Hyperhomocysteinemia in recurrent pregnancy loss and the effect of folic acid and vitamin B12 on homocysteine levels: a prospective analysis

Background: Recurrent pregnancy loss (RPL) affects about 5% of women. High levels of homocysteine, termed hyperhomocysteinemia, have been implicated in a number of pathologic processes in the venous and arterial vascular systems. Hyperhomocysteinemia in pregnant women has been associated with deep venous thrombosis, recurrent miscarriage, abruption placentae, preeclampsia, neural tube defects, and fetal growth restriction. This study aims at determining association between hyperhomocysteinemia and recurrent pregnancy loss and also association of folic acid (vitamin B 9) and vitamin B 12 with hyperhomocysteinemia (HHCY), in reducing its levels in the body and thus preventing obstetric complications.Methods: A prospective study of pregnant mothers booked at our hospital over a period of two years with history of unexplained RPL were included in the study and their serum homocysteine levels were assessed. Hyperhomocysteinemia (>12 micromol/l) patients were treated with folic acid and vitamin B12 supplements and homocysteine levels were assessed again, post treatment.Results: Out of the 100 patients who were assessed, 32% of RPL patients had hyperhomocysteinemia. Folic acid and VitB12 supplementation reduced homocysteine levels and this was found to be statistically significant.Conclusions: Hyperhomocysteinemia is associated with RPL. Vitamin supplementation to those with hyperhomocysteinemia, decreases homocysteine levels.

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http://www.jirb.dormaj.com/issues/Volume%205,%20Issue%204/Anti-Coagulant%20Therapy%20in%20Unexplained%20Recurrent%20Pregnancy%20Loss.pdf

Journal of Infertility and Reproductive Biology ◽

10.47277/jirb/5(4)/15 ◽

2017 ◽

Vol 5 (4) ◽

pp. 15-19

Keyword(s):

Molecular Weight ◽

Live Birth ◽

Low Molecular Weight Heparin ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Controlled Study ◽

Low Molecular Weight ◽

Antiphospholipid Antibody ◽

History Of

Recurrent pregnancy loss (RPL) is a heterogeneous reproductive problem with multiple aetiologies and contributing factors. It becomes quite challenging to form a work-up to detect the cause of RPL in the early months as a continuation of pregnancy involves many factors. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment.. In obstetric APLA Syndrome (Antiphospholipid antibody) the combination of aspirin and heparin has improved outcomes. The use of low molecular weight heparin (LMWH) has become a common practise in women with inherited thrombophilia and also those with unexplained miscarriage to help safeguard the ongoing pregnancy. To evaluate if there is any effectiveness of low molecular weight heparin (enoxaparin) in women with a history of at least two miscarriages without any apparent aetiology for recurrent pregnancy loss. A prospective randomised controlled study held at Vivekananda Institute of Medical Sciences, Kolkata from August 2015- July 2018. The study assessed the effect of anticoagulant treatment on the live-birth rate (primary outcome) in 80 antenatal women with a history of at least two miscarriages without any apparent causes. Interventions included low molecular weight heparin administration in one group and the other one was not given any anti-coagulant therapy. Similar live birth rates were observed with enoxaparin and the patients who did not receive any anti-coagulant, respectively 84% and 82% (RR 0.97, 95% CI 0.81 to 1.16). There were no significant differences in live birth weight and other pregnancy outcomes between the two groups. Therefore, there is no evidence to support any incremental benefit of adding LMWH to the treatment as a routine in unexplained cases of recurrent pregnancy loss.

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Thrombophilia gene mutations in relation to recurrent miscarriage

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20180857 ◽

2018 ◽

Vol 7 (3) ◽

pp. 796 ◽

Cited By ~ 1

Author(s):

Tawfik Abdelsalam ◽

Tarek Karkour ◽

Magdy Elbordiny ◽

Dina Shalaby ◽

Ziad S. Abouzeid

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Gene Mutations ◽

Factor V Leiden ◽

Mthfr C677t ◽

Factor V ◽

Total Prevalence ◽

History Of ◽

Prothrombin Gene

Background: Recurrent pregnancy loss is multifactorial involving clinical and biological risk factors. Evidence addressed the association of inherited thrombophilia with recurrent pregnancy loss and other serious pregnancy complications. However, the relation between thrombophilia associated gene mutations and adverse obstetric outcome is controversial and data in the literature are inconsistent. The aim of this study was to investigate the prevalence of thrombophilia associated gene mutations (factor V Leiden, prothrombin gene G20210A and methylene-tetrahydrofolate reductase MTHFR C677T) in relation to recurrent miscarriage.Methods: Case control study conducted on 200 women recruited from Elshatby Maternity Hospital clinics. The cases group included 100 women with history of three or more unexplained consecutive pregnancy losses, while 100 healthy age matched women with no history of recurrent miscarriages served as controls. Blood samples were collected from all women enrolled in the study for DNA extraction and genotype analysis. Factor V, prothrombin and MTHFR gene mutations were assayed based on polymerase chain reaction (PCR) and reverse-hybridization.Results: The prevalence of Factor V Leiden and prothrombin gene G20210A mutations did not differ significantly between cases and controls. However, MTHFR C667T mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls (p=0.001, p=0.003 respectively). The prevalence of combined thrombophilia of Factor V Leiden and MTHFR C677T was significantly increased in the patients group compared to controls (p=0.032). Regarding homozygosity of each of the gene mutations, no homozygosity was detected in controls and heterozygotes were significantly increased in the patients group compared to homozygotes.Conclusions: MTHFR mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls. There was a significant increase in the prevalence of combined thrombophilia (Factor V Leiden and MTHFR C677T) in the patients group compared to controls without involvement of prothrombin gene.

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The study of antiphospholipid antibodies in recurrent pregnancy loss

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20175039 ◽

2017 ◽

Vol 6 (11) ◽

pp. 5135

Author(s):

Sheela H. S. ◽

Lakshmidevi M. ◽

Babitha Koganti ◽

Shreedhar Venkatesh

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Research Centre ◽

Antiphospholipid Antibody ◽

Significant Difference ◽

Gynaecological Examination ◽

History Of ◽

Antibody Titers ◽

The Difference

Background: Around 15% of clinically recognised pregnancies in women less than 35 years old result in spontaneous miscarriage. However recurrent pregnancy loss (RPL) is encountered in 5% of couples with two or more losses and in around 1–2% of couples with three or more losses. In view of the increasing burden of recurrent pregnancy loss in the society and in view of Anti-phospholipid syndrome being one of the undisputed treatable cause for recurrent pregnancy loss, this study aims to evaluate the significance of the antibody profiles of APS in relation to RPL in OBG dept of VIMS and RC.Methods: Patients coming to the Obstetric and Gynaecology department of Vydehi Institute of Medical Sciences and Research Centre, Bangalore, from December 1st 2014 to June 30th 2016. A detailed history of patients was taken based on set questionnaires. Detailed general and gynaecological examination findings were taken. Routine blood investigations were sent along with investigations for aPLAs which included: - Lupus Anticoagulant (LA) - Anti Cardiolipin Antibody (ACA) - Anti β2 glycoprotein 1 (Anti-β2GP1Ab). Final results are statistically evaluated.Results: A total of 56 patients of recurrent miscarriage with two or more prior pregnancy losses were considered. Out of the 56 patients, 23 patients were excluded as per the exclusion criteria and 33 patients were included in the present study. The mean age of the study group was 24.63 years (Range: 20-32 years). Overall, seven patients (21.21%) were seen to have positive antiphospholipid antibody titers amongst the 33 patients, with repeat testing done after 12 weeks to confirm the positivity. Five patients (15.15%) were positive for ACA antibody. Four (12.12%) patients were positive for LA and B2GP1 each. Two patients (6.06%) were positive for both LA and ACA antibodies. Two patients (6.06%) were positive for LA and B2GP1 antibodies and two other (6.06%) patients were positive for ACA and Anti-β2GP1Ab. There was a statistically significant association noticed between ACA positivity and POG at 1st pregnancy loss. However, the overall association of APLA positivity and POG at pregnancy loss was not statistically significant.Conclusions: There was a significant difference of POG at first pregnancy loss in ACA positive patients as compared to the ACA negative patients. However, when all the APLA positive patients were considered the difference was not statistically significant.

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O-139 Complete removal of uterine septum tissue as a wedge, an alternative method for patients suffering from recurrent pregnancy loss or infertility, a retrospective cohort study

Human Reproduction ◽

10.1093/humrep/deab126.070 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

F Razzaghi Kashani ◽

R Zargham ◽

S Amirajam ◽

H Jadda ◽

S Razi ◽

...

Keyword(s):

Embryo Transfer ◽

Retrospective Cohort ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Complete Removal ◽

Septate Uterus ◽

History Of ◽

Uterine Septum

Abstract Study question Is hysteroscopic wedge septectomy (HWS) an effective and safe method for reducing the risk of miscarriage and improving the reproductive outcome in patients with recurrent pregnancy loss or infertility history? Summary answer HWS is a safe and effective method for RPL and infertility cases with statistically significant improvement in pregnancy chances and reproductive outcomes. What is known already With regard to the persisting uncertainty around the effectiveness of septum resection in recurrent miscarriage and infertility cases, there may be alternative methods to better address the pathophysiology of septum. There are different explanations for the poor reproductive performance with uterine septum: poor vascularisation of a highly fibrous implantation site, low sensitivity of endometrial receptors covering the septa, its “myoma-like” composition, and finally higher uterine vascular resistance. Complete removal of this abnormal tissue rather than just incising it may not only enhance challenging the pathogenesis but also expand the endometrial volume, an objective parameter by which to predict endometrial receptivity. Study design, size, duration In this retrospective cohort study, 214 consecutive patients, aged 33.3±4.8, diagnosed with a septate uterus based on ESHRE classification who had been under HWS between April 2017 and January 2020 due to recurrent miscarriage or at least one failed embryo transfer, met the enrollment criteria. With 11 to 36 months follow up, gathering of follow up data was managed between August till the end of Nov 2020, when the last new information was included. Participants/materials, setting, methods Patients with a history of RPL or at least one failed ET who were diagnosed as septate uterus by 2D, 3D, or hysteroscopy have been under HWS in a tertiary infertility and recurrent abortion treatment/educational setting. Those with BMI≥32, day 3 FSH≥13 mIU/mL, acquired or hereditary thrombophilia, thyroid disease, and myomatous uterus were excluded. HWS’s goal was to remove the septum as a wedge, cutting with 7Fr scissors, in its entirety as much as possible. Main results and the role of chance 39 patients who experienced 1 to 8 failed ET and 175 with 2 to 10 miscarriages, were enrolled in the study. The average septum size based on the depth of the removed wedge was 1.73±0.86 cm. There was an increase of 1.68±0.9 cm in uterine depth and 2.28±0.6 ml in uterine capacity measured by uterine sound and inflation of 8F Folley catheter balloon inside the cavity, respectively. The procedure took 35.75±8.7 minutes. Intraoperative, postoperative, or late complications during the next pregnancies were not reported. 7 patients (17.9%) in failed ET group, conceived spontaneously, before another embryo transfer attempt. Embryo transfer in the remaining 32 cases resulted in 25 (78.1%) clinical pregnancies. 2 miscarried (6.2%), 5(15.6%) are ongoing after 20 weeks of gestation and 25 (78.1%) have resulted in live births. Among 126 clinical pregnancies in RPL group, 16 patients (12.6%) experienced another miscarriage; 6%, 11.3%, and 25% in patients with a previous history of 2, 3, and 4 or more miscarriages, respectively. There was a significant drop in odds of post-procedure miscarriage from 22.7% to 6% (p:0.005) and from 27.8% to 11.3% (p:0.27) with 2 and 3 miscarriage history, respectively. This reduction was not significant with more than 3 losses. Limitations, reasons for caution We acknowledge the inherent limitations of this retrospective observational study, confining direct inferences. Our goal is to encourage future prospective studies to compare the effectiveness of different methods of hysteroscopy with or without involving the removal of septal tissue. An RCT comparing metroplasty vs expectant management seems infeasible, though. Wider implications of the findings Our findings suggest that timely removal of the uterine septal tissue with hysteroscopy will result in favorable reproductive outcomes in patients with RPL and/or infertility. Also, a history of a normal term pregnancy before subsequent successive losses does not rule out the uterine septum and calls for a thorough assessment. Trial registration number not applicable

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Thyroid Autoimmunity is a Risk Factor for Recurrent Pregnancy Loss

TAJ Journal of Teachers Association ◽

10.3329/taj.v30i1.39123 ◽

2018 ◽

Vol 30 (1) ◽

pp. 49-55

Author(s):

Sharmin Sultana ◽

Mosammat Nargis Shamima ◽

Sahela Jesmin ◽

Nargis Zahan ◽

Md Abu Zahid ◽

...

Keyword(s):

Risk Factor ◽

Pregnant Women ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Control Group ◽

Genital Organ ◽

Thyroid Antibodies ◽

History Of ◽

The Mean

This was a hospital based case control study. The study included patients attending in outdoor and indoor Department of Obstetrics and Gynaecology of Rajshahi Medical College, Hospital since July 2014 to June 2016. The aim of this study was to determine thyroid antibodies is a risk factor for recurrent pregnancy loss. Sixty seven pregnant or non pregnant women with history of recurrent miscarriage during 1st trimester were selected as case group and another sixty seven pregnant women who reached their 12 weeks uneventfully with no history of recurrent miscarriage were selected as control group. Patients with other cause of recurrent miscarriage such as metabolic or endocrinologic disorders, genital organ anomaly, uterine fibroid were excluded from the study. Thyroid function test and thyroid antibodies (FT4, TSH and TPO-Ab) were measured for the two groups. The result of this study showed that the percentage of positive TPO-Ab in target and control group is 67.16% and 5.95% respectively. The study observed that the mean serum concentrations of FT4 in the control subject was significantly higher than the mean of the target group (p-value <0.05). The TSH concentration was increased in miscarriage women with positive antibodies compared with the concentration of TSH in the control group with positive antibodies. The conclusions are that there is a deficiency in thyroid hormones or thyroid’s functional capacity is unable to meet the extra demands of pregnancy which may be one of the causes of recurrent miscarriage. Moreover positive thyroid antibodies pregnant women can reach term and have babies when the concentration of TSH is low during the first trimester, so the risk of miscarriage could be high in positive thyroid antibodies.TAJ 2017; 30(1): 49-55

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FOLIC ACID, VITAMIN B12, AND DNA METHYLATION: AN UPDATE.

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i1.21892 ◽

2018 ◽

Vol 11 (1) ◽

pp. 17 ◽

Cited By ~ 2

Author(s):

Bhongir Aparna Varma ◽

Srilatha Bashetti ◽

Rajagopalan Vijayaraghavan ◽

Kumar Sai Sailesh

Keyword(s):

Dna Methylation ◽

Folic Acid ◽

Vitamin B12 ◽

The Body ◽

Aberrant Methylation ◽

Restricted Diet ◽

Current Review ◽

Folate And Vitamin B12 ◽

Methylation Patterns

Epigenetics is one of the exciting and fastest expanding fields of biology; this is above genetics. Methylation is the process involved in the transfer of methyl group to amino acids, proteins, enzymes and DNA of all the cells, and tissues of the body. During cell-division low folate availability may result in decreased production of thymidine wherein uracil may be substituted in the place of thymidine in the DNA sequence. It was reported that folate and Vitamin B12 restricted diet resulted in aberrant methylation patterns. The current review was undertaken to explore the role of folic acid and Vitamin B12 in DNA methylation.

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Investigating Association of rs5918 Human Platelets Antigen 1 and rs1800790 Fibrinogen β Chain as Critical Players with Recurrent Pregnancy Loss

Medical Sciences ◽

10.3390/medsci6040098 ◽

2018 ◽

Vol 6 (4) ◽

pp. 98 ◽

Cited By ~ 3

Author(s):

Fatemeh Karami ◽

Maliheh Askari ◽

Mohammad Modarressi

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Human Platelets ◽

P Value ◽

Increased Risk ◽

History Of ◽

Polymerase Chain ◽

Β Chain ◽

Larger Sample

Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most important variants including rs5918 T > C and rs1800790 G > A were selected to be studied in women affected by RPL. Three milliliters of peripheral blood were drawn from 110 women with history of at least two consecutive spontaneous abortion and 110 healthy women controls. rs5918 T > C and rs1800790 G > A of HPA-1 and FGB genes, respectively, were selected to be analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR_RFLP) following DNA isolation using QIAamp DNA Blood Mini Kit. Heterozygote genotype (TC) of HPA-1 gene rs5918 polymorphism was significantly associated with risk of RPL (p-value = 0.02). Although, rs1800790 G > A of FGB gene was not associated with RPL, its combination with rs5918 polymorphism was associated with increased risk of RPL. Owing to the critical roles of FGB and HPA-1 genes in coagulation, and thrombosis and several confinements on the meaningful association between the combination of those polymorphism with risk of RPL, including them in the thrombophilia panel may increase detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are required to shed light on the exact role of the studied gene polymorphism, especially rs1800790 G > A of FGB gene variant in pathogenesis of RPL.

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Puzzle Out the Reason behind Habitual Miscarriage

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i3230938 ◽

2020 ◽

pp. 92-98

Author(s):

Waqas Ahmad ◽

Shahid Bilal ◽

Sarah Azhar ◽

Muhammad Aitmaud Uddolah Khan ◽

Nasima Iqbal ◽

...

Keyword(s):

Risk Factors ◽

Maternal Age ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Multinomial Logistic Regression ◽

Strong Association ◽

Multinomial Logistic Regression Model ◽

Multiple Risk Factors ◽

Bivariate Correlation ◽

History Of

Aims: As no data is available in Pakistan so the aim of current study is to find out the link of multiple risk factors with recurrent pregnancy loss (RPL) in Pakistan. Study Design: Case control study. Place and Duration of Study: Study conducted in Obstetrics and Gynecology Clinic of Benazir Bhutto Hospital, Holy Family Hospital Rawalpindi and Polyclinic Hospital Islamabad from November 2018 to April 2019. Methodology: Subjects were investigated on the basis of an in depth Performa. For data analysis Statistical package for social sciences version-20 was used. Beside this, height in cm, weight in kg and blood pressure in mmHg were recorded. All the statistical calculations were performed by using SPSS 20. For association analysis of qualitative variables Spearman bivariate correlation was calculated while for numerical variables ANOVA was applied. Multinomial logistic regression model was used and the odd ratio and relative risk were calculated. Results: Among cases 91.34% were having spontaneous miscarriage and majority (64.86%) were during first trimester. Spearman bivariate correlation reported a strong association of recurrent pregnancy loss with the risk factors including family history, smoking, obesity, history of hypertension and history of diabetes, having highly significant p-values, on the hand, significant association of maternal age with the frequency of recurrent pregnancy loss was found but not with the paternal age and parity. The multinomial logistic regression model showed that smokers were19.012 times more prone to develop recurrent pregnancy loss. Conclusion: The multiple risk factors including maternal age, obesity, smoking, family history, body mass index, hypertension and diabetes have a strong association with the recurrent pregnancy loss. So keeping these risk factors in mind a careful evaluation of each pregnancy is necessary to reduce the risk of recurrent pregnancy loss.

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