Abstract
The clomiphene citrate (CC) is a first line of medicine used for ovulation induction in women worldwide. CC has good ovulation induction ability in anovulatory women but the pregnancy rate is very poor. This discrepancy might be due to the anti-estrogenic effect of CC at various level including ovary and oocytes. The hypoestrogenic conditions due to CC treatment inhibit follicular growth and development, induce susceptibility of oocytes towards apoptosis and deteriorate oocyte quality after ovulation. CC induces reactive oxygen species (ROS) mediated granulosa cells as well as oocyte apoptosis within the follicle of the ovary. Apoptosis deteriorates oocyte quality and thereby reproductive outcome. Supplementation of estradiol 17I² or natural antioxidant such as melatonin prevents anti-estrogenic effects of CC and improves oocyte quality by scavenging CC induced generation of ROS. Thus, we propose that the supplementation of estradiol 17I² and/or melatonin along with CC may be beneficial to overcome the anti-estrogenic effect of CC during infertility management in human.
Highlights
Ovary is a dynamic organ and generates excess amount of reactive oxygen species (ROS) during follicular growth, development, maturation and ovulation [1]
Clomiphene citrate (CC) is a non-steroidal ovulation-inducing drug that has been used in humans for more than 40 years [11,12]
CC treatment generates dominant follicle and results in the ovulation of metaphase-II (M-II) arrested oocytes required for successful fertilization in various assisted reproductive technology (ART) programs (Figure 1)
Summary
Ovary is a dynamic organ and generates excess amount of reactive oxygen species (ROS) during follicular growth, development, maturation and ovulation [1]. The increased level of ROS is scavenged by antioxidant systems [2]. A moderate increase of ROS could be beneficial for oocyte meiotic maturation and reproductive outcome [3,4,5]. In the absence of other reproductive problems, successful ovulation induction and good quality oocyte often restores normal fertility in human [8].
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