The flow diagram of the study selection for the meta-analysis is illustrated in Fig. 1. A total of 3,223 studies were initially identified based on the search criteria. However, 3,159 studies were excluded as 2,364 were duplicate records; 793 studies were excluded based on title and abstract; 15 studies did not address the association between MTHFR C677T, MTHFR A1298C, MTRR A66G or MTR A2756G polymorphism and male fertility; relevant data could not be extracted from three studies; one study was a letter and one was a review article. Finally, 46 case–control studies with 20,639 participants were selected for the systematic review and meta-analysis (Fig. 1).

The flow diagram of the study selection for the systematic review

The publication years of the eligible studies ranged from 2003 to 2022. The genotyping methods varied between studies, with the most common being polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) [20, 37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68]; other methods in the 32 studies included polymerase chain reaction (PCR) (one study) [69]; competitive allele-specific PCR(one study) [70]; SnaPshot (one study) [71]; PCR combined with mass-spectrography(one study) [72]; PCR combined with DNA sequencing(four studies) [73,74,75,76] and Real-time PCR(five studies) [77,78,79,80,81]. A total of 30 articles reported participants from Asian countries [20, 37, 38, 40,41,42, 44, 45, 47, 49, 51, 54,55,56, 58,59,60,61,62,63,64,65, 67, 68, 71,72,73,74,75,76] and 16 articles reported participants from non-Asian countries [39, 43, 46, 48, 50, 52, 53, 57, 66, 69, 70, 77,78,79,80,81]. Moreover, 21 studies reported a sample size of less than 300 [20, 40, 43, 46, 48, 51,52,53,54, 57, 59, 60, 63, 65, 66, 68, 69, 75, 76, 79, 81] and 25 studies reported a sample size of 300 or more [37,38,39, 41, 42, 44, 45, 47, 49, 50, 55, 56, 58, 61, 62, 64, 67, 70,71,72,73,74, 77, 78, 80]. A detailed summary of the included studies is presented in Table 1.

Based on the NOS scores, 27 studies were assessed as low-quality (0–6 stars) [