Some Young People Who Undergo HCT Retain Ability to Conceive

By Lorraine L. Janeczko

October 21, 2021

NEW YORK (Reuters Health) - Young people who undergo hematopoietic-stem-cell transplantation (HCT) may be able to conceive even after being treated with highly gonadotoxic agents, a large European retrospective study shows.

"Conceptions after HCT, even after MAC (myeloablative conditioning), are possible, in some cases with the support of reproductive medicine," researchers write in Human Reproduction.

"Discussions concerning fertility/fertility preservation should be offered to parents of children and adolescents already diagnosed, and the children should be followed up regularly during, and especially after, treatment to allow those without the option of fertility preservation before HCT to take advantage of the 'fertility window' afterwards," Dr. Tamara Diesch-Furlanetto of the University Children's Hospital Basel, in Switzerland, and her colleagues write.

The team analyzed data from the European Society for Blood and Marrow Transplantation (EBMT) registry. The research team investigated natural or assisted conceptions and their outcomes in patients who were under 18 years of age before their first transplantation and who received HCT between 1995 and 2016.

Nearly 63,000 children received their first HCT in EBMT centers, and pregnancy was reported in 406 patients. The median age at transplantation was 15.7 years, and the median age at declared conception was 25 years.

Details from 99 patients about first pregnancy and pregnancy outcome were obtained through questionnaires. Among females, the median age at delivery or pregnancy interruption was 23.0 years, with a median time after transplant of 10.7 years.

The mean ages of healthy women compared with transplanted women at their first delivery were 29 and 24.3, respectively. Natural conception occurred in 96% (50/52) of females who did not receive total body irradiation (TBI) and in 52% (13/25) of those who did.

All seven male patients treated with TBI achieved fatherhood but needed assisted fertilization or used their cryopreserved sperm. Among females, 90% (63/70) of all conceptions resulted in live birth, with 84.5% (49/63) at term and 93% (43/46) having normal birthweight; 15% (9/61) of women, especially those who had received a myeloablative regimen, had cesarean deliveries.

"I was slightly surprised that pregnancies occurred after myeloablative conditioning without support of reproductive medicine, due to the intensity of the therapy," said Dr. Joy M. Fulbright of the Division of Hematology, Oncology and Bone Marrow Transplantation at Children's Mercy Kansas City, in Missouri, who was not involved in the study.

"This emphasizes the importance of discussing that there is a high risk of infertility, but that the risk is not 100%," Dr. Fulbright, also director of the Adolescent and Young Adult Program at Children's Mercy, told Reuters Health by email.

"Prior to transplantation or in survivorship, families often ask if they or their child will be able to have children; and if so, if the pregnancy will be normal," she said. "This is a difficult area to study, but it is important to gather as much information as possible to help inform patients and families."

"As the authors pointed out, because follow-up time was not adequate, they were unable to calculate the incidence of conception in this population," Dr. Fulbright added. "The average age at follow-up was 11.9 years, not the age of patients trying to conceive."

Dr. Saro H. Armenian, director of the Childhood Cancer Survivorship Program at City of Hope Comprehensive Cancer Center, in Duarte, California, said, "The study provides cause for optimism about the efficacy of pre-HCT fertility preservation techniques, as well as the potential to maintain fertility in a subset of survivors who never underwent fertility preservation before HCT."

"It is especially reassuring that the overwhelming majority of reported conceptions resulted in live births that were term and had normal weight," added Dr. Armenian, who also was not involved in the research. "That said, the number of actual pregnancies reported in the cohort was relatively small. As such, the findings from the study should be interpreted with caution."

"For many children who undergo HCT, long-term cure of their primary disease is an expected outcome," he noted. "The growing number of long-term HCT survivors makes it imperative that we continue to optimize the reproductive health of young patients who will live for decades past their HCT."

Dr. Diesch-Furlanetto was not available for comments.

SOURCE: Human Reproduction, online September 16, 2021.