Unsupervised analysis approach reveals increased endometrial NKp30 frequency in patients with idiopathic RPL

Research into fetal development and medicin

Immunological challenges during pregnancy : preeclampsia and egg donation

Human pregnancy is an interesting immunological paradox. The fetus is a semi-allograft, carrying paternal and maternal genes but is not rejected by the maternal immune system. The placenta is a key player in maintaining the pregnancy, since this fetus-derived organ is in direct contact with the mother. This thesis describes the results of investigations on the immune regulation at the fetal-maternal interface with emphasis on two immunological challenges during pregnancy. First, preeclampsia, which might be immunologically related to host versus graft disease as seen in solid organ transplantation and second, egg donation (ED) pregnancies, which show that even complete allogeneic fetal allografts can be tolerated by the mother. The immunological mechanisms involved in acceptance of the totally allogeneic fetus in ED pregnancies are not well understood yet. It is possible that it leads to differential immunological regulation. This hypothesis is tested in this thesis. We found differential immunological interactions in successful ED and in preeclamptic pregnancies compared with naturally conceived pregnancies. These results indicate that preeclampsia and ED pregnancies are indeed immunological challenges during pregnancy. It is a scientific challenge to further reveal the immunological mechanisms, contributing to precious information for the fields of immunology, transplantation and obstetrics

Value of Ethnicity or Race in More Accurate Prediction of Future Outcome in Couples with Recurrent Miscarriages

This special issue of Reproductive Sciences is focusing on ethnic health disparity and its impact on (fe)male reproduction. Indeed, studies regarding underlying mechanisms, interventions and prognosis in reproduction are underexposed for the non-White male and female. Here, we call for documentation of race and ethnicity in the analysis and management of couples with recurrent pregnancy loss

The Role of Macrophages in Oocyte Donation Pregnancy: A Systematic Review

The embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which leads to a more serious challenge for the maternal immune system to tolerize the fetus. It is thought that macrophages are essential in maintaining a healthy pregnancy, by acting in immunomodulation and spiral arterial remodeling. OD pregnancies represent an interesting model to study complex immunologic interactions between the fetus and the pregnant woman since the embryo is totally allogeneic compared to the mother. Here, we describe a narrative review on the role of macrophages and pregnancy and a systematic review was performed on the role of macrophages in OD pregnancies. Searches were made in different databases and the titles and abstracts were evaluated by three independent authors. In total, four articles were included on OD pregnancies and macrophages. Among these articles, some findings are conflicting between studies, indicating that more research is needed in this area. From current research, we could identify that there are multiple subtypes of macrophages, having diverse biological effects, and that the ratio between subtypes is altered during gestation and in aberrant pregnancy. The study of macrophages' phenotypes and their functions in OD pregnancies might be beneficial to better understand the maternal-fetal tolerance system.Research into fetal development and medicin

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

Gynecolog

Oocyte donation pregnancy, a major challenge for the maternal immune system

Transplantation and autoimmunit

Dizygotic twin pregnancy after transfer of one embryo

Objective: To consider the risk of intercourse without contraception during infertility treatment. Design: Case report. Setting: Leiden University Medical Center. Patient(s): An infertile couple underwent IVF for tubal pathology. Intervention(s): Transfer of one embryo during a natural cycle. Main Outcome Measure(s): Human leukocyte antigen typing, histochemical analysis of the fetal membranes, neonatal and maternal clinical outcomes. Result(s): A dizygotic twin pregnancy was confirmed after birth by human leukocyte antigen typing of both fetuses and mother and by histochemical analysis of the dividing fetal membranes. This suggests a pregnancy of concurrent IVF and spontaneous conception. Pregnancy was complicated by preeclampsia and intrauterine growth retardation of both fetuses. Conclusion(s): We state that couples should abstain from intercourse without contraception during infertility treatment to prevent multiple gestation and its related complications for mother and fetuses. (Fertil Steril (R) 2011;95:805.e1-e3. (C)2011 by American Society for Reproductive Medicine.)Transplantation and autoimmunit

Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

Appropriate development of the placenta is required for healthy pregnancy to occur. After implantation of the fertilized blastocyst, fetal trophoblasts invade the endometrium and myometrium of the mother's uterus to establish placentation. In this process, fetal trophoblasts encounter maternal immune cells. In this review, we focus on the role of maternal T cells and myeloid cells (macrophages, dendritic cells) in pregnancy and their interaction with trophoblasts. To retain immunologic tolerization, trophoblasts evade immune recognition by T cells and produce factors that modulate their phenotype and function. On top of that, the local environment at the maternal-fetal interface favors expansion of regulatory T cells. Macrophages and dendritic cells are essential in maintaining a healthy pregnancy. They produce soluble factors and act as antigen-presenting cells, thereby interacting with T cells. Herein, M2 macrophages, immature dendritic cells, CD4(+)Th2 cells, and regulatory T cells represent an axis that maintains a local immune tolerant environment. We consider outstanding issues concerning these cell types and their pathways, which need to be addressed in future investigations. Data from recent single-cell sequencing experiments of the placental bed, to study heterogeneity of maternal immune cells and to predict cell-cell interactions, are discussed. Novel ways for long-term culturing of primary trophoblasts allow for cell-cell interaction studies in a functional way. Future directions should include study of the functionality of currently known and newly identified decidual immune cell subsets in healthy and complicated pregnancies, and their interaction with and modulation by trophoblast cells.Research into fetal development and medicin

Defining recurrent pregnancy loss: associated factors and prognosis in couples with two versus three or more pregnancy losses

Research question: The definition of recurrent pregnancy loss (RPL) differs internationally. The European Society of Human Reproduction and Embryology (ESHRE) defines RPL as two or more pregnancy losses. Different definitions lead, however, to different approaches to care for couples with RPL. This study aimed to determine whether the distribution of RPL-associated factors was different in couples with two versus three or more pregnancy losses. If a similar distribution were found, couples with two pregnancy losses should be eligible for the same care pathway as couples with three pregnancy losses.Design: This single-centre, retrospective cohort study investigated 383 couples included from 2012 to 2016 at the Leiden University Medical Center RPL clinic. Details on age, body mass index, smoking status, number of pregnancy losses, mean time to pregnancy loss and performed investigations were collected. The prevalence of uterine anomalies, antiphospholipid syndrome, hereditary thrombophilia, hyperhomocysteinaemia, chromosomal abnormalities and positive thyroid peroxidase antibodies were compared in couples with two versus three or more pregnancy losses.Results: No associated factor was found in 71.5% of couples with RPL. This did not differ statistically between couples with two versus three or more pregnancy losses (73.6% versus 70.6%; P = 0.569). The distribution of investigated causes did not differ between the two groups.Conclusions: As the distribution of associated factors in couples with two versus three or more pregnancy losses is equal, couples with two pregnancy losses should be eligible for the same care pathway as couples with three. This study supports ESH RE's suggestion of including two pregnancy losses in the definition of RPL.Research into fetal development and medicin