Introduction The assisted reproductive technique of oocyte donation (OD) is comparable to in vitro fertilisation (IVF), with the distinction of using a donated oocyte and thus involving two women.... Show moreIntroduction The assisted reproductive technique of oocyte donation (OD) is comparable to in vitro fertilisation (IVF), with the distinction of using a donated oocyte and thus involving two women. Compared with IVF and naturally conceived (NC) pregnancies, OD pregnancies have a higher risk for pregnancy complications as pregnancy-induced hypertension (PIH) and pre-eclampsia (PE). Various covariates among women pregnant by OD, however, also contribute to an increased risk for developing hypertensive complications. Therefore, we will conduct the DONation of Oocytes in Reproduction individual participant data (DONOR IPD) meta-analysis to determine the risk for the development of hypertensive complications in OD pregnancy, in comparison to autologous oocyte pregnancy (non-donor IVF/intracytoplasmic sperm injection (ICSI) and NC pregnancy). The DONOR IPD meta-analysis will provide an opportunity to adjust for confounders and perform subgroup analyses. Furthermore, IPD will be used to externally validate a prediction model for the development of PE in OD pregnancy. Methods and analysis A systematic literature search will be performed to search for studies that included women pregnant by OD, and documented on hypertensive complications in OD pregnancy. The authors from each study will be asked to collaborate and share IPD. Using the pseudoanonymised combined IPD, we will perform statistical analyses with one-stage and two-stage approaches, subgroup analyses and possibly time-to-event analyses to investigate the risk of developing hypertensive complications in OD pregnancy. Furthermore, we will formally assess a prediction model on its performance in an external validation with the use of IPD. Ethics and dissemination Ethical approval and individual patient consent will not be required in most cases since this IPD meta-analysis will use existing pseudoanonymised data from cohort studies. Results will be disseminated through peer-reviewed journals and international conferences. PROSPERO registration number CRD42021267908. Show less
Bentem, K. van; Bos, M.; Keur, C. van der; Kapsenberg, H.; Lashley, E.; Eikmans, M.; Hoorn, M.L. van der 2022
Oocyte donation (OD) pregnancies are characterized by more fetal-maternal human leukocyte antigen (HLA) mismatches compared with naturally conceived (NC) and in vitro fertilization (IVF)... Show moreOocyte donation (OD) pregnancies are characterized by more fetal-maternal human leukocyte antigen (HLA) mismatches compared with naturally conceived (NC) and in vitro fertilization (IVF) pregnancies. The maternal immune system has to cope with greater immunogenetic dissimilarity, but involved immunoregulation remains poorly understood. We examined whether the amount of regulatory T cells (Tregs) and immunoregulatory cytokines in decidua basalis of OD pregnancies differs from NC and IVF pregnancies. The cohort included 25 OD, 11 IVF and 16 NC placentas, maternal peripheral blood, and umbilical cord blood of uncomplicated pregnancies. Placenta slides were stained for FOXP3, IL-10, IL-6, gal-1, TGF-0 and Flt-1. Semi-quantitative (FOXP3+ Tregs) and computerized analysis (cytokines) were executed. The blood samples were typed for HLA class I and II to calculate fetal-maternal HLA mismatches. The percentage of Tregs was significantly higher in pregnancies with 4-6 HLA class I mismatches (n = 17), compared to 0-3 mismatches (n = 35; p = 0.04). Cytokine analysis showed significant differences between OD, IVF and NC pregnancies. Flt-1 was significantly lower in pregnancies with 4-6 HLA class I mismatches (p = 0.004), and in pregnancies with 6-10 HLA mismatches in total (p = 0.024). This study suggests that immunoregulation at the fetal-maternal interface in OD pregnancies with more fetal-maternal HLA mismatches is altered.(c) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
Hoorn, M.L. van der; Bentem, K. van; Lashley, E. 2022
It is well known that oocyte donation (OD) pregnancies are associated with higher complication rates compared to autologous pregnancies. However, evidence-based information for pre-pregnancy... Show moreIt is well known that oocyte donation (OD) pregnancies are associated with higher complication rates compared to autologous pregnancies. However, evidence-based information for pre-pregnancy counseling designed for health care workers is scarce. Therefore, a systematic literature search was performed to find articles that address pre-pregnancy counseling before OD. A systematic search was conducted in September 2020 in various databases, including PubMed and Embase. Nine (systematic) reviews and meta-analyses were included that reported on pre-pregnancy advice in OD pregnancies. Studies are consistent in documenting a higher risk for hypertensive disorders, cesarean section, preterm birth, postpartum hemorrhage, and low birth weight. Based on these complications, pre-pregnancy advice is mentioned in all included systematic reviews to prevent complications in the next pregnancy. All studies recommend counseling women on the increased risk of complications during OD pregnancy. Other recommendations include the prophylactic use of aspirin in pregnancy and restriction to single embryo transfer. Individualized appropriate surveillance and management strategies should be considered for every patient achieving pregnancy by OD. Show less
Bentem, K. van; Bos, M.; Keur, C. van der; Kapsenberg, H.; Lashley, E.; Eikmans, M.; Hoorn, M.L. van der 2021
In oocyte donation (OD) pregnancy, a fetus can be completely allogeneic to the recipient. Consequently, the maternal immune system has to cope with greater immunogenetic dissimilarity compared to... Show moreIn oocyte donation (OD) pregnancy, a fetus can be completely allogeneic to the recipient. Consequently, the maternal immune system has to cope with greater immunogenetic dissimilarity compared to naturally conceived pregnancy. Previously, we showed an association between successful OD pregnancy and lower immunogenetic dissimilarity, reflected by the number of fetal-maternal Human Leukocyte Antigen (HLA) mismatches, than expected by chance. In this study we aimed to determine whether the development of preeclampsia in OD pregnancies is related to the number of fetal-maternal HLA mismatches.A retrospective, nested case-control study was performed within a cohort of 76 singleton OD pregnancies. Maternal and fetal umbilical cord blood was typed for HLA-A, -B, -C, -DR and -DQ, and the number of fetal-maternal HLA mismatches was calculated. In addition, the incidence of child-specific HLA antibodies was determined.13 pregnancies were complicated by preeclampsia. To demonstrate an influence of HLA mismatches on the development of preeclampsia, a univariate logistic regression analysis was performed adjusted for maternal age and socio-economic status. A significant association between the number of fetal-maternal HLA class II mismatches and the development of preeclampsia was observed (OR = 3.8, 95 % CI: 1.6-9.0; p = 0.003). This association was not linked to the development of HLA class II antibodies.According to our findings, an increased number of HLA class II mismatches is a risk factor for the development of preeclampsia in OD pregnancies. The effect of HLA class II mismatches might be explained by the induction of a cellular rather than a humoral immune response. Show less
Bentem, K. van; Lashley, E.; Bos, M.; Eikmans, M.; Heidt, S.; Claas, F.; ... ; Hoorn, M.L. van der 2019
