John Calvin Commentary Genesis 25:21

"And Isaac entreated Jehovah for his wife, because she was barren. And Jehovah was entreated of him, and Rebekah his wife conceived." — Genesis 25:21 (ASV)

And Isaac entreated the Lord for his wife. Some translate the passage, Isaac entreated the Lord in the presence of his wife, and understand this to have been done so that she also might add her prayers, and they might jointly supplicate God. But the version given here is simpler.

Moreover, this resort to prayer testifies that Isaac knew he was deprived of children because God had not blessed him. He also knew that fruitfulness was a special gift of God. For although the favor of obtaining offspring was widely spread throughout the whole human race, when God uttered the words increase and multiply, yet to show that humans are not born fortuitously, He distributes this power of production in various degrees.

Isaac, therefore, acknowledges that the blessing, which was not at human disposal, must be sought from God by prayer. It now truly appears that he was endowed with no ordinary constancy of faith. Since the covenant of God was known to him, he earnestly (if ever anyone did) desired seed.

Therefore, it was not now for the first time that it entered his mind to pray, since for more than twenty years he had been disappointed in his hope. Thus, although Moses, only in a brief statement, says that he had obtained offspring by his prayers to God, yet reason dictates that these prayers had continued through many years.

The patience of the holy man is evident here: while he seems to pour out his wishes into the air in vain, he still does not lessen the ardor of his devotion. And as Isaac teaches us by his example to persevere in prayer, so God also shows that He never turns a deaf ear to the wishes of His faithful people, although He may long delay the answer.