Journal of Clinical Medicine

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Open AccessEditorial

Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy

by Ole Bjarne Christiansen

J. Clin. Med. 2021, 10(21), 5040; https://doi.org/10.3390/jcm10215040 - 28 Oct 2021

Cited by 7 | Viewed by 1534

Abstract

The definition of recurrent pregnancy losses (RPL) varies between guidelines from different national and international scientific societies, but overall, a history of two or more (or alternatively, three or more) confirmed pregnancy losses is required for the diagnosis [...] Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

Research

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10 pages, 391 KiB

Open AccessArticle

Live Birth Rate in Women with Recurrent Pregnancy Loss after In Vitro Fertilization with Concomitant Intravenous Immunoglobulin and Prednisone

by Pia Egerup, Henriette Svarre Nielsen, Anders Nyboe Andersen and Ole Bjarne Christiansen

J. Clin. Med. 2022, 11(7), 1894; https://doi.org/10.3390/jcm11071894 - 29 Mar 2022

Cited by 2 | Viewed by 2983

Abstract

Pregnancy loss after in vitro fertilization (IVF) is at least as common as after spontaneous conception. Recurrent pregnancy loss (RPL) may often have an immunological background, and it is therefore relevant to test immune-based interventions in these patients. The objective was to investigate [...] Read more.

Pregnancy loss after in vitro fertilization (IVF) is at least as common as after spontaneous conception. Recurrent pregnancy loss (RPL) may often have an immunological background, and it is therefore relevant to test immune-based interventions in these patients. The objective was to investigate the effect of immunotherapy with intravenous immunoglobulin (IvIg) and prednisone (PRS) as concomitant therapy to IVF in women with RPL after earlier IVF treatments. In a cohort study conducted at The Danish RPL Clinic, 41 women with three or more consecutive pregnancy losses after IVF underwent at least one further IVF cycle with concomitant immunotherapy from 2012 to 2017. The immunotherapy with IvIg and PRS was given before embryo transfer and repeatedly in the first trimester when pregnancy was achieved. Fourteen women (34.2%) achieved a live birth after the first embryo transfer with immunotherapy, and a total of 32/41 (78%) achieved a live birth after up to 4 embryo transfers. Baseline characteristics and the presence of autoantibodies were not significantly different among women achieving live birth or not. The observed 34% birth rate in women with RPL after IVF receiving immunotherapy appears higher than the expected 16–19% birth rate without immunotherapy and is similar to findings in a previous cohort from our clinic. Concomitant immunotherapy as described may be a promising intervention for women with RPL after IVF; however, the effect must be tested in a randomized controlled trial. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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11 pages, 718 KiB

Open AccessArticle

Women with Recurrent Pregnancy Loss More Often Have an Older Brother and a Previous Birth of a Boy: Is Male Microchimerism a Risk Factor?

by Caroline Nørgaard-Pedersen, Ulrik Schiøler Kesmodel and Ole B. Christiansen

J. Clin. Med. 2021, 10(12), 2613; https://doi.org/10.3390/jcm10122613 - 14 Jun 2021

Cited by 2 | Viewed by 6367

Abstract

Known etiologic factors can only be found in about 50% of patients with recurrent pregnancy loss (RPL). We hypothesized that male microchimerism is a risk factor for RPL and aimed to explore whether information on family tree and reproductive history, obtained from 383 [...] Read more.

Known etiologic factors can only be found in about 50% of patients with recurrent pregnancy loss (RPL). We hypothesized that male microchimerism is a risk factor for RPL and aimed to explore whether information on family tree and reproductive history, obtained from 383 patients with unexplained RPL, was supportive of this hypothesis. The male:female sex ratio of older siblings was 1.49 (97:65) in all RPL patients and 1.79 (52:29) in secondary RPL (sRPL) patients, which differed significantly from the expected 1.04 ratio (p = 0.027 and p = 0.019, respectively). In contrast, the sex ratio of younger siblings was close to the expected ratio. Sex ratio of the firstborn child before sRPL was 1.51 (p = 0.026). When combined, 79.1% of sRPL patients had at least one older brother, a firstborn boy, or both. This differed significantly from what we expected based on the distribution of younger siblings and a general 1.04 sex ratio of newborns (p = 0.040). We speculate whether (s)RPL patients possibly acquired male microchimerism from older brother(s) and/or previous birth of boy(s) by transplacental cell trafficking. This could potentially have a detrimental impact on their immune system, causing a harmful response against the fetus or trophoblast, resulting in RPL. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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17 pages, 3845 KiB

Open AccessArticle

Extracellular Vesicles: An Important Biomarker in Recurrent Pregnancy Loss?

by Nina Rajaratnam, Nadja E. Ditlevsen, Jenni K. Sloth, Rikke Bæk, Malene M. Jørgensen and Ole B. Christiansen

J. Clin. Med. 2021, 10(12), 2549; https://doi.org/10.3390/jcm10122549 - 09 Jun 2021

Cited by 13 | Viewed by 2922

Abstract

Recurrent pregnancy loss (RPL) has an estimated incidence of 1–3% of all couples. The etiology is considered to be multifactorial. Extracellular vesicles (EVs) take part in numerous different physiological processes and their contents show the originating cell and pathophysiological states in different diseases. [...] Read more.

Recurrent pregnancy loss (RPL) has an estimated incidence of 1–3% of all couples. The etiology is considered to be multifactorial. Extracellular vesicles (EVs) take part in numerous different physiological processes and their contents show the originating cell and pathophysiological states in different diseases. In pregnancy disorders, changes can be seen in the composition, bioactivity and concentration of placental and non-placental EVs. RPL patients have an increased risk of pregnancy complications. The aim of this prospective study was to examine whether measuring different specific EV markers in plasma before and during pregnancy could be used as predictors of pregnancy loss (PL) in women with RPL. Thirty-one RPL patients were included in this study; 25 had a live birth (LB group) and six had a new PL (PL group). Five blood samples were obtained, one before achieved pregnancy and the others in gestational week 6, 8, 10 and 16. Moreover, some of the patients received intravenous immunoglobulin (IVIG) infusions as part of treatment, and it was also examined whether this treatment influenced the EV levels. Seventeen EV markers specific for the immune system, coagulation, placenta and hypoxia were analyzed in the samples with EV Array, a method able to capture small EVs by using an antibody panel targeting membrane proteins. Comparing the LB and PL groups, one EV marker, CD9, showed a significant increase from before pregnancy to gestational week 6 in the PL group. The changes in the other 16 markers were nonsignificant. One case of late-onset PL showed steeply increasing levels, with sudden decrease after gestational week 10 in nine of 17 markers. Moreover, there was an overall increase of all 17 markers after IVIG treatment in the LB group, which was significant in 15 of the markers. Whether increases in EVs positive for CD9 characterize RPL patients who subsequently miscarry should be investigated in future larger studies. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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13 pages, 656 KiB

Open AccessArticle

Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

by Daniel E. Pleguezuelo, Oscar Cabrera-Marante, Magdalena Abad, Edgard Alfonso Rodriguez-Frias, Laura Naranjo, Alicia Vazquez, Olga Villar, Francisco Javier Gil-Etayo, Manuel Serrano, Alfredo Perez-Rivilla, Laura de la Fuente-Bitaine and Antonio Serrano

J. Clin. Med. 2021, 10(10), 2094; https://doi.org/10.3390/jcm10102094 - 13 May 2021

Cited by 12 | Viewed by 2971

Abstract

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus [...] Read more.

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85–19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07–25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77–24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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9 pages, 385 KiB

Open AccessArticle

Modified Laparoscopic Transabdominal Cervicoisthmic Cerclage for the Surgical Management of Recurrent Pregnancy Loss due to Cervical Factors

by Hyewon Chung, Seungmee Lee, Changho Song, Tae-Kyu Jang, Jin-Gon Bae, Sang-Hoon Kwon, So-Jin Shin and Chi-Heum Cho

J. Clin. Med. 2021, 10(4), 693; https://doi.org/10.3390/jcm10040693 - 10 Feb 2021

Cited by 8 | Viewed by 1932

Abstract

This study aimed evaluate the feasibility of modified laparoscopic transabdominal cervicoisthmic cerclage (LTCC) and its impact on recurrent pregnancy loss (RPL) and is a retrospective observational cohort study of patients who underwent modified LTCC from 2003 to 2018 (n = 299). The surgery [...] Read more.

This study aimed evaluate the feasibility of modified laparoscopic transabdominal cervicoisthmic cerclage (LTCC) and its impact on recurrent pregnancy loss (RPL) and is a retrospective observational cohort study of patients who underwent modified LTCC from 2003 to 2018 (n = 299). The surgery was performed at a mean gestational age of 12.5 weeks (range 10.5–17.5 weeks). Of the 299 patients, 190 were reported as having undergone abortion (one abortion: 91 (47.9%), two: 59 (31.1%), three or more: 40 (21.1%)) before the present pregnancy and prior to the surgery. The mean operation time was 47.4 min (range 15–100 min). We followed up with 205 of 299 patients and recorded their obstetric outcomes. There were 176 successful deliveries via cesarean section, and the fetal survival rate was 85.9% (176/205). The results of this study suggest that modified LTCC is a safe and feasible surgical option during pregnancy for patients with a history of RPL due to cervical factors. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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11 pages, 1796 KiB

Open AccessArticle

Different Background: Natural Killer Cell Profiles in Secondary versus Primary Recurrent Pregnancy Loss

by Laura Strobel, Kilian Vomstein, Christiana Kyvelidou, Susanne Hofer-Tollinger, Katharina Feil, Ruben-Jeremias Kuon, Susanne Ebner, Jakob Troppmair and Bettina Toth

J. Clin. Med. 2021, 10(2), 194; https://doi.org/10.3390/jcm10020194 - 07 Jan 2021

Cited by 13 | Viewed by 3072

Abstract

(1) Background: Prior studies suggested a significant impact of previous live births on peripheral natural killer cells (pNK) in patients with recurrent pregnancy loss (RPL). Patients with primary RPL (pRPL, no live birth) showed higher numbers of pNK than secondary RPL patients (sRPL, [...] Read more.

(1) Background: Prior studies suggested a significant impact of previous live births on peripheral natural killer cells (pNK) in patients with recurrent pregnancy loss (RPL). Patients with primary RPL (pRPL, no live birth) showed higher numbers of pNK than secondary RPL patients (sRPL, ≥ 1 live birth). (2) Methods: To further determine immunological differences between RPL patients and controls, we analysed pNK subpopulations and activation markers in pRPL (n = 47), sRPL (n = 24) and controls with previous live birth (sCtrl, n = 25) and nullipara (pCtrl, n = 60) within a prospective study. Percentages and numbers of CD56^dimCD16^bright cells, subpopulations and activation markers (CD57+, CD62L+, NKG2D+, NKp46+) were measured in non-pregnant RPL patients and n = 85 controls (n = 60 pCtrl, n = 25 sCtrl) in the mid-luteal phase by flow cytometry. (3) Results: Compared to sRPL patients, sCtrls showed higher CD56⁺ and CD56^dimCD16^bright numbers. Further, sRPL patients showed lower numbers of CD56^dimCD16^brightNKG2D⁺ and CD56^dimCD16^brightNKp46⁺ than sCtrls. (4) Conclusion: We suggest a chronic immune stimulation leading to a lower NK-cell count in sRPL patients with a lower NK cytotoxicity. This underlines the necessity to investigate pNK subpopulations as well as pRPL and sRPL separately to delineate the immune alterations in RPL. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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12 pages, 271 KiB

Open AccessArticle

Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

by Emma Rasmark Roepke, Ole Bjarne Christiansen, Karin Källén and Stefan R. Hansson

J. Clin. Med. 2021, 10(2), 179; https://doi.org/10.3390/jcm10020179 - 06 Jan 2021

Cited by 13 | Viewed by 3182

Abstract

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to [...] Read more.

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

13 pages, 506 KiB

Open AccessFeature PaperArticle

by Carlo Ticconi, Adalgisa Pietropolli, Monia Specchia, Elena Nicastri, Carlo Chiaramonte, Emilio Piccione, Giovanni Scambia and Nicoletta Di Simone

J. Clin. Med. 2020, 9(9), 2833; https://doi.org/10.3390/jcm9092833 - 01 Sep 2020

Cited by 20 | Viewed by 3039

Abstract

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and [...] Read more.

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353–5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10–6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112–2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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Review

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26 pages, 855 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

by Jaume Alijotas-Reig, Enrique Esteve-Valverde, Ariadna Anunciación-Llunell, Joana Marques-Soares, Josep Pardos-Gea and Francesc Miró-Mur

J. Clin. Med. 2022, 11(3), 675; https://doi.org/10.3390/jcm11030675 - 28 Jan 2022

Cited by 33 | Viewed by 12217

Abstract

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified [...] Read more.

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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12 pages, 963 KiB

Open AccessReview

Emergency Cervical Cerclage

by Magdalena Wierzchowska-Opoka, Żaneta Kimber-Trojnar and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2021, 10(6), 1270; https://doi.org/10.3390/jcm10061270 - 18 Mar 2021

Cited by 13 | Viewed by 14463

Abstract

Despite the progress of medicine in the last decades, recurrent pregnancy loss, premature birth, and related complications are still a vast problem. The reasons for recurrent pregnancy loss and preterm delivery are diverse and multifactorial. One of the main reasons for these complications [...] Read more.

Despite the progress of medicine in the last decades, recurrent pregnancy loss, premature birth, and related complications are still a vast problem. The reasons for recurrent pregnancy loss and preterm delivery are diverse and multifactorial. One of the main reasons for these complications is cervical insufficiency, which means that the cervix is weak and unable to remain closed until the date of delivery. It manifests as painless softening and shortening of the cervix without contractions. The aim of the study was to review the available literature on rescue sutures, which are an emergency treatment in pregnancies with premature cervical dilatation and protrusion of the fetal membranes in the second trimester of pregnancy. This review confirms that emergency cerclage reduces the rate of preterm birth in patients with advanced cervical insufficiency. This procedure prolongs gestational age and improves the chances of survival of the newborn without increasing the risk of chorioamnionitis and preterm premature rupture of membranes. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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7 pages, 836 KiB

Open AccessReview

Overview of Neo-Vascular Lesions after Delivery or Miscarriage

by Yuji Shiina

J. Clin. Med. 2021, 10(5), 1084; https://doi.org/10.3390/jcm10051084 - 05 Mar 2021

Cited by 7 | Viewed by 2697

Abstract

The concept of intrauterine neo-vascular lesions after pregnancy, initially called placental polyps, has changed gradually. Now, based on diagnostic imaging, such lesions are defined as retained products of conception (RPOC) with vascularization. The lesions appear after delivery or miscarriage, and they are accompanied [...] Read more.

The concept of intrauterine neo-vascular lesions after pregnancy, initially called placental polyps, has changed gradually. Now, based on diagnostic imaging, such lesions are defined as retained products of conception (RPOC) with vascularization. The lesions appear after delivery or miscarriage, and they are accompanied by frequent abundant vascularization in the myometrium attached to the remnant. Many of these vascular lesions have been reported to resolve spontaneously within a few months. Acquired arteriovenous malformations (AVMs) must be considered in the differential diagnosis of RPOC with vascularization. AVMs are errors of morphogenesis. The lesions start to be constructed at the time of placenta formation. These lesions do not show spontaneous regression. Although these two lesions are recognized as neo-vascular lesions, neo-vascular lesions on imaging may represent conditions other than these two lesions (e.g., peritrophoblastic flow, uterine artery pseudoaneurysm, and villous-derived malignancies). Detecting vasculature at the placenta–myometrium interface and classifying vascular diseases according to hemodynamics in the remnant would facilitate the development of specific treatments. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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21 pages, 385 KiB

Open AccessReview

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art

by Kilian Vomstein, Katharina Feil, Laura Strobel, Anna Aulitzky, Susanne Hofer-Tollinger, Ruben-Jeremias Kuon and Bettina Toth

J. Clin. Med. 2021, 10(4), 869; https://doi.org/10.3390/jcm10040869 - 20 Feb 2021

Cited by 43 | Viewed by 6919

Abstract

Around 1–5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. [...] Read more.

Around 1–5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. Within this review, the current state of immunological risk factors in RPL in international guidelines of the European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) are evaluated. Special attention was drawn to recommendations in the guidelines regarding diagnostic factors such as autoantibodies, natural killer cells, regulatory T cells, dendritic cells, plasma cells, and human leukocyte antigen system (HLA)-sharing as well as treatment options such as corticosteroids, intralipids, intravenous immunoglobulins, aspirin and heparin in RPL. Finally, the current state of the art focusing on both diagnostic and therapeutic options was summarized. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

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