P-364 Is the frequency of low plasma-mannose-binding lectin levels increased in recurrent pregnancy loss after spontaneous conception or IVF/ICSI and recurrent implantation failure?
Authors: Nørgaard-Pedersen C , Kesmodel U. Schiøler , Christiansen O.B 
Published: June 2022

Abstract

Study question
Is the frequency of low plasma-mannose-binding lectin (p-MBL) levels increased in recurrent pregnancy loss (RPL) after spontaneous conception or IVF/ICSI and recurrent implantation failure (RIF)?

Summary answer
The frequency of low p-MBL levels in RPL after spontaneous conception and IVF/ICSI, and after RIF, respectively, was significantly increased compared to female controls.

What is known already
MBL is an important complement-related factor binding to surface-bound carbohydrates on pathogens and apoptotic cell debris. A low p-MBL level has been associated with RPL. RPL probably shares some risk factors with RIF and consequently, the same examinations and interventions are often used for both disorders. No study has explored if a low p-MBL level is equally associated with RPL after spontaneous conception, and RPL and RIF after IVF/ICSI.

Study design, size, duration
A cross sectional study including 540 patients admitted to the RPL Center of Western Denmark, from January 2016 to January 2022, who had a blood sample taken at the first consultation. P-MBL level was measured in all patients and in 185 non-pregnant female blood donors who comprised the control group. One laboratory performed all p-MBL measurements using a sandwich-ELISA with monoclonal antibodies selective for normally oligomerized MBL.

Participants/materials, setting, methods
Patients with chromosomal aberrations and uterine malformations as well as patients with &lt;3 pregnancy losses were excluded (n = 60). Patients were divided into four groups: 1) RPL after spontaneous conception (n = 366), 2) RPL after IVF/ICSI/FET (n = 84), 3) RPL after a combination of pregnancy losses after spontaneous conception and IVF/ICSI (n = 43) and 4) RIF with ≥3 embryo transfers and no clinical pregnancy (n = 47).

Main results and the role of chance
In all groups except from group 2 with RPL after assisted reproduction, a significantly higherfrequency of a low p-MBL levels (&lt;500 mg/l) was found compared to controls (Group 1) 39.1%, OR 1.9, 95% CI 1.3-2.9, p = 0.001; 2) 31.0%, OR 1.4, 95% CI 0.7-2.4, p = 0.29; 3) 41.9%, OR 2.2, 95% CI 1.1-4.3, p = 0.025; and 4) 53.2%, OR 3.4, 95% CI 1.8-6.7, p &lt; 0.001, respectively, versus controls 24.9%). Furthermore, in all four groups of patients, a significantly lower frequency of a high p-MBL level (&gt;3000 mg/l) was found (Group 1) 16.9%, OR 0.45, 95% CI 0.30-0.69, p &lt; 0.001; 2) 11.9%, OR 0.30, 95% CI 0.15-0.62, p &lt; 0.001; 3) 14.0%, OR 0.36, 95% CI 0.15-0.91, p = 0.026; and 4) 14.9%, OR 0.39, 95% CI 0.17-0.93, p = 0.029, respectively, versus controls 30.8%), while comparing the frequency of intermediate p-MBL levels between patient groups and controls showed no significant differences.

Limitations, reasons for caution
Patients referred to the tertiary RPL center have mainly experienced RPL after spontaneous conception. Therefore, data on only few patients with RPL and especially RIF after IVF/ICSI were available rendering estimates relatively uncertain. Nevertheless, the comparable ORs seem convincing for low p-MBL being a risk factor for reproductive failure.

Wider implications of the findings
This new information on MBL supports the theory that MBL is involved in the pathogenesis of reproductive failure, however, larger studies are needed to confirm the association and to elaborate the exact role of MBL in the RIF and RPL pathogenesis.

Trial registration number
2018-5