Effect of Estrogen Priming in Antagonist Cycles in Women With Poor Response to IVF Treatment

Introduction All female follicles and oocytes are formed in ovaries in utero while metaphase stops in meiotic prophase I. The continuance of cell division depends on the completion of menstrual cycles and occurrence of fertilization (1). With age, disorders occur in the process of chromosome segregation and meiosis division, especially in meiosis I (2-4). One of the most widely used assisted reproductive techniques (ART) in case of such disorders is in vitro fertilization (IVF). IVF requires ovarian hyper-stimulation to facilitate the release of the ovum by several follicles for fertilization to occur. Endometrial implantation after fertilization is closely associated with hormonal conditions. Owing to this, the ovarian hyper-stimulation process due to follicular overgrowth and increased serum concentrations of estradiol leads to an early increase in progesterone. This could, however, lead to implantation failure (5,6). The aforesaid factors are the reasons for the failure of assisted reproductive techniques. They eventually cause patients to respond poorly to treatments and lower the success rate. Studies have shown that the rate of poor response to assisted reproductive techniques is 5.6% to 35.1% (7,8). Regardless of conflicting definitions, poor response and treatment failure finally leads to increased rates of implantation failure, less activated oocytes, a reduced number of embryos derived from IVF and lower chance of fertility compared to people with a natural response to treatment (9,10). So far, several treatments have been introduced to improve the conditions of patients with poor response among which short protocol is the most common method of treatment. According to this method, low-dose agonist or antagonist is used. In this protocol, a higher endogenous follicular stimulating hormone (FSH) level is used to increase the number of follicles. An initial FSH increase in short protocol could result in follicular growth. Abstract Objectives: Despite inconsistencies in existing studies, the results of some research studies indicate that treatment with estrogen priming and gonadotropin-releasing hormone (GnRH) antagonist look promising for poor-responder patients. Materials and Methods: The study was conducted on 2 groups of poor-responder patients under treatment with GnRH antagonist and gonadotropin. Each group had 53 patients. The treatment was performed after considering the patients’ age, the number of previously failed in-vitro fertilization (IVF), antral follicles count and mean serum level of follicular stimulating hormone (FSH3), anti-Müllerian hormone (AMH), and estradiol (E2). In the intervention group, 4 mg of estradiol valerate was administered daily from the 21st day of the cycle before IVF and continued up to the second day of the cycle. Then, stimulation was initiated with human menopausal gonadotropin (HMG) and follicle-stimulating hormone (FSH) and the GnRH antagonist was implemented on the eighth day and continued until the prescription of human chorionic gonadotropin (HCG). Results: The average number of obtained large follicles (2.9±1.8 against 2.3±1.6), M2 oocytes (3.6±0.3 against 2.8±0.3) and embryo quality type II (1.3±0.2 against 0.9±0.1) and type III (0.7±0.1 against 0.3±0.1) in the intervention group was significantly higher compared to the control group (P value was respectively 0.05, 0.05, 0.05, and 0.01). The rate of successful pregnancy was higher in the intervention group (8.3%) than in the control group (6.7%). However, it was not statistically significant (P = 0.50). Conclusions: Estrogen priming has positive effects on GnRH antagonist cycles with an increase in the number of large follicles and better quality oocytes and embryos.