We show that a high key rate of Measurement-Device-Independent Quantum Key Distribution (MDIQKD) over asymmetric and unstable quantum channel can be obtained by full optimization and compensation. Employing a gradient optimization method, we make the full optimization taking both the global optimization for the 12 independent parameters and the joint constraints for statistical fluctuations. We present a loss-compensation method by monitoring the channel loss for an unstable channel. The numerical simulation shows that the method can produce high key rate for both the asymmetric channel and the unstable channel. Compared with the existing results of independent constraints, our result here improves the key rate by 1 to tens of times in typical experimental conditions.
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