Livebirth rates significantly lower among women diagnosed with cancer

Abstract

Women who are diagnosed with cancer during their reproductive years have significantly fewer livebirths than those without cancer, according to a Danish registry-based cohort study.

Researchers found that livebirth rates after a cancer diagnosis increasingly declined with age and varied with specific cancers. The rates of a first livebirth after cancer were lowest among women with leukemia, breast cancer, and cancers of the gynecological tract or central nervous system.

“The data affirms that most young people with cancer should be referred for fertility preservation counseling as soon as possible, even if they’re ambivalent about having children,” says Kutluk Oktay, MD, PhD, director of the Laboratory of Molecular Reproduction and Fertility Preservation at the Yale School of Medicine in New Haven, Connecticut. “I think we’ve made big progress in this area in the U.S., but around the world, and even here, there’s some heterogeneity.”

The study appears in the Journal of Cancer Survivorship (doi:10.1007/s11764-024-01720-1).

The study population came from the DANAC II cohort, which included women aged 18–39 years who were diagnosed with cancer between 1978 and 2016 and matched them with 60 women without a cancer diagnosis. Each woman came from a general population that included 21,596 women with cancer and 1,295,760 women without cancer.

The primary outcome was a livebirth after cancer with follow-up until death, emigration, or end of follow-up.

Findings showed that the 20-year cumulative incidence of livebirth after cancer was lower among women with cancer (0.22) than those without cancer (0.34).

The hazard ratio (HR) of a livebirth for all women diagnosed with cancer was 0.61 (95% CI, 0.59–0.63). Researchers excluded women with a livebirth within the 259 days after their cancer diagnosis and found that the HR of livebirth after cancer remained unchanged. It was highest among women aged 18–25 years (0.72) and lowest among women aged 33–39 years (0.50). The HR was lowest for women with breast, gynecological, and central nervous system cancers along with leukemia. In contrast, women with malignant melanoma had HRs of a first livebirth comparable to those of women who had not been diagnosed with cancer.

Women with and without cancer were comparable in terms of the initiation of assisted reproductive technology after their cancer diagnosis or study entry: 79% of the total population of women who initiated assisted reproductive technology after cancer had not had children, whereas 76% of the women not diagnosed with cancer had not had children. Only 21% of the women with a child or children before their cancer treatment initiated assistive reproductive technology after their diagnosis.

The results were similar to findings from a 2011 Norwegian study of women with and without cancer who were 16–45 years old between 1967 and 2004 according to Dr Oktay. That study was published in the International Journal of Cancer (doi:10.1002/ijc.26045).

The authors noted that the HR of a first livebirth after cancer diagnosis increased in several cancer groups over time. They attributed the finding to a shift toward offering fertility-sparing treatments instead of sterilizing surgery in women with early-stage gynecological cancers. Fertility preservation also may play a role.

The results are not surprising, notes Dr Oktay. He points out that breast cancer treatment is generally damaging to fertility. Although most initial leukemia treatments are not damaging to fertility, some women with the disease may end up needing a hematopoietic stem cell transplant with extremely high doses of alkylating agents, which can damage fertility. Central nervous system cancer treatments also may use these agents as well as radiation to the cranium, which can affect ovulation, he adds.

“I was surprised that the rates of assistive reproductive technology use were comparable between women with and without cancer,” he says. “I would expect more reproductive technology utility among women with cancer. But as a registration study, there is a limit to their ability to say why the technology use is similar.”

Christine Duffy, MD, MPH, director of the Adult Cancer Survivorship Program at the Brown University Health Cancer Institute in Lincoln, Rhode Island, says that she was surprised that people with melanoma had the highest livebirth rates.

“A problem with the study is that they didn’t look at the stage of cancer or what type of treatment people got,” she says. “But because Denmark has particularly good cancer screening, if they’re finding most people with melanoma early, it’s basically cured and there’s no treatment. So, that’s going to have a much lower impact on fertility.”

In the study, the average age of patients with a breast cancer diagnosis was older than the average ages of patients with other cancers; this means that women had less time to become pregnant, she adds.

Dr Duffy and Dr Oktay point to recent findings from other studies that offer hope for women who have undergone cancer treatment and want to have children. Dr Oktay recently authored a review of safety and effectiveness data and success rates in ovarian stimulation studies for women with cancer. The review was published in Current Opinion in Oncology (doi:10.1097/CCO.0000000000000977).

Findings showed that individualized ovarian stimulation approaches combined with improvements in cryopreservation increased the ability to preserve fertility. Women with BRCA mutations, however, were at higher risk of losing more of their ovarian reserve after chemotherapy than those without the mutations.

Dr Duffy cites a 2023 study published in The New England Journal of Medicine (doi:10.1056/NEJMoa2212856) showing that women with previous hormone receptor–positive breast cancer could temporarily pause their endocrine therapy to try to become pregnant. Because it blocks estrogen, this therapy can reduce women’s ability to do so. Study results showed that participants were able to pause their therapy without the short-term risk of their breast cancer returning. Although further follow- up is needed, 63.8% of the 497 women who were followed had at least one live birth.

“People were really happy to see the results because a lot of women have anxiety around pausing their endocrine therapy,” Dr Duffy says. “The caveat is that these are all women with early-stage cancers.”

In terms of fertility counseling, she adds, “I think there’s been a huge improvement in counseling around this issue, but there are still a lot of people who don’t get it or don’t get the proper counseling when they’re diagnosed.”