Luteinizing Research Articles

Decreased Circulating Gonadotropin-Releasing Hormone Associated with Keratoconus.

Keratoconus (KC) is a corneal thinning dystrophy that leads to visual impairment. While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of α-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic-pituitary-gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.

STUDY OF THE ENDOMETRIAL GLANDULAR COMPONENT IN WOMEN WITH FERTILITY AND POST-COVID SYNDROME IN ANAMNESIS

The aim. To increase the effectiveness of the endometrial endometrial glandular component study in women with infertility and post-COVID syndrome. Materials and methods. A study was conducted at the State institution "Carpathian Human Reproduction Centre" of the Ministry of Health of Ukraine in the period from 2022 to the end of the first half-year of 2024. There were included 80 women in the experimental group and 40 women in the control group. The selection criterion for the study group was the presence of documented post-COVID syndrome (COVID-19 symptoms lasted longer than 12 weeks). The selection criterion for the control group was the absence of confirmed SARS-CoV-2 virus in the anamnesis. The following characteristics were common for both groups: diagnosed infertility, age – 25-42 years, written informed consent of the patient to participate in the study. The criteria for exclusion from the study for patients of both groups were: detection of human immunodeficiency virus, viral hepatitis, other sexually transmitted infections, tuberculosis of the genitourinary system, malignant diseases, mental disorders that make communication with person impossible or the awareness of written consent is questioned. General clinical and laboratory examinations and transvaginal sonographic examination of the pelvic organs were performed in the middle stage of proliferation and the middle stage of secretion according to the calendar calculation the menstrual cycle. A visually guided diagnostic office hysteroscopy was performed with the collection of biological material from the most changed areas (biopsies were collected in the middle stage of proliferation and the middle stage of secretion in different menstrual cycles). A routine staining of samples with hematoxylin-eosin, morphometry of the endometrial glandular component, optical determination of the number of glands and measurement of the diameter of the lumen of the studied glands, considering the possible measurement error, glandular-stromal ratio, functional activity of the glands, were performed. A histochemical PAS-reaction to identify the glycoproteins of gland secretions and immunohistochemical staining of the glandular epithelium to express the receptivity of the glands to estrogen and progesterone were carried out. The results. After conducting the PAS-reaction, a higher secretion was noted in the glands than in the stroma of the endometrium during the period of the implantation window in both cohorts. No statistically significant difference between the groups in the amount of glycogen of the middle proliferative phase in the glands (p=0.315) or stroma (p=0.486). Glycogen in this phase was visualized of very small granules and coarse granules, without their formation in clusters. A decrease in secretion was established in 16 (40%) patients of the control group and 49 (61.3%) women of the experimental group in the middle secretory phase, which was statistically significant (p=0.028). A decrease in the expression level of the progesterone receptor in the middle secretory phase was found to be significantly more pronounced in the experimental group than in the control group (р=0.044). Conclusions. In the middle secretory phase, a decrease in the secretion of glycogen by the endometrial glands and a decrease in the level of expression of the progesterone receptor in endometrial biopsies were detected by the routine histological, histochemical techniques and immunohistochemical stude in women with infertility and a history of post-COVID syndrome.

Acupoint catgut embedding: a potential intervention strategy for obesity-related precocious puberty.

Obesity-related precocious puberty is induced by obesity, and acupoint catgut embedding (ACE) therapy is known to treat obesity. This study aims to validate the hypothesis that ACE can delay the onset of obesity-related precocious puberty. Female Sprague-Dawley rats, 21 days old, were randomly divided into three groups: the high-fat diet combined with ACE treatment group (ACE), the high-fat diet group (HFD), and the normal control diet group (NCD), with 8 rats in each group. The vaginal opening (VO) time was monitored, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total estradiol (E2) were measured, followed by statistical analysis. Kaplan-Meier survival curves, with VO as the endpoint, showed that vaginal opening was delayed in the ACE group compared to the HFD group, with a statistically significant difference (p < 0.05). The changes in levels of FSH, LH, and E2 indicated that sexual development was delayed in the ACE group compared to the HFD group and was more similar to the NCD group. Combining the vaginal opening time and changes in hormone levels, this study confirms the potential role of ACE in delaying the onset of obesity-related precocious puberty.

Thyroidectomy Induced Toxicity of Testis and Possible Amelioration by Chia (Salvia hispanica) Seeds Extract

Background: Thyroidectomy or thyroid surgery induces hypothyroidism and causes thyroid and testicular hormone deficiency. The current Study Aimed to examine the therapeutic effect of chia seeds extract against thyroidectomy-induced testicular toxicity, oxidative stress, DNA damage, proliferation in rats. Methods: 40 male rats were equally divided into 4 groups [Gp1, control ; Gp2, CSE ; Gp3, thyroidectomies rats; Gp4, treated thyroidectomies rats with chia seeds extract (Thy+CSE )]. Result: Following a thyroidectomy, significant reductions (P less than 0.05) were observed in The Levels of triiodothyronine (T3), thyroxine (T4), sexual hormones (Testosterone (tt), Follicle-Stimulating Hormone and Luteinizing Hormone And prolactin), count of sperm, index of morphology, vitality, progressive motility, total motility (PR+NP), Glutathione, Superoxide Dismutase, Glutathione S-Transferase and PCNA expressions compared to the control and CSE after three weeks. Additionally, thyroidectomy leads to significant (P less than 0.05) increases in the serum of thyrotropin (TSH), alanine transaminase, alkaline phosphatase, non-progressive sperms, immotile sperms, malondialdehyde, DNA damage and injury of testis and significant (P less than 0.05) decreases in blood. Thy+CSE treatment helped to modulate most of these changes and recover testicular injury when compared To The Control and CSE. Rats treated with CSE after thyroidectomy Showed gradual improvements in testicular functions, histology and spermatogenesis due to its beneficial affection in free radicals’ scavenger.

Deer Blood Hydrolysate Protects against D-Galactose-Induced Premature Ovarian Failure in Mice by Inhibiting Oxidative Stress and Apoptosis.

Premature ovarian failure (POF) is a common disease among women, which can cause many complications and seriously threaten women's physical and mental health. Currently, hormone replacement therapy is the primary treatment for premature ovarian failure. However, the side effects are serious and will increase the chance of breast cancer and endometrial cancer. Deer blood hydrolysate (DBH) is the product of enzymatic hydrolysis of deer blood, has antioxidant, anti-ageing, and anti-fatigue effects, and has the potential to improve premature ovarian failure. In our experiment, a mouse model of premature ovarian failure was established through intraperitoneal injection of 400 mg/kg/d of D-gal for 42 days. At the same time, different doses of DBH were gavaged to observe its ameliorative effect on premature ovarian failure. The experimental findings indicated that DBH could restore the irregular oestrus cycle of POF mice, improve the abnormal amounts in serum hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), progesterone (P) and estradiol (E2), increase the number of primordial follicles and decrease the number of atretic follicles. In addition, DBH also raised the level of superoxide dismutase (SOD) and reduced the level of malondialdehyde (MDA) and reduced the apoptosis of ovarian granulosa cells in mice. The WB assay results showed that gavage of DBH restored the decrease in the indication of nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1), and B-cell lymphoma-2 (Bcl-2) proteins and reduced the elevated expression of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2 associated X protein (Bax), and Cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins that were induced by D-gal. To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure.

Factors affecting the outcomes of in vitro fertilization in women with endometriosis: Preliminary data from Vietnam

Objectives: This study aimed to assess the efficacy of in vitro fertilization (IVF) in patients with endometriosis and identify related factors that may influence treatment outcomes. Methods: This retrospective descriptive study was conducted between November 2018 and November 2022. The study group comprised individuals who were diagnosed with endometriosis (endometrioma and/or adenomyosis) indicated for in vitro fertilization. The control group (129 patients with 249 cycles), which included patients without endometriosis and had an equivalent mean age as the study group patients. Results: In the endometriosis group, the quantities of retrieved oocytes and Anti-Müllerian Hormone (AMH) were reduced compared to the control group. The overall dose of gonadotropin and the duration of ovarian stimulation were significantly higher than the control group. The endometriosis group exhibited a Metaphase II (MII) oocyte rate of 82.3% and an oocyte fertilization rate of 82.2%. However, in patients with endometriosis, the rates of implantation, clinical pregnancy, and ongoing pregnancy were significantly lower than in patients without endometriosis. Besides, the clinical pregnancy rate of women with endometriosis was remarkably higher in the groups with maternal age ⩽35 years, a ratio of Follicle-stimulating Hormone to Luteinizing Hormone (FSH/LH) ⩽1.5, and over 10 retrieved oocytes. Conclusion: Endometriosis was associated with a decreased rate of implantation, clinical pregnancy, and ongoing pregnancy after in vitro fertilization treatment compared with patients without endometriosis. In vitro fertilization outcomes in patients with endometriosis were influenced by maternal age ⩽35 years, FSH/LH ratio ⩽1.5, and number of retrieved oocytes over 10.

Synchronously Mature Intersex Japanese Flounder (Paralichthys olivaceus): A Rare Case.

Japanese flounder is usually gonochoristic, with gonads that are either testes or ovaries. Here, we report an unusual case of hermaphroditism in Japanese flounder captured from the Bohai Sea. In the intersex flounder, the membrane of the upper ovary was closely connected to the abdominal muscles and internal organs, and the eggs filled the entire abdomen. The lower ovary was small and closely connected to the testes. The testes contained few fully mature sperm. Both eggs and sperm were capable of fertilization. The levels of several reproduction-related hormones (17β-estradiol, 11-ketotestosterone, 17α, 20β-dihydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone) in the intersex flounder were intermediate, between those in females and males. The results showed that the heterozygosity of the intersex flounder was 0.632, and there were 28 single-nucleotide polymorphisms in the cyp21a gene. Compared with that of wild flounder, the activity of 21-hydroxylase was reduced by approximately 20.0%, and expressions of cyp19a, amh, and dmrt1 differed. We present the first report of its kind, detailing the anatomy, hormonal endocrinology, molecular biology, and physiology of the intersex Japanese flounder.

Embryonic and larval development of black jewfish, Protonibea diacanthus: A new candidate for aquaculture in northern Australia

Black jewfish Protonibea diacanthus is a large, commercially important fish distributed across the tropical Indo-Pacific. In Australia, there is an established commercial wild fishery for the species but it’s aquaculture potential has not been investigated. This research presents hatchery production of native P. diacanthus in Darwin, Australia and documents ontogeny of early life stages of this species over three trial runs. Wild P. diacanthus were induced to spawn with luteinizing hormone-releasing hormone analog (LHRHa) and eggs were released approximately 25–28 h after injection (0.88 ± 0.01 mm in diameter with oil globule 0.24 ± 0.01 mm). Larvae hatched 12 h after spawning. At one day post hatch (dph) larvae were 2.68 ± 0.01 mm standard length with 0.15 ± 0.01 mm oil globule diameter. Larvae mouths opened at 31 h post hatch (hph) and first feeding was seen at 57 hph. Swim bladder inflation (92 %) occurred between 40 and 62 hph. Larvae were progressively fed rotifers, Artemia and Otohime microdiet, and metamorphosis occurred between 20 and 25 dph, completing as they reached over 13 mm standard length. Tail biting cannibalism began with the onset of metamorphosis and caused significant mortality until approximately 24 dph when metamorphosed juveniles could be handled and moved to low stocking density systems. This study demonstrates that northern Australian P. diacanthus is amenable to hatchery production and provides important foundational knowledge for this emerging aquaculture species.

Safety assessment of three common food additives: the reproductive, oxidative and enzymatic perspective

This investigation was designed to evaluate the reproductive toxicity induced by potassium bromate (at doses of 50, 40, 30, 20, and 10 mg/kg), sodium benzoate (at doses of 5, 4, 3, 2, and 1 mg/kg), and caramel IV (at a dose of 200 mg/kg for 1, 2, 3, 4, and 5 weeks) in male albino mice through the assessments of sperm abnormality and sperm count. The concentrations of the three additives tested were chosen purposefully based on the acceptable daily intake of each of the additives by standard organizations. The level of Total Testosterone (TT), Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH), as well as the activities of catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were also measured. The results obtained showed that all three tested food additives led to a statistically significant (p < 0.05) increase in abnormal sperm cells among exposed mice. The sperm abnormalities observed include folded sperm, amorphous heads, distal droplets, absent hooks, improper tail attachments, and looped tails. Furthermore, it was observed that only mice exposed to potassium bromate and caramel exhibited a statistically significant decrease in mean sperm count. Alterations in the levels and activities of TT, ALT, FSH, AST, LH, and ALP were also observed to be concentration-dependent in the exposed mice. The findings suggest that the reproductive toxicity and changes in enzyme activities in the treated mice are dependent on the concentration of potassium bromate and sodium benzoate, as well as the duration of exposure to caramel IV. These indicate that high consumption of foods or beverages containing potassium bromate, sodium benzoate, and caramel IV colourant may induce reproductive abnormalities in the consumers.

Impact of polyethylene microplastics exposure on kallikrein-3 levels, steroidal-thyroidal hormones, and antioxidant status in murine model: protective potentials of naringin

The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p < 0.005) in the level of kallikrein-3 (KLK-3) while it significantly reduces the levels of testosterone (TST), luteinizing hormone, thyroid stimulating hormone (TSH) and Free-triiodothyronine (fT3) and Total cholesterol (TChol) concentration. PE-MPs exposure also disrupted significantly (p < 0.005) antioxidant profile by down-regulating the activities of glutathione-S-transferase, catalase (CAT), superoxide dismutase (SOD) and reducing levels of glutathione (GSH) and ascorbic acid (AA) while concentration of malondialdehyde (MDA) levels were increased relative to control. However, the mitigating potentials of naringin on disruptions in hormonal and antioxidant profiles caused by PE-MPs exposure were demonstrated, as NAR normalized KLK-3, steroid, and thyroid hormone levels, cholesterol concentration, and enhanced antioxidant defense. This suggests that NAR is a promising protective agent against endocrine and oxidative damage induced by environmental contaminants such as microplastics.

Intermittent escitalopram treatment and reactive aggression in women with premenstrual irritability and anger: A crossover study

BackgroundSelective serotonin reuptake inhibitors (SSRI) are the primary treatment for premenstrual mood symptoms and particularly effective in reducing reactive aggression in the forms of irritability and anger.The present study examined whether behavioral responses in laboratory measures of reactive aggression are influenced by medication with the SSRI escitalopram in women reporting high levels of premenstrual irritability/anger. MethodsParticipants (N = 34) rated the cardinal mood symptoms of premenstrual dysphoric disorder over three menstrual cycles. During the second and third cycles, participants received escitalopram (20 mg) or placebo in a single-blind, cross-over design. In the luteal phase of the intervention cycles, participants completed two aggression tasks: The Anger-Infused Ultimatum Game (AI-UG) and the Point Subtraction Aggression Paradigm (PSAP). Additionally, they rated expression and control of anger using the State-Trait Anger Expression Inventory-2 (STAXI-2) once in the luteal phase and once in the follicular phase. ResultsWhile irritability/anger was reduced in the treatment (vs. placebo) cycle, no effect of escitalopram was detected in the PSAP. Escitalopram decreased reactive aggressive behavior in the AI-UG but only for a subset of participants who experienced a sharp premenstrual rise in outwardly expressed anger and/or did not experience a premenstrual rise in inwardly expressed anger. LimitationsThe participants' symptoms were based on the severity of only premenstrual irritability/anger, limiting the generalizability to the broader group of PMDD patients. ConclusionThe results suggest that the behavioral consequences of severe premenstrual irritability/anger are not easily captured by traditional measures of reactive aggression and underline the importance of considering individual differences in symptom expression.

LH-stimulated periodic lincRNA HEOE regulates follicular dynamics and influences estrous cycle and fertility via miR-16-ZMAT3 and PGF2α in pigs

Disruption of the estrous cycle affects fertility and reproductive health. Follicular dynamics are key to the regularity of the estrous cycle. We identified a novel lincRNA, HEOE, showing significant upregulation in the ovaries during the estrus phase across various pig breeds. Functional analysis revealed that HEOE is responsive to luteinizing hormone (LH) stimulation, modulating transcriptional suppression and alternative splicing in ovarian granulosa cells (GCs). This leads to increased GC apoptosis and inhibition of proliferation. Mechanistically, HEOE inhibits miR-16 maturation in the nucleus, and sequesters miR-16 in the cytoplasm, thereby collectively reducing miR-16's inhibition on ZMAT3, enhancing the expression of ZMAT3, a key factor in the p53 pathway and alternative splicing, thereby regulating follicular development. This effect was validated in both mice and pig follicles. Persistent overexpression or suppression of HEOE throughout the estrous cycle impairs cycle regularity and reduces litter size. These outcomes are associated with HEOE reduced follicular PGF2α levels and modulation of the cAMP signaling pathway. Our data, combined with public databases, indicate that the high expression of HEOE during the estrus phase is crucial for maintaining the estrous cycle. HEOE is a potential therapeutic target for regulating fertility and ensuring estrous cycle regularity in pigs.

Optimizing timing for intrauterine insemination (IUI) in donor sperm cycles: pre- versus post-ovulation insemination in natural cycles

Purpose To investigate whether pregnancy outcomes of natural cycle intrauterine insemination (IUI) with donor sperm can be improved by performing insemination after confirmation of ovulation. Methods This retrospective cohort study evaluated 751 couples undergoing 1170 cycles of artificial insemination with donor sperm (AID) in natural cycles between January 2018 and January 2021. Patients underwent AID either within 6–12 h after spontaneous luteinizing hormone (LH) surge (pre-ovulation group) or after ovulation was confirmed by ultrasound (post-ovulation group). Propensity score matching was performed to account for differences in baseline characteristics between groups. The main outcome measures of this study were clinical pregnancy rate and live birth rate. Results After propensity score matching, each group comprised 216 cycles. No significant differences were observed between the pre-ovulation and post-ovulation groups in terms of clinical pregnancy rate (30.6% vs 27.3%, respectively, p = .458) and live birth rate (25.0% vs 22.7%, respectively, p = .651). However, upon excluding cases of luteinized unruptured follicle syndrome (LUFS) from the pre-ovulation group, the clinical pregnancy rate (33.5% vs 27.3%, respectively, p = .043) and live birth rate (27.4% vs 22.7%, respectively, p = .039) were significantly higher in the pre-ovulation group. Conclusions For fertile women undergoing AID in natural cycles, pre-ovulation insemination timing yielded superior pregnancy outcomes compared to post-ovulation insemination when ovulation was achieved. However, due to the occurrence of LUFS, pre- and post-ovulation AID resulted in comparable overall pregnancy outcomes in natural cycles.

Estradiol-mediated enhancement of the human ectocervical epithelial barrier correlates with desmoglein-1 expression in the follicular menstrual phase.

The cervicovaginal epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections. Hormones, specifically estradiol and progesterone, along with their respective receptor expressions, play an important role in modulating this barrier. However, the influence of estradiol and progesterone on gene and protein expression in the ectocervical mucosa of naturally cycling women is not well understood. Mucosal and blood samples were collected from Kenyan female sex workers at high risk of sexually transmitted infections. All samples were obtained at two time points, separated by two weeks, aiming for the follicular and luteal phases of the menstrual cycle. Ectocervical tissue biopsies were analyzed by RNA-sequencing and in situ immunofluorescence staining, cervicovaginal lavage samples (CVL) were evaluated using protein profiling, and plasma samples were analyzed for hormone levels. Unsupervised clustering of RNA-sequencing data was performed using Weighted gene co-expression network analysis (WGCNA). In the follicular phase, estradiol levels positively correlated with a gene module representing epithelial structure and function, and negatively correlated with a gene module representing cell cycle regulation. These correlations were confirmed using regression analysis including adjustment for bacterial vaginosis status. Using WGCNA, no gene module correlated with progesterone levels in the follicular phase. In the luteal phase, no gene module correlated with either estradiol or progesterone levels. Protein profiling on CVL revealed that higher levels of estradiol during the follicular phase correlated with increased expression of epithelial barrier integrity markers, including DSG1. This contrasted to the limited correlations of protein expression with estradiol levels in the luteal phase. In situ imaging analysis confirmed that higher estradiol levels during the follicular phase correlated with increased DSG1 expression. We demonstrate that estradiol levels positively correlate with specific markers of ectocervical epithelial structure and function, particularly DSG1, during the follicular phase of the menstrual cycle. Neither progesterone levels during the follicular phase nor estradiol and progesterone levels during the luteal phase correlated with any specific sets of gene markers. These findings align with the expression of estradiol and progesterone receptors in the ectocervical epithelium during these menstrual phases.

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

Drug treatment of true gynecomastia in overweight adult men

BACKGROUND: True gynecomastia is associated with excess body mass, which is caused by an imbalance of androgens/estrogens. Therefore, there is an interest in evaluating the possibility of drug therapy for this condition through the use of antiestrogens or aromatase inhibitors.AIM: To evaluate the possibility of drug therapy for true gynecomastia in adult men with excess body mass through the use of clomiphene or letrozole.MATERIALS AND METHODS: A retrospective study included men with newly developed gynecomastia and excess body mass who sought medical help at the Endocrinology Research Center from January 2020 to May 2024, and received either clomiphene therapy or letrozole for a period of 4 weeks. All patients were evaluated for the condition of their breast glands, total bilirubin, liver transaminases, creatinine, urea, luteinizing hormone, prolactin, sex hormone-binding globulin, estradiol, total testosterone, alpha-fetoprotein, and chorionic gonadotropin. The baseline level of statistical significance was set at p&lt;0.05.RESULTS: With clomiphene treatment, no statistically significant differences were found in the evaluated parameters, except for estradiol and testosterone levels, which increased. Clomiphene therapy worsened the condition of three patients (13% (95% CI 2,8;33,6)) - they experienced breast pain that was not present at the time of prescription. With letrozole treatment, there was a positive trend - all evaluated parameters significantly improved. Comparing the changes in the studied parameters, it was found that letrozole treatment had a better effect in terms of the severity of gynecomastia (-1[0;-1] degree), reduction in estradiol levels (-31,7[-8,8;-90,8] pmol/l), and also reduced the number of patients willing to undergo surgical removal of gynecomastia (-63,4% (95% CI -46,9;-77,9)).CONCLUSION: The use of an aromatase inhibitor reduces the severity of gynecomastia and decreases the number of patients willing to undergo surgical removal.

Management of a granulosa-theca cell tumor in a female Rottweiler

A 4-year, multiparous Rottweiler female dog, was presented for breeding management. Dog had clinical signs of proestrus and estrus for &gt; 6 weeks, including cornification of vaginal epithelium and low circulating progesterone concentrations (&lt; 2 ng/ml). Transabdominal ultrasonography of the reproductive tract and measurement of circulating hormones (antimüllerian hormone, Inhibin-B, and progesterone) suggested granulosa-theca cell tumor. Affected ovary was removed via laparoscopy. Histopathology confirmed granulosa-theca cell tumor; dog resumed cyclicity 4 months after surgery, had normal estrus and was successfully mated with a young stud dog. Dog was diagnosed pregnant (30 days after LH surge) via transabdominal ultrasonography; 4 amniotic sacs were detected, and 3 grew to term but were not viable at delivery (via cesarian surgery).

Selective depletion of kisspeptin neurons in the hypothalamic arcuate nucleus in early juvenile life reduces pubertal LH secretion and delays puberty onset in mice.

Puberty is the critical developmental transition to reproductive capability driven by the activation of gonadotropin-releasing hormone (GnRH) neurons. The complex neural mechanisms underlying pubertal activation of GnRH secretion still remain unknown, yet likely include kisspeptin neurons. However, kisspeptin neurons reside in several hypothalamic areas and the specific kisspeptin population timing pubertal onset remains undetermined. To investigate this, we strategically capitalized on the differential ontological expression of the Kiss1 gene in different hypothalamic nuclei to selectively ablate just arcuate kisspeptin neurons (aka KNDy neurons) during the early juvenile period, well before puberty, while sparing RP3V kisspeptin neurons. Both male and female transgenic mice with a majority of their KNDy neurons ablated (KNDyABL) by diphtheria toxin treatment in juvenile life demonstrated significantly delayed puberty onset and lower peripubertal LH secretion than controls. In adulthood, KNDyABL mice demonstrated normal invivo LH pulse frequency with lower basal and peak LH levels, suggesting that only a small subset of KNDy neurons is sufficient for normal GnRH pulse timing but more KNDy cells are needed to secrete normal LH concentrations. Unlike prior KNDy ablation studies in rats, there was no alteration in the occurrence or magnitude of estradiol-induced LH surges in KNDyABL female mice, indicating that a complete KNDy neuronal population is not essential for normal LH surge generation. This study teases apart the contributions of different kisspeptin neural populations to the control of puberty onset, demonstrating that a majority of KNDy neurons in the arcuate nucleus are necessary for the proper timing of puberty in both sexes.

Additional Daily Intramuscular Progesterone for Luteal Phase Support does not Improve Live Birth Rates of Programmed Frozen-Thawed Embryo Transfer Cycles

This retrospective cohort study aims to investigate whether additional daily intramuscular progesterone (IMP) for luteal phase support improves live birth rates of programmed frozen-thawed embryo transfer (FET) cycles. The study was conducted at a tertiary level university hospital assisted reproductive technology (ART) center between January 2014 and Jan 2021. Six hundred four infertile patients with single-day 5-6 frozen-thawed blastocyst embryo transfer were enrolled in the study. All patients received either 8% micronized vaginal gel or vaginal progesterone capsules for luteal phase support. Intramuscular progesterone was added to vaginal progesterone depending on the in vitro fertilization (IVF) specialist’s choice. Luteal phase support (LPS) was started 6 days before transfer in frozen-thawed cycles and continued until the end of the first trimester. Cycles were compared depending on vaginal progesterone types (8% gel vs. capsule) and the presence of intramuscular progesterone. The primary outcome was the live birth rate. A total of 604 FET cycles were enrolled. Using 8% micronized progesterone or progesterone capsules did not change the live birth rates (24% vs. 25.9%). As the main result, intramuscular progesterone support with vaginal progesterone compared with only vaginal progesterone did not improve the live birth results (22% vs. 24%). In conclusion, this study demonstrated that routine IMP progesterone given in combination with vaginal progesterone does not improve ART outcomes. This combination may be beneficial in a selective population with a monitored luteal phase. Using any form of vaginal progesterone alone is adequate for LPS.

COVID-19 and Reproductive Function: A Detailed Review of Fertility Outcomes, Sperm Alterations, and Vertical Transmission Concerns

Background:The global COVID-19 pandemic, caused by SARS-CoV-2, raises concerns about its effects on reproductive health. Emerging evidence suggests potential impacts on male and female fertility, including hormonal changes, immune responses, and organ damage, though the virus’s direct influence on reproductive tissues and vertical transmission remains unclear. Objective:This review summarizes current evidence on COVID-19’s effects on male and female reproductive health, focusing on sperm count, fertility, and vertical transmission. Methods:A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Peer-reviewed studies were included based on their relevance to reproductive outcomes, sperm count, hormonal changes, and vertical transmission of SARS-CoV-2. Results:Most studies found no direct evidence of SARS-CoV-2 in male or female reproductive tissues. However, a temporary decline in sperm count and quality has been reported in men recovering from COVID-19. Hormonal fluctuations, particularly increased luteinizing hormone (LH) levels, were observed in some male patients. In females, the presence of ACE2 receptors in reproductive organs suggests a potential risk, but no conclusive evidence of impaired fertility has been found. Vertical transmission remains uncertain, with isolated cases reporting elevated IgM antibodies in newborns. Conclusion:Although direct evidence of SARS-CoV-2 impacting fertility is limited, temporary reproductive disruptions in males, including reduced sperm count, have been noted. The risk of vertical transmission remains unclear. Further research is essential to determine COVID-19’s long-term reproductive effects.