Association Between First-Trimester Intrauterine Hematoma and Twin Pregnancy Outcomes: A Retrospective Cohort Study

Abstract Background: In recent years, we have found that first-trimester intrauterine hematoma in twin pregnancy has become increasingly common. The majority of studies on intrauterine hematoma have excluded twin pregnancies, while others did not differentiate between singleton and twin pregnancies. The associations in twin pregnancy are not clear. Therefore, the primary objective of our study was to examine the associations between first-trimester intrauterine hematoma and pregnancy outcomes in twin pregnancy. Material and methods: 1020 twin pregnancies in women who underwent a routine examination from January 2014 to December 2018 were enrolled. According to the presence or absence of intrauterine hematoma, we compared the baseline data and pregnancy outcomes between two groups. Multivariable logistic regression analysis was used to adjust for possible confounding factors. Results: A total of 209 patients (21.3%) developed intrauterine hematoma in the first trimester. First-trimester intrauterine hematoma was significantly associated with increased odds of miscarriage (adjusted odds ratio 14.27, 95% CI 8.25-24.70) and the vanishing twin syndrome (adjusted odds ratio 3.26, 95% CI 1.11-4.61). However, It did not have increased odds of adverse pregnancy outcomes after 20 Weeks of Gestation .In the final regression model analysis, the associations of hematoma with previous miscarriage history, accepted assisted conception, accompanying vaginal bleeding and miscarriage and vanishing twin syndrome were no longer significant. No association was found between hematoma size or the presence of vaginal bleeding and the risk of pregnancy loss or the vanishing twin syndrome before 20 weeks of gestation (P>0.05). Conclusion: In women with twin pregnancies, the presence of intrauterine hematoma in the first trimester was associated with one or both fetal losses before 20 weeks of gestation. However, chorionicity in twins, the conception method, the intrauterine hematoma size and the presence of vaginal bleeding were not independently associated with pregnancy loss.

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Subchorionic Hematomas and Adverse Pregnancy Outcomes among Twin Pregnancies

American Journal of Perinatology ◽

10.1055/s-0039-3401852 ◽

2019 ◽

Author(s):

Mariam Naqvi ◽

Mackenzie N. Naert ◽

Hanaa Khadraoui ◽

Alberto M. Rodriguez ◽

Amalia G. Namath ◽

...

Keyword(s):

Gestational Age ◽

Pregnancy Outcomes ◽

Vaginal Bleeding ◽

Low Birthweight ◽

Univariate Analysis ◽

First Trimester ◽

Adverse Pregnancy Outcomes ◽

Spontaneous Reduction ◽

Adverse Pregnancy ◽

Twin Pregnancies

Abstract Objective This study estimates the association of a first trimester finding of subchorionic hematoma (SCH) with third trimester adverse pregnancy outcomes in women with twin pregnancies. Study Design Retrospective cohort study of twin pregnancies prior to 14 weeks at a single institution from 2005 to 2019, all of whom had a first trimester ultrasound. We excluded monoamniotic twins, fetal anomalies, history of fetal reduction or spontaneous reduction, and twin-to-twin transfusion syndrome. Ultrasound data were reviewed, and we compared pregnancy outcomes after 24 weeks in women with and without a SCH at their initial ultrasound 60/7 to 136/7 weeks. Regression analysis was used to control for any differences in baseline characteristics. Results A total of 760 women with twin pregnancies met inclusion criteria for the study, 68 (8.9%) of whom had a SCH. Women with SCH were more likely to have vaginal bleeding and had their initial ultrasound at earlier gestational ages. On univariate analysis, SCH was not significantly associated with gestational age at delivery, preterm birth, birthweight of either twin, low birthweight percentiles of either twin, fetal demise, or preeclampsia. SCH was associated with placental abruption on univariate analysis, but not after controlling for vaginal bleeding and gestational age at the time of the initial ultrasound (adjusted odds ratio: 2.00, 95% confidence interval: 0.63–6.42). Among women with SCH, SCH size was not associated with adverse pregnancy outcomes. Conclusion In women with twin pregnancies, the finding of a first trimester SCH is not associated with adverse pregnancy outcomes >24 weeks.

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Is twin pregnancy, calving and pregnancy loss predictable by serum pregnancy-specific protein b (pspb) concentration 28–35 days after ai in dairy cows?

Acta Veterinaria Hungarica ◽

10.1556/004.2018.040 ◽

2018 ◽

Vol 66 (3) ◽

pp. 451-461

Author(s):

Zoltán Szelényi ◽

Orsolya Gabriella Balogh ◽

Fernando Lopez-Gatius ◽

Irina Garcia-Ispierto ◽

Eszter Krikó ◽

...

Keyword(s):

Serum Concentration ◽

Milk Production ◽

Pregnancy Loss ◽

Twin Pregnancy ◽

First Trimester ◽

Specific Protein ◽

Holstein Friesian ◽

Study Population ◽

Twin Pregnancies ◽

Protein B

Double ovulation occurs more frequently in multiparous cows with high milk production than in primiparous cows and the rate of twin pregnancy/calving is increasing worldwide. Diagnosis of twin pregnancy is possible by ultrasound at the time of early pregnancy examination [28–34 days after artificial insemination (AI)]. Pregnancy proteins are also well-known indicators of gestation. The risk of pregnancy loss during the first trimester of gestation for cows carrying twins is three to nine times higher than for cows carrying singletons. Pregnancy-specific protein B (PSPB) is a good indicator not only of pregnancy but also of pregnancy loss. The aims of this study were (a) to collect calving data in some Hungarian Holstein-Friesian herds (n = 7,300) to compare PSPB serum concentrations (measured 29–35 days post insemination) in twin- and singleton-calving cows (Trial 1), and (b) to check the predictive value of PSPB serum concentration for twin pregnancy and pregnancy loss in high-producing Spanish Holstein-Friesian cows (n = 98; Trial 2). Our results showed almost 7% twin calving rate. Although hormonal treatments are commonly believed to be major causes of twin pregnancies, our data do not support this hypothesis. The only exception is the single PGF injection, which significantly increased twin calving. No effect of milk production on the risk of twin pregnancy was found, and twin pregnancy increased with parity. The AI bull, the bull’s sire, the bull’s grandfather and the cow’s father also affected twin calving (P ≤ 0.02). We found much higher frequency of twin calving in cows diagnosed pregnant with higher than 3 ng/ml serum PSPB concentrations at 29–35 days after insemination. In Trial 2, non-significant but well-marked differences were found in PSPB serum concentration between singleton- and twin-pregnant cow samples (2.1 and 2.9 ng/ml) at different bleeding times. Probably the small size of the study population and the effects of milk production on PSPB values may explain this lack of significance.

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Clinical Utility of Increased Nuchal Translucency at 11-13 weeks of Gestation in Twin Pregnancies based on the Chorionicity

10.20944/preprints202012.0410.v1 ◽

2020 ◽

Author(s):

Siwon Lee ◽

Hyun-Mi Lee ◽

You Jung Han ◽

Moon Young Kim ◽

Hye Yeon Boo ◽

...

Keyword(s):

Pregnancy Outcomes ◽

Odds Ratio ◽

First Trimester ◽

Nuchal Translucency ◽

Adverse Pregnancy ◽

Twin Pregnancies ◽

First Trimester Ultrasound ◽

Fetal Karyotype ◽

Increased Nuchal Translucency ◽

Structural Anomalies

Objectives: To assess clinical implications of increased nuchal translucency (INT) in twin pregnancies based on the chorionicity. Methods: This was a retrospective review of the twin pregnancies who underwent first trimester ultrasound with nuchal translucency (NT) measurement at 11-13 weeks of gestation from January 2006 to December 2014. Data were collected using the OB database and the chart review. Pregnancy outcomes including gestational weeks at the delivery, abnormal fetal karyotypes, fetal structural anomalies, twin specific complications were analyzed. Results: A total of 1,622 twin pregnancies with INT≥95th percentile in one or both fetuses were identified. In all twin pregnancies with INT, abnormal fetal karyotypes were identified in 17 (8.6%) patients (odds ratio=13.28, CI=5.990-29.447, P=0.000) and twin-specific complications were identified in 23 (11.6%) patients (odds ratio=2.398, CI=1.463-3.928, P=0.001) compared to those with normal NT. Among the INT group, when the groups were subdivided into monochorionic (MC) and dichorionic (DC) pregnancies, 14.8% and 29.6% of the MC pregnancies had structural anomalies in one or both fetuses (odds ratio=5.774, 95% CI=1.445-23.071, P=0.01) and twin-specific complications (odds ratio=4.379, 95% CI=1.641-11.684, P=0.03), respectively, compared to DC pregnancies. The prevalence of abnormal fetal karyotypes was not statistically different in patients with INT when compared between MC and DC pregnancies (P=0.329). Conclusions: INT was associated with a higher rate of twin-specific complications and fetal structural anomalies in MC twin pregnancies rather than abnormal fetal karyotype. Therefore, NT measurement in MC twin pregnancies can be a useful tool for prediction of adverse pregnancy outcomes. Appropriate counseling and surveillance based on the chorionicity is imperative in prenatal care of twin pregnancies.

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How does subchorionic hematoma in the first trimester affect pregnancy outcomes?

Archives of Medical Science ◽

10.5114/aoms/113645 ◽

2021 ◽

Author(s):

Taner Günay ◽

Oğuz Yardımcı

Keyword(s):

Pregnant Women ◽

Preterm Delivery ◽

Early Pregnancy ◽

Pregnancy Outcomes ◽

Vaginal Bleeding ◽

Pregnancy Loss ◽

Placental Abruption ◽

First Trimester ◽

Early Pregnancy Loss ◽

Adverse Pregnancy

IntroductionSubchorionic hematoma (SCH) in pregnancy has been associated with increased risk of adverse pregnancy outcomes. We aimed to investigate the association of SCH with adverse pregnancy outcomes in pregnant women in relation to size of hematoma and control subjects.Material and methodsThis study included 178 pregnant women with sonographically detected SCH in the 1st trimester, and 350 pregnant controls without SCH. Data on maternal age, smoking status, gestational week at diagnosis, location of SCH, medications before diagnosis, gestational week at delivery, delivery route and pregnancy outcomes (first trimester vaginal bleeding, pre-eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), placental abruption, preterm delivery < 37 weeks, early pregnancy loss and intrauterine death) were retrieved retrospectively from hospital records. Pregnant women with SCH were divided into 3 groups according to the size of hematoma including small SCH (SCH-I group, n = 47), medium- size SCH (SCH-II group, n = 110) and large SCH (SCH-III group, n = 21) groups.ResultsSubchorionic hematoma was associated with significantly lower gestational age at delivery (p < 0.001) and higher rate of first trimester bleeding (p < 0.001) compared with the control group, regardless of the size of the hematoma. Placental abruption (p = 0.002) and early pregnancy loss (p < 0.001) were significantly more common in SCH-II and -III groups than in the control group. SCH-III group was associated with a significantly higher rate of < 37 gestational weeks at delivery (p < 0.001), first trimester vaginal bleeding (p < 0.001), early pregnancy loss (p < 0.001), IUGR (p = 0.003) and preterm delivery (p < 0.001) compared to both lesser size hematoma and control groups.ConclusionsIn conclusion, our findings suggest that large SCH might indicate an increased risk of adverse pregnancy outcomes such as 1st trimester vaginal bleeding, early pregnancy loss, IUGR, placental abruption or preterm delivery. These findings are important to guide the patients with SCH for detailed clinical evaluation.

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Clinical Utility of Increased Nuchal Translucency at 11–13 Weeks of Gestation in Twin Pregnancies Based on the Chorionicity

Journal of Clinical Medicine ◽

10.3390/jcm10030433 ◽

2021 ◽

Vol 10 (3) ◽

pp. 433

Author(s):

SiWon Lee ◽

Hyun-Mi Lee ◽

You Jung Han ◽

Moon Young Kim ◽

Hye Yeon Boo ◽

...

Keyword(s):

Pregnancy Outcomes ◽

Odds Ratio ◽

First Trimester ◽

Nuchal Translucency ◽

Adverse Pregnancy ◽

Twin Pregnancies ◽

First Trimester Ultrasound ◽

Fetal Karyotype ◽

Increased Nuchal Translucency ◽

Structural Anomalies

To assess clinical implications of increased nuchal translucency (INT) in twin pregnancies based on the chorionicity. This was a retrospective review of the twin pregnancies who underwent first trimester ultrasound with nuchal translucency (NT) measurement at 11–13 weeks of gestation from January 2006 to December 2014. Data were collected using the OB database and the chart review. Pregnancy outcomes, including gestational weeks at the delivery, abnormal fetal karyotypes, fetal structural anomalies, and twin-specific complications, were analyzed. A total of 1622 twin pregnancies with INT ≥ 95th percentile in one or both fetuses were identified. In all twin pregnancies with INT, abnormal fetal karyotypes were identified in 17 (8.6%) patients (odds ratio = 13.28, CI = 5.990–29.447, p = 0.000) and twin-specific complications were identified in 23 (11.6%) patients (odds ratio = 2.398, CI = 1.463–3.928, p = 0.001) compared to those with normal NT. Among the INT group, when the groups were subdivided into monochorionic (MC) and dichorionic (DC) pregnancies, 14.8% and 29.6% of the MC pregnancies had structural anomalies in one or both fetuses (odds ratio = 5.774, 95% CI = 1.445–23.071, p = 0.01) and twin-specific complications (odds ratio = 4.379, 95% CI = 1.641–11.684, p = 0.03), respectively, compared to DC pregnancies with 2.9% for structural anomalies and 8.8% for twin-specific complications. The prevalence of abnormal fetal karyotypes was not statistically different in patients with INT when compared between MC and DC pregnancies (p = 0.329). INT was associated with a higher rate of twin-specific complications and fetal structural anomalies in MC twin pregnancies rather than abnormal fetal karyotype. Therefore, NT measurement in MC twin pregnancies can be a useful tool for predicting adverse pregnancy outcomes. Appropriate counseling and surveillance based on the chorionicity are imperative in the prenatal care of twin pregnancies.

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When diamniotic twins suddenly become monoamniotic twins: spontaneous septostomy of the dividing membrane

BMJ Case Reports ◽

10.1136/bcr-2021-243513 ◽

2021 ◽

Vol 14 (7) ◽

pp. e243513

Author(s):

Angela Vidal ◽

Cristina Nastasia ◽

Markus Hodel ◽

Joachim Kohl

Keyword(s):

Twin Pregnancy ◽

Rare Condition ◽

First Trimester ◽

Sonographic Diagnosis ◽

Sudden Failure ◽

Reliable Diagnosis ◽

Accepted Standard ◽

Perinatal Management ◽

Twin Pregnancies ◽

First Trimester Ultrasound

In twin pregnancies, amnionicity and chorionicity are crucial as they strongly determine prenatal and perinatal management. First trimester ultrasound allows a highly reliable diagnosis of amnionicity and chorionicity, making it an internationally accepted standard in antenatal care. However, in rare cases, amnionicity can change from diamniotic to monoamniotic throughout pregnancy, substantially impacting perinatal management. We report the case of a confirmed monochorionic diamniotic twin pregnancy with a diagnosis of spontaneous septostomy of the dividing membrane (SSDM) at 28 weeks of gestation, resulting in a pseudomonoamniotic pregnancy. Even though SSDM is a rare condition and its sonographic diagnosis might be challenging, it should be considered if, in a known diamniotic pregnancy, there is a sudden failure to visualise the intertwin membrane truly separating both twins.

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O-234 Using serum metabolomics to identify biomarkers of viable early, intrauterine pregnancy: an untargeted 1H NMR-based approach

Human Reproduction ◽

10.1093/humrep/deab128.058 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

C Hill ◽

M Phelan ◽

A Horne ◽

K Gemzell-Danielsson ◽

N Tempest ◽

...

Keyword(s):

Pregnant Women ◽

Pregnancy Outcome ◽

1H Nmr ◽

Early Pregnancy ◽

Pregnancy Outcomes ◽

Hydatidiform Mole ◽

First Trimester ◽

Intrauterine Pregnancy ◽

Ectopic Pregnancies ◽

Twin Pregnancies

Abstract Study question Which metabolites are associated with a viable intrauterine pregnancy (VIUP) when compared to other early pregnancy outcomes (failed intrauterine and ectopic pregnancies)? Summary answer Serum levels of four metabolites (phenylalanine, alanine, glutamate and glutamine) were significantly altered in VIUPs compared to other early pregnancy outcomes. What is known already Around 10% of all intrauterine pregnancies are lost in the first trimester. A further 1-2% of pregnancies are located outside the endometrial cavity; these ectopic pregnancies are the leading cause of maternal mortality in the first trimester of gestation. Early miscarriages may also cause significant morbidity when bleeding or infection occurs. The symptoms of miscarriages and ectopic pregnancy are often similar (pain and bleeding), however, such symptoms are also common in VIUPs. To date, no biomarkers have been identified to differentiate VIUPs from non-viable and ectopic pregnancies. Study design, size, duration This is a prospective cohort study that included 332 pregnant women at less than ten weeks of gestation, who attended the early pregnancy assessment unit (EPAU) at Liverpool Women’s Hospital with pain and/or bleeding. Participants/materials, setting, methods Blood samples were collected from the 332 pregnant women prior to final clinical diagnosis of pregnancy outcome. Serum samples were subjected to NMR metabolomics profiling (14 spectra that did not meet the recommended minimum reporting standards were removed from subsequent analysis). 1D 1H-NMR spectra were acquired at 37 °C on a 700 MHz spectrometer. Relative metabolite abundances underwent statistical analysis using MetaboAnalyst 5.0 (p-value FDR adjusted). Main results and the role of chance Final pregnancy outcomes were as follows: one hydatidiform mole (0.3%), 48 ectopic pregnancies (14.4%), three pregnancies of unknown location (PULs, 0.9%), 78 failed pregnancies of unknown location (FPULs, 23.4%), 47 miscarriages (14.1%), two vanishing twin pregnancies (0.6%) and 153 VIUPs (45.8%). Due to small sample numbers, the hydatidiform mole, PULs and vanishing twin pregnancies were excluded from further analysis. To compare VIUPs to other pregnancy outcomes, ectopic pregnancies, FPULs and miscarriages were grouped together. Univariate analysis of serum metabolite concentrations identified four metabolites (phenylalanine, alanine, glutamate and glutamine) as significantly different in VIUPs compared to other pregnancy outcomes. Multivariate partial least squared discriminant analysis provided only weak correlation between the serum metabolome and pregnancy outcome. In summary, we have identified differences in the metabolome of women with VIUPs compared to other common pregnancy outcomes, which may provide diagnostic utility. Limitations, reasons for caution In this study, women with VIUPs presented with pain and/or bleeding. The presence of symptoms may influence the metabolome of this group versus VIUPs without symptoms, thus limiting the translation of our findings. Furthermore, environmental factors were not controlled (e.g. fasting status), making it likely that cohort heterogeneity was enhanced. Wider implications of the findings This study identifies a metabolite profile associated with VIUPs. These findings may be useful in the development of a diagnostic test to confirm VIUPs and thus exclude potentially life-threatening pregnancy outcomes. Such a test would be invaluable in clinical emergencies. Trial registration number NA

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Few predictors of massive deep vein thrombosis

Thrombosis and Haemostasis ◽

10.1160/th05-05-0314 ◽

2005 ◽

Vol 94 (11) ◽

pp. 986-990 ◽

Cited By ~ 1

Author(s):

Hylton Joffe ◽

Nils Kucher ◽

Victor Tapson ◽

Samuel Goldhaber

Keyword(s):

Deep Vein Thrombosis ◽

Lower Extremity ◽

Odds Ratio ◽

Clinical Characteristics ◽

Adjusted Odds Ratio ◽

Independent Predictor ◽

Multivariable Logistic Regression Analysis ◽

Vein Thrombosis ◽

Younger Age ◽

Deep Vein

SummaryFactors that predispose to thrombus propagation from the femoropopliteal veins to the pelvic veins are poorly understood. Our goal was to determine whether there are characteristics that identify patients with massive deep vein thrombosis (DVT). We compared the 122 (2.5%) patients presenting with massive DVT (pelvic plus lower-extremity DVT) to the 4,674 (97.5%) patients with isolated lower-extremity DVT from a prospective United States multicenter DVT registry. Patients with massive DVT were younger (59.4±18.9 years vs. 64.3±16.8 years; p<0.01), less likely to have hypertension (40% vs. 51%; p=0.02), and more likely to smoke (21% vs. 13%; p=0.02) and have on- going radiation therapy (7% vs. 3%; p=0.02). The massive DVT group more commonly presented with extremity edema (80% vs. 69%; p<0.01) and erythema (21% vs. 12%; p<0.01) than the isolated lower-extremity DVT group. However, after multivariable logistic regression analysis, extremity erythema (adjusted odds ratio 1.86; 95% CI 1.13–3.04) was the only independent sequela of massive DVT and younger age (adjusted odds ratio 1.17 per decreasing decade of age; 95% confidence interval: 1.02-1.34) was the only independent predictor of massive DVT. Thrombus propagation from the femoropopliteal system cannot be reliably predicted using demographic or clinical characteristics.

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Association between Platelet-Specific Collagen Receptor Glycoprotein 6 Gene Variants, Selected Biomarkers, and Recurrent Pregnancy Loss in Korean Women

Genes ◽

10.3390/genes11080862 ◽

2020 ◽

Vol 11 (8) ◽

pp. 862

Author(s):

Hui Jeong An ◽

Eun Hee Ahn ◽

Jung Oh Kim ◽

Chang Soo Ryu ◽

Han Sung Park ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Confidence Interval ◽

Odds Ratio ◽

Pregnancy Loss ◽

Adjusted Odds Ratio ◽

Recurrent Pregnancy Loss ◽

Korean Women ◽

Chain Reaction ◽

Genotype Frequencies ◽

Polymerase Chain

This paper investigates whether glycoprotein 6 (GP6) gene polymorphisms are a risk factor for recurrent pregnancy loss (RPL) in Korean women. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction amplification. We identified five polymorphisms in the GP6 gene: rs1654410 T>C, rs1671153 T>G, rs1654419 G>A, rs12610286 A>G, and rs1654431 G>A. GP6 rs1654410 CC was associated with decreased RPL risk (adjusted odds ratio = 0.292, 95% confidence interval = 0.105–0.815, p = 0.019), and recessive genotypes were also significantly associated with decreased RPL risk (adjusted odds ratio = 0.348, 95% confidence interval = 0.128−0.944, p = 0.038). GP6 rs1654419 GA was associated with decreased RPL risk (adjusted odds ratio = 0.607, 95% confidence interval = 0.375-0.982, p = 0.042), and dominant genotypes were significantly associated with decreased RPL risk (adjusted odds ratio = 0.563, 95% confidence interval = 0.358−0.885, p = 0.013). Altogether, the genotype frequencies of GP6 rs1654410 T>C and GP6 rs1654419 G>A were significantly different between RPL patients and control participants. Therefore, although GP6 polymorphisms may be useful as biomarkers of RPL, additional studies with heterogeneous cohorts are required to better understand the influence of GP6 and assess its performance as a biomarker.

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Association Study between the Polymorphisms of Matrix Metalloproteinase (MMP) Genes and Idiopathic Recurrent Pregnancy Loss

Genes ◽

10.3390/genes10050347 ◽

2019 ◽

Vol 10 (5) ◽

pp. 347 ◽

Cited By ~ 2

Author(s):

Han Sung Park ◽

Ki Han Ko ◽

Jung Oh Kim ◽

Hui Jeong An ◽

Young Ran Kim ◽

...

Keyword(s):

Confidence Interval ◽

Odds Ratio ◽

Pregnancy Loss ◽

Adjusted Odds Ratio ◽

Recurrent Pregnancy Loss ◽

Proteolytic Enzymes ◽

Nucleotide Polymorphisms ◽

Genotype Combination ◽

History Of ◽

Consecutive Pregnancy

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257–0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483–0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

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