P-503 Immunological therapies in women undergoing assisted conception: a systematic review and meta-analysis

Abstract Study question What is the effectiveness and safety of immunological therapies in women undergoing assisted conception? Summary answer The evidence on overall immunomodulators was scarce uncertain, although some drugs may lead to improved outcomes selected women. known already Embryo implantation a pre-requisite for pregnancy success. It requires state immune tolerance within maternal endometrium permitting attachment subsequent invasion into decidua semi-allogenic blastocyst. Mechanistic data suggesting that heightened responses impair have led widespread use immunomodulatory clinical practice. These include such as aspirin, heparin, corticosteroids, intralipid intravenous immunoglobulin (IVIG). However, despite common having vitro fertilisation (IVF), there no consensus their safety, owing paucity well-designed interventional studies. design, size, duration We searched MEDLINE, EMBASE, PubMed CENTRAL until September 2022. randomised controlled trials (RCTs) investigating IVF, including granulocyte-colony stimulating factor (G-CSF), intralipid, (IVIG), tumour necrosis factor-alpha inhibitors peripheral blood mononuclear cells (PBMCs), evaluated alone or combination, versus intervention, placebo any other immunomodulator(s). primary were rates live birth ongoing (LBR/OPR) miscarriage per participant. Participants/materials, setting, methods Two reviewers independently studies extracted data. conducted pairwise meta-analyses according participants’ phenotypes reported by trialists, including: good prognosis, previous failure, autoimmunity, high inflammation, thin endometrium, low ovarian reserve. Using Cochrane-RoB-1 tool, we restricted our analyses RCTs at risk selection biases. presented effect estimates ratio (RR) with 95% confidence interval (CI) considered I2>50% representing substantial heterogeneity. Main results role chance Our searches identified 14,893 records. included total 84 qualitative synthesis, which 43 contributed meta-analyses, evaluating 7,301 participants 12 treatment comparisons. analysis showed aspirin resulted little difference LBR (RR 0.97, CI 0.94-1.23; n = 688 women; moderate-certainty evidence) MR 1.20, 0.73-1.99; 988 low-certainty compared placebo. did not identify LBR/OPR using subcutaneous heparin 1.30, 0.80-2.12; 150 very IVIG 1.28, 0.32-5.16; 51 For remaining interventions, uncertain an insufficient quantitative synthesis. sensitivity all studies, irrespective bias, corticosteroids improve thyroid autoimmunity 2.33, 1.04-5.25; 60 evidence); intrauterine G-CSF 2.57, 1.24-5.29; 304 PBMCs failure 2.03, 1.33-3.10; 312 evidence). Limitations, reasons caution most interventions under study, very-low certainty, limitations study imprecision, indirectness inconsistency. Further, few adverse events, highlighting worrying lack conception. Wider implications findings A scarcity limits IVF. positive signals specific conditions (e.g. failure). This merits further investigation high-quality trials. Trial registration number PROSPERO CRD42021294031