By Faith Reidenbach

“What’s frustrating‚” says Gina Fortunato of Nesconset‚ New York‚ “is the uncertainty in the answers you receive from doctors. They can’t tell you yes‚ you will be infertile‚ or no‚ you won’t.”

Fortunato‚ a human resources specialist‚ was 34 when she was diagnosed with ovarian cancer in 2001. “I was panicking not only with my diagnosis and what was to come‚ but also because I wasn’t yet married‚ and I didn’t have children.”

She didn’t have a complete hysterectomy‚ and just the one cancerous ovary was removed—an example of the new fertility–conserving surgical approaches that are sometimes suitable for ovarian or cervical cancer patients. But soon she got the warning so many men and women hear‚ regardless of their type of cancer: There was “a very strong possibility” that chemotherapy would make her infertile.

“We can’t tell a patient‚ ‘If you receive X dose of this drug‚ you have a Y chance of being sterilized‚’” explains Daniel Green‚ MD‚ head of the Long–Term Follow–Up Clinic at Roswell Park Cancer Institute‚ Buffalo‚ New York. “The data are much less precise than that.”

Research has lagged behind patient concerns because‚ until recently‚ the compelling issue for oncologists was survival. Now‚ 60% of cancer patients live for at least five years‚ and about 10% live longer than 25 years‚ according to the National Institutes of Health‚ Bethesda‚ Maryland.

Attention is therefore turning toward “survivorship” issues such as fertility. But not all oncologists counsel patients about future fertility. In April 2002‚ the Journal of Clinical Oncology reported that of 201 male cancer patients ages 14 to 40 who had been diagnosed within the previous two years‚ only 60% said their oncologists warned them about infertility‚ and only 51% were offered sperm banking.

“For women‚ it’s assumed that the number is much lower‚” says Lindsay Nohr‚ founder of Fertile Hope‚ an advocacy group for cancer patients. “Doctors in the cancer world aren’t as informed on the different options for women.”

“We should be receiving more phone calls‚” agrees Jairo Garcia‚ MD‚ director of the in vitro fertilization program at Johns Hopkins University‚ Baltimore‚ Maryland. Many doctors are not informed about fertility preservation options‚ he says‚ or if they are‚ it becomes less important compared to the seriousness of the cancer. Not all treatments are risky

Whether fertility preservation will be needed depends in part on the proposed treatment. Certain chemotherapy drugs are risky ‚ especially those known as alkylating agents‚ because they attack all rapidly dividing cells—cancer cells‚ sperm cells‚ and egg cells alike. Total–body irradiation and pelvic irradiation are also likely to kill some or all sperm and egg cells. Occasionally‚ though‚ even completely sterile men and women recover their fertility spontaneously‚ sometimes a decade or more after cancer treatment.

In women‚ the risk of infertility depends partly on age. Women are born with all the eggs they’re ever going to have‚ and with each menstrual period some are eliminated. The younger the woman‚ the larger the egg supply. Women who have cancer treatment prior to age 30 are considered to have the best chance of conceiving naturally afterward.

Even if a girl or woman remains fertile throughout cancer treatment‚ she may have a shortened “window of opportunity” to conceive due to premature ovarian failure (premature menopause) because of a reduced egg supply.

“We don’t have great statistics to tell women how much shorter it’s going to be‚” says Dr. Green. “But if they’ve been treated with pelvic radiation and/or alkylating agents‚ it is shorter.”

Compounding the time issue is some research that suggests waiting at least a year after chemotherapy before trying to conceive to reduce the risk of miscarriage and birth defects. “It isn’t clear that a year is either too long or too short‚” Dr. Green says. “Again‚ there really just are no data.”

The risk of birth defects also suggests‚ some researchers say‚ that cancer patients should not bank sperm or embryos during a break in chemotherapy. Consequently‚ patients who feel strongly about preserving fertility are under tremendous time pressure prior to treatment.

“Act as quickly as possible”
Two weeks before she was scheduled to start chemotherapy‚ Fortunato made an emergency appointment with a fertility specialist to discuss her options. Obliged to choose “literally overnight‚” she decided to freeze some eggs. She had to start immediately injecting Gonal–F® (follitropin alfa)‚ a synthetic hormone that stimulates the ovaries to release mature eggs.

“I did not have time to sit down and research‚” Fortunato remembers. “The only thing I was very‚ very concerned about was whether this would make the cancer run rampant through my system.”

After she told her oncologist of her plans‚ he conferred with the fertility specialist. He told her that since she was “so dead set on having children‚” he would approve one cycle of Gonal–F and egg retrieval.

Dr. Garcia says it’s typical for fertility specialists to get last–minute calls from cancer patients. “There’s not much we can do if the patient needs to start chemotherapy in a week. When the diagnosis is made‚ act as quickly as possible.”

Time can also be an issue for men and older boys. If a patient is acutely ill‚ Dr. Green says‚ treatment may need to start before samples can be collected for sperm banking. “The usual thing that we hear from the sperm banks is that you need to have two or three samples.” At least one day of abstinence is necessary between samples.

Cryopreservation (freezing) of sperm has been used successfully by cancer patients for decades‚ but there are no guarantees. “Sometimes men who are acutely ill have very low sperm counts‚” Dr. Green points out. Other potential problems‚ he says‚ are reduction in sperm activity or abnormally shaped sperm.

Reproductive science at work
Low sperm count is less a problem today due to a specialized method of in vitro fertilization called ICSI (intracytoplasmic sperm injection). “That changed the whole picture dramatically for men‚” says Dr. Garcia. He explains that for ICSI‚ only a single sperm is needed because it is injected directly into the center of an egg. Fertility clinics can also remove sperm from a testicle for use in ICSI.

For women‚ some doctors suggest injections of drugs such as Lupron® (leuprolide) during chemotherapy. Lupron‚ a gonadotropin–releasing hormone (GnRH) analog‚ belongs to a family of hormones that temporarily puts the ovaries into a pseudomenopausal state‚ suppressing egg production so that fewer eggs are harmed by chemotherapy. While not proven by the few human studies to date‚ doctors can prescribe these drugs for this experimental use because they are approved for other medical purposes.

Fortunato used Lupron on the advice of her oncologist and had a “horrible” experience with side effects such as severe hot flashes and weight gain‚ in addition to the chemotherapy side effects. She recalls‚ “The sweats were just unbearable‚ like your body was burning from the inside out.”

Fortunato‚ who was in a long–term relationship‚ had her “significant other” fertilize the eggs and had the embryos frozen.

“I was uncomfortable with that‚ but the fertility specialist pushed the issue‚” she explains. “He said there was a very slim chance of an oocyte [unfertilized egg] surviving.” Whereas sperm and embryo freezing are established procedures‚ egg freezing is highly experimental.

Dr. Garcia‚ who with colleagues reported that “oocyte banking” isn’t yet feasible in the April 2001 issue of the medical journal Fertility and Sterility‚ explains that cryopreservation of the unfertilized egg is troublesome because it is a very large cell containing a lot of water.

“When we’re trying to freeze it‚ it very easily forms crystals of ice that damage the membrane of the egg‚” Dr. Garcia explains. “This is why the emphasis has been placed on freezing fragments of ovarian tissue.”

In a very small number of patients‚ researchers have successfully removed the ovary before cancer treatment‚ cut the egg–producing section into tiny strips‚ frozen them‚ and reimplanted them later‚ usually in the arm for easy access to any eggs that develop. Dr. Garcia has retrieved eggs from at least one woman‚ but has yet to be successful with in vitro fertilization.

Similar experiments are under way with testicular tissue and with transplantation of the whole ovary and the whole testis. Ovarian and testicular tissue transplantation are the only fertility preservation techniques potentially suitable for prepubertal girls and boys‚ aside from freezing of immature eggs and sperm‚ which so far isn’t promising. But a major concern is whether the tissue can harbor cancerous cells that will later be reintroduced into the body.

A major commitment
Another concern is more commonplace: Will insurance pay for high–tech fertility preservation procedures? Even with existing procedures‚ “there’s a stigma‚” Nohr points out. “Insurance companies are wary of [healthy] women wanting to do things like freeze their eggs so they can delay childbirth.”

According to Resolve: The National Infertility Association‚ 14 states mandate that insurance companies cover fertility treatment or offer supplemental policies: Arkansas‚ California‚ Connecticut‚ Hawaii‚ Illinois‚ Maryland‚ Massachusetts‚ Montana‚ New Jersey‚ New York‚ Ohio‚ Rhode Island‚ Texas‚ and West Virginia (details vary‚ so check the organization’s website‚ www.resolve.org).

Nohr recommends that even outside these 14 states‚ cancer patients should petition if insurance companies deny their fertility–related claims. “A lot of times they’re accepted with the clause that infertility is a side effect of a life–saving medical treatment.” Without insurance coverage‚ the costs can be overwhelming.

“Having your eggs retrieved is a regular surgical procedure‚” Fortunato says. “I walked into the office for the actual retrieval procedure‚ and the receptionist says‚ ‘That’ll be $9‚989.’ My jaw dropped. Although my insurance company claims to cover all treatment up to the diagnosis of infertility‚ which I was never diagnosed with‚ all medication and the actual procedure were denied.”

The clinic worked out a payment plan for the procedure‚ but Fortunato had already put nearly $4‚000 for the Gonal–F injections on a credit card. She pays a monthly fee for storing the embryos‚ and has been told that the cost to attempt a pregnancy will be $10‚000 to $15‚000.

“I placed a serious financial burden on myself‚” she says. “But I would go through it again. A lot of people told me I was crazy‚ but I really want to have children. Hopefully‚ with the help of God‚ someday I will.”