Safe, successful pregnancies possible after alloHCT

During alloHCT, stem cells from a healthy donor are transplanted to individuals with hematologic cancers or benign hematologic disorders such as leukemia and sickle cell disease. Procedural improvements in the administration of alloHCT have led to more long-term survivors, especially young adults who hope to have children. However, transplant-related morbidity, long-term medication use, and prior receipt of total body irradiation or high-dose chemotherapies all pose significant fertility risks.

"Fertility is a very important topic for young female patients," said Katja Sockel, MD, senior physician at University Hospital Carl Gustav Carus Dresden in Germany, and lead study author. "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."

In the largest systemic study to date of adult female alloHCT recipients, Dr. Sockel and her team retrospectively analyzed data from the German Registry for Stem Cell Transplantation to estimate pregnancy and birth rates and determine risk factors for female patients aged 18 to 40. Of the 2,654 total study participants, 50 women reported 74 pregnancies, 57 of which resulted in live births, with a median time from transplantation to first pregnancy of 4.7 years.

The likelihood of pregnancy was positively correlated with women aged 18 to 35 years at the time of alloHCT, with a median age of pregnancy of 29.6 years. Despite the annual first birth rate for this patient group being more than six times lower than that of the general German population, these study results refute the widely accepted consensus that pregnancy is not possible after alloHCT. And while some of the study's recorded pregnancies were the result of assisted reproductive technology (ART), 72% of participants reported spontaneous pregnancies.

"Some study participants reported that they had not taken measures to prevent pregnancy because their doctor told them conception was not possible," said Dr. Sockel. "Spontaneous pregnancies should not be underestimated, and female patients should be educated about potential fertility restoration post-alloHCT to prevent unplanned or unwanted pregnancies."

A few factors were associated with a greater chance of a first live birth, including a reduced-intensity conditioning regimen, transplants for non-malignant conditions, and no or lower-dose total body irradiation. Maternal complications occurred in 25 out of 52 pregnancies, the most common of which were vascular (occurring in 16 pregnancies), including preeclampsia, edema, and hypertension. Although they did not exceed the complication risk of the general population, close interdisciplinary monitoring by transplant physicians and gynecologists is recommended to avoid maternal complications.

Fetal outcomes were collected from 44 pregnancies and were generally positive, without increased rates of childhood illnesses or developmental delays compared to the general population. However, there were higher incidences of preterm delivery (birth before 37 weeks of pregnancy) and low birth weight (1,500-2,500 g) in this group. Ten pregnancies resulted in preterm delivery, with the majority occurring between gestation weeks 28 and 32. Additionally, six newborns had low birth weights, while 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.

"The results of this study show that female alloHCT recipients can achieve successful and safe pregnancies," said Dr. Sockel. "These findings help provide a basis for counseling young women of childbearing age and raising awareness of and funding for different ART techniques so that patients can have a normal life after alloHCT."

There were a few limitations to the study given its retrospective nature. Measures of fertility, such as ovarian function before alloHCT or anti-Müllerian hormone levels, could not be obtained, and challenges arose in collecting comprehensive data from participant interviews retrospectively. Additionally, the study relied on self-reported pregnancy and pregnancy outcomes, which may have led to the underreporting of unsuccessful pregnancies. Finally, some types of ART were not available to patients during the decade-long study.

The authors hope prospective studies will advance understanding of how pre-alloHCT treatments, including new and targeted therapies, impact fertility in young patients with cancer. This knowledge will help move towards a more individualized therapy that balances anti-tumor effectiveness with minimizing toxicity and preserving fertility.