Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Bahia, Wael; Finan, Ramzi R.; Al-Mutawa, Mariam; Haddad, Anis; Soua, Aymen; Janhani, Faouzi; Mahjoub, Touhami; Almawi, Wassim Y.

doi:10.1111/1471-0528.14949

Cited by 26 publications

(18 citation statements)

References 30 publications

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“…1,2 We acknowledge that inclusion of data on tobacco usage (cigarettes, water pipe), vitamin D status, consumption of caffeine and alcohol, along with infection positivity [Mycobacterium tuberculosis, human papillomavirus (HPV)], as the clinically relevant covariates will strengthen the conclusion, as stated by Pandey et al 2 Smoking during pregnancy has long been associated with increased risks for miscarriage, preterm birth, and fetal morbidity and mortality.…”

Section: Authors' Replymentioning

confidence: 90%

“…The recently published article by Bahia et al 1 assessing the association of progesterone receptor (PGR) gene variants with susceptibility to recurrent pregnancy loss (RPL) provides critical clinical research insights in reproductive medicine. Pregnancy-related complications, including stillbirths, miscarriages and infertility, are emerging as major public health challenges among ethnically disparate populations worldwide, including women of Indian ethnicity.…”

Section: Sirmentioning

confidence: 99%

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Re: Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Pandey¹,

Murdia²,

Chandra³

et al. 2017

BJOG

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Re: Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case-control study Progesterone receptor genetic variants as predictors of recurrent pregnancy loss:an epidemiological study Sir, The recently published article by Bahia et al.1 assessing the association of progesterone receptor (PGR) gene variants with susceptibility to recurrent pregnancy loss (RPL) provides critical clinical research insights in reproductive medicine. Pregnancy-related complications, including stillbirths, miscarriages and infertility, are emerging as major public health challenges among ethnically disparate populations worldwide, including women of Indian ethnicity. 2 We wish to comment that the authors have elegantly conceptualised this pregnancy-related cohort study by incorporating a retrospective case-control gene epidemiological design with eligible participants enrolled from outpatient obstetrics/gynaecology clinics; the stringent inclusion/exclusion criteria added to study merits, and the core tenets of ethical research involving informed consent of participants were followed during the entire course of the study. A relatively higher sample size of cases (women with RPL 396) and controls (women 361) increased statistical power; moreover, RPL was defined as three or more consecutive miscarriages of unknown aetiology among pregnant women. An allelic exclusion method (real-time PCR) for PGR genotyping yielded high-quality, reliable results assessing PGR single nucleotide polymorphisms and comparative allelic, genotypic and haplotypic distributions. A major study strength was the sophisticated, selection-bias free, robust statistical data analyses using linkage disequilibrium, minor allele frequency and homozygous versus heterogyzous genotypic frequency distribution(s) in cases versus controls by multiple comparisons and adequate adjustments of co-variates/parameters, namely age, body mass index and menarche; as active clinical medicine researchers in reproductive medicine, we would like to suggest that the authors could have included further clinically relevant covariates for data analysis such as tobacco usage (chewers versus smokers), vitamin D deficiency, caffeine and alcohol usage, Mycobacterium tuberculosis and human papillomavirus positivity among RPL cases so as to draw more definitive conclusions, and accordingly devise cost-effective, predictive biomarkers in RPL management among women of reproductive age from varying genetic landscapes and sociocultural as well as socio-economic backgrounds. The findings demonstrated higher minor allele frequency of rs590688, rs10895068 and rs1942836 in women with RPL than in control women; interestingly, association analysis further indicated significantly higher frequencies of heterozygous (1/2) rs608995, along with heterozygous (1/2) and homozygous (2/ 2) rs590688, rs10895068 and rs1942836 genotype carriers between women with RPL versus control women, respectively. An increased risk of RPL associated with rs590688 and rs1942836 was depen...

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Section: Authors' Replymentioning

confidence: 90%

Section: Sirmentioning

confidence: 99%

Re: Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Pandey¹,

Murdia²,

Chandra³

et al. 2017

BJOG

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“…We agree with Pandey et al that a multi-centre collaborative study is warranted for assessment of the contribution of genetic variants in the progesterone receptor and progesterone signalling pathway, and probably for other sex hormones receptors also. Along with functional assays, transcriptomics, genomics, metabolomics and proteomics, this will be crucial in addressing the diagnostic/prognostic role for altered progesterone signalling in identifying RPL-susceptible women of diverse eth- Sir, The recent BJOG special edition on high-intensity focused ultrasound (HIFU) 1 provides refreshing topics for discussion about HIFU ablation for fibroids in reproductive women.…”

mentioning

confidence: 99%

“…Zou et al 1 reported retrospective data on 78 pregnancy outcomes in cases of fibroids treated by HIFU at a single centre, where 15 of the women delivered vaginally and 56 by caesarean section. They concluded that the pregnancy preparation time may be reduced by HIFU ablation, and fertility in women with infertility related to fibroids was improved.…”

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confidence: 99%

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Re: Pregnancy outcomes in patients with uterine fibroids treated with ultrasound‐guided high‐intensity focused ultrasound: Is the noninvasive nature of HIFU ablation for uterine fibroids and adenomyosis setting patients up for future operative delivery?

Jeng

Long

et al. 2018

BJOG

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Regulatory role of miR‐125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses

Manzoor,

Pandith,

Amin

et al. 2024

Intl J Gynecology & Obste

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ObjectivesStudies have investigated miR‐125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3.MethodsThe present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR‐125a was conducted by quantitative real‐time PCR (qPCR).ResultsThe expression of miR‐125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56‐fold, P < 0.0001). Among the target gene of miR‐125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58‐fold, P = 0.04; 1.87‐fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR‐125a cases depicted a significant association (P = 0.0005). Kaplan–Meier survival analysis revealed cases with low miR‐125a expression had significantly shorter time to miscarriages, (log‐rank P = 0.02). Also, decreased expression of miR‐125a significantly conferred >2‐fold increased risk for RPL (HR = 2.34: P < 0.05).ConclusionThe overall conclusion of the study was that altered miR‐125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy.

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Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Abstract: Genetic variants in progesterone receptor gene are associated with increased risk of recurrent pregnancy loss.

Cited by 26 publications

References 30 publications

Re: Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Re: Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case–control study

Re: Pregnancy outcomes in patients with uterine fibroids treated with ultrasound‐guided high‐intensity focused ultrasound: Is the noninvasive nature of HIFU ablation for uterine fibroids and adenomyosis setting patients up for future operative delivery?

Regulatory role of miR‐125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses

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