Intravenous Immunoglobulin and Prednisolone for RPL After ART.

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 the volume and activity of the immune system and the capillary permeability.

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 definitely is effective in patients with unexplained RPL after ART (defined as IVF or ICSI ad FER). Potentially, this study will be able to establish evidence for an effective treatment to women with unexplained RPL after ART, who otherwise have a poor prognosis.

Conditions

• Habitual Abortion
• Recurrent Pregnancy Loss
• Fertility Disorders
• Miscarriage

Interventions

DRUG

Human Intravenous Immunoglobulins, (Privigen (R), CLS Behring)

infusion: Initial infusion rate of 0.3 ml/kg BW/hr in about 30 min. If well-tolerated, the infusion rate may gradually be increased to 4.8 ml/kg BW/hr. During the infusion, health care personnel are present to secure immediate action in case of serious AR. Blood pressure and pulse is monitored before, during and after the treatment. In case of anaphylaxis, the treatment is discontinued and the participant is excluded. The hospital ward possess adrenaline 0.1 % solutions ready in case of anaphylaxis.

DRUG

Prednisolone Tablets

5 mg before ET and 10 mg after ET until gestational week 8+0

DRUG

Human Albumin Solution

Infusion: Initial infusion rate of 0.3 ml/kg BW/hr in about 30 min. If well-tolerated, the infusion rate may gradually be increased to 4.8 ml/kg BW/hr. During the infusion, health care personnel are present to secure immediate action in case of serious AR. Blood pressure and pulse is monitored before, during and after the treatment. In case of anaphylaxis, the treatment is discontinued and the participant is excluded. The hospital ward possess adrenaline 0.1 % solutions ready in case of anaphylaxis.

DRUG

Placebo tablet

1 tablet before ET and 2 tablets after ET until gestational week 8+0

Sponsors & Collaborators

• Svend Andersen Fonden

  collaborator UNKNOWN

• Beckett Foundation

  collaborator OTHER

• L.F. Foghts Foundation

  collaborator UNKNOWN

• Aalborg University Hospital

  lead OTHER

Principal Investigators

• Ole B Christiansen · Aalborg University Hospital, Denmark

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

41 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-01-28

Primary Completion

2024-04-18

Completion

2024-04-18

Countries

• Denmark

Study Locations