Time-to-conception and clinical pregnancy rate with myo-inositol, probiotics and micronutrient supplement: secondary outcomes of the NiPPeR Randomized Trial.: secondary outcomes of the NiPPeR randomized trial
Time-to-conception and clinical pregnancy rate with myo-inositol, probiotics and micronutrient supplement: secondary outcomes of the NiPPeR Randomized Trial.: secondary outcomes of the NiPPeR randomized trial
Objective: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates. Design: Secondary outcomes of a double-blind randomized controlled trial. Setting: Community recruitment. Patients: Women aged 18 to 38 years planning to conceive in the United Kingdom, Singapore, and New Zealand, excluding those with diabetes mellitus or receiving fertility treatment. Intervention: A standard (control) supplement (folic acid, iron, calcium, iodine, β-carotene), compared with an intervention additionally containing myo-inositol, probiotics, and other micronutrients (vitamins B2, B6, B12, D, zinc). Main Outcome Measures: Number of days between randomization and estimated date of natural conception of a clinical pregnancy, as well as cumulative pregnancy rates at 3, 6, and 12 months. Results: Of 1729 women randomized, 1437 (83%; intervention, n=736; control, n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% confidence interval: 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HRs) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, body mass index, and gravidity) were similar at 3, 6, and 12 months. Among both study groups combined, overall time-to-conception lengthened with higher preconception body mass index, and was longer in non-White than in White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12-month HR=1.47 [1.07, 2.02], P=.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to nonoverweight/nonobese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12-month HR=0.69 [0.47, 1.00]; P=.053; 20% conceived by 132.7 vs. 108.5 days); an effect predominantly observed in non-White women with obesity. Conclusions: Time-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the nonoverweight/nonobese women. Further studies are required to confirm this. Clinical Trial Registration Number: clinicaltrials.gov (NCT02509988)
fecundability, fertility, NiPPeR trial, nutritional supplement, preconception
1031-1042
Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Loy, See Ling
6fd10b64-1de2-419e-a5f4-b505be233e6e
Chan, Hsin Fang
99db3df4-d16d-407f-be00-a60e1683016d
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Wong, Jui-Tsung
c9b0cf5d-b75d-4a23-b13c-4e47f1fd83c3
Nield, Heidi
837b180c-0a9e-49ba-bc2e-a899ef761d34
El-Heis, Sarah
6d7d2e03-3d63-4510-8b7e-fcbe4653db13
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
June 2023
Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Loy, See Ling
6fd10b64-1de2-419e-a5f4-b505be233e6e
Chan, Hsin Fang
99db3df4-d16d-407f-be00-a60e1683016d
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Wong, Jui-Tsung
c9b0cf5d-b75d-4a23-b13c-4e47f1fd83c3
Nield, Heidi
837b180c-0a9e-49ba-bc2e-a899ef761d34
El-Heis, Sarah
6d7d2e03-3d63-4510-8b7e-fcbe4653db13
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Chan, Shiao-Yng, Barton, Sheila, Loy, See Ling, Chan, Hsin Fang, Titcombe, Philip, Wong, Jui-Tsung, Nield, Heidi, El-Heis, Sarah and Godfrey, Keith
(2023)
Time-to-conception and clinical pregnancy rate with myo-inositol, probiotics and micronutrient supplement: secondary outcomes of the NiPPeR Randomized Trial.: secondary outcomes of the NiPPeR randomized trial.
Fertility and Sterility, 119 (6), .
(doi:10.1016/j.fertnstert.2023.01.047).
Abstract
Objective: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates. Design: Secondary outcomes of a double-blind randomized controlled trial. Setting: Community recruitment. Patients: Women aged 18 to 38 years planning to conceive in the United Kingdom, Singapore, and New Zealand, excluding those with diabetes mellitus or receiving fertility treatment. Intervention: A standard (control) supplement (folic acid, iron, calcium, iodine, β-carotene), compared with an intervention additionally containing myo-inositol, probiotics, and other micronutrients (vitamins B2, B6, B12, D, zinc). Main Outcome Measures: Number of days between randomization and estimated date of natural conception of a clinical pregnancy, as well as cumulative pregnancy rates at 3, 6, and 12 months. Results: Of 1729 women randomized, 1437 (83%; intervention, n=736; control, n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% confidence interval: 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HRs) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, body mass index, and gravidity) were similar at 3, 6, and 12 months. Among both study groups combined, overall time-to-conception lengthened with higher preconception body mass index, and was longer in non-White than in White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12-month HR=1.47 [1.07, 2.02], P=.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to nonoverweight/nonobese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12-month HR=0.69 [0.47, 1.00]; P=.053; 20% conceived by 132.7 vs. 108.5 days); an effect predominantly observed in non-White women with obesity. Conclusions: Time-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the nonoverweight/nonobese women. Further studies are required to confirm this. Clinical Trial Registration Number: clinicaltrials.gov (NCT02509988)
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Accepted/In Press date: 30 January 2023
e-pub ahead of print date: 6 February 2023
Published date: June 2023
Additional Information:
Funding Information:
Public good funding for this investigator-led study is through the UK Medical Research Council (as part of an MRC award to the MRC Lifecourse Epidemiology Unit (MC_UU_12011/4)); the Singapore National Research Foundation, National Medical Research Council (NMRC, NMRC/TCR/012-NUHS/2014); the National University of Singapore (NUS) and the Agency of Science, Technology and Research (as part of the Growth, Development and Metabolism Programme of the Singapore Institute for Clinical Sciences (SICS) (H17/01/a0/005); and as part of Gravida, a New Zealand Government Centre of Research Excellence. Funding for provision of the intervention and control drinks and to cover aspects of the fieldwork for the study has been provided by Société Des Produits Nestlé S.A. under a Research Agreement with the University of Southampton, Auckland UniServices Ltd, SICS, National University Hospital Singapore PTE Ltd and NUS. K.M.G. is supported by the National Institute for Health Research (NIHR Senior Investigator ( NF-SI-0515-10042 ), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154) and NIHR Southampton Biomedical Research Center (IS-BRC-1215-20004)), British Heart Foundation (RG/15/17/3174), and the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP). S.Y.C. is supported by a Singapore NMRC Clinician Scientist Award (NMRC/CSA-INV/0010/2016; MOH-CSAINV19nov-0002). The funders had no role in the data collection and analysis, and the decision to submit for publication.
Funding Information:
Public good funding for this investigator-led study is through the UK Medical Research Council (as part of an MRC award to the MRC Lifecourse Epidemiology Unit (MC_UU_12011/4)); the Singapore National Research Foundation, National Medical Research Council (NMRC, NMRC/TCR/012-NUHS/2014); the National University of Singapore (NUS) and the Agency of Science, Technology and Research (as part of the Growth, Development and Metabolism Programme of the Singapore Institute for Clinical Sciences (SICS) (H17/01/a0/005); and as part of Gravida, a New Zealand Government Centre of Research Excellence. Funding for provision of the intervention and control drinks and to cover aspects of the fieldwork for the study has been provided by Société Des Produits Nestlé S.A. under a Research Agreement with the University of Southampton, Auckland UniServices Ltd, SICS, National University Hospital Singapore PTE Ltd and NUS. K.M.G. is supported by the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154) and NIHR Southampton Biomedical Research Center (IS-BRC-1215-20004)), British Heart Foundation (RG/15/17/3174), and the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP). S.Y.C. is supported by a Singapore NMRC Clinician Scientist Award (NMRC/CSA-INV/0010/2016; MOH-CSAINV19nov-0002). The funders had no role in the data collection and analysis, and the decision to submit for publication.K.G., Y.S.C., W.C., and S.C. report grants from Société Des Produits Nestlé S.A. during the conduct of the study and are co-inventors on patent filings by Nestlé S.A. relating to the NiPPeR intervention or its components. K.G., S.B., Y.S.C., W.C., and S.C. are part of an academic consortium that has received grants from Nestlé S.A. and Benevolent AI Bio Ltd outside the submitted work. All other authors declare no competing interests. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2023 The Authors
Keywords:
fecundability, fertility, NiPPeR trial, nutritional supplement, preconception
Identifiers
Local EPrints ID: 475980
URI: http://eprints.soton.ac.uk/id/eprint/475980
ISSN: 0015-0282
PURE UUID: a409e48e-9ee9-4650-b8be-269749ca3d06
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Date deposited: 03 Apr 2023 16:48
Last modified: 15 Aug 2024 01:46
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Contributors
Author:
Shiao-Yng Chan
Author:
See Ling Loy
Author:
Hsin Fang Chan
Author:
Philip Titcombe
Author:
Jui-Tsung Wong
Author:
Heidi Nield
Author:
Sarah El-Heis
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