Molecular Predictors of Effective Implantation and Live Birth in IVF Programs

The aim of the study was to improve the possibilities of predicting blastocyst implantation and live birth of ART programs in women of late reproductive age with tubal-peritoneal infertility based on immunohistochemical markers of the endometrium. Methods and Results: The results of IVF and IVF/ICSI programs were analyzed in 68 patients of late reproductive age (36-44 years of age) with tubal-peritoneal factor of infertility. Morphological examination of the endometrium was performed on Day 7 after confirmed ovulation in the cycle preceding ART. The expression of vitamin D receptors (VDR) and HOXA11 in endometrial stromal cells was assessed by immunohistochemical method. The effectiveness of using the endometrial markers VDR and HOXA11 as potential predictors of ART programs efficiency was confirmed by prognostic models. The levels of the stromal expression of VDR<8.7% and HOXA11<6.1% (probability >0.27) were determined to be favorable for successful blastocyst implantation. The expression levels of VDR<8.3% and HOXA11<6.1% in endometrial stromal cells are prognostically favorable for live birth (probability >0.19) in women of late reproductive age with tubal-peritoneal infertility who undergoing ART treatment with their own oocytes.

HIV Continuum of Care Among People Who Inject Drugs in Iran

Background:People who inject drugs (PWID) are at higher risk for HIV and may have lower access to care and treatment services when infected. We aimed to assess the HIV continuum of care among PWID in Iran. Methods:We collected data from 2,663 PWIDwho self-reported injection drug use at least once during the past 12 months. They were recruited via respondent-driven sampling to a national bio-behavioral surveillance survey from 11 cities of Iran between June 2019 and March 2020. For participants who were tested positive for HIV in the survey, we asked questions to calculate the proportionwho were 1) aware of their HIV status, 2) linkage to HIV care, 3) initiated an HIV treatment anti-retroviral therapy (ART), 4) retention on ART and 5) virally suppressed (< 1000 copies/mL).Results:Out of 95 PWID were tested positive for HIV, 100% (95% Confidence Intervals (CI): 96,100%) reported that they were aware of their HIV positive status, 57% (95% CI: 46, 66%) were linked to an HIV care service and initiated ART, 49% (95% CI: 39, 59%) retained on ART and only 15% (95% CI: 8, 23%) had viral load less than 1000 cp/ml.Conclusion:Our results indicated that about half of the PWID diagnosed with HIVever started ART, and less than one in six were virally suppressed.Strategies to improve linkage to ART programs, and to improve ART retention and adherence may improve HIV care outcomes among PWID in Iran.

Optimization of the sperm processing protocol for subsequent molecular cytogenetic studies

One of the causes of spontaneous pregnancy termination, infertility, and birth of children with development delay and malformations are chromosomal abnormalities (CA) as well as spontaneous aneuploidies in gametes of phenotypically normal parents. Often couples with reproductive problems, as well as spouses one of whom is a carrier of CA, turn to the programs of assisted reproductive technologies (ART) for preimplantation evaluation of the zygote chromosomal status. As part of ART programs, parental gametes are examined to assess the level of spontaneous aneuploidy. As a rule, the most accessible material for analysis is the ejaculate. Fluorescent in situ hybridization (FISH) is used to examine male gametes obtained from the ejaculate. However, this FISH-analysis has a number of limitations and difficulties because of the peculiarities of the sperm head structure, namely the supercondensed state of chromosome chromatin. In order to optimize the FISH protocol, five different protocols were used for pre-hybridization processing of ejaculate samples obtained from nine phenotypically normal men. A comparative analysis of hybridization efficiency showed that the protocol using tris(2-carboxyethyl)phosphine hydrochloride (TCEP) as a decondensation agent was the most effective for subsequent molecular cytogenetic studies. The developed hybrid protocol combining proteolytic pretreatment, TCEP and thermal decondensation can be used when other protocols for pre-hybridization treatment of ejaculate preparations are not effective.

Correlation analysis of clinical and medical history records of married couples receiving infertility treatment

Introduction. Despite the availability of general principles and regimens for ovarian stimulation on the assisted reproductive technology (ART) programs, an individual situational modification is required in each specific case.Objective. To optimize the ovarian stimulation protocols on the ART program based on the clinical and medical history records of the married couple.Materials and methods.The clinical and medical history records, as well as the stimulation cycle parameters of 60 married couples were analysed. The married couples enrolled in this study were diagnosed with infertility caused by tubo-peritoneal (44 married couples), male (5 married couples), combined factor (6 married couples), as well as external genital endometriosis combined with a male factor (3 married couples), and tubo-peritoneal factor (2 married couples). All married couples underwent IVF/ICSI procedures under the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and ovarian stimulation on day 2 or 3 of the menstrual cycle.Results. All married couples were divided into two groups: 38 couples with a negative implantation result and 20 married couples with positive implantation results. The surgical removal of fallopian tubes has been shown to be inversely correlated with the duration of infertility. The use of hCG positively correlates to the ratio of mature oocytes and oocyte-cumulus complexes (OCC) and the onset of pregnancy. A reduced percentage of morphologically healthy sperm with an overall high concentration of sperm in the ejaculate can be interpreted as fertile sperm.Conclusions. During ovarian stimulation on the ART program, special attention should be paid to the duration of stimulation, the types of interventions for triggering final oocyte maturation and the total gonadotropin dose. A differentiated approach to conducting the surgical removal of fallopian tubes is required. The reduced percentage of morphologically healthy sperm with an overall high concentration of sperm in the ejaculate serves as a favourable prognostic factor for the outcome of ART programs.

ENDOMETRIAL RECEPTIVITY AS THE KEY TO THE SUCCESS OF ART PROGRAMS: A LITERATURE REVIEW

Relevance: To date, the success of in vitro fertilization (IVF) programs in Kazakhstan is 38%. The purpose of the study was to evaluate the mechanisms of influence of various risk factors on endometrial receptivity in women in IVF programs. Materials and Methods: This review was based on a search conducted for domestic and foreign publications available in Russian and international search systems (PubMed, eLibrary) for the past 25 years. Results: Chronic endometritis is a verified cause of impaired receptivity. Many studies have proven the beneficial effect of complex empirical treatment using antibacterial, anti-inflammatory, hormonal therapy with transdermal forms of estrogens and vitamin therapy on the outcome of IVF. Conclusion: The problem of recurrent implantation disorders in IVF programs is multifactorial. Women with unrealized reproductive function require rehabilitation after an unsuccessful fertilization attempt to prevent disorders of homeostasis and ensure adequate pain relief during transvaginal puncture of ovarian follicles. In addition to hormone therapy with transdermal forms of estradiol, complex rehabilitation measures shall include immunomodulatory therapy, psychotherapy, and vitamin therapy.

Features of pregnancy and delivery course in women after programs of assisted reproductive technologies

Objective. To study the features of the course of pregnancy and childbirth in women after ART programs. Medical care for families with infertility, in particular through assisted reproductive technologies (ART) programs, is an important area of comprehensive government policy to promote fertility. Materials and methods. The retrospective study was carried out on the basis of GBUZ TO Perinatal Center, Tyumen. We analyzed 237 birth histories of women whose pregnancies occurred with the use of ART and 237 birth histories of patients whose pregnancies occurred on their own. The material for the study was the birth histories of patients. Results. The results showed a higher incidence of pregnancy complications in women after ART programs. Thus, a higher number of premature births, placental disorders, isthmic-cervical insufficiency (ICI) were noted, as well as a significantly higher percentage of operative delivery by cesarean section. Conclusions. The presence of an initially large "baggage" of concomitant and gynecological diseases in infertile patients, whose pregnancies occurred with the use of ART programs, leads to a higher percentage of pregnancy complications and a high number of surgical deliveries.

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.

The birth of a healthy child in the assisted reproductive technologies program after autologous co-culture of embryo with cumulus cells and a new CAT transfer technology. Case report

Cumulus cells are essential during oocytes growth and development, as well as during their maturation and fertilization. Research results have shown that embryo co-cultivation with autologous cumulus cells increases the frequency of blastocyst formation, and also improves the effectiveness of ART programs. Embryo transfer in such programs is recommended to be carried out using the CAT technology (Cumulus-Aided embryo Transfer), which includes embryo cultivation on a layer of cumulus cells and embryo transfer with a certain amount of diluted cumulus cells. Patient G., 38 years old, came to the department with infertility for 15 years and recurrent implantation failure in history. The patient had ART program with autologous co-cultivation of embryos with cumulus cells and a new CAT transfer technology. The patient fell pregnant and gave birth to a healthy child. Autologous cumulus cells can be a source of biologically active substances and improve embryological parameters and implantation rate in ART programs. Embryo co-cultivation with cumulus cells is especially important for patients with recurrent implantation failure. This technique can become an alternative for optimizing human embryos culturing.