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Free access

Konstantinos A Toulis, Dimitrios G Goulis, Christos A Venetis, Efstratios M Kolibianakis, Roberto Negro, Basil C Tarlatzis and Ioannis Papadimas


To investigate whether thyroid autoimmunity (TAI) is associated with increased risk for spontaneous miscarriage in subfertile, euthyroid women undergoing IVF.


Meta-analysis of observational studies.


Four prospective studies that reported data on 1098 subfertile women undergoing IVF (141 with TAI and 957 controls) were included in the meta-analysis.

Main outcome measure

Miscarriage risk ratio (RR).

Secondary outcome measures

Clinical pregnancy rate and delivery rate.


Euthyroid, subfertile women with TAI undergoing IVF demonstrated significantly higher risk for miscarriage compared with controls (four studies–fixed effects RR: 1.99, 95% confidence interval: 1.42– 2.79, P<0.001). No significant difference in clinical pregnancy and delivery rates was detected between groups.


Based on the currently available evidence, it appears that the presence of TAI is associated with an increased risk for spontaneous miscarriage in subfertile women achieving a pregnancy through an IVF procedure.

Restricted access

Antiopi Ntouva, Konstantinos A Toulis, Deepikshana Keerthy, Nicola J Adderley, Wasim Hanif, Rasiah Thayakaran, Krishna Gokhale, G Neil Thomas, Kamlesh Khunti, Abd A Tahrani and Krishnarajah Nirantharakumar


Type 2 diabetes is associated with an increased risk of fracture. Any factor that incrementally increases this risk should be taken into account when individualising treatment. Hypoglycaemia is a common complication of antidiabetes medications and suggested as a risk factor for fractures; yet, its real-life clinical impact is unclear.


A population-based, retrospective open cohort study using routinely collected data between 1st of January 1995 and 1st of May 2016 in The Health Improvement Network (THIN) database.


Patients with type 2 diabetes mellitus with documented hypoglycaemic events were compared to randomly matched patients with type 2 diabetes mellitus without documented hypoglycaemic events matched to exposed patients on age, sex, duration of diabetes and BMI. The primary outcome was any incident fracture. Secondary outcome was incident fragility (osteoporotic) fracture.


A total of 41 163 patients with type 2 diabetes were included: 14 147 patients in the exposed cohort and 27 016 patients in the unexposed cohort. Patients with a documented hypoglycaemic event were significantly more likely to sustain any fracture compared to patients with no record of hypoglycaemic events: adjusted IRR = 1.20 (95% CI: 1.12–1.30; P < 0.0001). Patients who had a documented hypoglycaemic event were significantly more likely to suffer a fragility fracture compared to controls: adjusted IRR = 1.24 (95% CI: 1.13–1.37; P < 0.0001).


Hypoglycaemic events are a significant risk factor for fractures in patients with diabetes mellitus. This observation is clinically relevant when individualising targets for glycaemic control and selecting antidiabetic agents.

Open access

Kumarendran Balachandran, Dana Sumilo, Michael W O'Reilly, Konstantinos A. Toulis, Krishna Gokhale, Chandrika Wijeyaratne, Arri Coomarasamy, Wiebke Arlt, Abd Tahrani and Krishnarajah Nirantharakumar

Objective: Obesity is very common in patients with obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS). Longitudinal studies assessing OSA risk in PCOS and examining the role of obesity are lacking. Our objective was to assess the risk of OSA in women with vs. without PCOS and to examine the role of obesity in the observed findings.

Design: Population-based retrospective cohort study utilizing The Health Improvement Network (THIN), UK.

Methods: 76,978 women with PCOS and 143,077 age-, BMI- and location-matched women without PCOS between January 2000 and May 2017 were identified. Hazard Ratio (HR) for OSA among women with and without PCOS were calculated after controlling for confounding variables using multivariate Cox models.

Results: Median patient age was 30 (IQR: 25 – 35) years; median follow-up was 3.5 (IQR: 1.4 – 7.1) years. We found 298 OSA cases in PCOS women vs. 222 in controls, with incidence rates for OSA of 8.1 and 3.3 per 10,000 person years, respectively. Women with PCOS were at increased risk of developing OSA (Adjusted HR=2.26, 95% CI: 1.89 – 2.69, p<0.001), with similar HRs for normal weight, overweight and obese PCOS women.

Conclusions: Women with PCOS are at increased risk of developing OSA compared to control women irrespective of obesity. Considering the significant metabolic morbidity associated with OSA, clinicians should have a low threshold to test for OSA in women with PCOS. Whether OSA treatment has an impact on PCOS symptoms and outcomes needs to be examined.

Free access

Athina Giomisi, Anargyros Kourtis, Konstantinos A Toulis, Athanasios D Anastasilakis, Kali G Makedou, Maria Mouzaki, Spyridon Gerou, Elpida Gavana, Theodoros Agorastos and Charalambos Giannoulis


Pregnancy represents a state of insulin resistance (IR). Vaspin (SERPINA12) is a novel insulin-sensitizing adipokine that might be implicated in endogenous glucose regulation. However, its role in pregnancy and its circulating levels have not been adequately studied. We aimed to evaluate serum vaspin levels in pregnancy and their correlation with known markers of IR.


A group of 106 women (age 27.9±0.4 years) at the 24–30th week of gestation (pregnancy group) and another 106 age-matched healthy non-pregnant controls (control group) were included in the study.


Serum glucose, insulin, vaspin, adiponectin, and lipid parameters were measured. The quantitative insulin sensitivity check index (QUICKI) was used as an insulin sensitivity index.


Pregnant women had significantly higher body mass index (BMI), lipids, and serum insulin and lower serum glucose and vaspin levels than controls. Vaspin was positively correlated to adiponectin in both groups (P<0.001 and P<0.004 respectively) but was not correlated to BMI, serum insulin levels, or the QUICKI index in either group. Furthermore, vaspin was negatively correlated to lipid parameters (total cholesterol, triglycerides, and low-density lipoproteins) in the pregnant but not in the non-pregnant women.


Vaspin cannot serve as a marker of IR in either pregnant or non-pregnant women, although it is significantly correlated with adiponectin. On the other hand, vaspin might be useful as a surrogate marker of lipid metabolism in pregnancy if confirmed by subsequent studies.