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.
The rate of infertility in married couples of reproductive age in this country makes up from 10 to 15%, in some regions this value is close to 20% - acritical level that has a negative impact on demographic figures. The rate of pregnancy depends directly on the women’s age and decreases by 3.3times starting from the age of 19 and by the age of 48. The decrease in the ability to conceive is accounted for by subtle mechanisms related to thedeterioration of the quality of oocytes. The patients who are prepared for an extracorporeal fertilization program (ECF) and do not respond tocontrolled ovarian hyperstimulation protocols are considered to be poor respondents. Many studies focused on the development of an optimaltreatment method. However, none of the approaches seems to be effective enough to guarantee a successful use. Platelet-rich plasma is a new andpromising method that is successfully used in the reproductive science to solve a number of medical problems. All the patients whose commonfeatures were low oocyte output and poor embryo quality as well as failed ECF attempts were offered a treatment method of autologous PRP therapyafter their written consent. Three months later, one obtained astonishing results, which by the markers of biochemical infertility alone could beclassified as a complete biological phenomenon and are also characterized by improved embryo quality. The results of hormonal homeostasis show adecrease in the level of the follicle-stimulating hormone by 67.33% while the level of the anti-muellerian hormone is 75.18% higher.Thus, the use of the PRP therapy in poor respondents helps them to overcome their problematic reproductive barrier.
The mother's older reproductive age is an important social and clinical issue. Currently, the proportion of women who postpone childbirth until the end of the 3rd - beginning of the 4th decade of life has increased significantly, especially in Western societies. The success rate of in vitro fertilization (IVF) decreases significantly when women enter the 5th decade of life. The aim of the research: to determine the features of infertility and its treatment by ART methods in women of older reproductive age. Materials. An analysis of 658 patient histories of IVF programs for 2015-2019. Given the purpose and objectives of our research for further analysis, we divided patients into 2 groups: the main group - 333 women aged 35 and over and the control group - 325 women under 35 years. Additionally, in the main group there were 2 subgroups: the first - 199 women aged 35-39 years, the second - 124 women over 40 years. Results. There is a tendency to a gradual increase in the share of older women who want to become mothers: in 2019 the share of women aged 35 and over increased by 6.1% compared to 2015 (from 47.6% to 53.7%), the share of the oldest age group over 40 years is also growing (from 18.3% in 2015 to 21.6% in 2019), and the total share of such patients is quite significant (on average 20.4% in 5 years, which even higher than patients under 30 years of age - 18.5%), which corresponds to the global trend of «delayed motherhood». In recent years, intraplasmic sperm injection (ICSI) has been the most frequently used among ART methods in both the main and control groups: 42.2% in the main group and 47.7% in the control group (p> 0.05), with the share of the oldest women age group was significantly lower than in the control (38.7%, p <0.05). Women in the assisted reproductive technology (ART) programs of the older age group were much more likely to be forced to use oocyte donation (14.2% vs. 3.7% under 35 years of age). After 40 years, this method of ART was used by almost a quarter of patients (23.4%). The analysis revealed a significant discrepancy in the distribution of the etiology of infertility: if in the control the largest share fell on a combination of factors (31.1%) and tubal factor (25.2%), then half (48.0%) of older women are classified in the subgroup «only another female factor», which includes endocrinological disorders, ovarian insufficiency and others. After the age of 35 and 40, the share of women with primary infertility decreases (34.1% and 27.4% against 48.0% under the age of 35) and the share of those who suffer from infertility for more than 5 years increases. Decreased ovarian reserve was diagnosed in 48.0% of patients after 35 years, after 40 years this figure reaches 57.3%, which corresponds to the rates of increase in follicle-stimulating hormone and decrease in anti-mullerian hormone relative to age. A quarter (24.0%) of women over the age of 35 have already had one failed IVF attempt, and 12.6% had 2 or more attempts. After 40 years, the proportion of women with at least two IVF attempts increases to 16.9%. After 35 years, the share of clinical pregnancies per started cycle (30.0% vs. 39.1%) and live births (21.1% vs. 30.2%) significantly decreases. After 40 years, these 2 indicators fall sharply and are 21.8% and 13.7%. Conclusions. Given the increase in the proportion of women who resort to ART in older reproductive age, as well as a number of factors that worsen the prognosis of ART, among which the reduction of ovarian reserve is the least controlled, it is important to find methods to optimize approaches to preparing patients of late reproductive age quality mature oocytes.
Purpose - to determine medical and social features of patients of late reproductive age with reduced ovarian reserve. Materials and methods. 130 patients with assisted reproductive technologies (ART) programs were divided into groups according to POSEIDON criteria. The main group of 80 patients of older reproductive age (35 years and older) is divided into 2 subgroups according to the POSEIDON criteria. Subgroup 1 consisted of 34 women with a predicted poor response to controlled ovarian stimulation (COS) - group 4 according to POSEIDON. Subgroup 2 - 46 patients with a predicted normal response to COS (POSEIDON group 2). The comparison group consisted of 50 patients under 35 years of age with a predicted normal response to COS (POSEIDON group 1). The quality of life was assessed according to the FertiQoL questionnaire, the presence and degree of depression according to the method of V. Zung. Results. The share of women aged 40 and older among patients with ART programs with a predicted poor response to COS is 3 times higher than the predicted normal respondents (32.4% vs. 10.9%), which reflects the decisive role of women’s age in reducing ovarian reserve. A significant proportion of women in this category report such a bad habit as smoking (17.6%), the third - a sedentary lifestyle (32.4%) and stress (29.4%), 26.5% - a violation of the daily routine and work. Problems with reproduction affect the quality of life of women and cause psychological changes. More than a third of women (35.3%) rate their health as poor and very poor, and more than half (53.0%) are dissatisfied with their quality of life. The emotional sphere suffers the most from fertility problems (score - 45.3±2.2), and the assessment of mental and physical health and social functioning is reduced. Although patients appreciate the quality of treatment, its tolerability is worse in these women. At the same time, the psychological state of half of women is assessed as subdepressive or masked depression (52.9%), and depression was diagnosed in 14.7% of respondents. Conclusions. Established medical and social characteristics of women of late reproductive age with reduced ovarian reserve (smoking, daily and work disorders, sedentary lifestyle, stress, low quality of life, subdepressive and depressed state) indicate the need for additional inclusion in ART training programs lifestyle and methods of psychocorrection. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Keywords: infertility, older reproductive age, reduced ovarian reserve, assisted reproductive technologies, quality of life, depression.
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