Follicular Waves in the Human Ovary: A New Physiological Paradigm for Novel Ovarian Stimulation Protocols

Abstract

Ovulation induction (OI) is a cornerstone of human assisted reproduction treatments (ART). Current OI protocols are based on the human follicular dynamics model known as propitious moment theory (PMT), by which follicles continuously grow from the primordial pool without any pattern, and follicular fate depend on the occurrence of a gonadotropin surge. Recently, a new paradigm of human follicular dynamics called follicular waves was revealed using sequential ultrasound examination of 1 interovulatory interval. Instead of random growth, follicles develop in coordinated groups or waves, occurring 2 to 3 times during an interovulatory interval. Follicular waves are common in several other mono-ovulatory species, like equines and bovines. In fact, this model was applied to the development of several OI protocols in veterinary medicine, especially in cows. It has been shown that synchronization of OI with the emergence of a follicular wave increases substantially success rates in animals, even with single embryo transfer. Veterinarians have already developed mechanisms to control wave emergence through mechanical or chemical ablation of the dominant follicle or corpus luteum. Considering the follicular dynamics similarities between humans and bovines regarding the follicular wave phenomenon, we hypothesize that synchronization of follicular wave emergence with ovarian stimulation produces more competent oocytes and embryos and will enhance ART efficiency in humans. At the end of this article, we propose 2 theoretical approaches to induce the emergence of a follicular wave in women: (1) a mechanical strategy by aspiration of the dominant follicle and (2) a pharmacological strategy by administering estradiol and progesterone.