FERTILITY GUIDELINES ADDRESS OFTEN-IGNORED TREATMENT SIDE EFFECT
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《临床癌症学报》
New guidelines from the American Society of Clinical Oncology (ASCO) say physicians should talk to young cancer patients about the possibility of infertility early in the course of discussing treatments, and be prepared to refer appropriate patients to specialists who can help them choose a method of preserving their fertility.
The ASCO Recommendations for Fertility Preservation in Cancer Patients were published in the Journal of Clinical Oncology (2006;24:2917–2931).
"We're at this amazing crossroads where survival rates are higher than they've ever been, and at the same time there are more reproductive options than there were before," said Lindsay Beck, a co-author of the new guidelines and founder of the patient group Fertile Hope. "If you don't have that discussion early on, patients will miss their opportunity."
Beck began Fertile Hope in 2001 after her own struggles to find a way to preserve her fertility in the face of cancer treatment. The group provides information and financial assistance to young patients with cancer who need fertility-preservation procedures. She says oncologists have not been doing enough to inform patients of the treatment risks or fertility preservation options.
"I don't think they're maliciously not doing it," she emphasized. "Oncologists aren't reproductive specialists, so this gives them information on what's available today."
Other experts agree there's room for improvement in the way physicians address the issue with young patients.
"Historically, many of the cancers we cure today were not cured in the past," said gynecologic oncologist Carolyn Runowicz, MD, National Volunteer President of the ACS and Director of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center. She was not involved in creating the guidelines. "Now with earlier detection and better treatment, we are increasing the number of cancer survivors, and for many, issues of fertility arise."
That was certainly the case for Antoinette Ramos of California, who was diagnosed with Hodgkin disease last year at age 25. While her doctor did mention the possibility of infertility after treatment, the discussion was cursory, she said.
"He said, ‘Don't worry, I've had lots of patients who've gone on to have children,’" Ramos recalled.
Although single, Ramos had always planned to have children one day. The possibility of infertility was a shock.
"The fact that that choice might be taken away from me really rocked my whole existence," she says. "I didn't cry when I found out I had cancer, I cried when I found out it could affect my fertility."
With the help of Fertile Hope, Ramos underwent ovarian stimulation and 19 unfertilized oocytes were harvested and cryopreserved before she began chemotherapy.
Runowicz said the new ASCO guidelines are informative for oncologists who may not know very much about modern methods of fertility preservation. Based on a systematic review of literature from 1987 to 2005, it lists cancer treatments that can cause infertility and reviews the quality of evidence supporting available methods of fertility preservation for males and females.
For men, sperm cryopreservation after masturbation is both effective and well-established, the guideline says, noting that sperm should be collected before cancer therapy begins because of the potential for even one course of treatment to cause damage. Successful collection of sperm by other methods, including testicular aspiration or extraction, electroejaculation under sedation, or from postmasturbation urine samples, hasbeen reported in a few case reports and case series. Testicular suppression with gonadotropin-releasing hormone analogs or antagonists, on the other hand, has not been shown to be successful. Shielding the testicles from radiation is also possible but requires considerable expertise to be done properly. The only options for prepubertal boys—testicular tissue cryopreservation or xenografting—have not been tested in humans and are considered investigational.
For women, embryo cryopreservation is the most established technique, but it may not be an option if a woman has no partner or cannot delay treatment long enough for oocyte harvesting. Oocyte cryopreservation presents the same timing problems and is still a relatively new technique with only a few studies of its efficacy. Gonadal shielding during radiotherapy and ovarian transposition (oophoropexy) are appropriate options for some women. Use of trachelectomy and other conservative gynecologic surgical procedures are limited to certain types and stages of disease. Ovarian suppression with gonadotropin-releasing hormone analogs or antagonists was considered controversial, with insufficient evidence of safety and effectiveness. The guidelines recommend that women interested in this option consider participation in a clinical trial. Concerns regarding ovarian tissue cryopreservation with orthotopic or heterotopic transplantation include loss of oocytes during freezing and the potential for reintroduction of cancer cells. The guidelines recommend that this technique be considered only in centers with necessary expertise and under a protocol approved by an institutional review board.
Deciding which fertility preservation treatment to use depends on each person's particular situation, said reproductive endocrinologist Kutluk Oktay, MD, co-chair of the guideline committee and Director of the Fertility Preservation Program at Weill Medical College of Cornell University in New York.
"So far the most established method is embryo freezing, but even there, there are areas that need further research," he said. For instance, Oktay is studying ways to stimulate maturation of oocytes for harvesting without increasing estrogen levels that could promote growth of hormone receptor–positive breast cancer.
Other methods, such as ovarian tissue freezing, are still so new that there simply are not any long-term data to show how effective or safe they really are. "The downside is most of the technologies we use have not been around for too long and don't have a long track record," Oktay said.
For this reason, Oktay said, evidence considered in developing the ASCO fertility preservation guidelines is not limited to randomized clinical trials (RCT) that clearly demonstrate the advantages of particular treatments. In the case of fertility, though, "you can't randomize a woman to not have fertility preservation, and you can't really compare methods because they are applicable in different scenarios," he explained.
"It's a different universe than what oncologists deal with, and we tried to reach over those barriers and come up with a guideline that doctors can use in their practice," Oktay added.(New ASCO guidelines urge oncologists to )
The ASCO Recommendations for Fertility Preservation in Cancer Patients were published in the Journal of Clinical Oncology (2006;24:2917–2931).
"We're at this amazing crossroads where survival rates are higher than they've ever been, and at the same time there are more reproductive options than there were before," said Lindsay Beck, a co-author of the new guidelines and founder of the patient group Fertile Hope. "If you don't have that discussion early on, patients will miss their opportunity."
Beck began Fertile Hope in 2001 after her own struggles to find a way to preserve her fertility in the face of cancer treatment. The group provides information and financial assistance to young patients with cancer who need fertility-preservation procedures. She says oncologists have not been doing enough to inform patients of the treatment risks or fertility preservation options.
"I don't think they're maliciously not doing it," she emphasized. "Oncologists aren't reproductive specialists, so this gives them information on what's available today."
Other experts agree there's room for improvement in the way physicians address the issue with young patients.
"Historically, many of the cancers we cure today were not cured in the past," said gynecologic oncologist Carolyn Runowicz, MD, National Volunteer President of the ACS and Director of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center. She was not involved in creating the guidelines. "Now with earlier detection and better treatment, we are increasing the number of cancer survivors, and for many, issues of fertility arise."
That was certainly the case for Antoinette Ramos of California, who was diagnosed with Hodgkin disease last year at age 25. While her doctor did mention the possibility of infertility after treatment, the discussion was cursory, she said.
"He said, ‘Don't worry, I've had lots of patients who've gone on to have children,’" Ramos recalled.
Although single, Ramos had always planned to have children one day. The possibility of infertility was a shock.
"The fact that that choice might be taken away from me really rocked my whole existence," she says. "I didn't cry when I found out I had cancer, I cried when I found out it could affect my fertility."
With the help of Fertile Hope, Ramos underwent ovarian stimulation and 19 unfertilized oocytes were harvested and cryopreserved before she began chemotherapy.
Runowicz said the new ASCO guidelines are informative for oncologists who may not know very much about modern methods of fertility preservation. Based on a systematic review of literature from 1987 to 2005, it lists cancer treatments that can cause infertility and reviews the quality of evidence supporting available methods of fertility preservation for males and females.
For men, sperm cryopreservation after masturbation is both effective and well-established, the guideline says, noting that sperm should be collected before cancer therapy begins because of the potential for even one course of treatment to cause damage. Successful collection of sperm by other methods, including testicular aspiration or extraction, electroejaculation under sedation, or from postmasturbation urine samples, hasbeen reported in a few case reports and case series. Testicular suppression with gonadotropin-releasing hormone analogs or antagonists, on the other hand, has not been shown to be successful. Shielding the testicles from radiation is also possible but requires considerable expertise to be done properly. The only options for prepubertal boys—testicular tissue cryopreservation or xenografting—have not been tested in humans and are considered investigational.
For women, embryo cryopreservation is the most established technique, but it may not be an option if a woman has no partner or cannot delay treatment long enough for oocyte harvesting. Oocyte cryopreservation presents the same timing problems and is still a relatively new technique with only a few studies of its efficacy. Gonadal shielding during radiotherapy and ovarian transposition (oophoropexy) are appropriate options for some women. Use of trachelectomy and other conservative gynecologic surgical procedures are limited to certain types and stages of disease. Ovarian suppression with gonadotropin-releasing hormone analogs or antagonists was considered controversial, with insufficient evidence of safety and effectiveness. The guidelines recommend that women interested in this option consider participation in a clinical trial. Concerns regarding ovarian tissue cryopreservation with orthotopic or heterotopic transplantation include loss of oocytes during freezing and the potential for reintroduction of cancer cells. The guidelines recommend that this technique be considered only in centers with necessary expertise and under a protocol approved by an institutional review board.
Deciding which fertility preservation treatment to use depends on each person's particular situation, said reproductive endocrinologist Kutluk Oktay, MD, co-chair of the guideline committee and Director of the Fertility Preservation Program at Weill Medical College of Cornell University in New York.
"So far the most established method is embryo freezing, but even there, there are areas that need further research," he said. For instance, Oktay is studying ways to stimulate maturation of oocytes for harvesting without increasing estrogen levels that could promote growth of hormone receptor–positive breast cancer.
Other methods, such as ovarian tissue freezing, are still so new that there simply are not any long-term data to show how effective or safe they really are. "The downside is most of the technologies we use have not been around for too long and don't have a long track record," Oktay said.
For this reason, Oktay said, evidence considered in developing the ASCO fertility preservation guidelines is not limited to randomized clinical trials (RCT) that clearly demonstrate the advantages of particular treatments. In the case of fertility, though, "you can't randomize a woman to not have fertility preservation, and you can't really compare methods because they are applicable in different scenarios," he explained.
"It's a different universe than what oncologists deal with, and we tried to reach over those barriers and come up with a guideline that doctors can use in their practice," Oktay added.(New ASCO guidelines urge oncologists to )