Search Results (18)

Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA^® MLPA^® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages. Full article

Objectives: The aim of the present study was to examine the growth dynamics of the ossification centers of the lesser wings of the sphenoid bone in the human fetus based on linear, planar, and volumetric parameters. Methods: The examinations were carried out on 37 human fetuses of both sexes (16 males and 21 females) after 18–30 weeks of gestation. These were obtained from spontaneous miscarriages and preterm deliveries. Using computed tomography (CT), digital image analysis software, 3D reconstruction, and statistical methods, the size and growth patterns of the ossification centers of the lesser wings of the sphenoid bone were evaluated. Results: All morphometric parameters—length, width, projected surface area, and volume—of the ossification centers of the lesser wings of the sphenoid bone increased proportionally with gestational age. No significant sex-related or lateral differences were observed. Conclusions: The numerical data obtained from CT-based analysis and the observed growth trends of the ossification centers of the lesser wings of the sphenoid bone may serve as age-specific normative references. These findings may support clinicians—including anatomists, radiologists, obstetricians, pediatricians, and craniofacial surgeons—in the assessment of normal fetal cranial development and the early diagnosis of congenital craniofacial anomalies. Full article

Recurrent spontaneous miscarriage (RSM) is defined as the loss of three or more clinically recognized pregnancies before 20 weeks of gestation. Angiogenesis, a crucial process in early pregnancy, is regulated by vascular endothelial growth factor (VEGF), a protein that plays a pivotal role in successful pregnancy. Disruptions in vascular development, such as those due to variations in VEGF gene expression, may contribute to infertility and pregnancy complications. Therefore, there is a need for more studies that show the effect of VEGF on RSM. This study investigated the impact of VEGF gene polymorphisms on RSM in Saudi women. Blood samples were collected from 200 Saudi women (100 cases with RSM and 100 controls). DNA was extracted from the buffy coat and analyzed for VEGF polymorphisms (rs10434, rs3025053, rs699947, rs2010963, rs833061, and rs25648) using TaqMan Real-Time PCR. Plasma VEGF levels were measured using the Human VEGF ELISA Kit. There was no significant association between rs10434, rs833061, and rs25648 and RSM. However, rs2010963, rs3025053, and rs699947 were significantly associated with an increased risk of miscarriage (p < 0.05). Furthermore, VEGF concentrations were significantly lower in the RSM case group (both pregnant and non-pregnant) compared to the control group (p < 0.05). VEGF polymorphisms, along with reduced VEGF serum levels, are associated with an increased risk of RSM in Saudi women. Further studies are needed to explore the underlying mechanisms and potential therapeutic targets. Full article

Background: The first trimester of pregnancy is known for its proinflammatory state, so it is considered a challenging period due to increased maternal vulnerability to viral infections. The main purpose of the current study was to evaluate the incidence trend of early miscarriages and whether there was any possible influence of the COVID-19 pandemic on pregnancy outcomes. Materials and Methods: We conducted a retrospective cohort study in which we included all pregnant women who had been admitted to our hospital between January 2018 and December 2022. Our aim was to compare the percentage of early miscarriages occurring in the pre-pandemic period (January 2018–February 2020) and during the pandemic (March 2020–December 2022). We decided to measure the total number and percentage of early pregnancy outcomes, including all viable pregnancies, ectopic pregnancies, and both medical and spontaneous abortions. Results: The annual incidence of registry-identified early miscarriages declined from 5.4% of 12–46-year-old women in 2018 to 3.6% in 2022 (p = 0.008). An overall incidence rate of 3.66% [95% C.I. 3.26–4.05] was calculated, with 4.25% [95% C.I. 3.35–4.41] in the pre-pandemic period and 3.24% [95% C.I. 2.82–3.57] during the pandemic. The highest incidence rate (p < 0.0001) was identified among nulliparous women (36.9%). Conclusions: To conclude, this study proved that the increase in the early miscarriage incidence rate could be assigned to an advanced maternal age, irrespective of one’s reproductive history. This study proved that no significant increase in the incidence rate of early miscarriage during the COVID-19 pandemic was noted, suggesting that this viral infection does not alter the risk of miscarriages. We hope that these findings help women deal with emotional stress and offer them reassurance about bearing children during pandemic periods. Full article

Spontaneous abortion, commonly known as miscarriage, is a significant concern during early pregnancy. Histopathological examination of tissue samples is a widely used method to diagnose and classify tissue phenotypes found in products of conception (POC) after spontaneous abortion. Background: Histopathological examination is subjective and dependent on the skill and experience of the examiner. In recent years, artificial intelligence (AI)-based techniques have emerged as a promising tool in medical imaging, offering the potential to revolutionize tissue phenotyping and improve the accuracy and reliability of the histopathological examination process. The goal of this study was to investigate the use of AI techniques for the detection of various tissue phenotypes in POC after spontaneous abortion and evaluate the accuracy and reliability of these techniques compared to traditional manual methods. Methods: We present a novel publicly available dataset named HistoPoC, which is believed to be the first of its kind, focusing on spontaneous abortion (miscarriage) in early pregnancy. A diverse dataset of 5666 annotated images was prepared from previously diagnosed cases of POC from Atia General Hospital, Karachi, Pakistan, for this purpose. The digital images were prepared at 10× through a camera-connected microscope by a consultant histopathologist. Results: The dataset’s effectiveness was validated using several deep learning-based models, demonstrating its applicability and supporting its use in intelligent diagnostic systems. Conclusions: The insights gained from this study could illuminate the causes of spontaneous abortion and guide the development of novel treatments. Additionally, this study could contribute to advancements in the field of tissue phenotyping and the wider application of deep learning techniques in medical diagnostics and treatment. Full article

Due to the genetic diversity between the mother and the fetus, heightened control over the immune system during pregnancy is crucial. Immunological parameters determined by clinicians in women with idiopathic recurrent spontaneous abortion (RSA) include the quantity and activity of Natural Killer (NK) and Natural Killer T (NKT) cells, the quantity of regulatory T lymphocytes, and the ratio of pro-inflammatory cytokines, which indicate imbalances in Th1 and Th2 cell response. The processes are controlled by immune checkpoint proteins (ICPs) expressed on the surface of immune cells. We aim to investigate differences in the expression of ICPs on T cells, T regulatory lymphocytes, NK cells, and NKT cells in peripheral blood samples collected from RSA women, pregnant women, and healthy multiparous women. We aim to discover new insights into the role of ICPs involved in recurrent pregnancy loss. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from blood samples obtained from 10 multiparous women, 20 pregnant women (11–14th week of pregnancy), and 20 RSA women, at maximum of 72 h after miscarriage. The PBMCs were stained for flow cytometry analysis. Standard flow cytometry immunophenotyping of PBMCs was performed using antibodies against classical lymphocyte markers, including CD3, CD4, CD8, CD56, CD25, and CD127. Additionally, ICPs were investigated using antibodies against Programmed Death Protein-1 (PD-1, CD279), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3, CD366), V-domain Ig suppressor of T cell activation (VISTA), T cell immunoglobulin and ITIM domain (TIGIT), and Lymphocyte activation gene 3 (LAG-3). We observed differences in the surface expression of ICPs in the analyzed subpopulations of lymphocytes between early pregnancy and RSA, after miscarriage, and in women. We noted diminished expression of PD-1 on T lymphocytes (p = 0.0046), T helper cells (CD3CD4 positive cells, p = 0.0165), T cytotoxic cells (CD3CD8 positive cells, p = 0.0046), T regulatory lymphocytes (CD3CD4CD25CD127 low positive cells, p = 0.0106), and NKT cells (CD3CD56/CD16 positive cells, p = 0.0438), as well as LAG-3 on lymphocytes T (p = 0.0225) T helper, p = 0.0426), T cytotoxic cells (p = 0.0458) and Treg (p = 0.0293), and cells from RSA women. Impaired expression of TIM-3 (p = 0.0226) and VISTA (p = 0.0039) on CD8 cytotoxic T and NK (TIM3 p = 0.0482; VISTA p = 0.0118) cells was shown, with an accompanying increased expression of TIGIT (p = 0.0211) on NKT cells. The changes in the expression of surface immune checkpoints indicate their involvement in the regulation of pregnancy. The data might be utilized to develop specific therapies for RSA women based on the modulation of ICP expression. Full article

Just World Beliefs are a tendency to believe the world is inherently fair. The strength of these beliefs correlates with victim derogation, including blaming victims of medical pathology. This cross-sectional study aimed to evaluate whether the strength of belief in a just world predicts beliefs about the etiologies of early pregnancy loss. In total, 911 adults living in the United States were recruited using Amazon Mechanical Turk. Participants completed a web-based assessment of their views on causes of pregnancy loss and a validated measure of just world beliefs. Pearson’s chi-squared test was used to evaluate the association between just world belief strength and beliefs about internal and external causes of spontaneous pregnancy loss. Compared to participants with weak just world beliefs, respondents with strong just world beliefs were more likely to attribute a pregnancy loss to benign reproductive choices (contraception use or a prior abortion) and daily activities (prolonged standing, engaging in an argument) that are within an individual’s control, while minimizing the contribution of factors that cannot be controlled (fetal genetic abnormalities). Understanding belief systems contributing to miscarriage stigma may help to develop stigma-reducing interventions for both patients and the general public. Full article

Background: Recurrent pregnancy loss refers to the spontaneous demise of two or more pregnancies before the 24 weeks of gestation. In almost half of the cases of recurrent miscarriages, the causes remain unknown since there is no reliable way of prognosis, early diagnosis, or treatment. Recent research has detected differential expression of certain miRNAs in reproductive system pathologies. Methods: The aim of the present review is to focus on microRNAs and their relationship with idiopathic recurrent miscarriages and to correlate miRNA expression with recurrent miscarriage and examine their potential role as biomarkers. Pubmed/Medline and Scopus databases were searched up to 31st January 2024 with terms related to recurrent pregnancy loss and miRNAs. Results: In total, 21 studies were selected for the review. A total of 75 different miRNAs were identified, showing a statistically significant differential expression. Around 40 miRNAs had increased expression, such as miR-520, miR-184 and miR-100-5p, 21 decreased, such as let-7c, and 14 had either increased or decreased expression depending on the study, such as miR-21. Conclusions: The dysregulation of miRNA expression is strongly associated with recurrent miscarriages. The circulating in the peripheral blood miRNAs, miR-100-5p and let-7c, might be utilized as biomarkers and establish a valuable non-invasive prognostic and diagnostic tool in the future. Full article

Background: Neither radiological phenotypic characteristics nor reconstruction CT scan has been used to study the early anatomical disruption of the cranial bone in children with the so-called idiopathic type of West syndrome. Material and Methods: The basic diagnostic measures and the classical antiepileptic treatments were applied to these children in accordance with the conventional protocol of investigations and treatment for children with West syndrome. Boys from three unrelated families were given the diagnosis of the idiopathic type of West syndrome, aged 7, 10 and 12 years old. Parents underwent extensive clinical examinations. Three parents (age range of 28–41 year) were included in this study. All children showed a history of intellectual disabilities, cryptogenic epileptic spasms and fragmented hypsarrhythmia. These children and their parents were referred to our orthopedic departments because of variable skeletal deformities. Variable forms of skeletal deformities were the motive for the families to seek orthopedic advice. A constellation of flat foot, torticollis and early-onset osteoarthritis were observed by the family doctor. Apparently, and from the first clinical session in our practice, we felt that all these children are manifesting variable forms of abnormal craniofacial contour. Thereby, we immediately performed detailed cranial radiological phenotypic characterization of every affected child, as well as the siblings and parents, and all were enrolled in this study. All affected children underwent whole-exome sequence analysis. Results: The craniofacial phenotype of all children revealed apparent developmental anatomical disruption of the cranial bones. Palpation of the skull bones showed unusual palpable bony ridges along different sutural locations. A 7-year-old child showed abnormal bulging over the sagittal suture, associated with bilateral bony ridges over the squamosal sutures. AP skull radiograph of a 7-year-old boy with West syndrome showed facial asymmetry with early closure of the metopic suture, and other sutures seemed ill-defined. A 3D reconstruction CT scan of the skull showed early closure of the metopic suture. Another 3D reconstruction CT scan of the skull while the patient was in flexion showed early closure of the squamosal sutures, pressing the brain contents upward, causing the development of a prominent bulge at the top of the mid-sagittal suture. A reformatted 3D reconstruction CT scan confirmed the bilateral closure of the squamosal suture. Examination of the parents revealed a similar skull radiographic abnormality in his mother. A 3D reformatted frontal cranial CT of a 35-year-old mother showed early closure of the metopic and sagittal sutures, causing a mid-sagittal bony bulge. A 10-year-old boy showed an extremely narrow frontal area, facial asymmetry and a well palpable ridge over the lambdoid sutures. A 3D axial reconstruction CT scan of a 10-year-old boy with West syndrome illustrated the asymmetry of the posterior cranial bones along the lambdoid sutures. Interestingly, his 28-year-old mother has been a client at the department of spine surgery since she was 14 years old. A 3D reconstruction CT scan of the mother showed a noticeable bony ridge extending from the metopic suture upwards to involve the sagittal suture (red arrow heads). The black arrow shows a well demarcated bony ridge over the squamosal suture. A 3D reconstruction CT scan of the skull and spine showed the thick bony ridge of the metopic and the anterior sagittal as well as bilateral involvement of the squamosal, causing apparent anterior narrowing of the craniofacial contour. Note the lumbar scoliosis. A 12-year-old boy showed brachycephaly. A lateral skull radiograph of a 12-year-old boy with West syndrome showed premature sutural fusion, begetting an abnormal growth pattern, resulting in cranial deformity. The nature of the deformity depends on which sutures are involved, the time of onset and the sequence in which individual sutures fuse. In this child, brachycephalic secondary to craniosynostosis, which occurred because of bilateral early ossification of the coronal sutures, led to bi-coronal craniosynostosis. Thickened frontal bones and an ossified interclinoid ligament of the sella turcica were encountered. The lateral skull radiograph of a 38-year-old mother with a history of poor schooling achievements showed a very similar cranial contour of brachycephaly, thickening of the frontal bones and massive ossification of the clinoid ligament of the sella turcica. Maternal history revealed a history of multiple spontaneous miscarriages in the first trimester of more than five times. Investigating his parents revealed a brachycephalic mother with borderline intelligence. We affirm that the pattern of inheritance in the three boys was compatible with the X-linked recessive pattern of inheritance. Whole-exome sequencing showed non-definite phenotype/genotype correlation. Conclusions: The aim of this study was sixfold: firstly, to refute the common usage of the term idiopathic; secondly, we feel that it could be possible that West syndrome is a symptom complex rather than a separate diagnostic entity; thirdly, to further detect the genetic carrier, we explored the connection between the cranial bones in children with West syndrome with what has been clinically observed in their parents; fourthly, the early life anatomical disruptions of the cranial bones among these children seem to be heterogeneous; fifthly, it shows that the progressive deceleration in the development of this group of children is highly connected to the progressive closure of the cranial sutures; sixthly, we affirm that our findings are novel. Full article

Immune checkpoints (ICPs) serve as regulatory switches on immune-competent cells. Soluble ICPs consist of fragments derived from ICP molecules typically located on cell membranes. Research has demonstrated that they perform similar functions to their membrane-bound counterparts but are directly present in the bloodstream. Effective control of the maternal immune system is vital for a successful pregnancy due to genetic differences between the mother and fetus. Abnormalities in the immune response are widely acknowledged as the primary cause of spontaneous abortions. In our research, we introduce a novel approach to understanding the immune-mediated mechanisms underlying recurrent miscarriages and explore new possibilities for diagnosing and preventing pregnancy loss. The female participants in the study were divided into three groups: RSA (recurrent spontaneous abortion), pregnant, and non-pregnant women. The analysis of soluble forms of immune checkpoints and their ligands in the serum of the study groups was conducted using the Luminex method Statistically significant differences in the concentrations of (ICPs) were observed between physiological pregnancies and the RSA group. Among patients with RSA, we noted reduced concentrations of sGalectin-9, sTIM-3, and sCD155, along with elevated concentrations of LAG-3, sCD80, and sCD86 ICPs, in comparison to physiological pregnancies. Our study indicates that sGalectin-9, TIM-3, sLAG-3, sCD80, sCD86, sVISTA, sNectin-2, and sCD155 could potentially serve as biological markers of a healthy, physiological pregnancy. These findings suggest that changes in the concentrations of soluble immune checkpoints may have the potential to act as markers for early pregnancy loss. Full article

Background and Objectives: The purpose of this study was to describe and evaluate the bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy. Secondarily, we assessed the associated complications in order to identify potential risk factors that could be used to select women at higher risk of adverse outcomes that could benefit from an early diagnosis and improved monitoring. Materials and Methods: We made a selection of all the women who consulted in the Emergency Department of the Hospital QuirónSalud in Malaga on 2015 presenting with first trimester metrorrhagia. We refer to first trimester metrorrhagia as that which occurs until week 12 + 6. Once these pregnant women were identified, we studied several variables not related to the gestation and some others associated with it and its natural course. Results: The average age of the patients assessed was 34.1. Associated gestational complications were metrorrhagia in the second trimester (6.3%), threatened preterm labor (7.4%), preeclampsia (2.5%), gestational diabetes (7.4%), late abortion (1.2%), and early postpartum hemorrhage (1.8%). We sought associations to assess possible risk factors, establishing an increased maternal age as an aggravating factor for the development of complications. We also studied gestational complications, finding a higher prevalence of them in older women, such as prematurity (33.11 vs. 34.48 years), gestational diabetes (33.11 vs. 36.06 years), and preeclampsia (33.25 vs. 35 years). Conclusions: Maternal age is a risk factor for first-trimester spontaneous miscarriage and for the development of complications of pregnancy. It is crucial to perform a correct screening of different pathologies throughout the pregnancy to anticipate potential complications. Full article

(1) Background: The aim of our study is to evaluate whether cell-free DNA testing can overlap the genetic testing of miscarriage tissue in women with early pregnancy loss (EPL) and length of recurrent pregnancy loss (RPL); (2) Methods: We conducted a prospective cohort study at the Pregnancy Loss Unit of the Fondazione Policlinico Universitario A. Gemelli (IRCCS), Rome, Italy between May 2021 and March 2022. We included women with EPL and length of RPL. Gestational age was >9 weeks + 2 days and <12 weeks + 0 days of gestation corresponding to a crown rump length measurement of >25 and <54 mm. Women underwent both dilation and curettage for the collection of miscarriage tissue and for blood sample collection. Chromosomal microarray analysis (CMA) on miscarriage tissues was performed by oligo-nucleotide- and single nucleotide polymorphisms (SNP)-based comparative genomic hybridization (CGH+SNP). Maternal blood samples were analyzed by Illumina VeriSeq non-invasive prenatal testing (NIPT) to evaluate the cell-free fetal DNA (cfDNA) and the corresponding fetal fraction and the presence of genetic abnormalities; (3) Results: CMA on miscarriage tissues revealed chromosome aneuploidies in 6/10 cases (60%), consisting of trisomy 21 (5 cases) and monosomy X (one case). cfDNA analysis was able to identify all cases of trisomy 21. It failed to detect monosomy X. A large 7p14.1p12.2 deletion concomitant to trisomy 21 was, in one case, detected by cfDNA analysis but it was not confirmed by CMA on miscarriage tissue. (4) Conclusions: cfDNA largely reproduces the chromosomal abnormalities underlying spontaneous miscarriages. However, diagnostic sensitivity of cfDNA analysis is lower with respect to the CMA of miscarriage tissues. In considering the limitations when obtaining biological samples from aborted fetuses suitable for CMA or standard chromosome analysis, cfDNA analysis is a useful, although not exhaustive, tool for the chromosome diagnosis of both early and recurrent pregnancy loss. Full article

The possible association between human papillomavirus (HPV) infection and negative pregnancy outcomes has been debated in the literature, with conflicting results from clinical trials. While some authors support a link between HPV and miscarriage, others argue that the mere detection of the virus does not necessarily indicate a causal relationship with negative pregnancy outcomes. In this study, we conducted a prospective, controlled investigation of the potential association between HPV infection and miscarriage. Our study included 59 women who had experienced a miscarriage and 57 women who had undergone voluntary termination of pregnancy (TOP) within the 12th week of gestation. We assessed HPV prevalence, maternal age, and HPV genotype in both groups and evaluated the relationship between these factors and pregnancy outcome. Unlike previous studies that only identified HPV in cases of abortion, we also correlated the positivity of chorionic villi with gestational age in both groups. We found a close correlation between positive chorionic villi and very early gestational age, with all 13 cases of virus-positive chorionic villi in the miscarriage group occurring in gestational periods of less than 8 + 5 weeks (<60 days) (RR = 28.6). Our analysis showed no correlation between HPV infection and maternal age or viral genotypes. The results suggest that the presence of HPV alone is not enough to cause spontaneous abortion, but a high viral load in early pregnancy may increase the risk of negative outcomes. These findings have important implications for the management of HPV infection during pregnancy and may provide a rationale for the use of HPV vaccines to reduce the incidence of spontaneous abortion and infertility due to preclinical spontaneous abortions. Full article

Functional embryo–maternal interactions occur during the embryo implantation and placentation. Extracellular vesicles with microRNA (miR) between cells have been considered of critical importance for embryo implantation and the programming of human pregnancy. MiR-138-5p functions as the transcriptional regulator of G protein-coupled receptor 124 (GPR124). However, the signaling pathway of miR138-5p- and GPR124-adjusted NLRP3 inflammasome activation remains unclear. In this study, we examine the roles of the miR138-5p and GPR124-regulated inflammasome in embryo implantation and early pregnancy. Human decidual stromal cells were isolated from the abortus tissue and collected by curettage from missed abortion patients and normal pregnant women at 6- to 12-week gestation, after informed consent. Isolated extracellular vesicles from decidua and decidual stromal cells were confirmed by transmission electron microscopy (TEM). Next-Generation Sequencing (NGS) and microarray were performed for miR analysis. The predicated target genes of the differentially expressed miR were analyzed to identify the target genes and their pathway. We demonstrated the down-regulation of miR-138-5p and the overexpression of GPR124 in spontaneous miscarriage compared to normal pregnancy. We also showed the excessive activation of the NLRP3 inflammasome in spontaneous miscarriage compared to normal pregnancy. Here, we newly demonstrate that the miR-138-5p and GPR124-adjusted NLRP3 inflammasome were expressed in extracellular vesicles derived from decidua and decidual stromal cells, indicating that the miR-138-5p, GPR124 and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome have a potential modulatory role on the decidual programming and placentation of human pregnancy. Our findings represent a new concept regarding the role of extracellular vesicles, miR-138-5p, GPR124, and the NLRP3 inflammasome in normal early pregnancy and spontaneous miscarriage. Full article

Early amniocentesis (EA)—before 15 gestational weeks—is not recommended because of a high rate of miscarriages. Most studies performed amniocentesis at very early stages of pregnancy (11–13 weeks of gestational age). However, amniocentesis performed at 14 gestational weeks could be an important alternative to mid-trimester amniocentesis (MA) because it shortens the time period between the screening (non-invasive prenatal test (NIPT)) and the diagnostic test (amniocentesis). This study aimed to compare the procedure-related risk of miscarriage between MA (15 + 0 to 17 + 6 weeks of gestational age) and EA (14 + 0–6 weeks of gestational age). This is a multicentric, retrospective cohort study from 1 January 2007 to 21 November 2018, comparing the MA to the EA cohort. Procedure-related fetal loss is defined as spontaneous abortion occurring within 4 weeks of the procedure. Multiple gestations, amniocenteses performed after 17 or before 14 weeks, indications other than prenatal genetic diagnoses and procedures performed by less experienced gynaecologists were excluded. Complete outcome data were available for 1107 out of 1515 women (73.1%): 809 (69.9%) in the MA and 298 (83.2%) in the EA cohort. No significant difference was found (EA 0.82% vs. MA 0.36%; p = 0.646). The difference was 0.46% (odds ratio = 0.673; 95% confidence interval = 0.123–3.699). This study found no significant difference in the procedure-related risk of miscarriage when EA was compared to MA. EA might be considered a safe alternative, though further research is necessary. Full article