Is Serum Homocysteine Level Associated With Repeated Implantation Failure In IVF?

Introduction: Repeated implantation failure (RIF) is common in IVF. Frequently it remains an unsolved enigma. Vitamin B12 is involved in homocysteine metabolism, which is associated with cardiovascular risk .Data is conflicting regarding involvement of vitamin B12 and homocysteine in embryo implantation.

Aim: Is there any association between serum levels of homocysteine, vitamin B12 and RIF?

Materials and Methods: Retrospective analysis based on data recorded from files of 127 couples with RIF (≥ 3 embryo transfers without pregnancy) during 2005-2015 in our unit. As part of the screening, serum levels for vitamin B12 and homocysteine were taken. Demographic, clinical and laboratory data of all previous IVF cycles was recorded and analyzed.

Results: Mean patient`s age was 33.2±5.2 years. Mean number of prior embryo transfers and total number of embryos transferred was 4.7±1.6 and 10.7±5.2, respectively. Mean serum levels of vitamin B12 and homocysteine were 302.64±160.52 ng/ml and 8.79±3.75µM/L, respectively. Homocysteine levels inversely correlated with those of vitamin B12 (P<0.006).Both total homocysteine levels and levels above median (≥ 8.2µM/L) correlated with the number of failed embryo transfers and total number of transferred embryos (P < 0.01, P < 0.003, respectively). When homocysteine levels were divided into quartiles, levels inversely associated with patients` BMI (P < 0.05). Low (< 200ng/ml) levels of vitamin B12 were inversely associated with patients` age (P<0.008).

Conclusions: Our findings may shed new light on the roles of homocysteine in embryo implantation. If validated, it may be possible, by alleviating homocysteine levels by nutritional supplementation of vitamins to improve treatment outcome among couples with RIF.