OBJECTIVE: To investigate the genetic characteristics and clinical utility of Optical genome mapping (OGM) in resolving complex genomic rearrangements in families with recurrent pregnancy loss. METHODS: A recurrent miscarriage family which presented at both the People's Hospital of Qianxinan Buyi and Miao Autonomous Prefecture and the Affiliated Women and Children's Hospital of Ningbo University in September 2024 was selected as the study subject. Relevant clinical information was collected. Peripheral blood samples of the couple were collected for G banding karyotyping analysis, and copy number variation sequencing (CNV-seq) and OGM were used for verification. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2024-148). RESULTS: CNV-seq in an external hospital detected a 10.67 Mb deletion in the 16q12.1q21 region, a 142.4 kb deletion in the 5p15.2 region, and a 359.55 kb duplication in the 7p22.2 region. No abnormality was found in the chromosomal karyotype of the male partner, and the initial karyotyping of the female partner suggested 46,XX,?del(16)(q12.1q22). The CNV-seq verification of her indicated only variations in the 5p15.2 and 7p22.2 fragments, and no deletion of 16q was detected. As indicated by precise OGM analysis, multiple intrachromosomal and interchromosomal translocation variations had occurred between chromosomes 10 and 16 in the female partner, with complex balanced rearrangements (including 5 transchromosomal breakpoints). CONCLUSION The complex balanced rearrangements of the female partner's chromosomes had occurred during meiosis, the resultant unbalanced gametes may be the cause of repeated miscarriage in this family. OGM can delineate complex rearrangement breakpoints and directions that are difficult to reveal by conventional karyotyping analysis and provide a basis for accurate reproductive genetic counseling.
Humans ; Abortion, Habitual/etiology* ; Female ; Pregnancy ; Male ; DNA Copy Number Variations/genetics* ; Adult ; Karyotyping ; Pedigree ; Gene Rearrangement ; Chromosome Mapping

Recurrent spontaneous abortion is one of the common complications in women of childbearing age during pregnancy. The immune factor accounts for a large proportion of many causes. Antiphospholipid antibody syndrome is the most common type of acquired thrombophilia disease. Autoimmune diseases that cause thrombosis and obstetric complications under the action of antibodies are also the most common type of immune-related recurrent abortion. At present, there is no unified opinion on the treatment of this disease, especially the treatment of immunoglobulins and other drugs like glucocorticoid. Here we reviewed the progress of diagnosis and treatment of antiphospholipid antibody-related recurrent abortions and retrospectively analyzed and summarized the drug regimens and pregnancy outcomes of this disease with pregnancy patients in our hospital. A total of 75 patients were included. According to their clinical manifestations and laboratory results, these patients were basically divided into two categories: classical antiphospholipid syndrome and non-classical antiphospholipid syndrome. The latter was further divided into serum-negative antiphospholipid syndrome and antiphospholipid antibody-related recurrent abortion patients based on their clinical manifestations and antiphospholipid antibody results. The patients were divided into four categories: aspirin + hydroxychloroquine, aspirin + low molecular weight heparin, aspirin + low molecular weight heparin + hydroxychloroquine, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoids. Among them, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoid treatment regimen was most commonly used. Most of the patients who received the above different treatment regimens achieved full-term infants, and a small number of patients had adverse pregnancy outcomes, such as premature delivery, placental abruption, eclampsia, and fetal malformation. And adverse pregnancy outcomes also occurred in this group. It might be related to the severity of the disease and the potential adverse effects of maternal fetal. However, further statistical analysis is needed for the risk factors affecting the pregnancy outcome of this part of patients.
Abortion, Habitual ; Abortion, Spontaneous/etiology* ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome/drug therapy* ; Aspirin/therapeutic use* ; Female ; Fibrinolytic Agents/therapeutic use* ; Heparin, Low-Molecular-Weight/therapeutic use* ; Humans ; Hydroxychloroquine/therapeutic use* ; Infant, Newborn ; Pharmaceutical Preparations ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Retrospective Studies

Recurrent spontaneous abortion (RSA) has a very complicated pathogenesis and male factors for this condition should not to be ignored, which are mainly related to genetics, immunology, infection, sperm quality, and others. In case of RSA, an etiological screening ought to be performed for the husband, which involves general, genetic and immunological examinations and infection detection. According to specific etiological factors, such measures as genetic consultation, immunotherapy, and traditional Chinese medication can be taken, which may contribute to the outcome of pregnancy.
Abortion, Habitual ; etiology ; therapy ; Abortion, Spontaneous ; etiology ; therapy ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunotherapy ; Male ; Pregnancy ; Semen Analysis

Here we describe a Syrian couple having recurrent pregnancy loss in the first trimester, fetal malformations, and/or neonatal death. The father had a balanced chromosomal translocation t(5;15), an sY125 microdeletion of locus b in the azoospermia factor (AZF) gene, and an MTHFR C677T homozygous polymorphism with normal phenotype. Interestingly, his healthy wife had another MTHFR A1298C homozygous polymorphism. The couple experienced two pregnancy losses and had two stillborn children with severe malformations due to partial trisomy of the short arm of chromosome 5. The couple does not have any living offspring after 10 years of marriage.
Abortion, Habitual ; genetics ; Azoospermia ; genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Female ; Fetal Death ; etiology ; Homozygote ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Pregnancy ; Translocation, Genetic ; Trisomy

Recurrent spontaneous abortion (RSA) has various complicated causes, and more and more researches are focused on its etiology. Genetic factors are the most common risk factors of RSA; immune factors, infection factors, male factors and female factors play an important role; environmental pollution and some other unknown factors may also be conspirators. This article presents an overview on the possible risk factors of RSA.
Abortion, Habitual ; etiology ; Female ; Humans ; Male ; Pregnancy ; Risk Factors

OBJECTIVETo evaluate and compare standard sperm parameters and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and a control group of men who had recently established their fertility.

METHODSSemen samples from 85 patients with a history of RPL and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by sperm chromatin dispersion test (SCD).

RESULTSA significant difference (P< 0.05) was observed in sperm motility but not other parameters between the two groups. The mean number of sperm cells with fragmented DNA, represented as DNA fragmentation index, was significantly increased in the RPL group [(34.99± 14.62)%] compared with controls [(10.82± 4.80)%].

CONCLUSIONThis study has indicated that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility compared with fertile males.

Abortion, Habitual ; etiology ; genetics ; Adult ; DNA Damage ; DNA Fragmentation ; Female ; Humans ; Male ; Pregnancy ; Sperm Motility

OBJECTIVETo explore the relationship of sperm DNA damage with unexplained recurrent spontaneous abortion (URSA).

METHODSSperm DNA fragmentation was evaluated by sperm chromatin dispersion (SCD), and the results were expressed in terms of DNA fragmentation index (DFI). DFIs were measured in the male partners of 56 women with URSA (the experiment group) and of 31 without URSA (the control group).

RESULTSThe DFI was shown to be (11.0% - 56.9%) in the experiment group, 21 (37.5%) of the subjects over 30%, as compared with (10.0% -36.8%) in the control group, only 8 (25.8%) of the subjects over 30%, significantly higher in the former than in the latter (29.4% vs 25.5%, P < 0.05).

CONCLUSIONThere is a relationship between sperm DNA damage and URSA.

Abortion, Habitual ; etiology ; Adult ; Case-Control Studies ; DNA Damage ; DNA Fragmentation ; Female ; Humans ; Male ; Pregnancy ; Spermatozoa ; pathology

OBJECTIVETo analyze the relation between recurrent miscarriage and routine semen parameters.

METHODSWe compared the semen parameters of normal healthy men with those of the spouses of recurrent miscarriage women through 1: 1 age-matched case-control study.

RESULTSCompared with the healthy controls, the men of the case group showed a significantly lower mean semen volume ([1.95 +/- 1.11] ml vs [2.74 +/- 1.43] ml), sperm concentration ([48.68 +/- 20.07] x 10(6)/ml vs [59.26 +/- 25.35] x 10(6)/ml), percentage of grade b sperm ([12.07 +/- 3.34] % vs [16.18 +/- 6.74] %), fruit-sugar content ([1.73 +/- 0.64] g/L vs [2.21 +/- 0.75] g/L), acrosomal enzyme activity ([84.34 +/- 26.69] U/mg prot vs [94.20 +/- 26.35] U/mg prot), alpha-glucuronidase (alpha-GLU) content ([36.28 +/- 15.98] U/ml vs [44.45 +/- 12. 54] U/ml), and acid phosphatase (ACP) content ([68.55 +/- 35.45] U/ml vs [84.78 +/- 51. 10] U/ml) (P < 0.05), but remarkably higher percentages of head teratospermia ([47.36 +/- 4.59] % vs [46.50 +/- 6.32] %) and tail teratospermia ([7.56 +/- 2.27] % vs [7.28 +/- 3.10] %), and elastase content ([885.64 +/- 1 272.30] ng/ml vs [661.08 +/- 764.64] ng/ml) (P < 0.05). Based on the results of discriminant analysis, the semen volume, percentages of grade b sperm and combined teratospermia, and contents of fruit-sugar, alpha-GLU and ACP could be used to evaluate the semen and sperm quality of the spouses of recurrent miscarriage women.

CONCLUSIONRoutine semen and sperm tests might help evaluate the seminal factors of recurrent miscarriage, but they lack specificity and need comprehensive analysis. Poorer semen quality is associated with higher incidence of recurrent miscarriage.

Abortion, Habitual ; etiology ; Adult ; Case-Control Studies ; Female ; Humans ; Male ; Pregnancy ; Semen ; Sperm Count ; Sperm Motility ; Spermatozoa

OBJECTIVEThis study was to investigate the association of Bisphenol A and unexplained recurrent spontaneous abortion.

METHODSA hospital-based 1:1 matched case-control study was conducted. Sixty patients with unexplained recurrent abortion were included. Each case was matched with one normal control by age (± 2 years), living district and the same gestational age. The levels of Bisphenol A in urine for 60 cases and 60 controls were detected using high performance liquid chromatography after fluorescent derivatization. The levels of urinary Bisphenol A in case was compared with that in control in education levels, occupation, smoking history. Data was analyzed by means of Wilcoxon-test, Student-Newman-Keuls after rank transform, univariate and multivariate conditional Logistic regression analysis. The software used was SAS 9.1.3.

RESULTSThe values of urinary Bisphenol A in cases and controls were (0.10 ± 0.21) µg/ml, (0.03 ± 0.08) µg/ml, respectively. The level of urinary Bisphenol A in cases was significantly higher than that in controls (Z = 3.988, P < 0.0001). The urinary Bisphenol A levels in cases were significant higher than those in controls from senior middle school (the levels were 0.10, 0.06 µg/ml respectively, Z = 1.996, P = 0.0459), college (the levels were 0.14, 0.03 µg/ml respectively, Z = 2.586, P = 0.0097), workers or farmers (the levels were 0.08, 0.03 µg/ml respectively, Z = 2.265, P = 0.0235), businessmen (the levels were 0.10, 0.03 µg/ml respectively, Z = 2.544, P = 0.0109), and no passive smokers (the levels were 0.09, 0.03 µg/ml respectively, Z = 3.767, P = 0.0002). After adjustment by age, body mass index, marital status during pregnancy and other factors, compared to Bisphenol A below 0.06 µg/ml, the adjusted OR was 4.03 (1.67 - 9.74) for Bisphenol A levels between 0.06 µg/ml and 0.20 µg/ml, and was 5.46 (1.95 - 15.27) for Bisphenol A over 0.20 µg/ml. The risk of unexplained recurrent spontaneous abortion increased progressively with the growth of urinary Bisphenol A levels (χ(2) = 13.042, trend test P = 0.0003). There were significant differences on Bisphenol A among controls, two abortions, and three or more abortions (the levels were 0.03 µg/ml, 0.09 µg/ml, 0.21 µg/ml respectively, F = 9.04, P = 0.0002).

CONCLUSIONExposure to Bisphenol A may be associated with unexplained recurrent spontaneous abortion.

Abortion, Habitual ; etiology ; Abortion, Spontaneous ; etiology ; Adult ; Benzhydryl Compounds ; Case-Control Studies ; Causality ; Female ; Humans ; Maternal Exposure ; adverse effects ; Phenols ; urine ; Pregnancy ; Young Adult

BACKGROUNDVarious etiologies that contribute to the loss of pregnancy have been proposed. Despite the lack of established and uniform screening methods for recurrent pregnancy loss (RPL), there are several factors considered to be definite (or probable) causes of RPL. Data describing the etiological characteristics of RPL consist almost entirely of Caucasian populations. As we were interested in the Chinese population, the goal of this study was to determine the etiological characteristics of RPL in the Chinese patients.

METHODSThe study was performed retrospectively by analyzing 1122 women with RPL. Patients were divided into three groups according to their number of pregnancy losses. Diagnostic tests included the following 9 critiria: parental genetics, uterine anatomy, autoimmune factors, alloimmune factors, thrombophilic factors, endocrine parameters, genital infection, toxoplasma, rubella, cytomegalovirus, herpes (TORCH) titers and RH blood groups. The criteria for abnormal results were defined before diagnosis.

RESULTSWe found that 87.1% (977/1122) patients had no more than 3 abnormal aspects, and the proportion of total abnormal results was similar among groups. The prevalence of abnormal results for each test did not differ among groups, except in the cases of parental genetics, uterine anatomy and presence of mixed lymphocyte reaction blocking antibodies (MLR-Bf). Absence of MLR-Bf, as well as abnormally increased levels of CD3⁺CD19⁺ and CD56⁺CD16⁺ cells, was commonly detected in Chinese RPL patients.

CONCLUSIONImmunological disorders play an important role in RPL among Chinese patients.

Abortion, Habitual ; etiology ; Adult ; Female ; Humans ; Pregnancy ; Retrospective Studies ; Young Adult