Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop A3-05, Durham, NC 27709, USA.
Diabetologia (Impact Factor: 6.88). 03/2011; 54(3):516-22. DOI: 10.1007/s00125-010-2003-6
Source: PubMed

ABSTRACT We assessed the effects of type 1 diabetes and type 2 diabetes on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large cohort of pregnant women.
This study is based on the Norwegian Mother and Child Cohort Study. Members of this large cohort were enrolled early in pregnancy and asked about TTP and other factors. Among the 58,004 women included in the analysis, we identified 221 cases of type 1 diabetes and 88 cases of type 2 diabetes using the Medical Birth Registry of Norway. A logistic analogue of the proportional probability model, a Cox-like discrete-time model, was used to compute fecundability odds ratios (FORs) and 95% CI for type 1 diabetes and type 2 diabetes, adjusted for maternal age and prepregnancy BMI.
Compared with non-diabetic women, the adjusted FOR for women with type 1 diabetes was 0.76 (95% CI 0.64-0.89) and the adjusted FOR for women with type 2 diabetes was 0.64 (95% CI 0.48-0.84). These FORs did not change substantively and remained statistically significant after excluding women with irregular menstrual cycles and accounting for cycle length.
The results from the present study provide evidence of substantially decreased fecundability for women with type 1 and type 2 diabetes, even among those with a normal menstrual cycle.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 µg/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-ß), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.
    Gynecological Endocrinology 11/2014; DOI:10.3109/09513590.2014.975686 · 1.14 Impact Factor
  • Diabetes Care 06/2014; 37(7). DOI:10.2337/dc14-1140 · 8.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: What is the magnitude of the association between a woman's gestational age at her own birth and her fecundability (cycle-specific probability of conception)? We found a 62% decrease in fecundability among women born <34 weeks of gestation relative to women born at 37-41 weeks of gestation, whereas there were few differences in fecundability among women born at later gestational ages. One study, using retrospectively collected data on time-to-pregnancy (TTP), and self-reported data on gestational age, found a prolonged TTP among women born <37 gestational weeks (preterm) and with a birthweight ≤1500 g. Other studies of women's gestational age at birth and subsequent fertility, based on data from national birth registries, have reported a reduced probability of giving birth among women born <32 weeks of gestation. We used data from a prospective cohort study of Danish pregnancy planners ('Snart-Gravid'), enrolled during 2007-2011 and followed until 2012. In all, 2814 women were enrolled in our study, of which 2569 had complete follow-up. Women eligible to participate were 18-40 years old at study entry, in a relationship with a male partner, and attempting to conceive. Participants completed a baseline questionnaire and up to six follow-up questionnaires until the report of pregnancy, discontinuation of pregnancy attempts, beginning of fertility treatment, loss to follow-up or end of study observation after 12 months. Among women born <34 gestational weeks, the cumulative probability of conception was 12, 28 and 48% within 3, 6 and 12 cycles, respectively. Among women born at 37-41 weeks of gestation, cumulative probability of conception was 47, 67 and 84% within 3, 6 and 12 cycles, respectively. Relative to women born at 37-41 weeks' gestation, women born <34 weeks had decreased fecundability (fecundability ratio (FR) 0.38, 95% confidence interval (CI): 0.17-0.82). Our data did not suggest reduced fecundability among women born at 34-36 weeks of gestation or at ≥42 weeks of gestation (FR 1.03, 95% CI: 0.80-1.34, and FR 1.13, 95% CI: 0.96-1.33, respectively). Data on gestational age, obtained from the Danish Medical Birth Registry, were more likely to be based on date of last menstrual period than early ultrasound examination, possibly leading to an overestimation of gestational age at birth. Such overestimation, however, would not explain the decrease in fecundability observed among women born <34 gestational weeks. Another limitation is that the proportion of women born before 34 weeks of gestation was low in our study population, which reduced the precision of the estimates. By using prospective data on TTP, our study elaborates on previous reports of impaired fertility among women born preterm, suggesting that women born <34 weeks of gestation have reduced fecundability. The study was supported by the National Institute of Child Health and Human Development (R21-050264), the Danish Medical Research Council (271-07-0338), and the Health Research Fund of Central Denmark Region (1-01-72-84-10). The authors have no competing interests to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:


Available from