Development of hypertensive complications in oocyte donation pregnancy: protocol for a systematic review and individual participant data meta-analysis (DONOR IPD).

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. 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.

Evidence-Based Pre-Pregnancy Counseling for Oocyte Donation Pregnancies: a Systematic Review and Guide for Physicians.

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 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.In conclusion, we provide a summary of the most important outcomes in OD pregnancies, and thereby offer a guide for pre-pregnancy counseling.

Different immunoregulatory components at the decidua basalis of oocyte donation pregnancies.

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) 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-ß 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.

Significance of specialised preconception counselling in oocyte donation pregnancy with prior history of postpartum eclampsia.

A well-known complication in oocyte donation (OD) pregnancy is preeclampsia. Here, we present a 31-year-old woman, pregnant after OD. She conceived by the reception of the oocyte from her partner (ROPA) and sperm from a sperm donor. She developed preeclampsia with severe features, necessitating caesarean delivery at 29 weeks' gestation due to deterioration of her clinical condition. Admission at the intensive care unit postpartum was necessary, because of recurrent postpartum eclampsia and administration of high dose magnesium sulphate for convulsion prophylaxis. This case illustrates the importance of preconception counselling for patients who are considering to conceive by OD and double gamete donation. In this specific case an alternative way to conceive was available. However, ROPA was preferred as part of shared lesbian motherhood. The risk of complications in the subsequent pregnancy has led to an alternative decision to accomplish a second pregnancy.

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.