To estimate the efficacy of growth hormone (GH) co-treatment within an antagonist protocol in IVF/ICSI cycles in poor responders. A prospective observational study involving 50 patients underwent a standard antagonist protocol with or without GH co-treatment. GH was administered by a daily subcutaneous injection of 1,33 mg (equivalent to 4 IU) starting from day 1 of ovarian stimulation until the day of 10,000 human chorionic gonadotropin (hCG) triggering . Concentrations of GH, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) in serum and follicular fluid were the subject matter of analysis. The GH co-treatment significantly lowered the effective dose of gonadotropins, duration of stimulation, IGFBP-3 level in serum and follicular fluid on the day of oocyte retrieval. The total number of oocytes as well as the number of metaphase II stage (MII) oocytes, two pronucleus (2 pn) zygotes, good-quality transferred embryos was significantly higher in the GH þ group. Pregnancy was achieved in patients GH þ group only. Positive correlation was found between IGF-I level in follicular fluid, dynamics of IGFBP-3 level changes during stimulation protocol and the number of good-quality transferred embryos in the GH þ group. GH administration in IVF/ICSI cycles for poor responders raises ovarian sensitivity to the gonadotropin exogenous influence, increasing number of high-quality embryos and the probability of pregnancy. ARTICLE HISTORY

We report three cases of effective management of infertility in women with a history of repeated unsuccessful IVF attempts, who have developed antibodies to hCG. A novel approach to conservative treatment of immunologic reproductive failure, suggested for selected patients, included membrane plasmapheresis, combined prednisolone, and intravenous immunoglobulin therapy. No adverse side effects were observed; all cases resulted in pregnancy and subsequent life births. In order to be given an adequate efficient treatment, women with recurrent implantation failure should be suspected for autoimmune factor of infertility and its possible association with anti-hCG autoimmunity.

Of the known causes of uterine factor infertility, Ashermans syndrome or the so-called intrauterine synechia, chronic endometritis and endometrial hypoplastic processes are most often distinguished. Thin endometrial syndrome is characterized by a decrease in the thickness of the endometrium to 7 mm or less in the proliferative phase of the menstrual cycle and a multiple decrease in the frequency of embryo implantation. Numerous treatment strategies have so far been proposed for treating refractory thin endometrium syndrome. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. Single center, prospective, open-label study of efficacy of cell-based therapy in the complex treatment of thin endometrium syndrome in patients with infertility was conducted. The study involved 36 women aged 28 to 36 years, the middle age was 34.2 1.1 years. All patients included in the study received 3 cycles of intrauterine administration of a suspension of autologous stem cells isolated from bone marrow. Bone marrow was successfully aspirated from the iliac crest in all patients. Mononuclear cells was isolated by density gradient centrifugation according to the standard method. The cell material was cryopreservated and thawed immediately before administration. The procedure for intrauterine transplantation of isolated but not cultured cells was performed on the 5th7th day of the menstrual cycle. There were no significant adverse events related to harvest or administration. The thickness of the endometrium before and after treatment was 2.39 0.64 and 6.56 0.94 mm (t = 21.94, p = 0.0001), respectively. The rate of patients with an endometrial thickness of more than 7 mm after treatment was 77.8%. The effectiveness of assisted reproductive technology in patients with normal endometrial (n = 28) was 32.1%. Immunohistochemistry confirms the presence of chronic endometritis before and after treatment in 22 (61.1%) and 19 (52.8%) patients, respectively, while after treatment a significant decrease in the levels inflammatory markers was found.

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The goal of the study was to estimate the efficacy of growth hormone (GH) co-treatment to the antagonist protocol in IVF/ ICSI cycles in poor responders. A prospective observational study involved 75 patients. All patients underwent standard antagonist protocol with or without GH co-treatment. GH additional was given a daily subcutaneous injection of 1.33 mg (equivalent to 4 IU) of GH from day 1 of ovarian stimulation until the day of human chorionic gonadotropin (hCG). Concentrations of GH, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) in serum and follicular fluid were analyzed. The GH co-treatment significantly lowered effective dose of gonadotropins, duration of stimulation, IGFBP-3 level in serum and follicular fluid day of oocytes retrieval. The number of oocytes recovered, metaphase II stage (MII) oocytes, 2 pronucleus (2 pn) zygote, good-quality transferred embryos were significantly higher in the GH+ group. Only patients GH+ group became pregnant. Positive correlation was found between IGF-I level in follicular fluid, dynamics of IGFBP-3 level changes during stimulation protocol and number of good-quality transferred embryos in the GH+ group. GH administration in IVF/ICSI cycles for poor responders raises ovarian sensitivity to the gonadotropin exogenous influence, this way, increasing number of high-quality embryos and the probability of pregnancy.

BACKGROUND: According to reports, the efficiency of in vitro fertilization and intra cytoplasmic sperm injection protocols is decreased in patients positive for various autoantibodies, as opposed to autoantibody negative patients. However, there are contradictory data indicating no autoantibody effect on the outcome of infertility treatment using assisted reproductive technology. AIM: The aim of this study was to evaluate the embryological outcome and clinical efficiency of infertility treatment in in vitro fertilization and intra cytoplasmic sperm injection protocols in women in the presence of reproductively significant autoantibodies. MATERIALS AND METHODS: This prospective study enrolled 90 infertile patients undergoing assisted reproductive technology treatment. The follicular fluid obtained on the day of oocyte retrieval was evaluated for a wide autoantibody panel using commercial ELISA kits. The main group (n = 52) included women with autoantibody levels determined in the follicular fluid of more than three standard deviations from the mean values determined among all patients. The comparison group consisted of 38 women with autoantibody levels of less than three standard deviations from all subjects. The intergroup comparative analysis included clinical and anamnestic data, hormonal parameters, ovarian reserve, embryological data, and in vitro fertilization and intra cytoplasmic sperm injection efficiency. RESULTS: Reliably lower ovarian reserve parameters (anti-Mullerian hormone levels 1.9 (1.4; 4.0) vs. 3.3 (2.2; 6.5) ng/ml; p = 0.005; number of antral follicles 8.5 (6.0; 12.0) vs. 11.0 (9.0; 17.0); p = 0.003) have been noted in the main group relatively to the comparison group. The autoantibodies to thyroid peroxidase and cardiolipin content in the follicular fluid has been shown to be negatively associated with the number of two-pronuclear zygotes, the presence of autoantibodies to aromatase correlating negatively with the fertilization rate. Furthermore, the follicular fluid levels of autoantibodies to thyroid peroxidase (105 IU/ml) and cardiolipin (5.1 IU/ml) are reliably associated with a higher frequency of a suboptimal response to previous controlled ovarian stimulation, a lower incidence of high quality embryos on days 3 and 4 of in vitro cultivation, a decreased number of top-quality blastocysts, and the clinical efficiency of in vitro fertilization and intra cytoplasmic sperm injection programs. CONCLUSIONS: The presence of reproductively significant autoantibodies is an independent risk factor for reducing the total efficiency of assisted reproductive technology treatment.

Hypothesis/Aims of study: According to the number of oocytes retrieved in IVF/ICSI protocols, the ovarian response to controlled ovarian stimulation is divided into: poor (03 oocytes), suboptimal (49 oocytes), normal (1015 oocytes) and excessive (15 oocytes) response. However, the effectiveness of IVF / ICSI programs in women with a suboptimal response is poorly understood, since this cohort of patients is often fallen into the category of women with a normal response. The aim of this study was to determine the main characteristics of IVF / ICSI programs in patients with suboptimal response to be further compared to those in women with normal response to controlled ovarian stimulation. Study design, materials and methods: This retrospective study included 568 patients: 470 women with suboptimal response and 98 women with normal response to controlled ovarian stimulation. The comparative analysis comprised clinical and anamnestic data, as well as the main characteristics of assisted reproductive technology programs in the selected clinical groups. Results: It was found that patients with suboptimal response to controlled ovarian stimulation had significantly more frequent history of pelvic surgery (71.3 % vs. 55.1 %; p 0.01) and pelvic inflammatory diseases (70.9% vs. 60.2%; p 0.05). Parameters of ovarian reserve (serum anti-Mllerian hormone level and antral follicle count) in women with suboptimal response were significantly lower (p 0.001). In addition, the number of mature oocytes, 2PN zygotes, good quality embryos (p 0.001), as well as the clinical pregnancy rate in women with suboptimal response were found to be significantly lower than in patients with normal response to controlled ovarian stimulation (27.2% vs. 41.7%; p 0.01). It was noted that concomitant uterine fibroids enhanced the negative impact on the effectiveness of IVF / ICSI programs in women with suboptimal response to controlled ovarian stimulation (OR = 0.5; 95% CI: 0.30.9; p = 0.03). ROC analysis identified predictors of suboptimal response to controlled ovarian stimulation, such as serum anti-Mllerian hormone level (AUC = 0.80) with the cut-off value of 2.57 ng / ml (sensitivity 74%, specificity 75%) and antral follicle count (AUC = 0.90) with the cut-off value of 10 follicles (sensitivity 80%, specificity 94%). Conclusion: In women with suboptimal response to controlled ovarian stimulation, IVF / ICSI success rates are significantly reduced when compared to those in women with normal response. Concomitant uterine fibroids may further decrease the effectiveness of IVF / ICSI protocols in patients with suboptimal response. Predictors of suboptimal response include the serum anti-Mllerian hormone level and antral follicle count.

BACKGROUND: Mitochondria play vital roles in oocyte functions and they are critical indicators of oocyte quality which is important for fertilization and development into viable offspring. Quality-compromised oocytes in which mitochondrial dysfunction plays a significant role are correlated with infertility, developmental disorders and embryo loss. A significant role in the oocytes of cytoplasmic accumulation and a sufficient amount of the mitochondrial pool of oocytes is played by the cumulus cells surrounding it. AIM: to conduct a comparative analysis between the state of mitochondrial networks of cumulus cells and the quality of oocytes. MATERIALS AND METHODS: The study included 22 women aged 28 to 37 years inclusive (mean age 32.3 1.2 years) with tubal infertility. During the assisted reproductive technology procedures, 74 oocytes were obtained. 39 good quality oocytes and their cumulus cells were compared with 35 bad quality oocytes and their cumulus cells respectively. After puncture of ovarian follicles cumulus cells were isolated and stained with fluorescent dye for cell tracing and mitochondrial imaging in vivo. The method of confocal microscopy was used to analyze the three-dimensional organization of mitochondria in 2030 cells of one pool of follicular fluid. The following parameters were used to evaluate the mitochondrial network: fluorescence decay time and fluorescence intensity. RESULTS: The decay time of fluorescence in cumulus cells associated with a good quality oocyte was significantly higher (p = 0.032) than in the case of identification of oocytes with negative signs. CONCLUSION: The structure of mitochondrial networks in cumulus cells correlates (r = 0.76) with the quality of oocytes.