Technique to Preserve Fertility in Young Women May Be Unsafe for Patients With Leukemia

/PRNewswire/ -- Although the use of ovarian tissue cryopreservation and transplantation has lead to 13 live births in women with lymphoma or solid tumors, this method of fertility preservation may be unsafe for patients with leukemia, according to a recent study published online in Blood, the journal of the American Society of Hematology. The method involves removing and freezing ovarian tissue before the patient undergoes aggressive chemotherapy and radiotherapy, and then reimplanting the tissue once the cancer has been brought under control. One major concern with leukemia patients is the risk that their frozen-thawed ovarian tissue might harbor malignant cells that could induce a recurrence of the disease after reimplantation.

"Our study provides clear evidence that cancer cells in women with acute and chronic leukemias can contaminate the ovaries," said Marie-Madeleine Dolmans, MD, professor at the Universite Catholique de Louvain in Brussels and lead author of the study. "If this tissue is reimplanted in these women when they're ready to have children, there's a good possibility that the cancer will come back."

As most acute lymphoblastic leukemia (ALL) patients are diagnosed with the disease at a young age, consideration of the preservation of their fertility is especially important. In fact, according to the National Cancer Institute, 71 percent of those diagnosed with ALL are less than 35 years old, as are nearly 10 percent of those with chronic myelogenous leukemia (CML)(1). In 2010, it is estimated that 2,180 women will be diagnosed with ALL and 2,070 with CML(1).

As aggressive chemotherapy and radiotherapy are damaging to the reproductive organs, the researchers wanted to examine the safety of using ovarian tissue cryopreservation to safeguard the fertility of patients with leukemia. In this study, researchers examined the implications of the technique in 12 women with ALL, a fast-growing cancer of the white blood cells, and six women with CML, a slowly progressing bone marrow cancer. The 18 patients included in this study were between 2 and 31 years of age when their ovarian tissue was cryopreserved (from 1999 to 2008). The mean age of the patients with ALL was 14.5 years and 24.7 years for those with CML.

Although initial microscopic examination did not reveal any cancerous cells in the ovarian tissue samples collected from each patient, by using a technique called real-time quantitative polymerase chain reaction (RT-qPCR), the scientists found cancerous cells in the ovarian tissue of 70 percent of the ALL patients and 33 percent of the CML patients. For further analysis, the researchers engrafted the ovarian tissue samples into 18 healthy mice for an observational period of six months. In the mice who received tissue from CML patients, the grafts looked normal and did not appear to contain any cancerous cells. In contrast, four of the mice who received ovarian tissue from ALL patients developed tumors. Through use of RT-qPCR and the mouse model, the researchers demonstrated the viability and malignant potential of leukemic cells present in the frozen ovarian tissue, especially from ALL patients.

"Given our findings, further research is needed to develop safer options for fertility preservation in patients with acute and chronic leukemias," said Jacques Donnez, MD, professor at the Universite Catholique de Louvain in Brussels and co-author of the study.

"Leukemia patients can benefit from fertility preservation techniques," added Brandon Hayes-Lattin, MD, the Director of the Adolescent and Young Adult Center at the Knight Cancer Institute in Portland, Oregon. "But the strategies offered must be both effective and safe. Among its other strengths, this work emphasizes that molecular methods can be successfully applied to assessments of safety."

(1) National Cancer Institute. SEER Stat Fact Sheets. Available at: http://seer.cancer.gov/statfacts.

The American Society of Hematology is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology. ASH provides Blood: The Vital Connection, a credible online resource addressing bleeding and clotting disorders, anemia, and cancer. The official journal of ASH is Blood, the most cited peer-reviewed publication in the field, which is available weekly in print and online.

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National Birth Defects Prevention Study Shows Assisted Reproductive Technology is Associated with an Increased Risk of Certain Birth Defects

Infants conceived with Assisted Reproductive Technology (ART) are two to four times more likely to have certain types of birth defects than children conceived naturally, according to a study by the CDC. The report, “Assisted Reproductive Technology and Major Structural Birth Defects, United States,” was released in the journal Human Reproduction.

“Today, more than 1 percent of infants are conceived through ART and this number may continue to increase,” says Jennita Reefhuis, Ph.D., epidemiologist at CDC′s National Center on Birth Defects and Developmental Disabilities. “While the risk is low, it is still important for parents who are considering using ART to think about all of the potential risks and benefits of this technology.”

The study shows that among pregnancies resulting in a single birth, ART (which includes all fertility treatments in which both eggs and sperm are handled, such as in vitro fertilization) was associated with twice the risk of some types of heart defects, more than twice the risk of cleft lip with or without cleft palate and over four times the risk of certain gastrointestinal defects compared with babies conceived without fertility treatments. Despite these findings, the absolute risk of any individual birth defect remains low. In the United States, cleft lip with or without palate affects approximately 1 in every 950 births; doubling the risk among infants conceived by ART would result in approximately 1 in every 425 infants being affected by cleft lip with or without palate.

The study examined multiple births separately from single births because ART increases the chance of a multiple birth. Children born as part of a multiple birth are more likely to have a birth defect regardless of use of ART. The study showed use of ART did not significantly increase the risk of birth defects among multiple births.

However, ART might contribute to the risk of major birth defects by directly increasing the risk of defects among single births. It may also have an indirect impact because ART increases the likelihood of having twins, which is a risk factor for many types of birth defects. Researchers believe this suggests the need for further studies to determine risk for ART in pregnancies with multiple births.

The study examined data from 281 births conceived with ART and 14,095 conceived without infertility treatments. The National Birth Defects Prevention Study is a population-based study that currently incorporates data from birth defects research centers in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah. These ten centers have been working on the largest study of birth defects causes ever undertaken in the United States. Information is gathered from more than 30,000 participants to look at key questions on potential causes of birth defects. While the causes of most birth defects are unknown, studies show that smoking, alcohol, and obesity increase a mother's risk of having a child with a birth defect.

Since 1981, ART has been used in the United States to help women become pregnant. It is defined as any procedure that involves surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman. ART does not include treatments in which only sperm are handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved.

The number of infants born after ART doubled in the United States from 1996 through 2004. According to data from the 2002 National Survey of Family Growth, almost 12 percent of U.S. women aged 15-44 years have reported using infertility services. In 2005, more than 134,000 ART procedures were performed and approximately 52,000 infants were born as a result of these procedures.

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