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

Einav Kadour Peero; Shorooq Banjar; Rabea Khoudja; Shaonie Ton-Leclerc; Coralie Beauchamp; Joanne Benoit; Marc Beltempo; Michael H Dahan; Phil Gold; Isaac Jacques Kadoch; Wael Jamal; Carl Laskin; Neal Mahutte; Simon Phillips; Camille Sylvestre; Shauna Reinblatt; Bruce D Mazer; William Buckett; Genevieve Genest

doi:10.1038/s41598-024-54423-z

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

Sci Rep. 2024 Feb 16;14(1):3876. doi: 10.1038/s41598-024-54423-z.

Authors

Einav Kadour Peero¹, Shorooq Banjar², Rabea Khoudja³, Shaonie Ton-Leclerc⁴, Coralie Beauchamp^{5

6}, Joanne Benoit^{5

6}, Marc Beltempo⁷, Michael H Dahan⁸, Phil Gold⁹, Isaac Jacques Kadoch^{5

6}, Wael Jamal^{10

11}, Carl Laskin^{12

13}, Neal Mahutte¹⁴, Simon Phillips^{10

15}, Camille Sylvestre^{5

16}, Shauna Reinblatt^{8

17}, Bruce D Mazer^{18

19}, William Buckett^{8

17}, Genevieve Genest²⁰

Affiliations

¹ Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Bnai-Zion Medical Center, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
² Division of Clinical Immunology and Allergy, Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Division of Clinical Immunology and Allergy, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada.
⁴ Department of Medicine, Queen's University, Kingston, ON, Canada.
⁵ Ovo Clinic, 8000 Boulevard Decarie, Montréal, QC, H4P 2S4, Canada.
⁶ Obstetrics and Gynaecology Department, University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, QC, H3T 1J4, Canada.
⁷ Division of Neonatology, Montreal Children's Hospital - McGill University Health Centre, Montreal, QC, Canada.
⁸ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, McGill University Health Centre, Montréal, QC, Canada.
⁹ Department of Allergy and Immunology, Montreal General Hospital, 1650 Cedar Ave. A6-123, Montreal, QC, H3G 1A4, Canada.
¹⁰ Clinique OVO, 8000 boulevard Décarie, Montréal, QC, H4P 2S4, Canada.
¹¹ Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.
¹² TRIO Fertility, 655 Bay St, Toronto, ON, M5G 2K4, Canada.
¹³ Deptartments of Medicine and Obstetrics & Gynecology University of Toronto, 27 King's College Cir, Toronto, ON, M5S, Canada.
¹⁴ The Montreal Fertility Centre, 5252 de Maisonneuve Blvd West, Suite 220, Montreal, QC, H4A 3S5, Canada.
¹⁵ Faculty of Medicine, University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, QC, H3T 1J4, Canada.
¹⁶ Division of Reproductive Endocrinology and Infertility, University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, QC, H3T1J4, Canada.
¹⁷ McGill University Health Care Reproductive Center, 888 Boul. De Maisonneuve E# 200, Montreal, QC, H2L 4S8, Canada.
¹⁸ Department of Pediatrics, Division of Allergy Immunology and Clinical Dermatology, Montreal Children's Hospital, McGill University, Montréal, QC, Canada.
¹⁹ Program in Translational Research in Respiratory Diseases, Research Institute of the McGill, University Health Centre, Montréal, QC, Canada.
²⁰ Division of Clinical Immunology and Allergy, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada. genevieve.genest@mail.mcgill.ca.

Abstract

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.

Keywords: Immune-mediated recurrent implantation failure; Intravenous immunoglobulin; Reproductive immunology; Unexplained recurrent implantation failure.

MeSH terms

Birth Rate
Female
Humans
Immunoglobulins, Intravenous* / adverse effects
Live Birth
Pregnancy
Retrospective Studies

Substances

Immunoglobulins, Intravenous