Yale findings expand understanding of fertility after chemotherapy

Women with a fairly common type of genetic mutation face a greater risk of infertility following chemotherapy for breast cancer, according to a new study from Yale fertility expert and scientist Dr. Kutluk Oktay. The findings suggest that women with the mutation should carefully consider their options for preserving fertility before initiating chemotherapy treatment.

The study appears in the March 31 edition of the journal Fertility and Sterility.

Funded by the National Institutes of Health, the study looked at 177 women, 14 of whom had a BRCA mutation - a gene mutation associated with breast, ovarian, prostate, and male breast cancer. Between 2% and 3% of the general population and 8% and 10% of the Jewish population carries the mutations.

All the women studied were undergoing chemotherapy for treatment of breast cancer. Oktay and his team of researchers monitored the women during chemotherapy and evaluated them again at 12, 18, and 24 months after treatment, measuring what happened to their ovarian reserves, or the number of eggs available for becoming pregnant, by testing the levels of a hormone called AMH, or anti-mullerian hormone. AMH is produced from follicles in the ovaries and is associated with fertility. Its level plummets as a result of chemotherapy.

The researchers found that women with BRCA mutations had much lower recovery rates of AMH post-chemotherapy.

" Everyone’s AMH levels go down to almost nothing after chemotherapy," said Oktay, professor of obstetrics & gynecology and reproductive sciences and director of the Laboratory of Molecular Reproduction and Fertility Preservation at Yale School of Medicine. "Though those levels partially recover in most women after several months, regardless of whether they had the BRCA cancer gene, our study found that women with a BRCA mutation have three to four times less recovery of AMH levels."

The drop in AMH levels following chemotherapy adds to the already diminished fertility in women with a BRCA mutation.

" Women with BRCA mutations already have lower ovarian reserves," Oktay said, "and they are also more likely to lose more eggs."

Oktay is a leading expert in fertility preservation, and first developed a way to perform in vitro fertilization of women with breast cancer 14 years ago. He also developed and performed the world’s first ovarian transplants. It was early in this research that he first perceived the impact of BRCA mutations on fertility, he said, finding that the mutations cause women to produce fewer eggs, lower ovarian reserves, and accelerating ovarian aging.

The latest study suggests that women who have breast cancer and BRCA mutations should seek counsel about their fertility options, Oktay said. These women, he noted, face a "triple whammy," with reduced fertility from the mutation, from chemotherapy, and then from the mutation and chemotherapy combined. Women with BRCA mutations should strongly consider "having their ovarian reserve tested and preserving their fertility earlier, even if they haven’t developed breast cancer," he said.

For women with BRCA mutations and breast cancer facing fertility decisions, there are typically three to four weeks between diagnosis and surgery, and another four to six weeks for healing before chemotherapy treatment begins - enough time to preserve fertility options through treatments such as ovarian simulation or ovarian tissue freezing, Oktay said.

Oktay is co-chair of the American Society for Clinical Oncology’s Fertility Preservation Guidelines Committee, which writes and update guidelines for cancer doctors.

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