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  1. Sakthiswary R, Rajalingam S, Norazman MR, Hussein H
    Clin Ter, 2015;166(2):e98-101.
    PMID: 25945451 DOI: 10.7417/CT.2015.1827
    OBJECTIVE: The etiology of recurrent pregnancy loss (RPL) is unknown in a significant proportion of patients. Autoimmune processes have been implicated in the pathogenesis. The role of antinuclear antibody (ANA) in this context is largely undetermined. In an attempt to address the lack of evidence in this area, we explored the clinical significance of antinuclear antibody (ANA) in unexplained RPL.
    MATERIALS AND METHODS: We studied 68 patients with RPL and 60 healthy controls from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1: 80 and above was considered positive. We compared the pregnancy outcome between the ANA positive and ANA negative RPL cases.
    RESULTS: The incidence of ANA positivity among the cases (35.3%) was significantly higher than the controls (13.3%) (p=0.005). ANA positive cases showed significantly higher number of RPL (p=0.006) and lower number of successful pregnancies (p=0.013) compared to the ANA negative cases . The ANA titre had a significant association with the number of RPL (p<0.05, r=0.724) but not with the number of successful pregnancies (p=0.054).
    CONCLUSIONS: ANA positivity predicts a less favorable pregnancy outcome in RPL. Our findings suggest that the ANA titre is a useful positive predictor of the number of RPL. Hence, ANA test is a potential prognostic tool for this condition which merits further research.
    Matched MeSH terms: Abortion, Habitual/blood*
  2. Ang KC, Bogdanova N, Markoff A, Ch'ng ES, Tang TH
    Fertil Steril, 2019 05;111(5):971-981.e2.
    PMID: 30922645 DOI: 10.1016/j.fertnstert.2019.01.015
    OBJECTIVE: To ascertain the magnitude and precision of the association between M2/ANXA5 haplotype and repeated pregnancy loss (RPL).

    DESIGN: Meta-analysis of odds ratios.

    SETTING: Not applicable.

    PATIENT(S): Subjects were women with RPL and their partners.

    INTERVENTION(S): Not applicable.

    MAIN OUTCOME MEASURE(S): The association between M2/ANXA5 haplotype and RPL was evaluated in a meta-analysis of odds ratios. We further scrutinized this association according to [1] the sequence of miscarriages, [2] the number of consecutive losses, [3] the extent of excluding other pathologies of RPL, and [4] the timing of fetal loss.

    RESULT(S): Fourteen individual studies (n = 4,664 subjects) were included in this meta-analysis. The results show that women with the M2/ANXA5 haplotype have 1.54 times (95% confidence interval, 1.08-2.20) the odds of having associated RPL compared with women with the normal haplotype, regardless of consecutive or nonconsecutive pregnancy losses. Acknowledging the clinical heterogeneity among the studies, this significant association comes with a caveat that the lower bound of the confidence interval is close to unity. In couple populations (n = 2,449), M2/ANXA5 haplotype subjects have an odds ratio of 1.48 (95% confidence interval, 1.14-1.91) of experiencing RPL, which suggests contributions from paternal M2/ANXA5 carriers in RPL.

    CONCLUSION(S): This meta-analysis ascertains that women with the M2/ANXA5 haplotype have a higher risk of experiencing RPL, especially consecutive early idiopathic RPL. Male partners with the M2/ANXA5 haplotype partly contribute to this risk. Hence, screening for the M2/ANXA5 haplotype as a panel of laboratory investigations for RPL is recommended.

    Matched MeSH terms: Abortion, Habitual/diagnosis*; Abortion, Habitual/genetics*; Abortion, Habitual/epidemiology
  3. Ayadurai T, Muniandy S, Omar SZ
    J Obstet Gynaecol Res, 2009 Dec;35(6):1061-8.
    PMID: 20144172 DOI: 10.1111/j.1447-0756.2009.01067.x
    The status of thrombophilia in Asian women with recurrent pregnancy loss (RPL) is obscure and poorly understood. Numerous studies suggest the non-existence or extreme rarity of the two important thrombophilia markers, factor V Leiden (FVL) and prothrombin G20210A (PTG) mutations, in patients of Asian ancestries. Thus, the consensus that thrombophilia is rare among Asians and laboratory investigations is irrelevant. We therefore investigated Malaysian women with RPL for thrombophilia abnormalities.
    Matched MeSH terms: Abortion, Habitual/blood*
  4. Mohd Fuad SK, Adznan N, Hayati AR, Virasamy V, Rahim NS
    Malays J Pathol, 2020 Dec;42(3):439-444.
    PMID: 33361726
    INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare placental lesion strongly associated with recurrent miscarriages and fetal losses. It requires histopathological diagnosis and can only be made after delivery of the products of conception (POC). We describe a case of CHI in a 41-yearold lady with a 16-year history of thirteen recurrent consecutive first trimester miscarriages.

    CASE REPORT: The patient is a 41-year-old lady who suffered first trimester miscarriages in all her thirteen pregnancies. The relevant clinical investigations revealed neither significant nor helpful findings in determining the cause of recurrent miscarriages. Histological findings in each except one of the submitted conceptual tissue showed similar features of histiocytic aggregates primarily within the intervillous spaces, a characteristic description of CHI. One of the samples showed degenerative changes.

    DISCUSSION: Practicing pathologists are not familiar with the histological features of CHI and this may be a potential pitfall in routine examination of POCs. Recognising this entity allows for accurate diagnosis and hence better management. The aetiology remains unclear, although an immunopathological basis are being explored.

    Matched MeSH terms: Abortion, Habitual/pathology*
  5. Ng KH
    Med J Malaya, 1971 Sep;26(1):59-61.
    PMID: 4258578
    Matched MeSH terms: Abortion, Habitual*
  6. MUN CT
    Med J Malaysia, 1964 Jun;18:223-5.
    PMID: 14199437
    Matched MeSH terms: Abortion, Habitual*
  7. Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.
    J Assist Reprod Genet, 2017 Apr;34(4):517-524.
    PMID: 28108842 DOI: 10.1007/s10815-017-0871-0
    PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.

    METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.

    RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.

    CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.

    Matched MeSH terms: Abortion, Habitual/genetics*; Abortion, Habitual/physiopathology
  8. Thean Hock T, Bogdanova N, Kai Cheen A, Kathirgamanathan S, Bin Abdullah R, Mohd Yusoff N, et al.
    Reprod Biomed Online, 2015 Apr;30(4):434-9.
    PMID: 25682309 DOI: 10.1016/j.rbmo.2014.12.014
    Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5-15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with 'early' spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.
    Matched MeSH terms: Abortion, Habitual/genetics*; Abortion, Habitual/epidemiology
  9. CHOON HS
    Med J Malaysia, 1963 Jun;17:282-7.
    PMID: 14060505
    Matched MeSH terms: Abortion, Habitual*
  10. MUN CT
    Am J Clin Hypn, 1964 Apr;6:340-4.
    PMID: 14136309
    Matched MeSH terms: Abortion, Habitual*
  11. Yusoff NM, Abdullah WZ, Ghazali S, Othman MS, Baba AA, Abdullah N, et al.
    Aust N Z J Obstet Gynaecol, 2002 May;42(2):164-6.
    PMID: 12069143 DOI: 10.1111/j.0004-8666.2002.00164.x
    OBJECTIVES: The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women.

    DESIGN: A prospective case control study between June 1999 and April 2000.

    SETTING: Hospital University Science of Malaysia, Kubang Kerian, Kelantan, and Maternal and Child Health Clinic, Pasir Mas, Kelantan, Malaysia.

    SAMPLES: A total of 46 Malay women with a history of three or more first or second trimester miscarriages were studied. The control group consisted of 46 parous women without obstetric complications.

    METHODS: Diagnosis of factor V Leiden mutation was made by examination of factor V Leiden allele product following Mnl I digestion of factor V Leiden alleles amplified by polymerase chain reaction.

    RESULTS: None of the 46 women with recurrent spontaneous abortion carried the mutation. Also, we found no subject carrying the factor V Leiden alleles in the control group.

    CONCLUSION: These results suggest that that there is no association between the factor V Leiden mutation and recurrent spontaneous abortion in the Malay population.
    Matched MeSH terms: Abortion, Habitual/genetics*; Abortion, Habitual/epidemiology
  12. Mohd Azri MS, Kunasegaran K, Azrina A, Siti Nadiah AK
    Indian J Hematol Blood Transfus, 2014 Sep;30(Suppl 1):405-8.
    PMID: 25332632 DOI: 10.1007/s12288-014-0439-4
    We report the first case of young woman with the p phenotype and anti-PP1P(k) antibody in the Malaysian population who was identified during a blood grouping and antibody screening procedure after her first miscarriage. Further family screening detected two other siblings who possessed the same rare phenotype and antibody. Because of difficulties in finding compatible units in the local population, the patient and her two siblings were advised to become regular blood donor. Their blood was frozen for future use. After she had two recurrent miscarriages, her third pregnancy was successfully managed using oral dydrogesterone, which was started from 10 weeks into the pregnancy. Her pregnancy was uneventful and she gave birth to a healthy term neonate.
    Matched MeSH terms: Abortion, Habitual
  13. Rathika Rajah, Alvin Oliver Payus, Norlaila Mustafa
    MyJurnal
    Antiphospholipid syndrome is a hypercoagulable autoimmune condition that predominantly affect the female and commonly manifest as arterio-venous thrombosis and recurrent miscarriage. Here, we present a unique case of a healthy young man who developed sudden onset of right leg swelling after exercise which was then found to be due to deep vein thrombosis via Doppler ultrasound. His blood investigations showed thrombocytopenia and prolonged coagulation profile. Therefore, antiphospholipid syndrome was suspected and later confirmed by positive autoim- mune antibodies. He was treated with long term moderate intensity oral warfarin. The objective of this case report is to share the uncommon occurrence of an unprovoked deep vein thrombosis secondary to antiphospholipid syn- drome in a healthy young man so that the possibility of deep vein thrombosis should be suspected in selected cases of non-resolving leg swelling after exercise as it can lead to fatal pulmonary embolism.
    Matched MeSH terms: Abortion, Habitual
  14. Aziati Azwari Annuar, Nik Mohd Zulfikri Mat Zin, Siti Mariam Ismail, Nurul Alia Mohd Nawi, Nazihah Mohd Yunus, Sarina Sulong, et al.
    MyJurnal
    Complex chromosome rearrangements (CCRs) are structural aberrations or rearrangements involving three or more cytogenetics breakpoints on two or more chromosomes [1]. Balanced and unbalanced are known to have significant risk of mental retardation and phenotypic anomalies. CCRs are also associated with infertility in males and recurrent abortion in females. Here we report one case of apparently balanced CCR involving three chromosomes 3, 5 and 12 in a child with abnormal features. G banding and FISH were performed to clarify the nature of this complex abnormality.
    Matched MeSH terms: Abortion, Habitual
  15. Jones HW, Ireland R, Senaldi G, Wang F, Khamashta M, Bellingham AJ, et al.
    Ann Rheum Dis, 1991 Mar;50(3):173-5.
    PMID: 2015010 DOI: 10.1136/ard.50.3.173
    Systemic lupus erythematosus (SLE) is highly prevalent in Malaysia, which has a mixed population of Malays, Chinese, and Indians. A quantitative enzyme linked immunosorbent assay (ELISA) was used to determine anticardiolipin antibody (aCL) levels (total immunoglobulin, IgG, and IgM) in 200 patients with SLE (164 Chinese, 26 Malay, and 10 Indian) attending the University Hospital of Kuala Lumpur, Malaysia, and 103 matched controls. Only 33 (16.5%) of the patients had raised aCL levels; 26 had raised IgG aCL, five IgM aCL, and two both IgG and IgM aCL. There was a low prevalence of raised levels of aCL in the population studied, which was seen in conjunction with a rare occurrence of thrombosis. The classical association of high aCL levels with thrombocytopenia and recurrent abortions was noted, though not with cerebral disease. The low prevalence of aCL in this study population of mixed racial origin contrasts with findings in European patients with SLE and lends support to the influence of local factors, be they genetic or environmental, on the clinical manifestations of this disease.
    Matched MeSH terms: Abortion, Habitual/immunology
  16. Othman R, Omar MH, Shan LP, Shafiee MN, Jamal R, Mokhtar NM
    Reprod Biol, 2012 Jul;12(2):183-99.
    PMID: 22850470
    The aim of the present study was to identify differentially expressed genes and their related biological pathways in the secretory phase endometrium from patients with recurrent miscarriage (RM) and fertile subjects. Endometrial samples from RM and fertile patients were analyzed using the Affymetrix GeneChip® ST Array. The bioinformatic analysis using the Partek Genomic Suite revealed 346 genes (175 up-regulated and 171 down-regulated) that were differentially expressed in the endometrium of RM patients compared to the fertile subjects (fold change ≥1.5, p<0.005). Validation step using quantitative real-time polymerase chain reaction (qPCR) confirmed a similar expression pattern of four exemplary genes: one up-regulated gene (fibroblast growth factor 9, FGF9) and three down-regulated genes: integrin β3 (ITGB3), colony stimulating factor 1 (CSF1) and matrix-metalloproteinases 19 (MMP19). The Gene Set Enrichment Analysis (GSEA) and the Pathway Studio software have found 101 signaling pathways (p<0.05) associated with the affected genes including the FGFR3 /signal transducer and activator of transcription (STAT) pathway and the CSF1R/STAT pathway. Cell adhesion, cell differentiation and angiogenesis were among biological processes indicated by this system. In conclusion, microarray technique is a useful tool to study gene expression in the secretory phase-endometrium of RM patients. The differences in endometrial gene expressions between healthy and RM subjects contribute to an increase in our knowledge on molecular mechanisms of RM development and may improve the outcome of pregnancies in high-risk women with RM.
    Matched MeSH terms: Abortion, Habitual/metabolism*
  17. Kee SK, See VH, Chia P, Tan WC, Tien SL, Lim ST
    J Pediatr Genet, 2013 Mar;2(1):37-41.
    PMID: 27625838 DOI: 10.3233/PGE-13046
    The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation. We present here a family with t(11;22). Of six siblings, three were found to be carriers following prenatal diagnosis of the proband fetus. Neither of the two married carrier siblings have a live born child. In keeping with the prevailing knowledge of the pregnancy outcomes of heterozygote carriers, between the siblings they had recurrent miscarriages, a fetus with a +der(22) chromosome, and other subfertility issues resulting in multiple failed in vitro fertilization cycles with preimplantation genetic diagnosis. However, unlike the siblings, their extended family comprising their heterozygote translocation mother, married aunts and an uncle had normal fertility and a lack of a history of miscarriages or an abnormal child. The differing outcomes may be related to the male partners having additional semen anomalies which may further exacerbate problems associated with the t(11;22). Because the t(11;22) rearrangement tends to run in families, it is recommended that chromosome studies are offered to family members of an affected relative as an option, and provide them with appropriate genetic counseling so that they will have the necessary information with regard to their risk for subfertility, miscarriages, and production of viable unbalanced offspring. Follow-up prenatal diagnosis should also be offered to affected expectant family members, especially after preimplantation genetic diagnosis.
    Matched MeSH terms: Abortion, Habitual
  18. Pandian RU
    Maturitas, 2009 Dec;65 Suppl 1:S47-50.
    PMID: 20005647 DOI: 10.1016/j.maturitas.2009.11.016
    Threatened miscarriage is a common problem during pregnancy.
    Matched MeSH terms: Abortion, Habitual
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