Female patients may become pregnant and give birth to healthy children despite treatment-related fertility challenges following allogeneic hematopoietic cell transplantation (allo-HCT), according to a recent study published by Sockel et al in Blood. The findings highlighted the need for increased fertility counseling.
Background
During allo-HCT, stem cells from a healthy donor are transplanted into patients with hematologic malignancies like leukemia or benign hematologic disorders such as sickle cell disease.
Procedural improvements in the administration of allo-HCT have led to more long-term survivors—especially young adult patients of child-bearing age—however, transplant-related morbidity, long-term medication use, and prior receipt of total body irradiation or high-dose chemotherapies may all pose significant fertility risks.
“Fertility is a very important topic for young female patients,” stressed lead study author Katja Sockel, MD, a senior physician at the University Hospital Carl Gustav Carus Dresden in Germany. “Some patients even opt out of receiving certain treatments because of concerns about fertility. For young adult cancer survivors especially, the return to a normal life includes family planning,” she added.
Study Methods and Results
In the recent study, the investigators used data from the German Registry for Stem Cell Transplantation to retrospectively analyze the pregnancy, birth rates, and risk factors in 2,654 female patients aged 18 to 40 years who underwent allo-HCT. They noted that 50 of the patients reported 74 pregnancies—57 of which resulted in live births—with a median time from transplantation to first pregnancy of 4.7 years.
The investigators found that the likelihood of pregnancy was positively correlated with female patients aged 18 to 35 years at the time of allo-HCT receipt, with a median age at pregnancy of 29.6 years. Although the annual first birth rate among these patients was over six times lower than that of the general German population, the study results may refute the widely accepted consensus that pregnancies posttransplant are nearly impossible. Some of the pregnancies recorded in the study were the result of assisted reproductive technology; however, 72% of the patients reported spontaneous pregnancies.
“Some study participants reported that they had not taken measures to prevent pregnancy because their [physicians] told them conception was not possible,” revealed Dr. Sockel. “Spontaneous pregnancies should not be underestimated, and female patients should be educated about potential fertility restoration post–allo-HCT to prevent unplanned or unwanted pregnancies,” she added.
The investigators discovered that factors associated with a greater likelihood of a first live birth included a reduced-intensity conditioning regimen, transplants for nonmalignant conditions, and no or lower-dose total body irradiation. Maternal complications occurred in 48.1% (n = 25/ 52) of the pregnancies—the most common of which were vascular (n = 16)—including preeclampsia, edema, and hypertension. While the patients didn’t exceed the complication risk of the general population, close interdisciplinary monitoring by transplant physicians and gynecologists was recommended to avoid maternal complications.
Fetal outcomes were collected from 44 of the pregnancies and were generally positive, without increased rates of childhood diseases or developmental delays compared with those in the general population. Nonetheless, the patients who had undergone allo-HCT experienced higher incidences of preterm delivery and low birth weight. For instance, 10 of the pregnancies resulted in preterm delivery—with the majority of them occurring between gestation weeks 28 and 32. Additionally, six newborns had low birth weights and one had a very low birth weight (less than 1,500 g). Overall, the live birth rate for this group was 78%, comparable to that of the general population.
Conclusions
“The results of this study show that female allo-HCT recipients can achieve successful and safe pregnancies. These findings help provide a basis for counseling young women of childbearing age and raising awareness of and funding for different [assisted reproductive technologies] techniques so that patients can have a normal life after allo-HCT,” Dr. Sockel underscored.
As a result of the study’s retrospective nature, the investigators noted that they faced limitations such as an inability to obtain measures of fertility like ovarian function before allo-HCT or anti-Müllerian hormone levels and challenges in collecting comprehensive data from participant interviews. The study also relied on self-reported pregnancy outcomes, which may have led to the underreporting of unsuccessful pregnancies. In addition, some types of assisted reproductive technologies were not available to patients during the decade-long study.
The investigators hope future prospective studies can advance the understanding of how pre–allo-HCT treatments like new and targeted therapies can impact fertility in young patients with cancer. This knowledge can lead to the development of novel individualized therapies that balance antitumor effectiveness with minimized toxicity and preserved fertility.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
