Relationship of insulin resistance with recurrent pregnancy loss

Background: The recurrent pregnancy loss (RPL) is defined as two and more failed pregnancies as documented by ultrasound and histopathological examination and suggested some assessment after each loss with a thorough evaluation after three or more losses. RPL is one of the most frustrating and difficult areas in reproductive medicine because the aetiology is often unknown and there are few evidence based diagnostic and treatment strategies.Methods: 150 Non pregnant females were taken as both cases and controls in the study. All the pregnancy losses were documented by ultrasound or histological examination after uterine curettage. The control group consisted of women with no RPL with at least one live birth. These two groups were matched on the basis of age and BMI. All the women underwent following examinations, viz. Hysterosalpingography, karyotype of both partners, serum TSH, FT4, prolactin and antibodies for APLA. In addition blood sample were taken for fasting serum glucose and serum insulin level later insulin resistance was calculate using three parameters Fasting insulin > 20IU/ml. Diagnostic of Insulin Resistance. (2) Fasting glucose / Fasting insulin. A ratio of < 4.5 being diagnostic of insulin resistance. (3) HOMA IR. FG (mg/dl) x FPI (IU/ml) FG (mmol/l) x FPI (IU/ml)------------------------------------ OR ----------------------------------- 405 22.5Where 1 mmol/l = 18mg/dl, A value of > 4.5 being diagnostic of insulin resistance.Results: 150 patients were enrolled in this study among which 75 were selected as cases and 75 as controls after fulfilling inclusion and exclusion criteria with mean age cases group was28.4+2.37 years and 29.1+2.70 years in control group mean miscarriage rate in study group was 3.17+83 and control group with 0.35+0.48 with statistically significant difference. Mean fasting glucose (96.5+ 7.86) mg/dl, Fasting Insulin (14.1±5.91) IU/ml. Mean Glucose Insulin ratio (8.1±3.39), HOMA-IR (3.4 ±1.51) in the study group and in control group mean fasting glucose was (87.1+11.49) mg/dl, Fasting Insulin (6.9 ± 4.99) IU/ml. Mean Glucose Insulin ratio (17.8 ±11.44), HOMA-IR (1.5 ±1.27) respectively with statistically significant difference.Conclusions: In women with recurrent pregnancy loss fasting insulin and insulin resistance are higher than those in women without spontaneous abortion. The most sensitive parameter for calculating insulin resistance was found to be fasting insulin followed by HOMA – IR and followed by fasting glucose/fasting insulin ratio. It is therefore important to recommend a fasting insulin and fasting glucose level while evaluating a case of recurrent pregnancy loss to assess for insulin resistance.

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High Fasting Insulin Levels and Insulin Resistance May Be Linked to Idiopathic Recurrent Pregnancy Loss: A Case-Control Study

International Journal of Endocrinology ◽

10.1155/2013/576926 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 7

Author(s):

Corina-Alina Ispasoiu ◽

Radu Chicea ◽

Florin Vasile Stamatian ◽

Florin Ispasoiu

Keyword(s):

Insulin Resistance ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Fasting Glucose ◽

Case Control ◽

Control Group ◽

Case Group ◽

Fasting Insulin ◽

Control Study

Objective. Patients with more than two spontaneous pregnancy losses are diagnosed with recurrent pregnancy loss. The aim of this study was to evaluate the IR (insulin resistance) in patients with idiopathic recurrent pregnancy loss.Material and Method. A single center, case control study was performed on one hundred eighteen women divided into case group (with at least two pregnancy losses, earlier than 20 weeks of gestation, and negative for the recurrent pregnancy loss testing) and control group (with at least one live birth, no pregnancy loss). FG (fasting glucose) and FI (fasting insulin) were determined for all patients. IR was evaluated by HOMA-IR index.Results. There were not significant differences between the mean age and BMI in cases and controls (P>0.05). Fasting glucose was significantly higher in the control group (85.6 versus 79.8P<0.01), but fasting insulin (15.24 versus 12.83,P<0.001) and HOMA-IR (2.98 versus 2.69,P<0.05) were significantly higher in the case group.Conclusion. In women with idiopathic recurrent pregnancy loss FI and IR are higher than those in women without spontaneous abortion.

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Pregnancy outcomes among patients with recurrent pregnancy loss and chromosomal aberration (CA) without PGD

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0408 ◽

2018 ◽

Vol 46 (7) ◽

pp. 764-770 ◽

Cited By ~ 4

Author(s):

Maor Kabessa ◽

Avi Harlev ◽

Michael Friger ◽

Ruslan Sergienko ◽

Baila Litwak ◽

...

Keyword(s):

Live Birth ◽

Pregnancy Outcomes ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Control Group ◽

Study Group ◽

Birth Rates ◽

Live Birth Rates ◽

Index Pregnancy ◽

Significant Difference

Abstract Background: Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies. Three to four percent of the couples with RPL have chromosomal aberrations (CA) in at least one partner. The parent’s structural chromosomal abnormalities may cause an unbalanced karyotype in the conceptus which could lead to implantation failure, early or late pregnancy loss, or delivery of a child with severe physical and/or mental disabilities. Objective: To compare live birth rates of couples with CA to couples with normal karyotypes and to investigate medical and obstetric characteristics and pregnancy outcomes of couples with CA and RPL who attend an RPL clinic at a tertiary hospital. Methods: A retrospective cohort study, including 349 patients with two or more consecutive pregnancy losses. The study group consisted of 52 patients with CA, and the control group consisted of 297 couples with normal karyotype. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center and had at least one subsequent spontaneous pregnancy. Results: The demographic and clinical characteristics were not found to be statistically different between the two groups. The group of carriers of CA had 28/52 (53.8%) live births in their index pregnancy vs. the normal 202/297 (68%) (P=0.067, CI 95%) in the control group. No statistically significant etiology was found between the study group and the control group. A statistically significant difference in live birth rates was found when comparing the total amount of pregnancies [index pregnancy (IP)+post index pregnancy (PIP)] between the study group and the control group (54.16% vs. 67.82%, respectively, P=0.0328). Conclusion: Patients with RPL and CA who have spontaneous pregnancies, have a good prognosis (63.4%) of a successful pregnancy with at least one of the pregnancies (index or post index) resulting in a live birth.

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Does recurrent pregnancy loss have an inflammatory background?

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.4.4 ◽

2021 ◽

Vol 38 (4) ◽

pp. 420-424

Author(s):

Huri GÜVEY ◽

Samettin ÇELİK ◽

Canan SOYER ÇALIŞKAN ◽

Burak YAŞAR ◽

Bahadır YAZICIOĞLU ◽

...

Keyword(s):

Pregnant Women ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Control Group ◽

Study Group ◽

Reactive Protein ◽

Randomized Controlled Studies ◽

Significant Difference ◽

Living Children

Although several pathophysiological mechanisms are defined in etiology recurrent pregnancy loss, still causes of half of the cases haven’t revealed yet. It is reported that inflammatory processes take place in the etiology of the disease. In our study, we aimed to reveal the relationship between recurrent pregnancy loss with white blood cell count (WBC), C-reactive protein (CRP) and ferritin levels. We included our study 90 pregnant women having recurrent miscarriage history and 101 pregnant women without recurrent miscarriages, 191 patients in total. Maternal and gestational age, height, weight, body mass index (BMI), gravidity, parity, abortion and living children count and WBC, CRP and ferritin levels of these pregnant were evaluated retrospectively. According to outcomes, while the age (p = 0.01; p<0.05), gravidity (p = 0.00; p<0.01) and abortion counts (p = 0.004; p<0.01) of the study group were found significantly to be higher than that of the control group, weight measurement of them was significantly lower than that of the control group (p = 0.04; p <0.05). Height and BMI measurements, parity and living children counts of the groups showed no statistically significant difference (p>0.05). While WBC levels of the study group was found to be lower (p=0.045, p<0,05) than that of control group, there was no significant difference regarding ferritin and CRP levels (p> 0.05). In our study, WBC, CRP and ferritin parameters did not indicate the inflammatory background in recurrent pregnancy loss. We think that further prospective randomized controlled studies are required regarding these parameters.

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Assesment of Endometrial Vascularization with Immunohistochemical CD34 Assay in Recurrent Pregnancy Loss: A Case Control Study

Gynecology Obstetrics and Reproductive Medicine ◽

10.21613/gorm.2016.664 ◽

2017 ◽

pp. 1

Author(s):

Emine Aydın ◽

Taner Usta

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Transmembrane Protein ◽

Vessel Diameter ◽

Control Group ◽

Control Groups ◽

Significant Difference ◽

And Control ◽

Control Study

Objectives: We compared the endometrial vascularization in hysteroscopic endometrial samplings between recurrent pregnancy loss (RPL) and control group.Study Design: We prospectively evaluated hysteroscopic endometrial samplings from RPL and control groups. CD34 transmembrane protein was used for evaluating endometrial vascularization. The vascularization was assessed based on thickness of vessels, diameter of the largest vessel, and number of vessels per mm2 in CD34-stained slides.Results: There was no significant difference in demographic findings and vascularization, such as largest vessel diameter (p: 0.572), and number of vessels per mm2 (p: 0.982) between the two groups.Conclusion: The cycling endometrium is a highly angiogenic tissue and may play a role in the etiology of RPL. However, we find a weak relationship between endometrial vascularization and RPL.

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Association of M55L and Q192R polymorphisms of paraoxonase 1 gene (PON1) with recurrent pregnancy loss risk: A case–control study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i6.9377 ◽

2021 ◽

Author(s):

Mehdi Alizadeh ◽

Mahboobeh Nasiri ◽

Morteza Samadi ◽

Nasrin Ghasemi ◽

Ali Moradi

Keyword(s):

Statistical Analysis ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Case Control ◽

Paraoxonase 1 ◽

Control Group ◽

Case Group ◽

Significant Difference ◽

Control Study

Background: Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL. Objective: To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL. Materials and Methods: In this case–control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Results: Statistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39–86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97–13.30, p = 0.042), but none for the LM and LL genotypes. Conclusion: The findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population. Key words: Pregnancy, Abortion, PON1, Polymorphism, Recurrent pregnancy loss.

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Fcγ Receptor IIA H/R131 Polymorphism in Patients with Antiphospholipid Antibodies

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615095 ◽

1998 ◽

Vol 79 (05) ◽

pp. 924-927 ◽

Cited By ~ 20

Author(s):

Tatsuya Atsumi ◽

Rafael Caliz ◽

Olga Amengual ◽

Munther A. Khamashta ◽

Graham R. V. Hughes

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Clinical Manifestations ◽

Control Group ◽

Fcγ Receptor ◽

Glycoprotein I ◽

Receptor Isoforms ◽

Significant Difference ◽

Pcr Rflp ◽

Caucasian Patients

SummaryA role for Fcγ receptor in the pathophysiology of thrombosis in APS has been hypothesized. The polymorphism of this receptor, FcγRIIA H/R131, is associated with the binding affinity for human IgG2 (i.e. FcγRIIA-H131 isoform has a higher affinity than FcγRIIA-R131). Since anti-β2 glycoprotein I antibodies (anti β2GPI), which play a major pathogenic role in APS, show IgG2 dominant distribution, we investigated the prevalence of receptor isoforms in patients with anti-phospholipid antibodies (aPL) by a PCR-RFLP method. We studied 100 Caucasian patients with aPL (57 primary APS, 32 secondary APS to SLE and 11 other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131 and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 29 (29%) in the patient group, and 9 (22%), 23 (56%) and 9 (22%) in control group, respectively. Thus there was no statistically significant difference in the prevalence of each genotype in these groups. None of the clinical manifestations of primary APS (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was significantly correlated with any FcγRIIA genotype. In conclusion, FcγRIIA polymorphism did not correlate with the manifestations of APS, and FcγRIIA genotype is not a genetic marker of APS.

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Evaluation of factor VIII value in normal women and whom encountered recurrent pregnancy loss: is there any significant difference?

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20200870 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1034

Author(s):

Douaa Al Rez ◽

Hasan Naser Eldine ◽

Marwan Alhalabi

Keyword(s):

Factor Viii ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Fetal Loss ◽

Control Group ◽

Increased Risk ◽

Significant Difference ◽

History Of ◽

Normal Women ◽

High Level

Background: Recurrent pregnancy loss (RPL) is a serious problem on the women, it defined as two or more consecutive pregnancy losses before the fetus has reached birth. The aim of this study is to evaluate the association between the elevation in the factor VIII and RPL. Because women who have thrombophilia have increased risk of fetal loss in most studies.Methods: A total 72 women were recruited in this case control study. They divided into two groups: the RPL group included 41 women with a history of recurrent pregnancy loss and the control group included 31 healthy women, who had at least one successful pregnancy and none of them had a history of fetal loss or complicated pregnancy.Results: A majority of the patients of this study didn't have a high level of factor VIII, 9 of 41 (22%) patients of RPL group in comparison with 21 of 32 (65,6%) of control group, that suffer from the increase rate of FVIII, this means that factor VIII doesn't effect on RPL.Conclusions: The present study showed that the serum elevation in the factor VIII is not significantly associated with RPL.

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Frequency of the rs 14035 polymorphism of RAN gen in recurrent pregnancy loss: A case-control study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i5.7156 ◽

2020 ◽

Author(s):

Zahrasadat Mortazavifar ◽

Hamidreza Ashrafzadeh ◽

Seyed Morteza Seifati ◽

Nasrin Ghasemi

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Case Group ◽

Nuclear Pore ◽

Normal Delivery ◽

Significant Difference ◽

Control Study

Background: Genetic factors could account for recurrent pregnancy loss (RPL). The RAN gene is a member of the ”large RAS family” and a small GTPase that is essential for the translocation of Ribonucleic acid (RNA) and proteins through the nuclear pore. Mutation in the RAN constitutive gene could stop DNA synthesis and alter the expression of genes in the uterus, likely playing a role in recurrent miscarriage. Objective: The aim was to investigate the frequency of RAN (rs 14035) polymorphism in women with RPL compared with women without abortion history. Materials and Methods: In this case-control study, 100 women with at least two consecutive miscarriages before the 20th wk of gestation and having spouses with karyotype and normal sperm parameters as the case group and 100 women with no history of abortion and having at least one successful pregnancy and normal delivery as the control group. The groups were age matched (20-40 yr). The rs 14035 polymorphism of RAN gene was investigated by Polymerase Chain Reaction- Restriction Fragment Length poly morphism technique and the frequency of which was compared between the two groups. Results: The frequency of TT, TC, and CC genotypes of RAN gene polymorphism in the case group were 9%, 40%, and 51%, respectively, and in the control group were 11%, 38%, and 51%, respectively. There was no significant difference in the genotypes between two groups (p = 0.882). Conclusion: According to our results, it seems that RAN polymorphism (rs 14035) is not associated with the risk of RPL in this study population. Key words: RAN gene, Repeated abortion, Polymorphism, PCR-RFLP.

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P–424 Evaluating the relationship between endoplasmic reticulum stress and recurrent pregnancy loss in a young population cohort

Human Reproduction ◽

10.1093/humrep/deab130.423 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

N F Topba. Selcuki ◽

K Cakmak ◽

S Yilmaz ◽

I Ozdemir ◽

E Oral

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Predictive Value ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Female Reproductive Tract ◽

Receiver Operating Curve ◽

Control Group ◽

Study Group ◽

The Mean

Abstract Study question Does endoplasmic reticulum (ER) stress evaluated by X-box binding protein 1 (XBP–1) among patients aged 18–30 years play a role in recurrent pregnancy loss (RPL)? Summary answer High levels of XBP–1 observed in patients with known RPL indicate that ER stress plays an important role in RPL. What is known already Female reproductive tract undergoes dynamic changes during oogenesis which require protein synthesis, folding, maturation, which take place in the ER. ER is also responsible for destruction of unfolded/misfolded proteins. Excess accumulation of these faulty proteins leads to ER stress, which actives unfolded protein response (UPR). XBP–1 is a transcription factor involved in UPR and regulates ER stress-mediated apoptosis. Regulation of ER homeostasis is important in folliculogenesis, oocyte maturation and embryogenesis. It is also known that ER stress has a positive correlation with age and it is associated with age-related diseases. Study design, size, duration This prospective case-controlled study was conducted at University of Health Sciences Turkey, Istanbul Kanuni Sultan Suleyman Training and Research Hospital Department of Obstetrics and Gynecology between March 2020 – September 2020. A total of 70 subjects were included in the study. All patients gave their written informed consent before their enrollment in the study. Participants/materials, setting, methods 38 patients aged 18–30 years with a history of RPL were included in the study. Patients who had miscarriages due to fetal abnormalities, patients with infections, endocrine or genetic disorders, smokers, alcohol and/or drug abusers, with acute/chronic inflammatory diseases, patients using steroids, anti-inflammatory and antioxidant medications were excluded from the study. Age-matched 32 healthy subjects without RPL were included in the control group. XBP–1 levels were determined using Human XBP–1 ELISA Kit (Elabscience Co., USA). Main results and the role of chance The mean age in the control group and in the study group were 25.21±3.3 and 25.26±2.6, respectively and they were statistically similar (p = 0.324). When groups were compared according to thyroid stimulating hormone (TSH) levels and body mass index (BMI), which are additional risk factors of RPL both groups were statistically similar (p = 0.642 and 0.942, respectively). As expected gravidity and abortus numbers were significantly higher in the study group (p < 0.001). A mean XBP–1 level of 1233.41± 3902.97 was determined in the control group. The mean value of the study group was calculated to be 2251.49± 9621.12. Mean XBP–1 level in the study group was significantly high (p < 0.001). A receiver operating curve (ROC) analysis was conducted in the study group. The area under the curve was found to be 87% (95% CI: 79% - 95%). The specificity was 75%, sensitivity was 89%, positive LR was 3.5, negative LR was 0.15, positive predictive value was 80% and negative predictive value was 87% for the cut-off XBP–1 level at 1364.68 pg/mL. Limitations, reasons for caution Small sample size is an important limitation of this study. In addition, evaluating XBP–1 only in serum samples does not let us drive any conclusions on the local changes of ER stress. Studies with larger samples sizes and studying XBP–1 levels in tissue samples of endometrial material is needed. Wider implications of the findings: The significantly high levels of XBP–1 in RPL patients younger than 30 years, indicate higher ER stress in this group even when age dependent increase in ER stress is calculated out of the equation. XBP–1 can be a promising marker in evaluating patients with a fertility wish for RPL risk. Trial registration number NCT04455256

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Insulin Resistance, Glycemia and Cortisol Levels in Surgical Patients who Had Preoperative Caloric Load with Amino Acids

PRILOZI ◽

10.1515/prilozi-2015-0079 ◽

2015 ◽

Vol 36 (3) ◽

pp. 61-70 ◽

Cited By ~ 2

Author(s):

Marija Jovanovski-Srceva ◽

Biljana Kuzmanovska ◽

Maja Mojsova ◽

Andrijan Kartalov ◽

Mirjana Shosholcheva ◽

...

Keyword(s):

Insulin Resistance ◽

Amino Acids ◽

Amino Acid ◽

Surgical Patients ◽

Control Group ◽

Study Group ◽

C Peptide ◽

Significant Difference ◽

Cortisol Levels ◽

The Impact

Abstract Introduction: Surgical stress response, results in elevated levels of anti-insulin hormones and reduced insulin secretion. This hormonal state may be detrimental for surgical patients due to the presence of insulin resistance and hyperglycemia. Additionally, pre-operative fasting favors this conditions. The aim of this study is to analyze the impact of pre-operative caloric load, with 440kJ from amino acid infusions on the levels of glucose, cortisol and insulin resistance in surgical patients.Material and Methods: The study included 20 female patients scheduled for mastectomy, aged 30-60 years without diabetes and BMI < 30 m2, divided into two groups. The study group A, the evening before the surgery, received 1000 ml amino acid infusions, while the control group B didn′t receive any infusion. In both groups glucose, C-peptide and cortisol levels were determinate preoperatively and postoperatively. From the obtained C-peptide and glucose values, with the help of computer model (HOMA2*), the insulin resistance (IR), functionality of beta cells (BETA) and insulin sensitivity (IS) were calculated. Results: Postoperative values of insulin resistance (0.94 ± 0.12 vs 1.13 ± 0.2; p = 0.02) and glucose (4.79 ± 0.5 vs 5.77 ± 0.6; p = 0.002) were lower in the study group compared to control group. Postoperative cortisol levels in both groups were higher than the preoperative, but no significant difference was found. The study group showed higher values for BETA and IS. Percentage changes between the groups were significant for all parameters. Conclusion: Pre-operative caloric load (amino acids) reduces the level of insulin resistance and glucose in the presence of elevated cortisol levels.

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