Hormonal and genetic causes of poor response to controlled ovarian stimulation in women of late reproductive age

Abstract

Objectives: to investigate the hormonal and genetic determinants of the poor response to controlled ovarian stimulation (COS) in women of late reproductive age. Materials and methods. 130 patients from assisted reproductive technology programs were examined. The main group of 80 older reproductive aged patients (35 years and older) was divided into 2 subgroups according to the POSEIDON criteria. Subgroup 1 included 34 women with a predicted poor response to COS, subgroup 2 – 46 patients with a predicted normal response to COS. The comparison group consisted of 50 patients under the age of 35 with a predicted normal response to COS. The pituitary hormones (luteinizing, follicle-stimulating hormones, prolactin), steroid hormones (testosterone, estradiol, progesterone), cortisol, anti-Mullerian hormone (AMH) and inhibin B values was determined in blood serum by the ELISA. Blood was taken on the third day of the menstrual cycle. A molecular genetic study of FSHR gene polymorphism (Ala307Thr, Ser680Asn) was performed. Results. AMH decrease, estradiol increase and inhibin B decrease in potentially poor responders to COS may be an additional indication of reduced ovarian reserve. The level of follicle-stimulating hormone increases with age, but does not have high specificity as a marker of ovarian reserve. Elevated levels of cortisol emphasize its role in reproduction and correspond to increased stress value. The effectiveness of IVF if there were 4 or more mature oocytes obtained is associated with higher levels of AMH and inhibin B, and lower estradiol and cortisol values. The multifaceted dependence of the COC effectiveness in women of older reproductive age on the parameters of the hormonal profile, confirmed by correlation analysis, reflects the complexity of the reproductive function implementation with the use of auxiliary reproductive technologies in such patients. The combination of AA/SS genotypes for the Thr307Ala and Asn680Ser polymorphisms of the FSHR gene can be an additional marker of COC inefficiency. Conclusions. Determination of the hormones levels (inhibin B, estradiol and cortisol), the study of Thr307Ala and Asn680Ser polymorphisms of the FSHR gene can provide additional information for predicting the response to COS in women of older reproductive age.

Keywords

• infertility
• older reproductive age
• poor response to controlled ovarian stimulation
• hormones
• thr307ala and asn680ser polymorphisms of the fshr gene