Spontaneous Pregnancy Loss Research Articles

Whole-body non-forensic fetal virtopsy using postmortem magnetic resonance imaging at 7 Tesla vs classical autopsy.

To determine the diagnostic accuracy of virtual autopsy using whole-body postmortem ultra-high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2-weighted imaging (T2-WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second-trimester fetuses. Thirty consecutive fetuses at 13-19 weeks' gestation (weight, 17-364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two-dimensional turbo high-resolution T2-WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational-age intervals (13-14, 15-16 and 17-19 weeks). Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42-96.29%) and a specificity of 97.87% (95% CI, 94.64-99.42%), with a positive predictive value of 96.30% (95% CI, 90.78-98.56%) and a negative predictive value of 95.34% (95% CI, 91.61-97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73-97.68%) for detecting structural abnormalities in second-trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. Virtual fetal autopsy using 7-T MRI and a turbo high-resolution T2-WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prospective Observational Study Of Hyperhomocysteinemia In Patients With Recurrent Pregnancy Loss In Teaching Hospital

Background: Spontaneous pregnancy loss can be physically and emotionally taxing for couples, especially when faced with recurrent losses. Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period . RPL is also defined by two or more failed consecutive pregnancies. It is estimated that fewer than 5% of women will experience two consecutive miscarriages and only 1% experience three or more. At present, there exists a small number of accepted etiologies for RPL. Most of the diagnosed etiologies include endocrine abnormalities, autoimmune disorders, uterine anomalies, and genetic factors. After evaluation for these causes, approximately half of all cases will still remain unexplained. Hence the present study was taken up to investigate the association between hyperhomocysteinemia and recurrent pregnancy loss, evaluating prevalence, potential mechanisms and implications for management. Materials and Methods: The prospective observational study was conducted on 50 patients in the Department of OBG in Dr. B. R. Ambedkar Medical College and Hospital for a period of 18 months. Prior to the initiation of the study, Ethical and Research Committee clearance was obtained from Institutional Ethical Committee. Results: The majority of participants in both groups were aged 35 to 40 years (32.35% in Group A and 37.5% in Group B).Statistically significant differences were observed between the groups regarding hypertensive disorders of pregnancy, co-morbidities, adverse pregnancy outcomes, the nature of abortion (primary vs. secondary), fetal outcomes, APGAR scores at 1 and 5 minutes, neonatal birth weight, and NICU admissions, with p-values of 0.001 across these measures.Group B (with hyperhomocysteinemia) showed higher instances of hypertensive disorders, co-morbidities, adverse pregnancy and fetal outcomes, abnormal APGAR scores at 1 and 5 minutes, lower neonatal birth weight, and NICU admissions.The mean homocysteine levels were 13.28 ± 1.8 µmol/L in Group A and 73.98 ± 5.1 µmol/L in Group B, with a highly significant difference (p: 0.0001).Most subjects in Group B had intermediately severe hyperhomocysteinemia (50%), with 37.5% experiencing moderately severe hyperhomocysteinemia and 12.5% with severe hyperhomocysteinemia. All abortions in Group A were primary, whereas Group B had 60% primary and 40% secondary abortions. Conclusion: Hyperhomocysteinemia is a risk factor for recurrent pregnancy loss. About 1 in 3 patients of RPL have hyperhomocysteinemia and therefore as a routine workup for RPL serum homocysteine measurement should also be included. Treatment of hyperhomocysteinemia with folic acid and vitamin B12 decreases homocysteine levels significantly.

The Effects of PON1 (Q192R, rs662) Gene Polymorphism, Heavy metals and Oxidative Stress on Risk of Recurrent Spontaneous Abortion in Samples of Iraqi Women

Recurrent spontaneous abortion (RSA) is defined as the occurrence of two or more spontaneous pregnancy losses before reaching the midpoint of gestation. Oxidative stress plays a pivotal role in the pathogenesis of RSA, serving as a key factor in its underlying causes. This research aims to investigate the connection between the Q192R polymorphisms identified in the PON1 gene, responsible for encoding an antioxidant enzyme and the vulnerability to RSA. Paraoxonase 1 (PON1) is a critical enzyme in the body's antioxidant defence system, safeguarding cells against damage caused by reactive oxygen species and heavy metal concentrations that affect pregnancy. The most prevalent PON1 polymorphism is Q192R (rs662), known to influence the antioxidant activity and power of the PON1 enzyme. In this research, blood samples were collected from two groups: 50 women with RSA and 50 women who were apparently in good health. Following DNA extraction, high-resolution melting (HRM) analysis was used to identify the studied SNP; Elisa was used to determine DNA damage and MDA concentrations in serum and heavy metals were determined by a Graphite Furnace-Atomic Absorption Spectrophotometer (GFAAS). The results of this study showed significantly higher levels of 8-OHdG, MDA, arsenic and lead in serum in RSA patients than in apparently healthy women. The genotype findings indicated that the prevalence of the QR (AG) genotype in women experiencing recurrent spontaneous abortion was notably greater than that in seemingly healthy women (74% compared to 16%, respectively, with an odds ratio of 27.2). The values of allele frequency for the A allele were 0.76 and 0.51 for apparently healthy women and women with recurrent spontaneous abortion respectively. The G allele frequency was 0.24 and 0.49 for apparently healthy women and women with recurrent spontaneous abortion respectively. The heterozygous QR genotype is related to the risk of RSA and the minor allele (G allele) is increased in women with RSA.

Pharmacological and toxicological characteristics of baicalin in preventing spontaneous abortion and recurrent pregnancy loss: A multi-level critical review

RelevanceSpontaneous abortion (SAB) and recurrent pregnancy loss (RPL) occur alone or concurrently with increasing incidences recently. Scutellaria baicalensis Georgi (SBG) has been used to prevent pregnancy loss for thousands of years, which is recognized as a “pregnancy-stabilizing herb” in ancient China. Baicalin (BA) and its metabolite baicalein (BE) are the main bioactive flavonoids in the root of SBG. MethodsIn this study, we focused particularly on the metabolism, toxicology, and pharmacological effects of BA at the maternal-fetal interface based on the biological process prediction by network pharmacology. Focused on the systematic review of BA's regulatory mechanisms of immune homeostasis, cell proliferation and invasion, programmed cell death, inflammatory microenvironment, angiogenesis, oxidative stress and vascular remodeling at the maternal-fetal interface, it was found that BA exerts its biological effects to treat SAB and RPL through multiple perspectives and targets. We also critically elucidated the limitations of using BA from a clinical perspective. ResultsWe explored the bioavailability, targeting and efficacy of BA from a new perspective (optimization of the BA delivery system, organoid studies based on BA, potential effects of BA on uterine flora and bioactive components). Finally, we propose a multimodal stereo sequencing study of biologically active components based on pathological dynamics incorporating single-cell RNA sequencing, spatially resolved transcriptomics, and single-cell multimodal omics to delve deeper into the fetal-preserving mechanism of BA and to promote the application of BA in clinical practice.

ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.

Aneuploidy, the presence of a chromosomal anomaly, is a major cause of spontaneous abortions and recurrent pregnancy loss in humans. However, the underlying molecular mechanisms still remain poorly understood. Here, we report that ARHGAP26, a putative tumor suppressor gene, is a newly identified regulator of oocyte quality to maintain mitochondrial integrity and chromosome euploidy, thus ensuring normal embryonic development and fertility. Taking advantage of knockout mouse model, we revealed that genetic ablation of Arhgap26 caused the oocyte death at GV stage due to the mitochondrial dysfunction-induced ROS accumulation. Lack of Arhgap26 also impaired both in vitro and in vivo maturation of survived oocytes which results in maturation arrest and aneuploidy, and consequently leading to early embryonic development defects and subfertility. These observations were further verified by transcriptome analysis. Mechanistically, we discovered that Arhgap26 interacted with Cofilin1 to maintain the mitochondrial integrity by regulating Drp1 dynamics, and restoration of Arhgap26 protein level recovered the quality of Arhgap26-null oocytes. Importantly, we found an ARHGAP26 mutation in a patient with history of recurrent miscarriage by chromosomal microarray analysis. Altogether, our findings uncover a novel function of ARHGAP26 in the oocyte quality control and prevention of aneuploidy and provide a potential treatment strategy for infertile women caused by ARHGAP26 mutation.

Predictors of spontaneous pregnancy loss in single ventricle physiology

BackgroundPregnant patients with single ventricle (SV) physiology carry a high risk of spontaneous pregnancy loss (SPL), yet the clinical factors contributing to this risk are not well defined.MethodsSingle-centre retrospective study...

PLCZ1 Mutation and Failed IUI, ICSI, and Spontaneous Pregnancy Loss: Insights from a Case Study.

PLCZ1 Mutation and Failed IUI, ICSI, and Spontaneous Pregnancy Loss: Insights from a Case Study.

The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. No specific funding was used. The authors have no conflicts of interest to declare. N/A.

O-153 Clinical utility of preimplantation genetic testing for aneuploidy origin (PGT-AO) to enhance embryo selection for monogenic disorders: a retrospective pan-country integrative genomic and clinical study

Abstract Study question What is PGT-AO’s impact on implantation and pregnancy rate per embryo transfer, by determining the prevalence and effect of (mosaic) aneuploidies and their segregational origin? Summary answer PGT-AO potentially enhances the efficiency of PGT and increases the pregnancy rate per embryo transfer by minimizing transfers with poor outcomes and improving implantation rates. What is known already Demographic factors such as advanced parental age increases risk of aneuploid offspring, driving demand for advanced PGT. Randomized controlled trials revealed that PGT-A does not increase live birth rates after IVF. PGT-A, the most frequent form of PGT, overlooks the mosaic nature and segregational origin of aneuploidies in IVF embryos. This possibly leads to avoiding the transfer of mosaic embryos and reduces the pregnancy rate per cycle. Prompting this study, five embryos transferred based on PGT-M, led to trisomic pregnancies terminated following invasive prenatal diagnosis. Subsequent genome haplarithmisis revealed that these embryos carried (meiotic) trisomies not previously detected by PGT-M. Study design, size, duration In this retrospective study, we included 1944 embryos (816 PGT-M embryos, 323 couples, 224 indications). Currently, 284 have been processed by genome haplarithmisis-based PGT-AO and analyzed to assess if (mosaic) aneuploidies and segregational origin would have altered transfer decisions and subsequent clinical outcomes. We evaluated our novel PGT- A approach, termed PGT-AO, providing a nuanced understanding of early embryonic development in clinical practice and more responsible PGT-A, potentially leading to viable mosaic embryo transfer. Participants/materials, setting, methods The couples were counseled by clinical geneticists at Dutch University Medical Centers (UMCs), in Maastricht, Amsterdam, Utrecht, and Groningen, and enrolled in the diagnostic PGT-M procedure after signing an informed consent form. Embryos (n = 816) eligible for transfer based on absence of the monogenic aberration of interest by PGT-M were analyzed by haplarithmisis-based PGT-AO including parental information. This information allows for the detection of (mosaic) chromosomal abnormalities and their parental and segregational origin. Main results and the role of chance Of 816 included embryos (323 couples, 224 indications), 284 were found to be suitable for transfer by PGT-M and were analyzed by PGT-AO. Of these, 183 were transferred. Of the transferred embryos, 65 (35.5%) had a positive HCG and 48 (26.3%) resulted in a liveborn. 14.6% (7/48) carried abnormalities following our PGT-AO approach. These abnormalities consisted of mitotic mosaic trisomies, mosaic monosomies, and mosaic duplications and a deletion. Of the transferred embryos, 132 (72.1%) did not result in a liveborn and 115 (62.8%) had negative HCG tests. Of the transferred embryos with negative HCG, 38.3% (44/115) contained a total of 90 abnormalities, consisting of 37 monosomies, 35 trisomies, 12 deletions, 2 duplications, 2 UPD and 1 ring chromosome. The 35 trisomies occurred in 20 embryos, of which 9 were of meiotic origin and 5 of mitotic origin, 1 of both meiotic and mitotic, and 5 could not be determined. Based on these preliminary results, PGT-AO can avoid the transfer of embryos with aneuploidy of meiotic origin and non-mosaic status. In contrast, embryos with aneuploidy of mitotic origin are often mosaic and the abnormality may not be uniformly distributed throughout the blastocyst and could potentially be considered for transfer. Limitations, reasons for caution Haplarithmisis relies on the inclusion of parental DNA to phase the embryonic genome and thus determine the segregational origin of aberrations. Additionally, mitosis and meiosis II trisomies cannot be discerned where a crossover event is absent for a chromosome with trisomy. Wider implications of the findings Implementation of PGT-AO will re-define the current embryo selection system. This enhances PGT by increasing pregnancy rate per embryo transfer and minimizing transfers with poor outcomes, disposal of potentially viable embryos, spontaneous pregnancy losses, and termination of aneuploid pregnancies. This reduces the emotional and financial burdens on families and healthcare. Trial registration number Not applicable

Association of Serum Proteins Electrophoretic Pattern and Serum Hormones in Women with Spontaneous Pregnancy Loss.

Pregnancy is the state of carrying a developing embryo or fetus within a female body. Once pregnancy is established, a range of endocrinological events appear in its maintenance, finally helping in the successful pregnancy. The complications which are usually observed in pregnancy are gestational diabetes, preeclampsia, preterm labor, and spontaneous pregnancy loss or miscarriage, while 10%-15% of clinically recognized pregnancies terminate into spontaneous miscarriage. Thus, many attempts have been made by different researchers for the diagnosis of high-risk pregnancy on altered protein pattern using placental villous tissue or follicular fluid, but these are difficult to obtain and results of different studies are not constant. This study was designed to identify the association (if any) among serum protein(s) electrophoretic pattern and different serum hormones in normal pregnant women (controls) and gestational age-matched women with spontaneous pregnancy loss (cases). This study was carried out for 1½ year from October 2018 to March 2020 and included 120 participants (60 normal pregnant women and 60 women with spontaneous pregnancy loss) between 20 and 45 years of age with no mean age difference. The electrophoresis of serum was carried out using slab gel electrophoretic unit and serum thyroid-stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and beta human chorionic gonadotropin (β-hCG) levels were analyzed using TSOSH AIA analyzer at Adesh University, Bathinda. Significant variations in the expression of proteins with molecular weight around ~150 kDa, ~50 kDa, and ~25 kDa were observed in normal pregnant women and women with spontaneous pregnancy loss. However, the protein band of ~50 kDa was found to be highly expressed in the serum of 1st and 2nd trimester women experiencing spontaneous pregnancy loss. Therefore, selected protein band of ~50 kDa was further processed by ECI-mass spectrophotometry QUAD time of flight and 365 different proteins were found, out of these; 34 proteins were found to be unidentified protein products (Verified using NCBI data base). Further, TT3, total proteins, β-hCG, and prolactin level were found to be low, whereas, TSH was found to be high in women experiencing spontaneous pregnancy loss. However, difference in the level of β-hCG in the 1st trimester and TT4 among normal pregnant women and women with spontaneous pregnancy loss was observed to be statistically insignificant. This study indicated that the evaluation of serum protein variations along with hormonal profile may provide valuable information about high-risk pregnancy. Moreover, the differential expression of proteins in women with spontaneous pregnancy loss can be further explored to develop potential biomarker for the early identification of high-risk pregnancy and appropriate preventive measure.

Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania.

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.

HLA-G isoforms, HLA-C allotype and their expressions differ between early abortus and placenta in relation to spontaneous abortions

IntroductionSpontaneous abortion (SAB) affects approximately 10% of clinically recognized pregnancies. Fetal trophobalst invasion and remodeling of maternal spiral arteries is reported to be dependent on crosstalk between HLA-C/HLA-G expressed on extra villous trophoblast (EVTs)and Killer cell Immunoglobin like receptors (KIRs) of decidual NK (dNK). Immune dysfunction in decidua contributes to early miscarriage. MethodologyThe study used mother neonate paired cord blood and term placenta samples (n = 46), elective abortus (n = 17,gestational age = 10–12 weeks of pregnancy) and SAB abortus (n = 24, gestational age = 12–15 weeks of pregnancy) for HLA-G, KIR2D and HLA-C. In addition, term placenta was collected from women with history of spontaneous pregnancy loss (n = 24) and women with history of live birth (n = 32). SSP-PCR was used for genotyping, RT-PCR for gene expression, copy number variation (CNVs) and HLA-C allotyping and ELISA for protein expression studies. ResultsMembrane bound HLA-G4 isoform proportion was higher 39.28%, p = 0.02) in term placenta. SAB abortus had higher proportion of HLA-G3 (50%),while elective abortus exhibited higher proportion of soluble isoforms (HLA-G5, = 5.9, HLA-G6 = 5.9%, HLA-G7 = 11.8%).Higher inhibitory KIR2DL1 content and copy numbers with lower HLA-C2 in SAB contrasted with higher copy numbers of KIR2DS1(p = 0.001), KIR2DS1+/2DL1+- HLA-C2 combined genotype in healthy placenta. Elevated KIR2D protein levels (p = 0.001), and concurrently, HLA-C levels were upregulated in healthy placenta. ConclusionOur data supports lower cognate receptor ligand KIR2DS1+/2DL1+ HLA–C2 together with predominance of HLA-G3 isoform in SAB as confounding factors in spontaneous pregnancy loss. HLA-G isoforms and expression differed between first trimester abortus and term placenta suggesting temporal modulation and marks novelty of the study.

The paternal role in pregnancy loss.

In this comprehensive review, the intricate relationship between paternal factors and pregnancy loss is examined. While pregnancy loss has historically been predominantly attributed to maternal factors, recent research underscores the significant contribution of the male partner. The review delves into various aspects of paternal influence, including paternal age, health, chromosome abnormalities, Y chromosome deletions, and sperm DNA fragmentation. Notably, advanced paternal age is found to be associated with an increased risk of recurrent pregnancy loss, shedding light on the importance of understanding the impact of aging on male fertility. Additionally, paternal health, particularly metabolic syndrome, emerges as a noteworthy factor contributing to pregnancy loss. Chromosome abnormalities in male partners, such as balanced translocations, and Y chromosome microdeletions are explored in the context of pregnancy loss risk. Moreover, the review highlights the growing body of evidence linking sperm DNA fragmentation and sperm protein abnormalities to spontaneous pregnancy loss, emphasizing the significance of sperm health in reproductive outcomes. Overall, this review provides a comprehensive overview of the multifaceted role of the male partner in pregnancy loss, calling for a more inclusive approach to pregnancy loss investigations that encompasses both maternal and paternal factors.

A new insight into the pathway behind spontaneous recurrent pregnancy loss: decreased CYR61 gene expression.

Investigating the potential role of CYR61 in recurrent pregnancy loss is critical for developing diagnostic approaches and treatments for recurrent pregnancy loss. In this prospective case-control study, we have investigated the expression patterns of CYR61 in blood samples from participants with recurrent pregnancy loss in their medical history and control group (n=20 vs n=10). Peripheral blood mononuclear cells from study and control groups were isolated and the expression patterns of the CYR61 gene were determined by real-time semi-quantitative reverse transcriptase PCR. A significant decrease in CYR61 gene expression was demonstrated in patients with two or more clinically recognized miscarriages compared with patients without miscarriages or with a history of miscarriage (p<0.01), which may make the CYR61 gene a potential candidate for predicting the risk of recurrent pregnancy loss. This study provides a basis for a detailed investigation of candidate biomarkers and molecular players involved in the development of recurrent pregnancy loss and for the development of potential treatment approaches to prevent recurrent pregnancy loss.

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Role of the CD40–CD40L expression level pathway in the diagnosis of unexplained recurrent pregnancy loss

Background Unexplained recurrent spontaneous pregnancy loss (URPL) lacks effective treatment and reliable early diagnosis and prediction. Immunologic dysfunction can be an underlying cause of recurrent pregnancy loss (RPL). Considering the regulatory role of CD40–CD40L in immune responses, we explored its clinical significance in URPL. Methods The 108 women with URPL who were treated in Hebei Yanda Hospital from January 2020 to December 2022 were selected as study subjects, and another 108 healthy women who were not pregnant and matched with the age and body mass index of the study group were selected as the control group. CD40 and CD4 + CD25 + Treg cells in peripheral blood mononuclear cells (PBMCs) and CD40L in peripheral blood platelets were measured by flow cytometry. The predictive value of CD40–CD40L in URPL for the risk of RPL was determined by receiver operating characteristic (ROC) curves. The correlations of CD40–CD40L with CD4 + CD25 + Treg cells and serum pro-inflammatory factors were assessed by Pearson’s analysis. Results CD40 on the surface of PBMCs and CD40L on the surface of platelets were up-regulated in URPL patients. CD40 in combination with CD40L had high predictive value for the risk of RPL in URPL patients. Peripheral blood CD40–CD40L was positively linked to IL-17 and IL-23, and negatively to CD4 + CD25 + Treg cells and IL-10 in URPL patients. Conclusions The CD40–CD40L pathway expression in peripheral blood can help predict the risk of RPL in URPL patients.

Split protocol for next successful pregnancy after spontaneous abortions and pregnancy loss in Genetic Counselling Unit Split

Aim: Spontaneous abortion, early neonatal death and stillbirth are tragic events for the whole family. Sporadic abortion in the general population occurs at 12-15%, before the 12th weeks. The percentage increases with the age of the mother, up to 23%. Successful next pregnancy is the goal. Methods: In a retrospective analysis from 1985 to 2010, 451 couples with one or more SAs before the 16th week of pregnancy were examined at the Genetic Counselling Unit, Pediatrics Clinics, UH Split. Results: The highest number of SAs was recorded in the period 8-10th weeks of gestation. Furthermore, 69% of women and 66% of men had a positive family history (especially in a second-generation relative) for SA or sterility. Adverse habits (smoking, alcohol consumption) and exposure to pollutants and / or teratogens (chemicals, exposure to excessive heat or cold) did not affect the incidence of SA. Examination of serological signs (IgM + and EA +) in the presence of reactivation of infection with viruses most commonly revealed reactivation to viruses of the genus herpes viride such as HSV1, CMV and EBV, more often in women. Sideropenia or anemia with very low ferritin values ​​were found in 40% of tested women. Conclusion: The theory of “two hits” (multifactorial inheritance) is still in the basis of SA. Under these circumstances, it is possible to achieve a normal pregnancy as needed with prenatal or preimplantation diagnostics. If there is a need for assisted fertilisation, the same procedure should be followed.

Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss

Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extra-embryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extra-embryonic mesoderm rather than chorionic villi. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.

Pregnancy Outcomes in Patients with Early-Onset Idiopathic Chronic Pancreatitis.

Early-onset idiopathic chronic pancreatitis (EOICP) is a disease that affects young individuals. Data on pregnancy outcomes in EOICP are limited. To assess the pregnancy outcomes in patients with EOICP andthe effect of pregnancy on the course of EOICP. Patients with EOICP with disease onset before their pregnancy were recruited. Data regarding demographic variables, disease duration, pregnancy outcomes, and course of illness were noted. 50 patients were included in the study contributing to a total of 86 pregnancies. The mean age of onset of symptoms and at the time of delivery was 17.95 (5.71) and 23.44 (4.28) years, respectively. Gestational diabetes (GD) and gestational hypertension (GH) noted in one (1.5%) each. 3 (4.5%) pregnancies were preterm. 19 (22.1%) pregnancies did not have successful outcomes (7 (8.1%) were induced abortions). 12 (15.2%) pregnancies had spontaneous pregnancy losses. 8 (10.1%) were spontaneous abortions and 4 (5.1%) were stillbirths. Of 67 successful pregnancies, 33 (49.3%) pregnancies were delivered by LSCS. Compared to average rates of LSCS in India, this was significantly higher (21.5% vs 49.3%-p ≤ 0.001). The average birth weight was 2.87 (0.48)kg. There was one (1.5%) neonatal death. Compared to the published Indian data, there was no significant difference in the incidence of spontaneous pregnancy losses, GD, GH, preterm labor, and birth weight. Pancreatic pain was reported by 21 (42%) women in total 27 (31.4%) pregnancies. There was no difference in maternal or fetal outcomes between pregnancies with or without pancreatic pain. There were no pancreatitis-related complications reported during the pregnancies. The present study shows that mothers affected with EOICP have pregnancy outcomes similar to healthy women in India.

Neighborhood deprivation and racial differences in in vitro fertilization outcomes

BACKGROUNDThere are significant racial disparities in in vitro fertilization outcomes, which are poorly explained by individual-level characteristics. Environmental factors such as neighborhood-level socioeconomic factors may contribute to disparities in in vitro fertilization outcomes; however, few studies have directly addressed this research question in a large, racially diverse cohort. OBJECTIVETo investigate whether neighborhood deprivation is associated with differences in in vitro fertilization outcomes. STUDY DESIGNOur retrospective cohort study included 1110 patients who underwent 2254 autologous in vitro fertilization cycles between 2014 and 2019 at an academic fertility center in the Southeastern United States. Neighborhood deprivation was estimated using the neighborhood deprivation index, a composite variable measuring community levels of material capital based off poverty, occupation, housing, and education domains. Using multivariable log-binomial generalized estimating equations with cluster weighting, risk ratios (RR) and 95% confidence intervals (CI) were estimated for cycle cancellation, miscarriage (defined as spontaneous pregnancy loss before twenty weeks after a confirmed intrauterine gestation), and live birth according to patient neighborhood deprivation index. RESULTSThere were positive associations between increasing neighborhood deprivation index (indicating worsening neighborhood deprivation) and body mass index, as well as increasing prevalence of tubal and uterine factor infertility diagnoses. The crude probability of live birth per cycle was lower in Black (24%) versus White patients (32%) and the crude probability of miscarriage per clinical pregnancy was elevated in Black (22%) as compared to White patients (12%). After adjustment, neighborhood deprivation index was not significantly associated with risk of cycle cancellation or live birth. Results were consistent when analyses were stratified by race. CONCLUSIONOur research demonstrates racial disparities between Black and White women in the incidence of miscarriage and live birth following in vitro fertilization. While level of neighborhood deprivation was closely related to race, it did not have strong associations with in vitro fertilization outcomes in our population as a whole or within strata of race.