The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway

Abstract

Graphical abstract Abstract This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare’s serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries. Lay summary Today, approximately 10–15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman’s body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman’s menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.