Recurrent miscarriages (RM) affects 3% of all fertile couples, but remains unexplained in most cases, limiting therapeutic options. Possibly the maternal immune system plays a role in recurrent miscarriage. Prednisolone suppresses the immune system and might enable development of normal pregnancy.
In this randomized controlled clinical trial the investigators will study the effect of prednisolone on the live birth rate in patients with RM. Secondary, the tolerability and safety for mother and child and the cost-effectiveness is investigated.
In the study one group of pregnant women with RM and gestational age \<7 weeks will receive prednisolone, the other group will receive a placebo. Total use of the medicine during this study is 8 weeks, further care during the study is routinely antenatal care. Subjects will be asked to fill in 4 short questionnaires and will have contact with a research nurse at different time points to gain information on the course of the pregnancy and possible side effects.
Results of the study will be implemented in (inter) national guidelines, to effect everyday practice.
Unexplained recurrent pregnancy loss: defined as the loss of ≥2 pregnancies, without any known cause for RM (parental chromosomal abnormalities, uterine anomalies, acquired or hereditary thrombophilia, endocrine diseases (such as hypothyroidism or diabetes)).
all consecutive or non-consecutive pregnancy losses before the 24th week of gestation verified by ultrasonography or uterine curettage and histology
non-visualized pregnancies (including biochemical pregnancy losses and/or resolved and treated pregnancies of unknown location), verified by positive urine or serum hCG Ectopic and molar pregnancies are not included
Age 18 - 39 years at randomization (likelihood of miscarriages due to chromosomal aberrations is higher when age > 39 years. Such miscarriages are unlikely to be pre-vented by prednisolone therapy)
Any of the following diagnosis for the recurrent miscarriages
Antiphospholipid syndrome (lupus anticoagulant and/ or anticardiolipin anti-bodies and/or beta-2 glycoprotein [IgG or IgM)
Congenital uterine abnormalities (as assessed by 2D or 3d ultrasound, hys-terosonography, hysterosalpingogram or hysteroscopy)
Abnormal parental karyotype
Parallel
Prednisolone
DrugPrednisolone tablets (20 mg daily for 6 weeks, 10 mg daily for 1 week, 5 mg daily for 1 week) or identical placebo tablets for 8 weeks
Placebo
DrugPlacebo identical to prednisolone tablets
Live birth rate
Birth of a living child beyond 24 weeks
Ongoing pregnancy
Fetal heartbeat on ultrasound scan at 12 weeks
Congenital abnormalities
Number of children born with congenital deformity (such as cleft palate)
Gestational age
Gestational age measured in weeks after conception until delivery
Survival at 28 days of neonatal life
Is newborn still alive 28 days after birth
Level of immune cells post intervention
level of uNK cells, regulatory T cells and CD14+/CD163+ macrophages in placenta or miscarriage tissue
Click on the lead sponsor to view all of their trials.
Leiden University Medical Center
Lead sponsor
Amsterdam University Medical Center
Collaborator
Erasmus Medical Center
Collaborator
Academisch Ziekenhuis Groningen
Collaborator
Maastricht University Medical Center
Collaborator
Isala
Collaborator
Catharina Ziekenhuis Eindhoven
Collaborator
Haaglanden Medical Centre
Collaborator
Amphia Hospital
Collaborator
Radboud University Medical Center
Collaborator
Jeroen Bosch Ziekenhuis
Collaborator
Onze Lieve Vrouwe Gasthuis
Collaborator
