Search Results (59)

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released pre-prandially and during periods of negative energy balance, exhibiting anti-fertility properties. In this study, twenty ewes were divided into two groups: a ghrelin-treated group receiving 1.25 μg/kg body weight (BW) of ghrelin per day via mini-pumps for 28 days and an untreated control group. Estrus was synchronized, superovulation was induced with FSH, and embryos and follicular fluid were collected six days post-estrus. Blood samples were taken to measure LH, progesterone, and anti-Müllerian hormone (AMH) concentrations. Results indicated that in treated animals, preovulatory LH surge was weaker, and progesterone levels were lower than in controls. Differences were observed in the superovulatory response and the number of collected embryos, both being higher in controls. While AMH levels did not differ between groups at the beginning of the experiment, they were lower in treated animals at the time of FSH administration. Treated ewes exhibited a reduced number of small follicles, and their follicular fluid contained lower AMH concentrations than the controls. These findings suggest that ghrelin plays a direct role in regulating LH secretion from the pituitary and in controlling ovarian follicle development, highlighting the strong interaction between nutrition and fertility. Full article

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE’s antioxidant activity was evaluated in vitro through DPPH, H₂O₂, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride–Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment. Full article

This study aimed to investigate the effect of Artemisia absinthium extract on testicular dysfunction in rats and explain the involvement of the androgen receptor signaling pathway as a biomarker in maintaining fertility during sodium fluoride (NaF) treatment. Thirty-two male rats were divided equally into four groups and received treatment for 60 days. The control group (I) received normal saline; group II received Artemisia extract at 100 mg/kg b.w.; group III received NaF at 12 mg/kg b.w. orally; and group IV received NaF (12 mg/kg b.w.) and Artemisia extract (100 mg/kg b.w.). The testis weights and the lipid peroxidation, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were estimated. The genital organs were prepared and immunoreacted with a receptor. Histomorphometric analyses were performed to obtain the diameter of the seminiferous tubules and the height of the germinal epithelia in the testes. The results showed that exposure to NaF caused a significant increase in testis weight and malondialdehyde (MDA) and a decrease in serum LH, FSH, and testosterone concentrations compared to the control group, while extract administration induced an increase in the levels of these hormones in group IV. Testicular histological and histomorphometric changes were observed in group III: degenerative seminiferous tubules with vascular congestion, disorganization of the germinal layer, and decreased seminiferous tubule diameter and germinal epithelium height. The expression of androgen receptors in the testes of the NaF-treated rats was significantly reduced. In contrast, these testicular histological changes were ameliorated in rats treated with the extract. The results allow us to conclude that the administration of Artemisia absinthium confers positive effects on male reproductive function by inhibiting fluoride, maybe via ameliorative testicular function. Full article

Male hormonal contraception has been the focus of extensive research efforts aimed at identifying effective and reversible methods for male fertility control. This review summarizes the current state of knowledge, key achievements, and future directions in the development of male hormonal contraception. A review was conducted using the PubMed, Embase, and Scopus databases. The search strategy included terms such as “male hormonal contraception”, “Nestorone”, “7α,11β-Dimethyl-19-nortestosterone 17β-undecanoate (DMAU)” and “11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC)”. A total of 107 references were analyzed to synthesize the most relevant findings regarding the hormonal contraceptive agents under investigation. The review outlines historical and recent advancements in male hormonal contraception, highlighting compounds that have demonstrated limitations in effectiveness, side effects, or inconvenient administration. Notable candidates under study include 7α-methyl-19-nortestosterone (MENT), DMAU, 11β-MNTDC, and the combination of segesterone acetate with testosterone in gel form. These agents show promise due to their ability to suppress follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to effective spermatogenesis inhibition with minimal side effects. Additionally, the phenomenon of spermatogenic rebound is considered. Among the investigated agents, oral DMAU, 11β-MNTDC, and the Nestorone–testosterone gel appear to be the most promising candidates for male hormonal contraception due to their high efficacy, user-friendly administration, and favorable safety profiles. However, further large-scale clinical trials are necessary to confirm their long-term effects on human health and fertility, ensuring their viability as future contraceptive options. Full article

Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems. Full article

Embryo transfer technology is extensively utilized in cattle breeding, with superovulation serving as its foundation. Superovulation currently relies on the administration of exogenous hormones to stimulate follicular development and maturation in the ovaries, with porcine pituitary-derived follicle-stimulating hormone (FSH) being the most commonly used. However, pituitary-derived FSH requires multiple injections, contains luteinizing hormone (LH) and other proteins, and carries a risk of disease transmission. The development of recombinant FSH proteins through protein recombinant technology represents a significant research direction for addressing the aforementioned challenges. Over the past 30 years, extensive studies have been conducted on the development of recombinant bovine, ovine, or porcine FSH. Nevertheless, to date, no commercially recombinant FSH has been widely applied in the superovulation of cattle. This review provides an overview of the molecular design, selection of expression systems, and biological activity of recombinant bovine, ovine, or porcine FSH. This review also summarizes the results of utilizing recombinant FSH in superovulation protocols for cattle. The utilization of recombinant proteins as an alternative to traditionally extracted products in livestock production represents an irreversible trend. The livestock industry is highly sensitive to costs; therefore, it is essential to develop high-quality and cost-effective recombinant FSH products through appropriate molecular design and the use of suitable expression systems. Full article

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca²⁺ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy. Full article

Objective: To study the effect of switching to a follicle-stimulating hormone (FSH) preparation other than that to which infertile male patients have not had an effective response. Patients and methods: Seventy-four normogonadotropinemic, non-obstructive, oligozoospermic patients who were poor responders to the administration of highly purified FSH (hpFSH) (Group 1 (n = 22) and Group 3 (n = 15)) or to recombinant human FSH (rhFSH) (Group 2 (n = 22) and Group 4 (n = 15)) were selected for this prospective study. After 3 months of washout from treatment with the first FSH preparation of choice, rhFSH was administered to patients in Groups 1 and 4 and hpFSH to those in Groups 2 and 3. Serum luteinizing hormone, FSH, total testosterone levels, conventional sperm parameters, testicular volume, and the number of pregnancies were evaluated at study entry and after the first and second treatment cycles. Results: Comparing treatment groups, the greatest improvement in sperm parameters was recorded in the groups of patients prescribed the switch in FSH preparation. Group 1 had the greatest benefit from therapy, with the highest pregnancy rate after the second treatment cycle. Indeed, eight couples achieved pregnancy (36.4%), compared to Groups 2 (n = 4; 18.2%), 3 (n = 1; 6.7%), and 4 (n = 2; 13.3%) (p = 0.04). Conclusions: The results of this study suggest that a therapeutic scheme involving the “switching” of the FSH preparation yields better results than a protocol using the same FSH preparation for six months. These findings, if confirmed by further studies, will help us better design a treatment strategy with FSH for infertile patients with oligozoospermia. Full article

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10–18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as “non-responders”. For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review’s objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men. Full article

Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups based on serum progesterone levels at the time of hCG administration: 526 cycles had levels below 1.5 ng/mL, while 149 cycles had levels equal to or above 1.5 ng/mL. Results: The findings revealed a significantly higher number of mature follicles and retrieved oocytes in patients with PPR across all AMH categories. Multiple analyses revealed factors influencing PPR, including the duration of induction and the number of retrieved oocytes. Within the same oocyte retrieval number group, patients with PPR demonstrated non-inferior pregnancy outcomes compared to non-PPR patients. Upon adjustment for age, AMH, and total follicle-stimulating hormone (FSH) dosage, PPR maintained a positive correlation with the cumulative live birth rate (LBR). Conclusions: The study showed that PPR correlates with an increase in retrieved oocytes while maintaining similar embryo quality and oocyte retrieval rates and results in a higher cumulative LBR. Full article

Adiponectin is an important adipokine involved in glucose and lipid metabolism, but its secretion and potential role in regulating glucose utilization during ovarian development remains unclear. This study aims to investigate the mechanism and effects of follicle-stimulating hormones (FSHs) on adiponectin secretion and its following impact on glucose transport in the granulosa cells of rat ovaries. A range of experimental techniques were utilized to test our research, including immunoblotting, immunohistochemistry, immunofluorescence, ELISA, histological staining, real-time quantitative PCR, and transcriptome analysis. The immunohistochemistry results indicated that adiponectin was primarily located in the granulosa cells of rat ovaries. In primary granulosa cells cultured in vitro, both Western blot and immunofluorescence assays demonstrated that FSH significantly induced adiponectin secretion within 2 h of incubation, primarily via the PKA signaling pathway rather than the PI3K/AKT pathway. Concurrently, the addition of the AdipoR1/AdipoR2 dual agonist AdipoRon to the culture medium significantly stimulated the protein expression of GLUT1 in rat granulosa cells, resulting in enhanced glucose absorption. Consistent with these in vitro findings, rats injected with eCG (which shares structural and functional similarities with FSH) exhibited significantly increased adiponectin levels in both the ovaries and blood. Moreover, there was a notable elevation in mRNA and protein levels of AdipoRs and GLUTs following eCG administration. Transcriptomic analysis further revealed a positive correlation between the expression of the intraovarian adiponectin system and glucose transporter. The present study represents a novel investigation, demonstrating that FSH stimulates adiponectin secretion in ovarian granulosa cells through the PKA signaling pathway. This mechanism potentially influences glucose transport (GLUT1) and utilization within the ovaries. Full article

(1) Background: In this paper we aim to study the relationship between the expression levels of molecules involved in apoptotic/survival pathways, considered as molecular markers of oocyte competence (i.e., AKT, p-AKT, ERK1/2, and p-ERK1/2) in mural granulosa cells (MGCs) and the administration of r-FSH alone or combined with exogenous r-LH, in ovarian stimulation protocol. Moreover, we aim to evaluate oocyte competence by comparing normally cleaved embryos that were transferred in the uterus, with embryos that were arrested during in vitro culture. (2) Methods: The study included 34 normo-responder women undergoing ICSI procedures. All subjects were divided into two groups. Group A consisted of 18 women stimulated with r-FSH and used as a control group; Group B consisted of 14 women stimulated with r-FSH combined with r-LH. The MGCs were obtained from individual follicles. Immunoblot analyses were carried out to analyze the AKT, p-AKT, ERK1/2, and p-ERK1/2 levels in MGCs and to correlate them with the ovarian stimulation protocol. Furthermore, the oocyte competence was evaluated, for each follicle, according to the development of the embryo during in vitro culture and the pregnancy outcome. (3) Results: We found no significant difference in the levels of molecules in isolated MGCs between groups A and B. These results, in light of our previous research, suggest for the first time, to our knowledge, that cumulus cells and mural granulosa cells in the same follicle show different expression levels of molecules involved in the apoptotic mechanism. (4) Conclusions: Our results could clarify some controversial data in the literature where cumulative cell pools of cumulus and granulosa were analyzed, described as ovarian follicle cells, and used as markers of oocyte competence. In this paper, we found evidence that cumulus and granulosa cells need to be analyzed separately. Full article

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a nonsignificant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure. Full article

The study tested the hypothesis that a single administration of hCG supports the LH-dependent phase of terminal follicular development in synchronized sheep during anestrus, using eCG as a functional reference. Using a clinical approach, four experiments were designed to achieve the following: (1) Identify the inhibitory influence of anestrus on reproduction efficiency; (2) Assess the potential of hCG to keep functional blood concentrations after a single dose; (3) Characterize the effect of different doses of hCG on reproductive functional markers; (4) To compare the ability of hCG to that of eCG to support follicular development and fertility based on the same markers. The results showed that anestrus seems to affect follicular and luteal function under LH dependency as FSH-dependent markers are not compromised; hCG maintains higher blood concentrations than controls for at least 48 h; hCG improves follicular development and ovulatory rates compared to controls and at standards comparable to a breeding season; and ewes treated with hCG exhibit similar performance to those treated with eCG. Our results conclude that hCG can be used to support follicular function during anestrus in sheep, aiming to perfect its regulation in assisted reproduction. Full article