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Metabolic health status and fecundability in a Singapore preconception cohort study

Metabolic health status and fecundability in a Singapore preconception cohort study
Metabolic health status and fecundability in a Singapore preconception cohort study
Background: obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown.

Objective: this study aimed to: (1) determine the metabolic health status, and (2) examine the association between metabolic health status and fecundability of overweight and obese women trying to conceive in the Singapore PREconception Study of long-Term maternal and child Outcomes cohort study.

Study Design: we conducted a prospective preconception cohort study of Asian women (Chinese, Malay, and Indian) aged 18 to 45 years trying to conceive who were treated from 2015 to 2017 in KK Women’s and Children’s Hospital in Singapore (n=834). We defined women to have metabolically unhealthy status if they: (1) met 3 or more modified Joint Interim Statement metabolic syndrome criteria; or (2) had homeostasis model assessment-insulin resistance index ≥2.5. Body mass index was categorized as normal (18.5–22.9 kg/m2), overweight (23–27.4 kg/m2), or obese (≥27.5 kg/m2) on the basis of cutoff points for Asian populations. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrolment. Discrete-time proportional hazards models were used to estimate fecundability odds ratios, with adjustment for confounders and accounting for left truncation and right censoring.

Results: of 232 overweight women, 28 (12.1%) and 25 (10.8%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Of 175 obese women, 54 (30.9%) and 93 (53.1%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Compared with metabolically healthy normal-weight women, lower fecundability was observed in metabolically unhealthy overweight women on the basis of metabolic syndrome criteria (fecundability odds ratios, 0.38 [95% confidence interval, 0.15–0.92]) and homeostasis model assessment-insulin resistance (fecundability odds ratios, 0.68 [95% confidence interval, 0.33–1.39]), with metabolic syndrome criteria showing a stronger association. Metabolically unhealthy obese women showed lower fecundability than the healthy normal-weight reference group by both metabolic syndrome (fecundability odds ratios, 0.35; 95% confidence interval, 0.17–0.72) and homeostasis model assessment-insulin resistance criteria (fecundability odds ratios, 0.43; 95% confidence interval, 0.26–0.71). Reduced fecundability was not observed in overweight or obese women who showed healthy metabolic profiles by either definition.

Conclusion: overweight or obesity was not synonymous with having metabolic syndrome or insulin resistance. In our preconception cohort, metabolically unhealthy overweight and obese women showed reduced fecundability, unlike their counterparts who were metabolically healthy. These findings suggest that metabolic health status, rather than simply being overweight and obese per se, plays an important role in fecundability.
conception, fertility, insulin resistance, lipids, metabolic syndrome, obesity, overweight, pregnancy planning, time to pregnancy
0002-9378
Loy, S.L.
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Chan, Daniel Wei Keong
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Ku, Chee Wai
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Cheung, Yin Bun
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Godfrey, Keith
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Tan, Karen Mei Ling
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Chong, Yap-Seng
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Shek, Lynette P.
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Tan, Kok Hian
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Chan, Shiao-Yng
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Chan, Jerry Kok Yen
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Yap, Fabian
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Loy, S.L.
967951b0-5a39-4824-abee-abf33a2cd309
Chan, Daniel Wei Keong
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Ku, Chee Wai
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Cheung, Yin Bun
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Godfrey, Keith
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Tan, Karen Mei Ling
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Chong, Yap-Seng
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Shek, Lynette P.
9a77403c-0e0c-4536-a5ad-628ce94b279a
Tan, Kok Hian
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Chan, Shiao-Yng
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Chan, Jerry Kok Yen
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Yap, Fabian
22f6b954-31fc-4696-a52b-e985a424b95b

Loy, S.L., Chan, Daniel Wei Keong, Ku, Chee Wai, Cheung, Yin Bun, Godfrey, Keith, Tan, Karen Mei Ling, Chong, Yap-Seng, Shek, Lynette P., Tan, Kok Hian, Chan, Shiao-Yng, Chan, Jerry Kok Yen and Yap, Fabian (2021) Metabolic health status and fecundability in a Singapore preconception cohort study. American Journal of Obstetrics and Gynecology. (doi:10.1016/j.ajog.2021.11.1374).

Record type: Article

Abstract

Background: obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown.

Objective: this study aimed to: (1) determine the metabolic health status, and (2) examine the association between metabolic health status and fecundability of overweight and obese women trying to conceive in the Singapore PREconception Study of long-Term maternal and child Outcomes cohort study.

Study Design: we conducted a prospective preconception cohort study of Asian women (Chinese, Malay, and Indian) aged 18 to 45 years trying to conceive who were treated from 2015 to 2017 in KK Women’s and Children’s Hospital in Singapore (n=834). We defined women to have metabolically unhealthy status if they: (1) met 3 or more modified Joint Interim Statement metabolic syndrome criteria; or (2) had homeostasis model assessment-insulin resistance index ≥2.5. Body mass index was categorized as normal (18.5–22.9 kg/m2), overweight (23–27.4 kg/m2), or obese (≥27.5 kg/m2) on the basis of cutoff points for Asian populations. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrolment. Discrete-time proportional hazards models were used to estimate fecundability odds ratios, with adjustment for confounders and accounting for left truncation and right censoring.

Results: of 232 overweight women, 28 (12.1%) and 25 (10.8%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Of 175 obese women, 54 (30.9%) and 93 (53.1%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Compared with metabolically healthy normal-weight women, lower fecundability was observed in metabolically unhealthy overweight women on the basis of metabolic syndrome criteria (fecundability odds ratios, 0.38 [95% confidence interval, 0.15–0.92]) and homeostasis model assessment-insulin resistance (fecundability odds ratios, 0.68 [95% confidence interval, 0.33–1.39]), with metabolic syndrome criteria showing a stronger association. Metabolically unhealthy obese women showed lower fecundability than the healthy normal-weight reference group by both metabolic syndrome (fecundability odds ratios, 0.35; 95% confidence interval, 0.17–0.72) and homeostasis model assessment-insulin resistance criteria (fecundability odds ratios, 0.43; 95% confidence interval, 0.26–0.71). Reduced fecundability was not observed in overweight or obese women who showed healthy metabolic profiles by either definition.

Conclusion: overweight or obesity was not synonymous with having metabolic syndrome or insulin resistance. In our preconception cohort, metabolically unhealthy overweight and obese women showed reduced fecundability, unlike their counterparts who were metabolically healthy. These findings suggest that metabolic health status, rather than simply being overweight and obese per se, plays an important role in fecundability.

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Accepted/In Press date: 20 November 2021
e-pub ahead of print date: 16 December 2021
Additional Information: Funding Information: K.M.G. and Y.S.C. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. K.M.G., Y.S.C., and S.Y.C. are part of an academic consortium who have received research funding from Abbott, Nutrition, Nestle and Danone. Other authors report no conflict of interest. Funding Information: This research is supported by the Singapore National Research Foundation, Singapore under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Singapore, Agency for Science Technology and Research (A?STAR), Singapore. Y.B.C. is supported by a Clinician Scientist Award from the Singapore NMRC (NMRC/CSA/0039/2012). K.M.G. is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research, United Kingdom (NIHR Senior Investigator (NF-SI-0515-10042)) and NIHR Southampton Biomedical Research Centre, United Kingdom (IS-BRC-1215-20004), the European Union (Erasmus+ Program ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation, United Kingdom (RG/15/17/3174). S.Y.C. is supported by a Clinician Scientist Award from the Singapore NMRC (NMRC/CSA-INV/0010/2016). J.K.Y.C. is supported by a Clinician Scientist Award from the Singapore NMRC (CSA(SI)/008/2016). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: This research is supported by the Singapore National Research Foundation , Singapore under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences , Singapore, Agency for Science Technology and Research (A∗STAR), Singapore. Y.B.C. is supported by a Clinician Scientist Award from the Singapore NMRC (NMRC/CSA/0039/2012). K.M.G. is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research , United Kingdom (NIHR Senior Investigator (NF-SI-0515-10042)) and NIHR Southampton Biomedical Research Centre , United Kingdom (IS-BRC-1215-20004), the European Union (Erasmus+ Program ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation , United Kingdom (RG/15/17/3174). S.Y.C. is supported by a Clinician Scientist Award from the Singapore NMRC (NMRC/CSA-INV/0010/2016). J.K.Y.C. is supported by a Clinician Scientist Award from the Singapore NMRC (CSA(SI)/008/2016). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2021 Elsevier Inc.
Keywords: conception, fertility, insulin resistance, lipids, metabolic syndrome, obesity, overweight, pregnancy planning, time to pregnancy

Identifiers

Local EPrints ID: 453174
URI: http://eprints.soton.ac.uk/id/eprint/453174
ISSN: 0002-9378
PURE UUID: fb0154d1-de7c-48ab-bd3e-f7384b8da2e0
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

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Date deposited: 10 Jan 2022 18:00
Last modified: 17 Mar 2024 07:01

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Contributors

Author: S.L. Loy
Author: Daniel Wei Keong Chan
Author: Chee Wai Ku
Author: Yin Bun Cheung
Author: Keith Godfrey ORCID iD
Author: Karen Mei Ling Tan
Author: Yap-Seng Chong
Author: Lynette P. Shek
Author: Kok Hian Tan
Author: Shiao-Yng Chan
Author: Jerry Kok Yen Chan
Author: Fabian Yap

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