Fertility Issues in Patients With Inherited Bone Marrow Failure Syndromes

More patients with inherited bone marrow failure syndromes (IBMFS) are surviving to adulthood. As they do, they face barriers to pregnancy. It is still not clear how to counsel them on anticipated pregnancy outcomes, or optimal pregnancy management.

In two Letters to the Editor published in Blood, authors reported case studies of patients with IBMFS (such as Fanconi anemia [FA], Diamond-Blackfan anemia [DBA], Shwachman-Diamond syndrome [SDS], and severe congenital neutropenia [SCN]) who became pregnant. Both research teams found that infertility and pregnancy loss were significant issues, but, despite complications related to the underlying disease, healthy live births were possible.

To better understand these issues, John M. Gansner, MD, PhD, of the Hematology Division at Brigham and Women’s Hospital in Boston, Massachusetts, and co-authors searched the Partners HealthCare Research Patient Data Registry for women who were diagnosed with IBMFS and saw an obstetrician or gynecologist in the Partners HealthCare system between January 1991 and December 2016.1

They identified 25 women with IBMFS:

  • 7 with FA
  • 4 with DBA
  • 3 with telomere biology disorder/dyskeratosis congenita (TBD/DKC)
  • 2 with SDS
  • 1 with SCN

Seventeen patients were excluded from the analysis because they had no documented pregnancies. “Infertility was strikingly common [in this IBMFS population],” the authors wrote, noting that no pregnancies occurred in the seven patients with FA, which may be attributed to premature ovarian failure. “Given [this finding], it would be reasonable to consider oocyte preservation at a young age in [patients with FA],” the authors wrote.

There were a total of 17 pregnancies among the remaining eight patients: four with DBA, two with TBD/DKC, and two with SDS. The pregnancies resulted in five successful live births (4 cesarean sections and 1 spontaneous vaginal delivery), eight spontaneous abortions (4 with documented fetal cardiac activity prior to demise), two elective abortions, one intrauterine fetal death, and one ongoing pregnancy.

All but one pregnancy was conceived without in vitro fertilization and none of the patients became pregnant after hematopoietic cell transplantation (HCT).

Though “the optimal management of cytopenias during pregnancy in patients with IBMFS has not been defined,” the authors reported that some did receive transfusion support.

For example, in one patient with TBD/DKC who had short telomeres and a heterozygous TERC mutation previously reported to be disease-causing, anemia and thrombocytopenia worsened early in each of her three pregnancies but rebounded. Epoetin alfa did not prevent the need for red blood cell (RBC) transfusion during her first pregnancy, which ended in intrauterine fetal death. RBC and platelet transfusions were performed during third pregnancy, but she developed transient severe hypertension in the setting of an RBC transfusion and was monitored until delivery.

Another patient who had SDS was supported with platelet transfusions during her fourth pregnancy. She received romiplostim 5 mg/kg in two doses during pregnancy, but there was no clear effect on the platelet count.

A third patient with severe congenital neutropenia received granulocyte colony-stimulating factor, but, despite maintaining an absolute neutrophil count >1.0×109/L, she still suffered infectious complications, including chorioamnionitis, mastitis, and poor wound healing at cesarean section site.

“Our experience supports the need for multidisciplinary collaboration in caring for patients with IBMFS who are pregnant or desire pregnancy,” the authors concluded. “In addition to the team of hematologists, maternal-fetal medicine specialists, fertility specialists, and neonatologists, input from other specialists may be helpful.”

In a follow-up to Dr. Gansner’s article, Neelam Giri, MD, MBBS, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI) in Bethesda, Maryland, and co-authors presented data from a larger cohort of women with IBMFS who became pregnant, noting that their findings reinforce “that these rare patients have reduced numbers [of pregnancies] and complicated pregnancies.”2

Using data from the NCI’s IBMFS program, which opened in 2002 and enrolls volunteer patients based on self-referral and chart review, the authors identified 67 women with IBMFS who had 102 pregnancies:

  • 25 with FA
  • 23 with DKC
  • 16 with DBA
  • 3 with SDS

Seven patients had undergone HCT.

The pregnancies resulted in 25 miscarriages and 71 live births (including 16 preterm births, 55 full-term births, and 26 cesarean sections). The researchers noted that the number of primary cesarean sections appeared to be high, which was “perhaps related to material hematopoietic problems and preeclampsia.”

As in the Partners HealthCare population, NCI IBMFS patients likely due to primary ovarian insufficiency. Patients with FA also had an increase in premature births and cesarean sections, as well as decreased hematopoiesis during gestation.

Patients with DKC had normal fertility, but also an increase in miscarriages, premature births, and cesarean sections, as well as decreased hematopoiesis.

Although hematologic complications will worsen during pregnancy, “in most cases, [these] will be transient, and the women will return to pre-pregnancy hematologic status,” the authors concluded, adding that, “despite the increased maternal and obstetric complication, most of the live-born babies were clinically well, although half of the babies from mothers with a dominant syndrome would be expected to be affected” with the same IBMFS.

The NCI researchers agreed with the conclusions by Dr. Gansner and colleagues that “women with any IBMFS who desire pregnancy or are pregnant would benefit from care provided by a multidisciplinary team of fertility specialists, high-risk maternal-fetal specialists, neonatologists, and hematologists with expertise in bone marrow failure disorders.”

Also, because this patient population is at a variably increased risk of cancer, they should receive appropriate counseling and surveillance during and after pregnancy.

The findings presented in each of these reports will need to be explored in larger patient populations, the authors noted, and the findings are limited by the inclusion of patients who were cared for at specialty centers, and missing data about referrals.

Authors on both research teams report no conflicts.


  1. Giri N, Stratton P, Savage SA, et al. Pregnancies in patients with inherited bone marrow failure syndromes in the NCI cohort. Blood. 2017 August 24. [Epub ahead of print]
  2. Gansner JM, Achebe MM, Gray KJ, et al. Pregnancy outcomes in inherited bone marrow failure syndromes. Blood. 2017 August 10. [Epub ahead of print]