With the advent of metagenomics and 16S ribosomal RNA sequencing, growing attention has been dedicated to the endometrial microbiome. Research involving a relatively large cohort of healthy female participants has reported Lactobacillus dominance (LD) in the endometrial microbiome. Multiple studies have also shown that the loss of LD and/or increased microbial diversity within the endometrium are associated with reproductive failure. This phenomenon may stem from the loss of the immunomodulatory effects of Lactobacillus and the rise of proinflammatory responses triggered by pathogenic proliferation. Recent research has employed personalized antibiotic therapy followed by probiotic supplementation, tailored to the endometrial microbial composition of women with repeated implantation failure. The findings suggest that metagenomic analysis of the endometrial microbiome could be a valuable tool in addressing reproductive failure.

Objective: This study aimed to compare the thiol/disulfide balance, myeloperoxidase, and ischemia-modified albumin levels in the follicular fluid (FF) of poor ovarian response (POR) and normal ovarian response (NOR) women who received intracytoplasmic sperm injection (ICSI). Methods: The study was performed between March 2021 and April 2022 at the Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Ankara City Hospital. The study included 27 POR and 35 NOR women who underwent ICSI. FF was obtained after the controlled ovarian stimulation cycle. The FF thiol/disulfide balance was detected using spectrophotometric methods. A correlation analysis was conducted to determine whether these oxidative stress markers could contribute to predicting oocyte quality. Results: Disulfide levels were significantly higher in the NOR group than in the POR group (p=0.014). The number of fertilized egg (2PN) oocytes was positively correlated with the total thiol level (r=0.258, p=0.046). The disulfide level was positively correlated with the anti-Müllerian hormone level (r=0.262, p=0.039) and the total number of retrieved oocytes (r=0.335, p=0.008). Conclusion The disulfide levels differed significantly between the NOR and POR groups. The statistically significant differences of fewer metaphase II oocytes and lower percentage of good-quality embryos in the NOR group compared to the POR group might have resulted from the NOR group’s elevated disulfide levels. The total thiol levels correlated with the total of 2PN oocytes. Future studies should examine the thiol/disulfide balance at assisted reproductive technology centers to predict which oocytes could be fertilized.

Objective: Mechanical trauma to the testicles poses a potential risk of tissue destruction, disruption of local blood supply, and impairment of spermatogenesis, which can ultimately lead to infertility. Therefore, investigating this topic is crucial. The study aimed to identify cytological and morphological changes in the testicular tissue of laboratory rats following mechanical trauma to the organ. Methods: Observations were recorded on days 7, 14, 30, and 90 post-trauma. The experiment involved two groups of animals: a control group of healthy animals and an experimental group that sustained blunt mechanical trauma. Tissue samples were collected, fixed, dehydrated, and embedded in paraffin; subsequently, sections were prepared and stained. Structural changes in tissues and cells were documented using light and transmission electron microscopy. Results: In the experimental sample, notable changes included a decrease in organ weight, thickening of the protein shell and tubule walls, sclerotisation of the tubule membrane, narrowing of tubule diameter, reduced spermatozoa and spermatids titre, diminished capillary network and spermatogenic epithelium, uneven blood vessel lumen expansion, and decreased volume of Leydig cell nuclei. Additionally, in cells under different functional loads, the cytoplasm was vacuolated, mitochondrial cristae and the Golgi apparatus were diminished, cytoplasm volume decreased, karyopyknosis was observed, and uncharacteristic protrusions appeared on the surface of the cytoplasmic membrane. The severity of destruction at the cellular and tissue levels showed a positive correlation with time. Conclusion The data obtained from these model sites can be predictive for clinical trials.

Objective: For successful embryo implantation in women with high pulsatility, uterine vascular resistance and pulsatility must be reduced. We examined the effects of amlodipine on uterine pulsatility index (PI), resistance index (RI), and embryo transfer (ET) outcomes in women with prior implantation failure and at least one elevated uterine PI measurement (especially higher than 3). Methods: Between February and November 2023, our reproductive facility conducted a single-center randomized clinical trial, enrolling 100 patients with previous implantation failure and at least one uterine PI measurement exceeding 3. Participants were randomly assigned to receive either amlodipine (5 mg) or placebo (n=50 per group). Hormone replacement therapy was the predominant method for endometrial preparation. Transvaginal ultrasonography was used to measure uterine artery resistance and pulsatility on day 1 or 2 of menstruation. Women in the amlodipine group received 5 mg nightly. Following repeat transvaginal ultrasound to assess PI and RI, ET was performed. If a positive pregnancy test was obtained, treatment continued for a total of 7 weeks. Results: Amlodipine reduced blood flow indices in the uterine artery. Among placebo recipients, 18% tested positive for beta-human chorionic gonadotropin, compared to 26% of medication recipients. However, this difference was statistically insignificant (p=0.472). Gestational sacs were observed in 12% of the placebo group and 22% of the medication group, but this difference was also insignificant (p=0.28). Conclusion Amlodipine appears to reduce uterine pulsatility and resistance during ET. Despite the absence of significant differences in pregnancy outcomes, this promising drug merits further study in women with implantation failure.

Objective: Several chemotherapeutic agents, including cyclophosphamide (CP) and busulfan, have been shown to interfere with spermatogenesis. Accordingly, the main objective of this study was to evaluate the potential therapeutic effects of curcumin nanoemulsion (CUR-NE) on spermatogenesis in mice with CP-induced testicular toxicity. Methods: A total of 28 adult male mice were equally divided into four groups: control, CUR-NE (30 mg/kg, daily for 5 weeks), CP (200 mg/kg, single dose), and CP+CUR-NE. Each group was evaluated regarding sperm parameters, DNA fragmentation index, chromatin maturation, reactive oxygen species (ROS) levels, and histological parameters of the testes. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone, and testosterone were also assessed in all groups. Results: In CP-induced mice, CUR-NE treatment significantly improved sperm parameters, including total sperm count, motility, morphology, and DNA integrity. CUR-NE administration was also associated with significantly higher serum levels of testosterone and FSH, as well as testis weight and volume, in the mice treated with CP. Furthermore, CUR-NE treatment significantly increased the number of spermatogonia, primary spermatocytes, round spermatids, and Leydig cells in the testicular tissue of these animals. A marked reduction in ROS levels in the testes tissue was observed following administration of CUR-NE to CP-induced mice. Conclusion CUR-NE appears to promote spermatogenesis in mice with CP-induced testicular toxicity by reducing ROS levels, improving testicular stereological parameters, and strengthening the reproductive hormone profile.

Objective: Ciprofloxacin (CPFX) is frequently prescribed by fertility specialists and urologists to manage infections in male reproductive organs. However, it is toxic to the testicles and can lead to infertility. Dietary antioxidants are known to protect the testis from damage. This study aimed to investigate the effects of coenzyme Q10 (CoQ10) on the adverse side effects of CPFX using stereological methods. Methods: Sixty rats were divided into six groups: control (distilled water), CoQ10 (10 mg/kg/day), and low-dose (103 mg/kg/day) and high-dose (206 mg/kg/day) of CPFX (LD-CPFX, HD-CPFX) with or without CoQ10 consumption. The treatments lasted for 45 days. Sperm count, serum testosterone levels, and testicular parameters were evaluated. Results: Significant decreases in sperm count, motility, normal morphology, viability, and testosterone levels were observed in the LD-CPFX (p<0.003) and HD-CPFX- treated rats (p=0.0001) compared to the control groups. A 10% to 36% reduction in the volume of seminiferous tubules, tubular epithelium, and tubule length was noted in LD-CPFX (p<0.01) and HD-CPFX-treated rats (p<0.006), while the volume of the interstitium increased by 25% to 28% in LD-CPFX (p=0.03) and HD-CPFX (p=0.008) groups. The number of cells, including spermatogonia, spermatocytes, spermatids, Sertoli cells, and Leydig cells, decreased by 36% to 75% in the testes exposed to LD-CPFX (p<0.04) and HD-CPFX (p<0.01), compared to the control groups. However, these changes normalized in rats that received CoQ10. Conclusion CPFX exposure for 45 days, regardless of the dose, has detrimental effects on testicular parameters. CoQ10 can prevent CPFX-induced testicular structural impairments.

Objective: This study investigated potential relationships between the kinetics of nucleolar precursor bodies (NPBs) in the pronucleus and developmental morphokinetics and euploidy in human preimplantation genetic testing for aneuploidy (PGT-A) cycles. Methods: The morphokinetic analysis of 200 blastocysts obtained from 53 PGT-A cycles was performed retrospectively in a time-lapse incubator. At the time of pronuclear breakdown (PNBD), we categorized the blastocysts into two groups based on the kinetic degree of clustering NPBs at the interface of the two pronuclei: clustered NPBs (CL) and non-clustered NPBs (NCL). We then compared morphokinetic parameters, abnormal behavioral events, and the rate of aneuploidy between the two groups. Results: Pronuclear fading and the first cleavage occurred earlier in the NCL group than in the CL group. However, the initiation of blastocyst formation and blastocyst expansion was delayed in the NCL group relative to the CL group. No differences were found in the rate of abnormal cleavage events, such as multinucleation at the 2-cell stage, direct cleavage from one to three cells, and from two to five cells between the CL and NCL groups. However, the fragmentation rate at the 8-cell stage was higher in the NCL group than in the CL group (10.3% vs. 1.9%, p<0.05). Additionally, the euploid rate in the CL group was significantly higher than in the NCL group (37.9% vs. 12.4%, p<0.05). Conclusion These results demonstrate the effectiveness of combining NPB clustering at PNBD with morphokinetics as a parameter for selecting embryos with higher developmental potential in in vitro fertilization.

Objective: The duration of progesterone exposure is critical for establishing and maintaining a pregnancy in hormone replacement treatment (HRT)–frozen embryo transfer (FET) cycles. This study compared the live birth rates (LBRs) of patients undergoing day-6 warmed blastocyst transfer on either the 6th or 7th day of progesterone administration in HRT-FET cycles. Methods: A retrospective cohort study was conducted using data from the central registry of Indira IVF Hospital Private Limited. In total, 2,633 patients who underwent day-6 blastocyst transfer cycles with HRT-FET were identified. The cycles were categorized based on the timing of the day-6 blastocysts transfer: P+6 vs. P+7 (initiation date: P+1). Propensity scores were calculated. The primary outcome measure was the LBR. Results: Following propensity score matching, a total of 1,401 patients were included in the final analysis (P+6: n=1,212; P+7: n=189). The number of previous attempts was significantly higher in the P+6 group, whereas the rate of preimplantation genetic testing for aneuploidy was significantly higher in the P+7 group. The LBRs were 59.2% and 54.5% in the P+6 and P+7 groups, respectively (p=0.21). Multivariate regression analysis revealed that the number of previous in vitro fertilization attempts (odds ratio [OR], 3.246; 95% confidence interval [CI], 2.429 to 4.337; p<0.001), the number of blastocysts transferred (OR, 2.011; 95% CI, 1.461 to 2.768; p<0.01), and endometrial thickness on the day of progesterone initiation (OR, 1.143; 95% CI, 1.022 to 1.28; p=0.02) were independent predictors of live birth. Conclusions The LBRs were comparable in patients who underwent day-6 warmed blastocyst transfer on day 6 or 7 post-progesterone initiation in HRT-FET cycles.

Modern drug discovery is driven by high demand in the pharmaceutical industry to test growing libraries of compounds against potential targets. High-throughput screening (HTS) is characterized by fully automated experimentation that leverages robotic liquid handling systems, analytical techniques, and advanced computing and statistics, including the recent integration of artificial intelligence. To align with this trend, it is crucial to develop and implement new HTS platforms that offer improved predictivity and physiological relevance. In recent years, microphysiological systems, commonly known as organ-on-chip (OoC) systems, have progressed from a theoretical concept to a powerful alternative to conventional in vitro and animal models. High-throughput OoC (HT-OoC) systems could represent the disruptive technology sought by pharmaceutical companies to address their enormous research and development (R&D) expenses. In this study, we provide a brief overview of commercial products utilizing modern HT-OoC systems in drug discovery and development. Additionally, we discuss recent trends in R&D aimed at industrialization.

Errors in human DNA may cause genetic disorders. Technological developments have raised hopes for reducing the risks of genetic inheritance among married couples who have a history of such disorders. Among the developments in reproductive health technology that reduce those risks is the in vitro fertilization (IVF) process. This review aimed to describe the current strategies using IVF and preimplantation genetic testing (PGT), which would be effective for couples with genetic disorders to have healthy offspring. The literature review included full-text, open-access research articles from ScienceDirect, PubMed, and Google Scholar that were published between 2013 and 2023, with 65 articles obtained from various journals. The keywords were ‘in vitro fertilization,’ ‘reproductive genetic disorders,’ ‘PGT-A,’ ‘PGT-M,’ ‘PGT-SR,’ and ‘oocyte donor.’ A total of 46 articles were selected as the most relevant to the review topic, and the results show that the IVF process can be an option for couples with a history of genetic disorders. Several additional procedures can be performed following IVF, such as oocyte donation and PGT, to help couples who want to have offspring without transmitting their genetic disorders. IVF can be an option for couples who have or carry genetic disorders. With IVF, couples can undertake several procedures such as oocyte donation and PGT for aneuploidy, monogenic disorders, or structural rearrangement.