Supporting the One-Carbon Cycle Restores Ovarian Reserve in Subfertile Women: Absence of Correlation with Urinary Bisphenol A Concentration

Abstract

Environmental endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), induce DNA methylation errors and oxidative stress, and alter fertility. Animal studies have demonstrated that supporting the one-carbon cycle (1-CC) with appropriate dietary supplements can reduce the effects of EDCs. Anti-Mullerian hormone (AMH), a marker of ovarian functionality, has been tested in subfertile female patients, to control this hypothesis in humans. Fifty-five women with a history of 3–7 years of infertility, with at least two assisted reproductive technology (ART) treatment failures, and low serum levels of AMH were enrolled in the study. Before starting any further ART treatment, they were tested for AMH and for follicular count. A urinary control of BPA was proposed. Then a support of the 1-CC, already tested in other clinical studies, was initiated and continued for 4 months. At the end of this period, antral follicle count and serum AMH levels were re-evaluated. The AMH levels before and after treatment were compared using the Wilcoxon test (nonparametric test, non-Gaussian population). Out of the 55 patients, 35 accepted a BPA dosage in the urine. No correlation was found between BPA and serum AMH concentrations. Forty-nine patients followed the full treatment with 1-CC supplements, which resulted in increased AMH levels, independent of initial AMH levels and maternal age (in the range studied), p = 0.0001. Eight patients spontaneously conceived ongoing pregnancies within 3 months, at the end of the protocol. A support of the 1-CC can partly alleviate metabolic derangements induced by environment, as observed in animal models, and improve endocrine background in women.

Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women

“…A combination of micronutrients similar to the one here tested administered to infertile women with low ovarian reserve achieved a significant increase of their AMH level and resulted in improved fertility with spontaneous pregnancies occurring in ladies waiting for oocyte donation [26]. Aiming to confirm this effect also in PCOS ladies, we included AMH among the tested parameters and found that also in our study, the treatment group recorded an increase of the AMH level.…”

“…A total of 33 PCOS ladies (mean age 26.8, range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] were enrolled between June 2017 and October 2018, and one patient withdrew her participation for personal reasons after the basal visit. Out of 32 patients randomized, 22 entered the active treatment group, and 10 the no treatment group.…”

MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series

“…Following the work on the impact of MTHFR C677T and A1298C isoforms on male [16] and female gametes [2], it was decided during fall 2016 to study patients with normal caryotypes that had a long history (at least 4 years) of recurrent miscarriages or infertility.…”

“…Also it regulates the balance between folates for nucleotide synthesis and those for methionine synthesis. Support of the 1-CC has demonstrated to be efficient for both male and female gametes [2][3][4][5]. MTHFR isoforms are well-known genetic variants impairing the efficacy to form 5-MTHF and eventually the methylation process.…”

The negative impact of the environment on methylation/epigenetic marking in gametes and embryos: A plea for action to protect the fertility of future generations

“…This strategy may also be beneficial via increasing the efficiency of DNA repair. It can solve some idiopathic infertility problems (Dattilo, Giuseppe, Ettore, & Ménézo, ; Silvestris et al, ) probably related to undetected/undefined environmental problems affecting methylation processes.…”