSH level.
AMH and antral follicles. Recently, two other variables have been introduced in clinical practice: the AMH concentration and the antral follicle count (the number of small antral follicles within the ovary) as assessed by transvaginal ultrasonography.
AMH is released by the granulosa cells of small, growing follicles. Because its level is much more stable over the menstrual cycle than the FSH level, it can be measured on any day of the cycle.3 In cancer survivors, AMH is particularly useful in demonstrating the degree of ovarian tissue damage induced by radiotherapy and chemotherapy and in evaluating the ovarian reserve.4
A reduced number of antral follicles causes a diminished AMH production, which becomes undetectable with menopause. The AMH level is strongly associated with the basal antral follicle count. Various threshold values (0.2–1.26 ng/mL) have been used to identify women with low ovarian reserve.
