Jamieson, Fausset and Brown on Genesis 25:21

21. Isaac entreated the Lord for his wife--Though tried in a similar way to his father, he did not follow the same crooked policy. Twenty years he continued unblessed with offspring, whose seed was to be "as the stars" [Ge 26:4]. But in answer to their mutual prayers (1Pe 3:7), Rebekah was divinely informed that she was to be the mother of twins, who should be the progenitors of two independent nations; that the descendants of the younger should be the more powerful and subdue those of the other (Ro 9:12; 2Ch 21:8).