Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men.

STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. STUDY DESIGN, SIZE, DURATION: This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). LIMITATIONS, REASONS FOR CAUTION: All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal. WIDER IMPLICATIONS OF THE FINDINGS: The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT01304927. DATE OF TRIAL REGISTRATION: 25 February 2011. DATE OF ENROLMENT OF FIRST PATIENT: 8 March 2011.

Elevated third-trimester haemoglobin A 1c predicts preterm delivery in type 1 diabetes.

The prevalence of preterm delivery is considerably elevated in women with type 1 diabetes. The aim of the study was to evaluate haemoglobin A(1c) (HbA(1c)) as a predictor of preterm delivery. Two hundred thirteen consecutive pregnant women with type 1 diabetes and normal urinary albumin excretion were included prospectively. HbA(1c) was analyzed at 10, 20 and 28 weeks of gestation. Seventy-one women (33%) delivered pre term and 142 at term. At 10 weeks of gestation, HbA(1c) was 7.3% (S.D. 1.0) vs. 6.9% (S.D. 0.9) (P<.01), at 20 weeks of gestation 6.6% (S.D. 0.7) vs. 6.1% (S.D. 0.7) (P<.001) and at 28 weeks of gestation 6.7% (S.D. 0.8) vs. 6.1% (S.D. 0.7) (P<.001). When comparing HbA(1c) at 10, 20 and 28 weeks of gestation, HbA(1c) at 28 weeks of gestation (P<.001) was the best predictor of preterm delivery. The adjusted odds ratio per 1% increment in HbA(1c) at 28 weeks of gestation was 2.8 (95% CI 1.7-4.4). HbA(1c) at 28 weeks of gestation was a clinical significant predictor of preterm delivery in type 1 diabetes.

Signs of maternal vascular dysfunction precede preeclampsia in women with type 1 diabetes.

AIM: This study aims to test the hypothesis that vascular dysfunction is present early in pregnancy in women with type 1 diabetes who subsequently develop preeclampsia. METHODS: Eighty-three women with type 1 diabetes of more than 10 years duration were followed up prospectively during pregnancy. External ultrasound was used to measure the dilatory response of the brachial artery to postischemic increased blood flow (endothelium-dependent, flow-associated dilatation) and to nitroglycerin (NTG) [endothelium-independent, NTG-induced dilatation (NID)] at Gestational Weeks 11 and 29. Plasma concentrations of the vascular markers vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor antigen were also measured together with 24-h urinary albumin excretion (UAE), blood pressure (BP), and HbA(1C). RESULTS: Fourteen (17%) of the 83 women developed preeclampsia. NID was significantly impaired at Week 29 in women prone to preeclampsia (108.8+/-7.0% vs. 116.8+/-8.9%, mean+/-S.D., P<.05), and the plasma concentrations of VCAM-1 and ICAM-1 were significantly elevated at Gestational Week 11 (612+/-82 vs. 516+/-109 microg/l, P<.005 and 293+/-67 vs. 255+/-57 microg/l, P<.05, respectively). Women who later developed preeclampsia were also characterized by higher UAE, higher BP, and higher HbA(1C) than women who did not [Gestational Week 11: 194 (3-1104) vs. 7 (0-412) mg/24 h, median (range), P=.0003; 122+/-12/75+/-6 vs. 111+/-11/69+/-9 mmHg, mean+/-S.D., P<.01; and 8.2% (5.9-10.5%) vs. 7.2% (5.3-10.9%), P=.008, respectively]. CONCLUSION: This prospective study indicates that signs of maternal vascular dysfunction precede development of preeclampsia in women with type 1 diabetes.

Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies.

BACKGROUND: Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful as predictors of pre-eclampsia. METHODS: In a prospective study, maternal serum was analyzed for activin A and inhibin A in 115 women with type 1 diabetes at 10, 14, 22, 28, and 33 weeks of gestation. RESULTS: Fourteen women (12%) developed pre-eclampsia (26-37 weeks of gestation) and 101 did not. The two groups were comparable regarding age, body mass index, and diabetes duration. There was no difference between serum concentrations of activin A and inhibin A in women developing pre-eclampsia and women who did not at any gestational period. CONCLUSIONS: Serum concentrations of activin A and inhibin A could not predict preeclampsia in type I diabetes.

Poor pregnancy outcome in women with type 2 diabetes.

OBJECTIVE: To evaluate the perinatal outcome and the frequency of maternal complications in pregnancies of women with type 2 diabetes during 1996-2001. RESEARCH DESIGN AND METHODS: Medical records of 61 consecutive singleton pregnancies in women with type 2 diabetes from 1996 to 2001 were studied. Pregnancy outcome was compared with that of pregnant women with type 1 diabetes during 1996-2000, the background population, and pregnant women with type 2 diabetes during 1980-1992 from the same department. RESULTS: The perinatal mortality in pregnancies complicated by type 2 diabetes (4/61, 6.6%) was increased four- and ninefold, respectively, and the rate of major congenital malformations (4/60, 6.7%) was more than doubled, although not statistically significant, compared with type 1 diabetic pregnancies and the background population. The glycemic control was similar or better in women with type 2 diabetes compared with women with type 1 diabetes. Multivariate logistic regression analysis in the pooled group of pregnancies with pregestational diabetes from 1996 to 2001 showed that high HbA(1c) at admission and type 2 diabetes were independently associated with a serious adverse fetal outcome (perinatal mortality and/or major congenital malformations). The perinatal mortality and the rate of major congenital malformations in type 2 diabetic pregnancies have increased during the last decade. CONCLUSIONS: The perinatal outcome of pregnancies in women with type 2 diabetes during 1996-2001 is poor. It is worse than the outcome of pregnancies in women with type 1 diabetes and the background population in the same period, as well as in women with type 2 diabetes studied during 1982-1990.

Audit on stillbirths in women with pregestational type 1 diabetes.

OBJECTIVE: To audit stillbirth cases in women with type 1 diabetes to search for specific characteristics in order to improve antenatal care and treatment. RESEARCH DESIGN AND METHODS: Retrospectively identified cases of stillbirths in women with type 1 diabetes during 1990-2000 were analyzed regarding characteristics of the mother, the pregnancy, glycemic control, and the stillborn. The cause of stillbirth was categorized as explainable, likely, or without obvious cause. RESULTS: We found 22 women with 25 stillbirths among 1,361 singleton births by women with type 1 diabetes. In seven stillbirths the cause was categorized as explainable and in six as likely. In 12 cases no obvious cause was found; however, glycemic control was suboptimal in 9 of these cases. A total of 14 women reported daily smoking, and 10 of 19 with low education were unemployed. CONCLUSIONS: Women experiencing stillbirth were characterized by a high incidence of suboptimal glycemic control, diabetic nephropathy, smoking, and low social status.