Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. METHOD OF THE STUDY: Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2 , non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6-0.8 g/kg was given prior to conception and monthly during pregnancy until 16-20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. RESULTS: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15-10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. CONCLUSION: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL.

Successful Desensitization to mRNA COVID-19 Vaccine in a Case Series of Patients With a History of Anaphylaxis to the First Vaccine Dose.

Background: Coronavirus disease 2109 (COVID-19) vaccines have recently been approved to curb the global pandemic. The risk of allergic reactions to the vaccine polyethylene glycol (PEG) component has raised significant public concern. Desensitization is suggested in cases of vaccine related hypersensitivity reactions. After comprehensive literature review on the topic, our aim was to establish a safe and effective desensitization protocol for patients with suspected or confirmed immediate type hypersensitivity reactions to the COVID-19 vaccine. Methods: Participants were referred to the McGill University Health Center (MUHC) Allergy-Immunology department for clinical evaluation following a reported reaction to their first dose of Moderna® mRNA-1273 or Pfizer-BioNTech® BNT162b2 vaccines. They underwent skin prick testing (SPT) with higher and lower molecular weight (MW) PEG and polysorbate 80, as per published protocols. Their second dose was administered following a desensitization protocol consisting of multiple dose-administration steps followed by a 60-min observation period. Results: Among a cohort of 142 patients with an increased risk for allergic reactions to the COVID-19 vaccines, six individuals were selected to undergo desensitization. All were female with allergic background including chronic spontaneous urticaria, anaphylaxis to medications, and/or vaccines. The main symptom after their first dose was difficulty swallowing with lightheadedness or immediate urticaria, angioedema, and/or dizziness. Two patients had positive skin testing. One patient was on chronic antihistamines which resulted in an inconclusive PEG skin test and the skin testing was negative for the three other patients. During the desensitization, two patients reported cutaneous symptoms of an immediate reaction and were managed with antihistamines. One of these patients also complained of ear pressure and had a drop in her systolic blood pressure, treated with intravenous fluids. Conclusion: This study suggests that some individuals with an immediate-type hypersensitivity reaction to their first dose of mRNA COVID-19 vaccine may safely receive their second dose using a desensitization protocol. The success of this desensitization protocol is a step forward in the fight against COVID-19, allowing more individuals to be immunized.