Interview with Dr. Karine Chung, MD, founder and the director of USC Fertility Preservation Program for cancer patients
by Diana Price Medically reviewed by C. H. Weaver M.D. 01/2018
Q. Is pregnancy still a possibility for me after completing cancer treatment?
If you have undergone cancer treatment, you may already be aware that cancer therapies—including chemotherapy and radiation—can cause infertility and premature menopause. These treatments can dramatically reduce your egg supply, with higher doses leading to greater degrees of loss. As a result, the remaining pool of eggs (or ovarian reserve) may become so low that pregnancy using your own eggs is no longer possible regardless of whether menstrual cycles are occurring. Once you have completed cancer therapy, some of the following tests may be useful in estimating your egg supply, an important determinant of your current fertility.
Egg Supply Testing after Cancer Treatment
The most reliable way to assess fertility after cancer therapy is to measure hormone levels in the blood, typically timed to specific phases of the menstrual cycle. An ultrasound of the ovaries can also be useful to approximate fertility potential. These tests are best performed and interpreted by a reproductive endocrinologist.
Basal (Day 3) Follicle-stimulating Hormone
Every woman is born with a set supply of eggs. Each egg is contained within a structure called a follicle, which is composed of layers of ovarian cells surrounding fluid that provides nutrients for the egg. Follicle-stimulating hormone (FSH) is produced by the pituitary gland in the brain, and its purpose is to stimulate follicles to grow. At the beginning of a menstrual period, FSH acts as the signal to the ovaries that it is time to prepare eggs for ovulation. One of the earliest indications that the ovarian reserve (the number of remaining eggs) is becoming critically low is an increase in FSH levels at the beginning of a menstrual period. FSH production increases as though it is trying to compensate for the tiring ovaries. For this reason, measurement of FSH in the blood is commonly used as a test of fertility.
It is important that this test be performed on or very near the third day of the menstrual cycle to be informative, and the test should be measured in conjunction with the estrogen level to ensure accurate interpretation. Higher day 3 FSH values correspond to reduced fertility. Normal values are different, depending on where your blood is drawn, but in general values above 10 to 15 international units per liter (IU/L) are considered abnormal. It is expected that the values will fluctuate from month to month, but even with one elevated test result, the chances of becoming pregnant are much lower.
Clomid Challenge Test
Because the basal FSH level will not detect every occurrence of a diminishing egg supply, the Clomid® (clomiphene citrate) challenge test can be used to unmask the problem. Clomid is a pill that is taken for five days starting on the fifth day of the menstrual cycle. FSH levels are measured on day 3 and day 10. In women with a normal supply of eggs, the FSH levels will be low on day 3 and day 10 after the five days of Clomid are completed. If either value is high (greater than 10 to 15 IU/L), the test result is considered abnormal.
Antral Follicle Count
Follicles can be seen and counted during a vaginal ultrasound examination in the early part of a menstrual period (on or around day 3). These follicles are thought to represent the ones that are getting ready to grow during that menstrual cycle. They also reflect the total number of follicles left inside the ovary. There are no well-established cutoff values for normal and abnormal, however, and the expected count definitely varies depending on a woman’s age. In general, the more antral follicles there are, the more plentiful the total egg supply is likely to be. For a woman under 40, 10 or more on each side is promising. For a woman who is 40 or older, six or more on each side is a good sign.
Using vaginal ultrasound, three diameters of each ovary (length, width, and height) can be measured in the early part of the menstrual period (on or around day 3), and total ovarian volume can be calculated. In general, ovarian volume is known to decrease with age and has been used to approximate ovarian reserve. Ovarian volume of less than 3 centimeters cubed (3 cm3) per ovary has been reported to indicate severely reduced ovarian reserve and very low likelihood of pregnancy.
Inhibin B and Anti-Müllerian Hormones
Inhibin B (ONHB) and anti-Müllerian hormone (AMH) are produced by the cells in the ovary that make up the outer layers of follicles. When these hormone levels are low, it suggests that the number of remaining follicles is low. Like FSH, inhibin B should be measured on or around day 3 of the menstrual period. AMH levels, however, do not vary throughout the menstrual cycle and can therefore be measured at any time. ONHB levels of less than 50 picograms per milliliter (pg/mL) and AMH levels less than 0.2 micrograms per liter (mcg/L) have been proposed to indicate severely diminished ovarian reserve. While these are very promising tests for fertility and ovarian reserve, they are not available everywhere, and doctors have not yet agreed upon the best way to interpret their results.
If you are interested in having children after completing cancer treatment, you should consider consulting a fertility specialist and having your ovarian reserve evaluated. Because the impact of cancer treatment on a woman’s fertility varies from individual to individual, it is helpful to be informed about your current fertility status before you begin trying to conceive.
Karine Chung, MD, MSCE, is one of three physician partners at USC Fertility (USCF), the not-for-profit private fertility practice of the University of Southern California, Los Angeles. She is also the founder and the director of USCF’s Fertility Preservation Program for cancer patients. For more information please visit www.uscfertility.org or www.uscfertilitypreservation.org.