Folate Metabolism and Human Reproduction

Abstract

Folate metabolism affects ovarian function, implantation, embryogenesis and the entire process of pregnancy. In addition to its well-established effect on the incidence of neural tube defects, associations have been found between reduced folic acid levels and increased homocysteine concentrations on the one hand, and recurrent spontaneous abortions and other complications of pregnancy on the other. In infertility patients undergoing IVF/ICSI treatment, a clear correlation was found between plasma folate concentrations and the incidence of dichorionic twin pregnancies. In patients supplemented with 0.4 mg/d folic acid undergoing ovarian hyperstimulation and oocyte pick-up, carriers of the MTHFR 677T mutation were found to have lower serum estradiol concentrations at ovulation and fewer oocytes could be retrieved from them. It appears that these negative effects can be compensated for in full by increasing the daily dose of folic acid to at least 0.8 mg. In carriers of the MTHFR 677TT genotype who receive appropriate supplementation, AMH concentrations were found to be significantly increased, which could indicate a compensatory mechanism. AMH concentrations in homozygous carriers of the MTHFR 677TT genotype could even be overestimated, as almost 20 % fewer oocytes are retrieved from these patients per AMH unit compared to MTHFR 677CC wild-type individuals.

Zusammenfassung

Der Folatmetabolismus hat vielfältige Effekte auf ovarielle Funktion, Implantation, Embryogenese und den gesamten Verlauf der Schwangerschaft. Neben dem gut etablierten Einfluss auf die Inzidenz neuraler Fusionsdefekte finden sich Zusammenhänge zwischen verminderten Folsäure- und erhöhten Homocysteinkonzentrationen einerseits und gehäuften Spontanaborten und anderen Schwangerschaftskomplikationen andererseits. Zusätzlich zeigt sich bei Kinderwunschpatientinnen im Rahmen der IVF/ICSI-Behandlung ein deutlicher Zusammenhang zwischen Plasma-Folat-Konzentrationen und der Inzidenz dichorialer Geminischwangerschaften. Im Rahmen der ovariellen Hyperstimulation finden sich bei Trägerinnen der MTHFR-677T-Mutation unter einer Folsäure-Substitution mit täglich 0,4 mg negative Effekte auf die Zahl gewonnener Oozyten sowie die maximale Konzentration von Östradiol am Tag der Ovulationsauslösung. Diese Effekte sind offenbar vollständig kompensierbar durch Erhöhung der täglichen Folsäuredosis auf mind. 0,8 mg. Bei entsprechend substituierten Trägerinnen des MTHFR-677TT-Genotyps finden sich die AMH-Konzentrationen signifikant erhöht, was auf einen Kompensationsmechanismus hindeuten könnte. Tatsächlich könnten die AMH-Konzentrationen homozygoter Trägerinnen des MTHFR-677TT-Genotyps allerdings überschätzt werden, denn bei ihnen konnten durchschnittlich fast 20 % weniger Oozyten pro AMH-Einheit gewonnen werden als bei Individuen mit dem MTHFR-677CC-Wildtyp-Genotyp.

Key words

assisted reproduction - folate metabolism - homocysteine - human reproduction - folliculogenesis

Schlüsselwörter

assistierte Reproduktion - Folatmetabolismus - Homocystein - menschliche Fortpflanzung - Follikulogenese

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