> During reproduction, the chromosomes have to line up in order for them to produce offspring.

Just to be clear, chromosomes do not line up during reproduction. They only pair during meiosis, which is the production of sperm or eggs, but not during fertilization or embryonic development (mitosis). So chromosome number has absolutely zero effect on whether two individuals can produce offspring together, but may affect the fertility of their offspring.

This confusion over when chromosome pairing happens leads to a lot of the misconceptions around chromosome number.

The two unfused chromosomes from the parent with 46 will usually both pair with the fused chromosome that came from the parent with 44. This is called a trivalent, instead of the usual bivalent that forms in meiosis. The pairing actually usually goes just fine since the genetic content is not changed and these chhromosome fusions usually involve chromosomes that only had one arm before (acrosomes). What this means is that it's not as random as all that. There is still a chance that separating the chromosomes can go wrong, but the offspring of people who've had a fusion of this type are usually not infertile, just reduced fertility sometimes. Often not even by much and many, many cases are believed to be undiagnosed since there's no "symptoms."