Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy

Abstract

STUDY QUESTION What is the relationship between pre-pregnancy maternal glucose levels and fecundability in Chinese couples? SUMMARY ANSWER Elevated pre-pregnancy maternal glucose levels were associated with fecundability, as reflected by prolonged time to pregnancy (TTP) among the couples with no prior gravidity. STUDY DESIGN, SIZE, DURATION Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 2 226 048 eligible couples attempting first pregnancy and participating in the project from 2015 to 2016 were included. They were followed-up for 1 year or until they reported pregnancy. PARTICIPANTS/MATERIALS, SETTINGS, METHODS The Kaplan–Meier method was used to estimate the cumulative pregnancy rate in each menstrual cycle, and the discrete-time analogue of the Cox models was used to estimate the fecundability odds ratios (FORs) and 95% CIs by different pre-pregnancy maternal glucose levels (impaired fasting glucose (IFG) or diabetes as compared to normal). MAIN RESULTS AND THE ROLE OF CHANCE The cumulative pregnancy rate for 12 cycles of the normal fasting plasma glucose (FPG) level group was 42.29%, significantly higher than that of the IFG (35.52%) and diabetes groups (31.52%). After adjusting for confounding factors, the FORs were 0.82 (95% CI: 0.81–0.83) and 0.74 (95% CI: 0.72–0.76) for the IFG and diabetes groups, respectively, as compared to the normal group. The association between pre-pregnancy maternal FPG levels and the FORs was non-linear, and the optimal FPG level for greatest fecundability (shortest TTP) was 3.90–4.89 mmol/L. LIMITATIONS, REASONS FOR CAUTION The findings from this register-based cohort study require cautious interpretation given that information bias would be inevitable for single FPG measurements and for TTP calculations that were based on telephone follow-up information. Additionally, because couples who achieved pregnancy during their first menstrual cycle in the study were excluded, the pregnancy rates reported were low and possibly biased. WIDER IMPLICATIONS OF THE FINDINGS The current report suggests that elevated pre-pregnancy maternal glucose levels were associated with prolonged TTP. Early evaluation and preventive treatment for female partners with IFG or diabetes in a pre-pregnancy examination are necessary. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the National Key Research and Development Program of China (grants No. 2016YFC1000300 and 2016YFC1000307), the National Natural Science Foundation of China (grant No. 81872634), the CAMS Innovation Fund for Medical Sciences (grant No. 2018-I2M-1-004), the National Human Genetic Resources Sharing Service Platform (grant No. 2005DKA21300) and the National Population and Reproductive Health Science Data Center (grant No. 2005DKA32408), People’s Republic of China. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A

Glycemic status and fertility—implications for preconception care

“…However, the overall shape of the relationship between fasting glucose and fecundity suggests that fecundity decreases with increasing fasting glucose even within the normal range. This interpretation is consistent with findings from a recent study among Chinese couples seeking preconception care, which also found that women with diabetes and impaired fasting glucose had lower fecundity and documented important variability in fecundity within the normal range of fasting glucose levels (1).…”

“…Much of the focus to date has been on clinically overt disease. For example, there is a growing literature showing that time to conception is longer for women with diabetes than for women without diabetes (1). Conversely, women with a history of infertility also seem to be at greater risk of developing diabetes (2).…”

Risk score to stratify miscarriage risk levels in preconception women

“…Our cohort showed that 46.5% women spontaneously conceived after 12 cycles of pregnancy attempts, which is lower than the reported rates of greater than 70% in other studies 33 – 35 . However, similarly low conception rates of 42% after 12 cycles of natural conception have been previously shown in a study of Chinese women 36 . The low conception rate may help to explain the relatively low total fertility rate in Singapore of 1.10 37 .…”

Fertility outcomes in women with pre-existing type 2 diabetes—a prospective cohort study

“…To our knowledge, this is the first study to report birthrates among women who developed type 2 diabetes before any reproductive outcome. A Chinese study, comprising >2 million couples, reported a lower cumulative pregnancy rate among women with increased fasting plasma glucose levels than among women with normal fasting glucose levels after 12 months of follow-up (31.5% vs. 42.3%) (13). The women had no prior childbirth at inclusion, but it should be noted that no distinction was possible between type 1 and 2 diabetes in this study.…”

“…Prior research has been hampered by difficulties in enrolling a sufficient number of individuals, and there is almost no research on reproductive function in terms of achievement of pregnancy or live birth in women with type 2 diabetes, as noted in a recent review (4). Four studies report longer time to pregnancy and reduced fecundability odds ratios in women with diabetes (5,(12)(13)(14); however, the studies either were small (5,12), did not differentiate between type 1 and type 2 diabetes (12)(13)(14), could not rule out medical intervention bias (13), or used a pregnancy-based design, excluding the most subfecund or sterile women (5).…”