ANALYSIS OF CHANGES IN ELECTROLYTE PARAMETERS IN WOMEN DURING IN VITRO FERTILIZATION PROGRAM

Aim of the research. To determine the concentration of basic plasma electrolytes in women in in vitro fertilization program who received more individualized medication correction on the basis of determination the clinical and pathogenetic role of disorders of the neuroendocrine regulation of water-salt metabolism, as well as to study data of the modern methods of prevention and correction of electrolyte disorders. Research materials. 110 patients in vitro fertilization program were examined. Conclusions. Thus, when using standard protocols for ovulation stimulation in in vitro fertilization program patients are more prone to have potassium and sodium imbalance. Ovarian hyperstimulation syndrome was detected only in patients of the main group with the standard ovulation induction protocols. This syndrome was not observed in patients receiving the combination therapy.

Comparative characteristics of patients with infertility when applying melatonin in complex preparation for assisted reproductive technologies

Оbjective of the study was to conduct a retrospective comparative characterization of patients with infertility who took or did not take melatonin with assisted reproductive technologies (ART).Materials and methods. In our study, we examined 89 women. The first (control) group included 13 healthy women oocyte donors who got pregnant on their own and gave birth to their own healthy children, the second group - 33 patients with infertility, who took 3 mg of the preparation "Vita-melatonin" produced by "Kyiv Vitamin Plant" at the same time before bedtime, two weeks before and during ovulation stimulation, the third group - 43 patients with infertility who did not take melatonin preparation before and during ovulation stimulation. There were no women who worked night shifts among the patients. Medical documentation of women of the control group and those with infertility, data of gynecological, ultrasound examination, hormones blood were analyzed. Ultrasound examination of the pelvic organs was performed on all patients with the device "Mindray DC-80 X-Insight", and measurements were performed using a transvaginal sensor. The thickness and structure of the endometrium were evaluated, and the number of antral follicles (NAF) ranging in size from 2 to 10 mm was counted in each ovary. All patients were tested for serum levels of the anti-mullerian hormone (AMG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), progesterone (P), thyroid-stimulating hormone (TSH), triiodothyronine (T4).Results. The average age of women in the first (control) group was 27.08 ± 12.38 years, the second (taking melatonin) - 33.12 ± 8.18 years, the third (not taking melatonin) - 30.95 ± 7.07 years > 0.05), i. e. the age of the patients of the examined groups was equal. It should be noted that in the studied patients of both groups, the occurrence of primary infertility exceeded secondary infertility 2.7 times in the second group (p < 0.05) and 1.7 times in the third (p < 0.05). Infertility factors such as reduced ovarian reserve, habitual miscarriage and infertility of unknown origin were more common in patients of the second group, and endometriosis, tubal factor and male factor in the third, although the difference was not significant. The available extragenital pathology did not differ in the patients of the examined groups. The number of antral follicles was significantly higher in both ovaries of women in the control group compared with patients of the second and third groups. While the thickness of the endometrium did not differ significantly in groups, although in women of the control group it was slightly less. Regarding the study of hormonal status, it should be noted that we did not find a significant difference in the levels of hormones in the blood of women we examined. Exceptionally, there was a significant difference (p < 0.001) in progesterone content between the second (0.62 ± 0.052 nmol/l) and third (181.63 ± 13.87 nmol/l) groups. Also, the patients of the third group had significantly (p < 0.05) higher levels of FSH in blood (8.25 ± 0.63 mUn/ml) compared with the control group (4.93 ± 0.69 mUn/ml).Conclusions. The examined women in the control group, as well as infertility patients who received melatonin two weeks before the expected menstruation and during ovulation stimulation, and infertility patients who did not receive this preparation in similar programs, did not differ in age, occurrence of primary and secondary infertility, the factor that led to infertility, concomitant extragenital pathology, ovarian reserve and hormone levels of the reproductive panel. That is, they were equal in our study.

Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study

Protocols utilizing gonadotropin-releasing hormone (GnRH) antagonists have emerged as mainstream procedures for ovarian stimulation; however, GnRH increases the risk for periodic cancellation of embryos. Therefore, this study aimed to compare the pregnancy outcomes of a fixed GnRH antagonist protocol and a flexible progestin-primed ovarian stimulation (fPPOS) protocol in patients with asynchronous follicular development during controlled ovulation stimulation and to explore the feasibility of converting patients undergoing a fixed GnRH antagonist protocol to an fPPOS protocol. This was the first retrospective study exploring the fPPOS protocol in patients with asynchronous follicular development, and it was conducted in a public reproductive medicine center from January to December 2020. We included infertile women. All participants were scheduled to undergo administration of a GnRH antagonist on the fifth day of controlled ovulation stimulation. The study group included 129 women who were converted from the fixed GnRH antagonist protocol to the fPPOS protocol for their asynchronous follicular development, while the antagonist group consisted of 258 women (ratio 1:2) who proceeded with a fixed GnRH antagonist protocol. On the second or third day of the menstrual period, 100–300 IU/day gonadotropin injections were administered. For patients who were converted to the fPPOS protocol, medroxyprogesterone acetate tablets at 10 mg/day were started on the fifth day of stimulation or when only one leading follicle reached 14 mm and the other follicles were ≤10 mm in diameter, whichever came first. The rates of embryo implantation, clinical pregnancy, and early pregnancy loss were obtained. The number of oocytes retrieved and the number of high-quality embryos in the antagonist group were significantly higher than those in the fPPOS group (P = 0.039 and P = 0.025, respectively). No significant differences in the rates of embryo implantation, clinical pregnancy, and early pregnancy loss were observed between the two groups. Our study found that in patients who were scheduled for administration of GnRH antagonists but presented with asynchronous follicular development on the fifth stimulation day, it was feasible to switch to the fPPOS protocol.

The level of melatonin in the blood and follicular fluid in women with infertility in the program of assisted reproductive technologies and the effectiveness of its application

Objective was to investigate the level of melatonin in the blood and follicular fluid in women treated with infertility by ART method and evaluate the effectiveness of melatonin in their preparation for programs.Material and methods. 89 women were examined. The first (control) group included 13 healthy women oocyte donors who gave birth to their own healthy children, the second group - 33 women with infertility, who two weeks before and during ovulation stimulation were taken simultaneously at the same time before bedtime 3 mg of the drug "Vita-melatonin" produced by "Kyiv Vitamin Plant", the third group - 43 women with infertility who did not take the drug melatonin during ovulation stimulation. ELISA (Germany) reagent kits were used to determine melatonin levels. Melatonin levels were determined in blood plasma, and follicular fluid obtained during the puncture at 9:00 am.Results. The level of melatonin in the blood of female donor oocytes was 130.85 ± 16.91 pg/ml. This rate in the blood of women who used the drug melatonin before and during ovulation stimulation was significantly higher than in the blood of women who did not take the drug (respectively, 143.06 ± 14.87 pg/ml and 123.40 ± 12.65 pg / ml, p <0.05), and in the follicular fluid there was an inverse relationship: the level of melatonin in women of the first group was 97.15 ± 8.69 pg / ml, the second group - 39.46 ± 4.52 pg/ml, which is significantly less (p <0.05), the third group - 62.34 ± 3.94 pg / ml, which is almost twice more (p <0.05) compared with women who took melatonin, but less (p <0.05) compared with the first group. The frequency of pregnancy on transfer in patients of the first group was 80.0 ± 11.01%, in women of the second group probably less - 60.6 ± 8.25% (p <0.05), but also probably higher compared to women in the third group - 45.0 ± 7.62% (p <0.05). A similar pattern was observed by us on the onset of pregnancy in general: in the first group - 100.0%, in the second - 68.9 ± 8.05% (p <0.05), in the third - 60.5 ± 7.47% (p> 0.05).Conclusions. The low level of melatonin in the follicular fluid obtained by us in women who underwent ovulation stimulation in ART programs in the treatment of infertility requires further scientific interpretation. At the same time, the best results of pregnancy in women in ART programs who took melatonin in preparation are encouraging.

Combination of pioglitazone and clomiphene citrate versus clomiphene citrate alone for infertile women with the polycystic ovarian syndrome

Background Anovulation is one of the common causes of infertility. Polycystic ovary syndrome (PCOS) is the most common disorder with chronic Anovulation. To the best of our knowledge, insulin resistance relates significantly to PCOS. Therefore administration of insulin-sensitizing drugs such as pioglitazone can be used for ovulation stimulation in PCO patients. Methods After obtaining approval from the Ethics Committee of Mashhad University of Medical Sciences, 61 patients with PCOS were enrolled in the study based on inclusion/ exclusion criteria. Patients were divided into two groups. The first group received 30 mg (mg) of pioglitazone daily from the second day of the menstrual period. The second one received a placebo. 150 mg clomiphene citrate was administered from the third to the seventh day of the menstrual cycle. Vaginal sonography was performed in all women, and in cases with the mature follicle, intrauterine insemination was conducted after human chorionic gonadotropin injection. Ovary stimulation and pregnancy rate were compared between groups. Results There were no differences between groups regard to demographic characteristics and infertility type. Body mass index was higher in the pioglitazone group (28.3 ± 3.8 versus 26.2 ± 3.5, P value = 0.047). The size of the follicle was not significantly different between groups (2.2 ± 1.4 versus 1.3 ± 1.1, P value = 0.742). pregnancy rate [4 (12.9%) versus 4 (13.3%), P value = 1] had no differences between groups. Conclusion Although the number of follicles was higher in the pioglitazone group, our study showed no differences in ovary stimulation and pregnancy rate.

A flexible short protocol in women with poor ovarian response over 40 years old

Background Ovarian responsiveness to controlled ovarian stimulation is essential for a successful clinical outcome in assisted reproductive technology (ART) cycles. We aimed to find a suitable new ovulation stimulation protocol for poor ovarian response (POR) patients over 40 years old. Methods A retrospective analysis of 488 ART cycles was evaluated from January 2015 to June 2019. Comparisons were made between the flexible short protocol (FSP), routine short protocol and mild stimulation protocol. Results Compared with the routine short protocol, the FSP delayed the gonadotropin start time and reduced the total gonadotropin dose per stimulation cycle. At the same time, compared with the mild stimulation protocol, the FSP improved oocyte quality and embryo quality and improved embryo implantation potential after transfer. Furthermore, the use of the FSP reduced the probability of premature ovulation, as it inhibited the premature luteinizing hormone (LH) surge to a certain extent. Conclusions The FSP yielded better outcomes than other protocols for patients with POR over 40 years old in our study. However, further prospective studies are needed to provide more substantial evidence and to determine whether the FSP can be successful for both patients over 40 years group and younger POR patients.

Effectiveness of Letrozole and Human Chorionic Gonadotropin Injection in Ovulation Induction: A Cohort Study

Introduction: Ovulation stimulation followed by timed intercourse or Intrauterine Insemination (IUI) is widely used for treatment of anovulatory infertility. Aim: To compare the effectiveness of Letrozole (LE) alone versus LE and human chorionic gonadotropin injection in ovulation induction and pregnancy rates in women undergoing ovulation induction/follicular tracking in Enugu, Nigeria. Materials and Methods: The longitudinal cohort study was carried out in University of Nigeria Teaching Hospital and Livingston Specialist Gynaecological Hospital in Enugu, Nigeria. Study population were women coming for ovulation stimulation/follicular tracking. Ovulation was confirmed by ultrasound evidence of ovulation with a progesterone level of greater or equal to 25 nmol/L on day 21, positive pregnancy test/ultrasound detection of a gestational sac. Patients were consecutively assigned to group A or B. Group A received LE only for the induction while group B received 10000 IU of human chorionic gonadotropin injection in addition to LE. A total of 5 mg of LE was given daily from day 3 to day 7. The primary outcome measured was the number of ruptured/crenated follicles on either arm while the secondary outcomes were the number of Luteinised Unruptured Follicles (LUF) and pregnancy rates. The Statistical analysis was performed using the Statistical Package for the Social Sciences version 21.0 software (SPSS Inc., Chicago, IL, United States). Results: A total of 50 women were in each arm of the study. There was no significant difference in age and parity between the two arms. There was no significance difference between the period of infertility and the number of the previous cycles of ovulation stimulation. (p=0.444 and 0.526, respectively). Ovulation was significantly associated with HCG injection (p=0.001). However, there was no statistical significance between both arms regarding the number of LUF (p=0.216). HCG injection was significantly associated with pregnancy. Subjects who took HCG injection were over two times more likely to become pregnant than those without HCG injection (OR=2.488, 95% CI for OR=1.057-5.857, p=0.037). Conclusion: This study showed that both the ovulation rate and pregnancy rate are significantly improved when human chorionic gonadotrophin injection is given after ovarian stimulation.

The effect of hormone therapy on the condition of the mammary glands in women with menstrual disorders of endocrine origin

The objective: to study the effect of stimulating hormone therapy on the condition of the mammary glands depending on the initial endocrine status of women with menstrual disorders in the background and after ovulation stimulation.Materials and methods. The study selected a group of 130 patients (n=130) of reproductive age (mean age 27±2,3 years), which by the nature of menstrual disorders are divided into 2 subgroups: 1 subgroup (n=57) – women with regular menstrual rhythm and insufficiency of the luteal phase (ILP), 2 subgroup (n=73) – women with secondary amenorrhea and oligomenorrhea on the background of chronic anovulation. All patients complained of no pregnancy for an average of 4±1,2 years. After a comprehensive assessment of the reproductive system and hormone-dependent organs, women received the proposed treatment with estrogen-progestogen drug, bromocriptine and ovulation stimulation with clomifene citrate.Results. During the preparatory (diagnostic) phase of the study it was found that in 1 subgroup in 89,5% of patients with concomitant diseases of the pelvic organs and only endocrine disorders of the ILP type in 10,5%. In women of 2 subgroup, the frequency of combined pathology was 23,3%, and endocrine disorders – 76,7%. These results confirmed the need for laparoscopic and hysteroscopic examination of all patients with infertility in addressing the issue of ovulation stimulation. After short cycles (3 months) of monophasic estrogen-progestogen therapy, 31,6% of patients with ILP and 17,1% with anovulation had a positive effect on reducing the incidence of pain in the mammary glands, with the most sensitive to therapy were patients with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components. When resuming biphasic ovulatory cycles with clomifene citrate stimulation, only 5,7% of women complained of breast pain during the first 1–2 cycles. No additional foci in the subgroups were detected, and previously diagnosed fibroadenomas did not increase.Conclusion. Analyzing the obtained data, a positive effect of different types of hormone therapy on the condition of the mammary glands in patients with menstrual and reproductive dysfunction, in particular with diffuse forms of fibrocystic disease with a predominance of cystic and glandular components, is structures most sensitive to normal progesterone levels. Despite the lack of negative dynamics on the background of ovulation stimulation and restoration of normal mammary gland structure after therapy in women with menstrual disorders of endocrine origin, menstrual cycle regulation and dynamic monitoring of the mammary glands are shown to prevent the development of hyperplastic processes.