O-275 Becoming parents after hematopoietic stem cells transplantation: obstetrics outcomes of spontaneous pregnancies
Authors: Massarotti C , Chiodi S , Spinelli S , Stigliani S , Angelucci E , Anserini P 
Published: June 2023

Abstract

Study question
Are spontaneous pregnancies after hematopoietic stem cells transplantation (HSCT) of one of the two partners burdened with an increased risk of obstetric complications?

Summary answer
We found a higher risk of Intrauterine growth restriction (IUGR) and preterm delivery after both maternal and paternal HSCT and of pre-eclampsia after maternal HSCT.

What is known already
Conditioning therapies for HSCT are highly gonadotoxic and result in permanent amenorrhea or azoospermia in 70% of patients. Small cohorts of pregnancies after HSCT show an increased risk of complications such as dysfunctional placentation, IUGR or preterm birth. With no more than 9% of survivors reporting a spontaneous pregnancy and the others using of cryopreserved material or gametes donation, it is difficult to untangle the effect of assisted reproduction techniques, gametes donation, radiation on the uterus, and HSCT itself.

Study design, size, duration
This is a retrospective analysis of all spontaneous pregnancies among patients who underwent HSCT for haematological malignancies in a single national referral centre between 1990 and 2016. Obstetric and neonatal outcomes are reported to be compared to the expected incidence in the general population. All patients signed a general informed consent for the use of their anonymized data for research and we obtained the local ethics committee approval.

Participants/materials, setting, methods
We collected the outcome of 53 pregnancies in 30 women after HSCT and 33 pregnancies from 22 men after HSCT. The malignancies treated with HSCT were leukaemia (15 females and 14 males), severe aplastic anaemia (12 and 10), Hodgkin’s lymphoma (2 and 1) and myelofibrosis (1 and 1). The conditioning regimen included total body irradiation (TBI) in 20 women (66.7%) and 8 men (36.4%). All patients we included conceived spontaneously after HSCT.

Main results and the role of chance
We observed 53 pregnancies (52 singletons and 1 monochorionic diamniotic twin pregnancy) in women, 12±5.3 years after HSCT. Nine (16.9%) resulted in an early miscarriage. Of the other 44, 15 (34.1%) were uneventful and resulted in a healthy baby born at term. We observed 10 (22.7%) preterm deliveries: 4 very preterm births (1 at 29 and 3 at 31 weeks; 2 spontaneous 2 iatrogenic for pre-eclampsia); 5 moderate preterm births (32 weeks; 4 spontaneous and 1 iatrogenic for pre-eclampsia); 1 late preterm birth (36 weeks, iatrogenic for pre-eclampsia). The incidence of hypertensive disorders in all pregnancies was high (10, 22.7%). In 9 pregnancies (20.5%) there was evidence of IUGR, one of which resulted in an intrauterine foetal death at 35 weeks of gestation. Half of the patients delivered through caesarean section (20, 45.5%). We also reported 33 pregnancies fathered by 22 men who underwent HSCT 7.3±4.3 years earlier. Two pregnancies (6.1%) ended in an early miscarriage. Sixteen of the other 31 pregnancies (51.6%) were uneventful. In 12 cases (38.7%) there was evidence of IUGR, leading to 5 iatrogenic preterm births (16.1%). No maternal hypertensive disorder of pregnancy was reported.

Limitations, reasons for caution
While this is, as far as we know, the largest cohort of spontaneous pregnancies after HSCT present in the literature, the numerosity is still low and we cannot exclude larger numbers would have produced different results.

Wider implications of the findings
HSCT has consequences on reproduction, behind infertility. Pregnancies after HSCT should be followed in a high-risk setting, collecting data collaboratively. The next research effort should be focused on understanding the specific action of the different conditioning therapies used in females and males, to unveil the biological rationale behind these findings.

Trial registration number
not applicable