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This study questioned whether raised pre-pregnancy two-hour (2 h) insulin levels, measured in recurrent embryonic miscarriage (RM) patients via a 75 g Oral Glucose Tolerance Test (OGTT), are associated with an increased risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Patients had a 75 g OGTT and insulin levels evaluated (n = 170). 54.1% had normal glucose and insulin levels, 45.9% had levels indicating hyperinsulinism (HI). In the 98 patients who achieved a pregnancy, the prevalence of GDM was 3.7% in those without HI, and 35.7% in the patients who only had raised 2 h insulin levels. While HI has been described as a risk factor for miscarriages only in relation to raised fasting (basal) insulin levels, this study demonstrated that raised 2 h insulin levels predict an increased risk of GDM in a subsequent pregnancy. Thus raised 2 h insulin levels likely confer a similar risk to raised fasting insulin levels in RM patients.Impact statementWhat is already known on this subject? Fasting hyperinsulinism is known to be associated with an increased risk of gestational diabetes mellitus (GDM) in pregnancy. Hyperinsulinism, as reflected by the fasting (basal) insulin levels >20mU/L, has been recognized as a risk factor for recurrent miscarriages, particularly in patients with polycystic ovarian syndrome (PCOS), in the World literature. Raised two-hour insulin levels have not been considered as a risk factor in the literature before.What do the results of the study add? We have demonstrated a 10-fold increase in the development of GDM in patients with fasting insulin resistance, and/or raised 2h insulin levels, and an almost 10-fold increase in patients with only raised 2h levels. 58.8% of the patients who subsequently developed GDM only had raised 2h levels and would have been missed with routine testing.What are the implications of these findings for clinical practice and/or further research? Our study has demonstrated that GDM was three times more prevalent in the patients with only raised 2h levels, than in those only with raised fasting levels, reflecting insulin resistance/hyperinsulinism. Insulin studies including 2h insulin levels are therefore an important factor to consider when working up these patients. Insulin studies pre-pregnancy may be useful in identifying women at risk of suffering miscarriages or of developing GDM in a subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between parental MTHFR 677C > T (RS1801133) and 1298A > C (RS1801131), and fetal loss (FL).Design: Case-control study.Setting: Department of Obstetrics and Gynecology, Lyell McEwin Hospital (LMH), and the Women's and Children's Hospital (WCH) in Adelaide, Australia.Patients: A total of 222 couples with FL and 988 couples with uncomplicated pregnancies.Measurements: The main outcomes were FL and hyperhomocysteinemia (HHcy). All couples were tested for MTHFR 677C > T and 1298A > C. Fasting homocysteine was measured in the women with FL.Results: The main finding was a significant difference between the FL group and controls in couples with ≥4 abnormal alleles compared to <4 [p=.0232, OR 1.9 (95% CI 1.1-3.3)]. None of the couples with FL had zero abnormal alleles (both parents 677CC/1298 AA). However, this was also rare amongst the controls. Maternal carriage of both 677C > T and the 1298A > C polymorphisms was similar between the FL group and controls. The prevalence of paternal 677TT/1298AA and 677CC/1298AC was significantly higher in the FL group compared with controls. HHcy was significantly more common in the FL group compared with controls.Conclusion: The presence of parental MTHFR 677C > T and 1298A > C is associated with FL. The association between maternal MTHFR genotypes with FL is less pronounced than in previously published articles investigating first trimester miscarriages. Maternal HHcy is a significant risk factor for FL. [ABSTRACT FROM AUTHOR]

Aims: Some studies have suggested that vitamin D deficiency is associated with an increased risk of first trimester miscarriages, others have suggested that it is associated with an increased risk of hyperinsulinism/insulin resistance and the development of gestational diabetes. Hyperinsulinism is also thought to increase miscarriages. We investigated the association between vitamin D levels and hyperinsulinism in a cohort of recurrent miscarriage patients. Methods: Patients undergoing miscarriage investigations had insulin and vitamin D levels tested. Vitamin D levels were classified as: sufficient (≥75 nmol/L), insufficient (50-74.9 nmol/L) or deficient (<50 nmol/L). Hyperinsulinism was assessed via a 75 g oral glucose tolerance test (OGTT) with insulin studies. Results: One hundred and fifty-five patients underwent the testing. Hyperinsulinism was detected in 58.3% of the vitamin D deficient group, 38.7% of the insufficient group, and 33.3% of the sufficient group (chi-square p = .034). There were no significant associations between BMI and vitamin D levels, or BMI and hyperinsulinism. Caucasians comprised 82% of the clinic, and 67% of these women had vitamin D insufficiency/deficiency. Noncaucasians comprised 18% of the clinic but 89% of these patients had vitamin D insufficiency/deficiency. Discussion: We found that insufficient or deficient vitamin D levels were significantly associated with hyperinsulinism in these patients. Vitamin D deficiency is also thought to contribute to an increased risk of adverse pregnancy outcomes including preeclampsia, preterm birth, small-for-gestational-age gestational diabetes mellitus, and miscarriages. Larger level one trials are needed to establish if increasing serum vitamin D levels prior to conception or in early pregnancy improves adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]