Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy
Authors: Zhao Jun , Hong Xiang , Zhang Hongguang , Dai Qiaoyun , Huang Kaiping , Zhang Xu , Liu Yuxiang , Wu Jingwei , Wang Qiaomei , Shen Haiping , Xu Zongyu , Zhang Yiping , Yan Donghai , Qi Daxun , Yang Xueying , Zhang Yue , Wang Bei , Ma Xu 
Published: April 2019

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
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