PMID- 37705678
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230916
IS  - 2673-3153 (Electronic)
IS  - 2673-3153 (Print)
IS  - 2673-3153 (Linking)
VI  - 5
DP  - 2023
TI  - Hyperhomocysteinemia in hypofertile male patients can be alleviated by 
      supplementation with 5MTHF associated with one carbon cycle support.
PG  - 1229997
LID - 10.3389/frph.2023.1229997 [doi]
LID - 1229997
AB  - INTRODUCTION: Homocysteine (Hcy) is a cellular poison, side product of the 
      hydrolysis of S-Adenosyl Homocysteine, produced after the universal methylation 
      effector S -Adenosylmethionine liberates a methyl group to recipient targets. It 
      inhibits the methylation processes and its rising is associated with multiple 
      disease states and ultimately is both a cause and a consequence of oxidative 
      stress, affecting male gametogenesis. We have determined hyper homocysteinhemia 
      (HHcy) levels can be reliably reduced in hypofertile patients in order to 
      decrease/avoid associated epigenetic problems and protect the health of future 
      children, in consideration of the fact that treatment with high doses of folic 
      acid is inappropriate. METHODS: Homocysteine levels were screened in male 
      patients consulting for long-standing infertility associated with at least three 
      failed Assisted Reproductive Technology (ART) attempts and/or repeat 
      miscarriages. Seventy-seven patients with Hcy levels > 15 microM were treated for 
      three months with a combination of micronutrients including 5- 
      MethylTetraHydroFolate (5-MTHF), the compound downstream to the MTHFR enzyme, to 
      support the one carbon cycle; re-testing was performed at the end of a 3 months 
      treatment period. Genetic status for Methylenetetrahydrofolate Reductase (MTHFR) 
      Single nucleotide polymorphisms (SNPs) 677CT (c.6777C > T) and 1298AC 
      (c.1298A > C) was determined. RESULTS: Micronutrients/5-MTHF were highly 
      efficient in decreasing circulating Hcy, from averages 27.4 to 10.7 microM, with a 
      mean observed decrease of 16.7 microM. The MTHFR SNP 677TT (homozygous form) and 
      combined heterozygous 677CT/1298AC status represent 77.9% of the patients with 
      elevated Hcy. DISCUSSION: Estimation HHcy should not be overlooked in men 
      suffering infertility of long duration. MTHFR SNPs, especially 677TT, are a major 
      cause of high homocysteinhemia (HHcy). In these hypofertile patients, treatment 
      with micronutrients including 5-MTHF reduces Hcy and even allows spontaneous 
      pregnancies post treatment. This type of therapy should be considered in order to 
      ensure these patients' quality of life and avoid future epigenetic problems in 
      their descendants.
CI  - (c) 2023 Clement, Amar, Clement, Sedbon, Brami, Alvarez and Menezo.
FAU - Clement, Arthur
AU  - Clement A
AD  - Laboratoire Clement, Genetics and IVF, Avenue d'Eylau, Paris, France.
FAU - Amar, Edouard
AU  - Amar E
AD  - Cabinet Medical Urology, Andrology, Avenue Victor Hugo, Paris, France.
FAU - Clement, Patrice
AU  - Clement P
AD  - Laboratoire Clement, Genetics and IVF, Avenue d'Eylau, Paris, France.
FAU - Sedbon, Eric
AU  - Sedbon E
AD  - Cabinet Medical, Gyn Obst, 17 rue Petrarque, Paris, France.
FAU - Brami, Charles
AU  - Brami C
AD  - Cabinet Medical, Gyn Obst, 16 Avenue Paul Doumer, Paris, France.
FAU - Alvarez, Silvia
AU  - Alvarez S
AD  - Cabinet Medical, Gyn Obst, 15 Avenue Pointcarre, Paris, France.
FAU - Menezo, Yves
AU  - Menezo Y
AD  - Laboratoire Clement, Genetics and IVF, Avenue d'Eylau, Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20230829
PL  - Switzerland
TA  - Front Reprod Health
JT  - Frontiers in reproductive health
JID - 9918230899006676
PMC - PMC10495983
OTO - NOTNLM
OT  - 5 MTHF
OT  - MTHFR SNP
OT  - folates cycle
OT  - homocysteine
OT  - male hypofertility
OT  - one carbon cycle
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/09/14 06:42
MHDA- 2023/09/14 06:43
PMCR- 2023/08/29
CRDT- 2023/09/14 04:03
PHST- 2023/05/27 00:00 [received]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2023/09/14 06:43 [medline]
PHST- 2023/09/14 06:42 [pubmed]
PHST- 2023/09/14 04:03 [entrez]
PHST- 2023/08/29 00:00 [pmc-release]
AID - 10.3389/frph.2023.1229997 [doi]
PST - epublish
SO  - Front Reprod Health. 2023 Aug 29;5:1229997. doi: 10.3389/frph.2023.1229997. 
      eCollection 2023.