ABSTRACT
Objective To compare steroid profiles in the follicular fluid (FF) from women homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation and wildtype controls and to correlate it with the folic acid administration scheme applied at the time of oocyte retrieval. Design Retrospective single center study. Subjects and Methods Infertile patients treated by using assisted reproductive techniques were genotyped routinely for the MTHFR 677C>T mutation. In 2006 they had received folic acid supplementation doses of 400 µg daily per os. This group was designated Group-400 (n = 10). From 2008 onwards, all of our infertility patients received a daily dose of 800 µg folic acid per os. Women from this group were designated Group-800 (n = 28). FF were collected and a panel of steroid hormones (estradiol, estrone, estriol, cortisol, progesterone, 17-OH progesterone, testosterone, androstenedione, aldosterone, DHEA, and DHEA-S) was measured by isotope dilution liquid chromatography-tandem mass spectrometry employing atmospheric pressure photo ionization (APPI). Results In Group-400, the FF hormone profile confirmed a significant reduction of estradiol in homozygous 677TT carriers (0.52 ± 0.08-fold, exact p = 0.032) and for the first time also revealed significantly reduced estriol concentrations in these individuals (0.54 ± 0.05-fold, p = 0.016), as compared to wildtype controls. In Group-800, no significant differences were found for concentrations of any of the steroid hormones between homozygous 677TT carriers and wildtype controls. Conclusions The current findings support and extend previous reports on reduced concentrations of specific steroid hormones in follicular fluids of homozygous MTHFR 677C>T mutation carriers. The restoration of the FF hormone profile by elevated-dose folic acid supplementation might impact performing ART in infertile women with the MTHFR 677TT-genotype. Further adequately powered studies are necessary to verify our finding and to demonstrate the clinical effect of enhanced folic supplementation on ovarian function.
ABSTRACT
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. METHODS: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. FINDINGS: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. INTERPRETATION: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. FUNDING: None.
