Female recipients of allogeneic hematopoietic cell transplantation (alloHCT) were able to get pregnant but had lower birth rates than the general population, a new study published in Blood showed.1
“Long-term survival after alloHCT has significantly improved over the last decades, making family planning an essential goal for young adult cancer survivors,” said lead author Katja Sockel, MD, of University Hospital Carl Gustav Carus in Dresden, Germany. “Our findings provide a valuable basis in the daily routine for counseling young women and their families before alloHCT, increase awareness of fertility aspects in women undergoing HCT, and stimulate further research, particularly prospective data collection to advance understanding of how peri-transplant decisions impact fertility.”
Dr. Sockel and colleagues conducted a large national multicenter study using data from the German Transplant Study Registry to estimate pregnancy and birth rates among adult female HCT recipients in the current transplant era. The study included 2,654 adult women aged 18 to 40 who had undergone alloHCT from 2003 to 2018.
Of the included women, 50 became pregnant at least once, resulting in 74 pregnancies. Pregnancies occurred at a median of 4.7 years after transplant. About three-quarters (77%) of pregnancies resulted in live births. However, compared with the general population, preterm birth (23%) and low birth weight (14%) occurred more frequently among women who had undergone alloHCT. Maternal complications during pregnancy were documented in 25 out of 52 pregnancies; the most frequent complications were vascular related, occurring in 16 pregnancies.
Nearly three-quarters of pregnancies (72%) occurred spontaneously without the use of assisted reproductive technologies (ART), a finding that Dr. Sockel called “unexpected.” The median age at which women became pregnant after alloHCT was 29.6 years (range = 21.7-39.3; interquartile range = 6.8).
“Although ART techniques are crucial in this patient cohort and funding should be made available for all patients, the chances for spontaneous pregnancies should not be underestimated, and patients should be aware of the possibility of fertility restoration post-transplant to prevent unexpected or unwanted pregnancies,” Dr. Sockel said.
The annual first live birth rate was 0.45%. Looking at German population data of women aged 18 to 40 as a comparator, the first birth rate was 3.02%. The probability of a live birth 10 years after HCT was 3.4% (95% CI 2.3-4.5).
“Although the annual first birth rate after alloHCT was more than six times lower than in the general German population, our findings offer hope that, despite intensive treatment and health challenges, successful pregnancies are realistic in these women,” Dr. Sockel said. “Factors such as younger age (<35 years), less intensive conditioning, lower total body irradiation doses (<8 Gray), and nonmalignant indications were associated with increased chances of motherhood.”
According to Dr. Sockel, fertility counseling should be offered to all individuals who have the ability to become pregnant before undergoing alloHCT. However, research has shown that only 55% of transplant physicians refer patients to fertility specialists because of disease-related factors, time constraints, or the assumption of preexisting infertility due to previous therapies.2
“Counseling young adults facing a potentially life-threatening illness about future fertility is a critical topic and should be handled with sensitivity and comprehensive information,” Dr. Sockel said. “A multidisciplinary team can help to cover all issues.”
This multidisciplinary team should develop a plan that balances fertility preservation with effective disease control and should include a transplant physician, fertility specialist, psychosocial support, and even genetic counseling in some cases, Dr. Sockel said.
This study was limited by its retrospective nature, making it impossible to gather information on the pregnancy desires and attempts of the nonpregnant population. There was also a lack of retrospective information on ovarian function prior to transplant and the use of GnRH analogues. Structured questions on pregnancy desires and conception methods should be added to the data repositories of transplant registries to adequately address fertility issues. In addition, the study relied on self-reported pregnancy and pregnancy outcomes, which could lead to underreporting of unsuccessful pregnancies.
“Moving toward a more individualized treatment strategy also includes reducing gonadotoxicity in young women who wish to have children,” Dr. Sockel said. “Findings from the present study provide important insights to improve treatment strategies and reduce long-term toxicities. However, prospective trials are necessary to determine the most effective conditioning regimens that both preserve fertility and provide a strong anti-tumor effect.”
Any conflicts of interest declared by the authors can be found in the original article.
References
- Sockel K, Neu A, Goeckenjan M, et al. Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation - a National Multicenter Study [published online ahead of print, 2024 July 12]. Blood. doi: 10.1182/blood.2024024342.
- Loren AW. Fertility issues in patients with hematologic malignancies. Hematology Am Soc Hematol Educ Program. 2015;2015:138-145.
