Certolizumab in Recurrent Implantation Failure (RIF)
Condition(s) studied
Investigational drug(s) / intervention(s)
Certolizumab (CIMZIA® ; TNF-α antagonist): 400mg of certolizumab injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.
Placebo (NaCl 0.9 % solution): NaCl 0,9% injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.
Study summary
Recurrent implantation failure (RIF), defined as the absence of clinical pregnancy after the transfer of three good-quality embryos, concerns up to 40% of IVF couples and is associated with a low success rate. The causes remain unexplained in over 50% of cases.
Various dysimmune changes (related to immune T cells profiles, pro-inflammatory cytokines levels) have been described in unexplained RIF as compared to fertile controls, and it has been estimated that such dysimmunity may occur in 50% of unexplained RIFs. Previous data on a benefit of general immune modulation by steroids or immunoglobulins are heterogenous and failed to demonstrate clinically significant benefit. The proinflammatory cytokine Tumor Necrosis Factor (TNF) α participates in the regulation of the immune balance of the endometrium, its peripheral blood and endometrial concentrations are increased in RIF patients as compared to fertile controls. In 2009, a pilot placebo controlled study showed that TNF-α antagonist treatment allowed a 56% live birth rate (versus 13% in controls) in 13 women with unexplained RIF. Due to the lack of maternal and fetal tolerance data, TNF-α antagonists were not further evaluated. Today, safety data issued from 1200 pregnancies are reassuring allowing the use of TNF-α antagonists during pregnancy (www.lecrat.org). In addition the TNF-α antagonist certolizumab does not cross the placental barrier.
We hypothesize that certolizumab may improve clinical pregnancy rates in women with unexplained RIF with a good safety profile.
Eligibility
Primary outcome measure(s)
- Clinical pregnancy defined as the presence of cardiac activity on ultrasound scan — 5 weeks +/- 6 days of gestation
Presence of cardiac activity on ultrasound scan at 5 weeks +/- 6 days of gestation
Trial sites (1)
| Facility | City | Region | Status |
|---|---|---|---|
| Saint-Antoine Hospital - APHP | Paris | France | Recruiting |
More Assistance Publique - Hôpitaux de Paris trials in France
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT05930613 on ClinicalTrials.gov ↗ ← All trials in France