Intravenous Immunoglobulin and Prednisolone for RPL After ART.

• Status: Recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: Female

Summary

Recurrent pregnancy loss (RPL) affects around 5 % of women in reproductive age. The underlying cause of RPL is most often unknown, probably multifactorial, and no treatment with documented effect on chance of live birth exists. In unexplained cases of RPL, primarily the immune system is hypothesized to play a pivotal, causative role, since autoantibodies and specific human leukocyte antigen (HLA) alleles as well as unbalanced distribution of leucocyte subsets, especially natural killer (NK) cells and T-helper (Th) cells, occurs more frequently in patients with unexplained RPL. For that reason, many treatment regimens used in autoimmune diseases have been tested on RPL patients, as for example prednisolone and intravenous immunoglobulin (IVIg).

IVIg (Privigen) consist of a broad spectrum of structurally and functionally intact IgG antibodies. The mechanism of action is not fully elucidated, but certainly IVIg do help opsonise and neutralize foreign cells and pathogens. Prednisolone support this anti-inflammatory action by suppressing migration of polymorphonuclear leukocytes, and reducing volume of the immune system, capillary permeability, and immune cell activity.

A retrospective, observational pilot study suggested that a combination of prednisone and IVIg in first trimester improves the chance of a live birth in women with RPL after assisted reproductive technologies (ART) (Nyborg et al., 2014).

A randomized controlled study is necessary for determining if this immunomodulatory treatment is definitely effective in patients with unexplained RPL after ART (defined as IVF or ICSI treatment). Potentially, this study will be able to establish a new treatment to women with unexplained RPL after ART, who otherwise have a poor prognosis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Caroline Nørgaard-Pedersen
• Collaborators: Beckett Foundation; Clinical Immunological Department, Aalborg University Hospital; GCP department of Aalborg University Hospital; L.F. Foghts Foundation; Svend Andersen Fonden; The Pharmacy of Aalborg University Hospital
• Treatments: Antibodies; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Prednisolone; Rho(D) Immune Globulin

Criteria

Inclusion Criteria:

• Women with ≥ 2 consecutive pregnancy losses (miscarriages or biochemical pregnancies) ≤ completed gestational week 10 after ART with the present partner or with an egg/semen donor

Exclusion Criteria:

1. BMI ≥35

2. Age ≥41

3. Significant uterine malformation(s)

4. Known parental balanced chromosomal translocations

5. ≥2 previous pregnancies with fetuses with known abnormal karyotype

6. Patients with IgA deficiency, IgA-autoantibodies or hyperprolinaemia

7. Treatment with medication interacting with prednisolone

• CYP3A4-inhibitors (fx erythromycin, itraconazole, ritonavir, lopinavir), CYP3A4-inductors (fx phenobarbital, phenytoin og rifampicin), loop diuretics, thiazides, amphotericin B, beta2-agonists, antidiabetics, interleukin-2, somatotropins, anticholinergics and regular treatment with NSAIDs.

8. Patients with moderate/severe hypertension, diabetes mellitus, heart insufficiency, severe mental disorders, Cushing syndrome, myasthenia gravis, ocular herpes simplex, pheochromocytoma, systemic sclerosis, and moderate/severe renal dysfunction.

9. Patients with a clinical or biochemical profile indicating need for heparin or levothyroxine treatment during pregnancy

10. Previous treatment with IVIg

11. Allergy to prednisolone and/or IVIg

12. AMH <4 pmol/L. If transfer of donor egg is planned for her IVF cycle, the AMH value will not be an exclusion criterion.