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  1. M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study
    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/epidemiology
  2. Association between M2/ANXA5 haplotype and repeated pregnancy loss: a meta-analysis
    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/epidemiology
  3. The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions
    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/epidemiology
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