The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report

Abstract

BackgroundSperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants.MethodsMale partners of couples resistant to at least 2 assisted reproductive technology (ART) attempts, with no evidence of organic causes of infertility and with either DNA fragmentation index (DFI) measured by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear decondensation index (SDI) measured by aniline blue staining exceeding 20%, were invited to take part in a trial of a nutritional support in preparation for a further ART attempt. The treatment consisted of a combination of B vitamins, zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine and Vitamin E (Condensyl™), all effectors of the one carbon cycle.Results84 patients were enrolled, they took 1 or 2 Condensyl™ tablets per day for 2 to 12 months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy before the planned ART cycle, all ended with a live birth. The remaining 66 couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22 further clinical pregnancies and 15 live births. The clinical pregnancy rate (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full responders, i.e. the 40 patients achieving an improvement of both SDI and DFI, reported a CPR of 70% and a LBR of 57.5% (p < 0.001).ConclusionsNutritional support of the one carbon cycle without strong antioxidants improves both the SDI and the DFI in ART resistant male partners and results in high pregnancy rates suggesting a positive effect on their fertility potential.

Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet

“…Indeed betalaines have the property to stratify on plasma membranes where they act as suicide oxidation substrates to prevent the trigger of the lipoperoxidative cascade so to further aid sperm motility. This nutritional intervention was tested in male [44–46] and female [46] partners in couples with previous IVF/ICSI failures willing to undergo another ART attempt. These studies included couples with at least 2 previous ART failures and with a male partner showing sperm DNA Fragmentation Index (DFI—Measure of oxidative molecular damage, as assessed by TUNEL) and/or a Sperm nuclear Decondensation Index (SDI—Measure of integrity of chromatin tertiary structure, as assessed by aniline blue staining) > 20 % irrespective of the other sperm parameters.…”

“…A total of 84 patients fulfilled the entry criteria of this non comparative study [44], in 28 cases (33 %) there was an associated female factor. For the first time ever, both sperm indexes significantly improved (DFI from 29.7 to 23.1 %, p  < 0.001; SDI from 40.1 to 36.3 %, p  < 0.001) confirming that the new support strategy is effective in counteracting oxidative damage without negatively influencing (reductive stress) the nuclear decondensation.…”

“…Surprisingly, the pregnancy gain from the female treatment [46] was at least as high as the one recorded with male treatments, suggesting that the impact of oxidative damage on female infertility may be similar if not even larger. The pregnancy outcomes of the male partners and their controls [44, 45] and of the female partners and their controls [46] are summarized in Table 2.…”

Epigenetic imprinting during assisted reproductive technologies: The effect of temporal and cumulative fluctuations in methionine cycling on the DNA methylation state

“…Therefore measuring substrate abundance and enzyme activities related to the folate and methionine cycle are important indicators of possible disruptions in the methylation cycle. Indeed, several studies point toward beneficial effects of inducing a well‐balanced folate and methionine cycle in both males (Dattilo et al, ) and females (Haggarty et al, ; Boxmeer et al, ,; Gaskins et al, ; Murto et al, ) for pregnancy success in ART. Furthermore, a recent study in mouse blastocysts showed the necessity of folate and BHMT homocysteine recycling pathways to ensure that sufficient levels of S‐adenosylmethionine enable a sufficient DNA methylation level (Zhang et al, ).…”

Abnormal Chromatin Condensation in Spermatozoa and Dna Fragmentation in Spermatozoa: Is There a Correlation?

“…Эти данные позволяют сделать заключение, что нарушение конденсации хроматина может служить предиктивным показателем аномалий развития эмбри-она как in vivo, так и in vitro. Причем негативные по-следствия нарушения компактизации проявляются в раннее время после оплодотворения [77], приводя к раннему эмбриональному аресту [78] и спонтанным абортам [27,79].…”