Relating the number of human leucocytes antigen mismatches to pregnancy complications in oocyte donation pregnancies: study protocol for a prospective multicentre cohort study (DONOR study)

INTRODUCTION: Oocyte donation (OD) enables women with reproductive failure to conceive. Compared with naturally conceived (NC) and in vitrofertilisation (IVF) pregnancies, OD pregnancies are associated with a higher risk of pregnancy complications. The allogeneic nature of the fetus in OD pregnancies possibly plays a role in the development of these complications. The objective of the current study is therefore to study the number and nature of human leucocyte antigen (HLA) mismatches between fetus and mother and its association with the development of hypertensive pregnancy complications. METHODS AND ANALYSIS: In this prospective multicentre cohort study, 200 patients visiting one of the 11 participating fertility centres in the Netherlands to perform OD or embryo donation or surrogacy will be invited to participate. These patients will be included as the exposed group. In addition, 146 patients with a NC pregnancy and 146 patients who applied for non-donor IVF are included as non-exposed subjects. These groups are frequency matched on age and ethnicity and only singleton pregnancies will be included. The primary clinical outcome of the study is the development of hypertensive disease during pregnancy. Secondary outcomes are the severity of the pre-eclampsia, time to development of pre-eclampsia and development of other pregnancy complications. The association of high number of HLA mismatches (>5) between mother and fetus will be determined and related to clinical outcome and pregnancy complication. ETHICS AND DISSEMINATION: This study received ethical approval from the medical ethics committee in the Leiden University Medical Centre, the Netherlands (P16.048, ABR NL56308.058.16). Study findings will be presented at (inter) national conferences and published in peer-reviewed journals.