The homocysteine pathway in human subfertility

Subfertility, defined as at least one year of unprotected intercourse with the same partner without conception, affects ten to fifteen percent of couples in the western world. Depending on the duration of the subfertility, a female factor is the dominant cause of subfertility in around 50%, a male factor in 20-26% and the cause is unexplained in 25-30%. In most couples, subfertility is of multifactorial origin and should therefore be considered as a complex disease. Whereas genetic causes are difficult to modulate, environmental and lifestyle factors implicated in reproduction are potentially amendable to curative or preventive measures. Worldwide, an increasing number of couples are treated by assisted reproductive technology (ART) to achieve pregnancy. Currently, the chance of achieving a clinical pregnancy is around 28-31% per started in vitro fertilization (IVF) cycle with or without intracytoplasmic sperm injection (ICSI) in the Netherlands. The advantage of the introduction of IVF and ICSI treatment is that it gives access to and information about the direct environment of the gametes and early developing embryo. On the other hand, IVF and ICSI treatment is introducing an artifactual endocrinologic milieu which may affect the quality of the embryo. Whether concentrations of nutrients and enzymes change due to ovarian hyperstimulation is unclear, but it has already been demonstrated that different ovarian stimulation regimens increase the rates of embryo aneuploidy

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

Low folate in seminal plasma is associated with increased sperm DNA damage

Objective: To determine associations between vitamin B status, homocysteine (tHcy), semen parameters, and sperm DNA damage.Design: Observational study.Setting: A tertiary referral fertility clinic.Patients: Two hundred fifty-one men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men (n = 63) defined according to semen concentration and proven fertility.Intervention: None.Main Outcome Measure: The DNA fragmentation index (DFI) as marker of sperm DNA damage determined using the sperm chromatin structure assay (SCSA), and semen parameters assessed according to World Health Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations determined in seminal plasma and blood.Result: In the total group of fertile and subfertile men, all biomarkers in blood were statistically significantly correlated with those in seminal plasma. No correlation was found between the biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and cobalamin positively correlated with sperm count. Folate, cobalamin, and pyridoxine were inversely correlated with ejaculate volume. In fertile men, seminal plasma folate showed an inverse correlation with the DNA fragmentation index.Conclusion: Low concentrations of folate in seminal plasma may be detrimental for sperm DNA stability.<br/