The Effectiveness of 5-methyltetrahydrofolate Versus Folic Acid Prenatal Multivitamins in Couples with a history of Recurrent Pregnancy Loss: A Randomised, Controlled Feasibility Trial

Ledowsky, Carolyn Jane

The Effectiveness of 5-methyltetrahydrofolate Versus Folic Acid Prenatal Multivitamins in Couples with a history of Recurrent Pregnancy Loss: A Randomised, Controlled Feasibility Trial

Ledowsky, Carolyn Jane

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Publication Type:: Thesis
Issue Date:: 2025

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Field	Value	Language
dc.contributor.author	Ledowsky, Carolyn Jane
dc.date.accessioned	2026-10-14T02:07:53Z
dc.date.available	2026-10-14T02:07:53Z
dc.date.issued	2025
dc.identifier.uri	http://hdl.handle.net/10453/197220
dc.description	University of Technology Sydney. Faculty of Health.	en_US.UTF-8
dc.description.abstract	𝗕𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱 Recurrent pregnancy loss (RPL) remains a significant clinical challenge. Emerging evidence suggests high cumulative folic acid (FA) exposure may have biochemical implications in some individuals. Alternative folate forms, including 5 methyltetrahydrofolate (5 MTHF), are increasingly available, yet evidence in RPL is limited. MTHFR polymorphisms may influence folate availability. 𝗠𝗲𝘁𝗵𝗼𝗱𝘀 A two phase design was undertaken. Phase 1 was a double blind controlled feasibility trial of 22 couples with RPL, comparing a prenatal multivitamin containing 2,500 mcg FA or 5 MTHF. Outcomes included recruitment, adherence, acceptability and biochemical responsiveness. A qualitative sub study explored women’s experiences following pregnancy loss. Phase 2 was a national cross sectional survey of Australian health professionals. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀 Participants demonstrated high adherence to the study protocol and supplementation. All couples carried MTHFR polymorphisms. Qualitative findings identified gaps in continuity of care and support following loss. Among 175 health professionals, most routinely prescribed FA, rarely included male partners, and reported a strong need for clinical guidance. 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻 This thesis provides novel feasibility data and contextual insights into the use of different folate forms in couples experiencing recurrent pregnancy loss. While clinical effectiveness cannot be inferred, the findings support the need for adequately powered trials evaluating folate form, dose, and metabolic context in RPL.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/197220/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2025 Carolyn Jane Ledowsky
dc.rights	au.edu.uts.lib/cph
dc.title	The Effectiveness of 5-methyltetrahydrofolate Versus Folic Acid Prenatal Multivitamins in Couples with a history of Recurrent Pregnancy Loss: A Randomised, Controlled Feasibility Trial	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

𝗕𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱 Recurrent pregnancy loss (RPL) remains a significant clinical challenge. Emerging evidence suggests high cumulative folic acid (FA) exposure may have biochemical implications in some individuals. Alternative folate forms, including 5 methyltetrahydrofolate (5 MTHF), are increasingly available, yet evidence in RPL is limited. MTHFR polymorphisms may influence folate availability. 𝗠𝗲𝘁𝗵𝗼𝗱𝘀 A two phase design was undertaken. Phase 1 was a double blind controlled feasibility trial of 22 couples with RPL, comparing a prenatal multivitamin containing 2,500 mcg FA or 5 MTHF. Outcomes included recruitment, adherence, acceptability and biochemical responsiveness. A qualitative sub study explored women’s experiences following pregnancy loss. Phase 2 was a national cross sectional survey of Australian health professionals. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀 Participants demonstrated high adherence to the study protocol and supplementation. All couples carried MTHFR polymorphisms. Qualitative findings identified gaps in continuity of care and support following loss. Among 175 health professionals, most routinely prescribed FA, rarely included male partners, and reported a strong need for clinical guidance. 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻 This thesis provides novel feasibility data and contextual insights into the use of different folate forms in couples experiencing recurrent pregnancy loss. While clinical effectiveness cannot be inferred, the findings support the need for adequately powered trials evaluating folate form, dose, and metabolic context in RPL.

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http://hdl.handle.net/10453/197220