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EVALUATING AND PROTECTING FERTILITY

From Washington University Physicians, written by Mary Jo Blackwood, RN, MPH, posted June 8, 2012

Concerns about present or future infertility can take an emotional toll on families who want to have children and either don’t know why they cannot or are facing a disease for which treatment could negate future fertility. The Washington University Infertility and Reproductive Medicine Center is working to find solutions.

Dr. Amber Cooper, (pictured left) is a surgeon and researcher in the Center, studying and treating a variety of fertility issues. “Most clinicians believe that the greatest number of eggs a woman will ever have, about 5 million, is before she is born.

By birth that has dropped to one million, and by puberty, we’re down to 300,000 to 500,000. Because the average woman ovulates a very small number of these over her reproductive span, that should be plenty of eggs.

However, any insult to the ovaries could severely deplete the remaining eggs. Insults might include surgery, certain medications, chemotherapy, radiation, smoking, or environmental exposures. Often we don’t know what causes the loss or destruction of eggs. . We can’t replace those eggs but we can slow depletion by getting to the root problem or working ahead to protect eggs with cryopreservation.”

Getting to the Root of Ovarian Depletion

Dr. Cooper’s research goal is to determine the causes of premature depletion of the egg pool such as genetic mutations in women with unexplained premature ovarian failure, environmental causes, or chemotherapeutic medications.

She is also working to improve blood and ultrasound markers of ovarian reserve to determine who has a depleted or damaged pool. “We can start to see clinical signs of insufficiency by looking at the ovaries on ultrasound and in blood samples, rather than waiting for irregularities in the menstrual cycle when it could be too late to use fertility therapies to assist with pregnancy.”

Of particular interest to Cooper is evaluating ovarian reserve in females age 4 to 50 with diagnoses of rheumatoid arthritis (RA), psoriatic arthritis, spondyloarthropathies, or juvenile idiopathic arthritis.

People often associate loss of ovarian function with cancer, but some autoimmune diseases and/or treatments can potentially alter ovarian function and reserve over time. Because these conditions are treated with methotrexate (a chemotherapeutic agent) and biological agents, Cooper, in collaboration with pediatric and adult rheumatologists, is evaluating the effect of these treatments on ovarian function in an ongoing study started in 2008.

Primary ovarian insufficiency (POI) is often called premature menopause or premature ovarian failure, and is defined by the presence of menopausal-level serum gonadotropine along with irregular periods in adolescent girls or women younger than 40.

A new study, in collaboration with the Genome Institute, Department of Genetics, and NIH, will look at the whole exome DNA sequencing in over 500 women with POI, using DNA that has been stored to try to determine underlying factors. Says Cooper, “Our ultimate goal is to understand normal ovarian function and oocyte (egg) loss, determine what causes ovarian insufficiency, and identify who may benefit from early therapies to preserve fertility in high-risk women.”

Preservation of fertility

Whether at high risk for POI, or facing cancer treatment, the goal of the center is helping men and women preserve fertility by a variety of means:

Options for men include sperm banking, which is the primary way to preserve male fertility. Sperm is retrieved by ejaculation or surgery and cryopreserved (frozen) and can be safely stored for many years.

Options for women are more varied and have been refined in recent years.
Embryo banking: This well-studied choice for fertility involves freezing fertilized eggs, or embryos. Following cancer treatment, the woman who wants to get pregnant can have embryos transferred back into the uterus in hopes for future pregnancy. This is the
Oocyte (egg) banking: A woman may choose to have unfertilized eggs frozen. In the past, this met with only moderate success because of the tendency of eggs to develop ice crystals during freezing. New techniques of flash freezing, or vitrification, have made this a much better option, though some techniques are still under study.

Ovarian tissue freezing: Another option is to remove part or all of an ovary for later implantation, or attempt to mature the eggs in culture to make embryos. This requires an outpatient surgery to obtain ovarian tissue. While still in the earlier phases of research, it may be an option for some young girls and women with limited time to attempt preservation of fertility.

Hormone suppression: Some patients may opt to be given medications that create a menopause-like state during chemotherapy to minimize ovarian activity, but researchers still disagree about whether it protects the ovary. Newer medications are under study.

Other options: In certain scenarios requiring radiation therapy, pelvic shielding or ovarian transposition may have some benefit.
The Center is getting increasing numbers of referrals from oncologists for discussions on fertility preservation in concerned patients. Cooper says they want more doctors to refer their patients to the Center to learn about their options prior to cancer treatment.

“A large number of patients who do come in elect to do nothing, but they feel better considering their options, rather than never having dealt with the issue. Our main goal is to protect patient autonomy, safety, and to consider the patient and any future child. We try to provide a support structure for each unique case.”
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Copyright 2013 Washington University School of Medicine
Copyright 2013 Washington University School of Medicine