Mehmet Cincik

Background: Infertility is increasingly recognized as a significant global public health concern. A thorough understanding of the diverse causes of infertility and their influence on treatment outcomes is essential for optimizing therapeutic strategies and improving success rates. Methods: In this study, we analyzed data from 9132 couples who underwent IVF treatment at a fertility center in Istanbul, Turkey, between 2010 and 2020. Results: Female factor infertility was the most prevalent among all participants (35.4%), followed by male infertility (26.4%), combined infertility (22.3%), and unexplained infertility (15.8%). Diminished ovarian reserve was found to be the most common indication in the female and combined infertility groups. Embryo transfer (ET) was performed in 7485 cases. Within this cohort, the antral follicle count was higher in the combined and unexplained infertility groups compared with the female and male infertility groups. The highest number of MII oocytes was found in the unexplained infertility group. Pregnancy rates varied significantly across groups, being higher in the male infertility and unexplained infertility groups than in the female infertility and combined infertility groups. Live birth rates also varied significantly across groups. The highest rate was observed in the unexplained infertility group. Conclusions: The distribution of infertility etiologies and their association with ICSI outcomes underscore the necessity to enhance the efficacy of ART protocols and to adopt evidence-based approaches to treatment strategies. Female factor infertility remains a significant clinical challenge, whereas unexplained infertility presents relatively favorable outcomes.

The chemotherapeutic combination of bleomycin, etoposide, and cisplatin (BEP) is well-documented to exert gonadotoxic effects, ultimately leading to impaired fertility. This experimental rat study investigated the potential protective role of repeated medical ozone therapy in mitigating the deleterious effects of BEP treatment in male rats. Thirty-two adult male Sprague Dawley rats were randomly assigned to four groups: (i) a healthy control group, (ii) a group receiving injections of the BEP regimen over nine weeks, (iii) a group receiving the same BEP regimen plus medical ozone (1 mg/kg IP) twice weekly, and (iv) a group receiving only ozone therapy. BEP treatment significantly reduced sperm concentration and increased morphological abnormalities, both of which were partially restored by ozone co-administration. Ozone therapy also elevated testosterone and thyroid-stimulating hormone (TSH) levels when co-administered with BEP compared to BEP treatment alone. Oxidative stress analysis demonstrated that total oxidative status (TOS) and total antioxidant status (TAS) levels were significantly improved in the BEP + ozone group. Histopathological analysis revealed that ozone treatment ameliorated BEP-induced testicular damage, as evidenced by improved Johnsen scores and increased thickness of the seminiferous tubule epithelium. In conclusion, repeated medical ozone therapy appears to mitigate BEP-induced reproductive toxicity by preserving sperm quality, endocrine function, and redox homeostasis.

Mitochondria is an important organelle for the oocyte-to-embryo transition in the early embryonic development period. The oocyte uses mitochondria functionally and its mitochondrial DNA (mtDNA) content as the main energy source in the embryo development at the preimplantation stage. The aim of this study is to compare mitophagic, apoptotic and humanin gene expressions from the culture medium fluid in which embryos are developed and monitored among normoresponder (NOR), polycystic ovary syndrome (PCOS), young and older patients with poor ovarian reserve (POR). The study groups consisted of infertile patients who applied to the Bahçeci Umut IVF Center as NOR (Control), PCOS, POR-Advanced (POR-A) and POR-Young (POR-Y). After the isolation of total RNA from the collected samples, MFN1, MFN2, PINK1, PARKIN, SMN1, SMN2, p53 and Humanin gene expressions were determined by Real Time-PCR. The average age of only the POR-A was determined to be higher than the NOR (p < 0.001). The MFN1, SMN2 (p < 0.05), Humanin and p53 gene expressions (p < 0.001) increased, while PINK1 gene expression decreased (p < 0.05), in the POR-Y compared to the NOR. A decrease in MFN2, PARKIN (p < 0.05) and PINK1 gene expressions was determined in the PCOS compared to the NOR (p < 0.001). Furthermore, a decrease was observed in MFN2, PINK1 (p < 0.001) and Humanin gene expressions compared to the NOR (p < 0.05). The current data are the first in the literature determining the apoptotic and mitophagic status of the oocyte. The current results prove that waste embryo culture fluid may provide a non-invasive profile for important cellular parameters such as mitochondrial dysfunction in female infertility. The evaluation of significant cellular parameters can be performed much earlier without any intervention into the embryo.

Chemotherapeutic agents used in the treatment of testicular cancer cause damage to healthy tissues, including the testis. We investigated the effects of glutathione on sperm DNA integrity and testicular histomorphology in bleomycin etoposide cisplatin (BEP) treated rats. Twelve-week-old male rats of reproductive age (n = 24) were randomly divided into three groups, the (i) control group, (ii) BEP group, and (iii) BEP+ glutathione group. Weight gain increase and testes indices of the control group were found to be higher than that of the BEP group and BEP+ glutathione group. While the BEP treatment increased sperm DNA fragmentation and morphological abnormalities when compared to the control group, GSH treatment resulted in a marked decrease for both parameters. Moreover, BEP treatment significantly decreased serum testosterone levels and sperm counts in comparison to the control group, yet this reduction was recovered in the BEP+ glutathione treated group. Similarly, seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were higher in the control and BEP+ glutathione groups than in the BEP-treated group. In conclusion, exogenous glutathione might prevent the deterioration of male reproductive functions by alleviating the detrimental effects of BEP treatment on sperm quality and testicular histomorphology.

Immature oocytes are retrieved and matured through in vitro maturation (IVM). Maturation, fertilization rates, and embryo development via IVM are all lower than those found in vitro fertilization (IVF) cycles. We investigated the effects of oncostatin M (OSM), insulin-like growth factor-1 (IGF-I), and growth hormone (GH) in rescue IVM. A total of 111 germinal vesicle (GV) and 17 metaphase I (MI) oocytes were obtained after conventional IVF from 28 female Wistar albino rats. Denuded immature oocytes were cultured in maturation medium supplemented with OSM, IGF-1, or GH. The quantities of metaphase II (MII) oocytes matured from the GV stage were 17 of 30 (56.6%), 15 of 28 (53.5%), 10 of 30 (33.3%), and 7 of 23 (30.3%), in control, OSM, IGF-I, and GH groups, respectively. Maturation rates in control and OSM groups were higher than those in IGF-I and GH groups (p = 0.001). The quantities of MII oocytes matured from MI stage were 7 of 7 (100%), 4 of 4 (100%), 1 of 1 (100%), and 1 of 5 (20%) in control, OSM, IGF-I, and GH groups, respectively. Maturation rates from MI to MII stages in control, OSM, and IGF-I groups were higher than those in the GH group (p = 0.004). Acceptable maturation rates are observed with OSM in rat oocytes in rescue IVM.

Article: Anti-Müllerian hormone as a predictor of pregnancy in women under 35 years with unexplained infertility undergoing ICSI: a retrospective study - Minerva Obstetrics and Gynecology 2022 April;74(2):117-22 - Minerva Medica - Journals

Introduction: Compaction is the first event in embryo morphogenesis. Blastocyst transfer on day five or six has been widely performed in the last decade. We investigated the clinical value of early compaction on day three for evaluation of the transferred embryo quality and pregnancy. Methods: Four hundred patients with female factor infertility and 776 fresh embryo transfers were included. Two groups were formed: Early compaction group had embryo transfer with at least one day-three embryo exhibiting early compaction. Transferred embryos without early compaction comprised the control group. Embryo transfer was performed on day three or five after the assessment of embryo compaction by a time-lapse technology system. Each patient underwent only a single cycle of embryo transfer. We analyzed fertilization, pregnancy, and live birth rates. Results: We detected significantly higher numbers of the retrieved oocytes, metaphase II (MII) oocytes, and fertilized oocytes in the early compaction group. Moreover, the transfer of the early compacting embryos on day three resulted in higher pregnancy and live birth rates. Conclusion: Our data suggest that early compaction might be a factor to determine good quality embryos and embryo transfer day.

In recent years, microfluidic chip-based sperm sorting has emerged as an alternative tool to centrifugation-based conventional techniques for in vitro fertilization. This prospective study aims to compare the effects of density gradient centrifugation and microfluidic chip sperm preparation methods on embryo development in patient populations with astheno-teratozoospermia. In the study, the semen samples of the patients were divided into two groups for preparation with either the microfluidic or density gradient methods. Selected spermatozoa were then used to fertilize mature sibling oocytes and the semen parameters and embryo development on days 3 and 5 were assessed. While the density gradient group was associated with a higher sperm concentration, motility (progressive and total) was significantly higher in the microfluidic chip group. No significant differences were observed in the fertilization rates or grade 1 (G1) and grade 2 (G2) proportions of the third-day embryos. Furthermore, while the proportions of the poor, fair and good blastocysts on day 5 did not differ significantly, excellent blastocysts (indicating high-quality embryos) were observed in a significantly higher proportion of the microfluidic chip group. When compared to the classical density gradient method, the microfluidic chip sperm preparation yielded sperm with higher motility and higher quality blastocysts at day 5; in patients with astheno-teratozoospermia.