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IntroductionFemale reproductive function depends on a choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, acute LPS-induced inflammation inhibits gonadotropin production and secretion from the pituitary, thereby impacting the downstream production of sex hormones. These outcomes have only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on pituitary function and consequent luteinizing and follicle stimulating hormone secretion.MethodsA chronic inflammatory state was induced in female mice by twice weekly injections with LPS over 6 weeks. Serum gonadotropins were measured and bulk RNAseq was performed on the pituitaries from these mice, along with basic measurements of reproductive biology.ResultsSurprisingly, serum luteinizing and follicle stimulating hormone was not inhibited and instead we found it was increased with repeated LPS treatments.DiscussionAnalysis of bulk RNA-sequencing of murine pituitary revealed paracrine activation of TGFβ pathways as a potential mechanism regulating FSH secretion in response to chronic LPS. These results provide a framework with which to begin dissecting the impacts of chronic inflammation on reproductive physiology.

This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To compare fertility outcomes of obese patients (body mass index [BMI] ≥ 30 kg/m2) undergoing superovulation and intrauterine insemination (SO-IUI) using gonadotropins versus letrozole. Methods: A single centre retrospective cohort study of obese patients undergoing SO-IUI using gonadotropins or letrozole between January/2019 and June/2022. Primary outcome was clinical pregnancy rate (intrauterine pregnancy with positive fetal heart rate). Secondary outcomes included rates of multifollicular development, multiple pregnancy, spontaneous abortion and cycle cancellation. Subgroup analysis was done stratifying by obesity class. A multivariate logistic regression model was used for primary/secondary outcomes, adjusting for clinically determined covariates. Results: Out of 802 total identified SO-IUI cycles, 715 cycles were completed (518-gonadotropins and 197-letrozole cycles). The clinical pregnancy rates were not significantly different in obese patients undergoing SO-IUI with gonadotropins versus letrozole when adjusted for age, gravidity, parity, cause of infertility, IUI cycle number, endometrial thickness, sperm source and post-wash motile sperm count (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 0.72–2.59). Similarly, no significant associations were found in spontaneous abortion (aOR1.46, 95%CI 0.42–5.08), multiple pregnancy (aOR1.33, 95%CI 0.20–8.88) or cancellation rates (OR0.89, 95%CI 0.55–1.45) between the two groups. The rates of multifollicular development were also comparable between the two groups (aOR0.51, 95% CI 0.19–1.38). For cycles involving gonadotropins, higher BMI classes required higher total gonadotropin dose (p < 0.001). Conclusion: After adjusting for patient and cycle factors, gonadotropins and letrozole led to comparable odds of achieving pregnancy in obese patients undergoing SO-IUI. Future research in the obese population will help to better understand how to optimize fertility treatments for this growing population. [ABSTRACT FROM AUTHOR]

Background/Objectives: The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and their receptors are major regulators of reproduction in mammals and are absent in insects. We previously established transgenic Drosophila lines expressing a constitutively active human LH receptor variant (LHRD578Y) and the wild-type receptor (LHRwt; inactive in the absence of an agonist). That study showed that ubiquitously expression of LHRD578Y—but not of LHRwt—resulted in pupal lethality, and targeted expression in midline cells resulted in thorax/bristles defects. To further study the Drosophila model for an in vivo drug screening platform, we investigated here whether expressing LHRD578Y in the fly gonads alters reproduction, as shown in a transgenic mice model. Methods: The receptor was expressed in somatic cells of the gonads using the tissue-specific traffic jam-Gal4 driver. Western blot analysis confirmed receptor expression in the ovaries. Results: A fecundity assay indicated that the ectopic expression of LHRD578Y resulted in a decrease in egg laying compared to control flies carrying, but not expressing the transgene (~40% decrease in two independent fly lines, p < 0.001). No significant reduction in the number of laid eggs was seen in flies expressing the LHRWT (<10% decrease compared to non-driven flies, p > 0.05). The decreased egg laying demonstrates a phenotype of the active receptor in the fly gonads, the prime target organs of the gonadotropins in mammals. We suggest that this versatile Drosophila model can be used for the pharmacological search for gonadotropin modulators. Conclusions: This is expected to provide: (a) new mimetic drug candidates (receptor-agonists/signaling-activators) for assisted reproduction treatment, (b) blockers for potential fertility regulation, and (c) leads relevant for the purpose of managing extra gonadotropic reported activities. [ABSTRACT FROM AUTHOR]

The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during this time. As post-reproductive lifespan continues to increase it is likely that the incidence of dementia will also increase unless therapies are developed to prevent, slow or cure dementia. A growing body of evidence implicates age-related endocrine dyscrasia and the length of time that the brain is subjected to this endocrine dyscrasia, as a key causal event leading to the cognitive decline associated with aging and Alzheimer's disease (AD), the major form of dementia in our society. In particular, the elevations in circulating gonadotropins, resulting from the loss of gonadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with either gonadotropin-releasing hormone analogues, or via physiological hormone replacement therapy, has been demonstrated to halt or significantly slow cognitive decline in those with AD. This review provides an overview of past and present studies demonstrating the importance of hypothalamic-pituitary-gonadal hormone balance for normal cognitive functioning, and how targeting age-related endocrine dyscrasia with hormone rebalancing strategies provides an alternative treatment route for those with AD. [ABSTRACT FROM AUTHOR]

Introduction: Co-administration of clomiphene citrate during the early phase in in vitro fertilisation (IVF) cycles has been used by clinicians for several years to improve outcomes. Materials and methods: This is a single centre retrospective study involving 222 patients with 81 patients underwent IVF using co-administration of Clomiphene Citrate (CC) with gonadotropins (study group - group A) and 141 patients used only gonadotropins (control group - group B) were compared. The outcome data of the IVF cycles were focused on four major aspects of which are the total gonadotropin usage, number of oocytes obtained, fertilisation rate and top-quality embryos produced. Results: The Mean ± Standard Deviation (SD) of patients age is (34.72 ± 3.25) and (34.39 ± 3.39) years old from group A and B respectively. Mean ± (SD) of total usage of gonadotropins (1834.57 ± 477.34iu) vs (2645.04 ± 669.66iu), (p< 0.0001), mean number of oocytes ± (SD) retrieved (8.54 ± 5.95) vs (10.32 ± 6.67), (p = 0.048), mean ± (SD) fertilisation rate (39.82 ± 30.46) vs (49.04 ± 27.62), (p=0.027) and mean percentage ± (SD) of the top-quality embryos are (17.96 ± 25.68) vs (28.02 ± 32.19), (p=0.02) from group A and B respectively. Conclusion: Co-administration of CC with gonadotropins in IVF reduces the total amount of gonadotropins required in the IVF cycle however it also reduces the number of oocytes retrieved, fertilization rate and top quality embryos. [ABSTRACT FROM AUTHOR]

This article discusses the use of gonadotropin treatment as an alternative to surgery for adults with congenital hypogonadotropic hypogonadism (CHH) and cryptorchidism. CHH is a condition where there is a deficiency of certain hormones, leading to absent or incomplete puberty. Cryptorchidism, or undescended testis, is more common in individuals with CHH. The article presents three case studies of adult males with CHH and persistent cryptorchidism who were successfully treated with gonadotropin therapy. The findings suggest that this treatment can be a safe and effective alternative to surgery for correcting cryptorchidism in young adult males with CHH. Further research is needed to explore this treatment in larger patient groups. [Extracted from the article]

The reproductive performance of female chickens is critical for determining the efficiency of production and productivity and thus profitability. Studies have shown that the reproductive performance of female chickens is mainly regulated by the feed, hormones, genes, and light conditions. Herein, we review the major factors regulating female chicken reproductive performance and assess the reproductive organs and their functions. In the current review, we highlight how the interconnections of hormones, candidate genes, and photo-stimulation regulate female chicken reproductive hormones and thus regulate the reproductive organ performance. In this regard, the roles of main hormones [gonadotropinreleasing hormone (GnRH) and genes (GnRH-I)] in regulating sexual maturation and ovarian development and maintenance by influencing the survival and function of follicular granulosa cells were also reviewed. In addition, the current review also highlights how feeding female chickens with diets and artificial light-emitting diodes (LEDs) support the effective functioning of their reproductive capacity through the stimulation of sexual maturity at an appropriate age and regeneration of aged reproductive organs.

Among mammals, post-reproductive life spans are currently documented only in humans and a few species of toothed whales. Here we show that a post-reproductive life span exists among wild chimpanzees in the Ngogo community of Kibale National Park, Uganda. Post-reproductive representation was 0.195, indicating that a female who reached adulthood could expect to live about one-fifth of her adult life in a post-reproductive state, around half as long as human hunter-gatherers. Post-reproductive females exhibited hormonal signatures of menopause, including sharply increasing gonadotropins after age 50. We discuss whether post-reproductive life spans in wild chimpanzees occur only rarely, as a short-term response to favorable ecological conditions, or instead are an evolved species-typical trait as well as the implications of these alternatives for our understanding of the evolution of post-reproductive life spans.

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways. • Apelin and its receptor are expressed in porcine anterior and posterior pituitary. • Apelin and APJ expression levels change during the cycle and early pregnancy. • Apelin changes LH and FSH secretion by gonadotropes during the oestrous cycle. • Apelin affects Akt, MAPK/Erk1/2 and AMPK phosphorylation in the pituitary. • Apelin may play a role in the regulation of pituitary functions. [ABSTRACT FROM AUTHOR]

Abstract Background Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The present study aimed to elucidate the mechanisms whereby SFRP4 antagonizes FSH action. Methods Primary cultures of granulosa cells from wild-type mice were treated with FSH and/or SFRP4, and effects of treatment on gene expression were evaluated by RT-qPCR and RNAseq. Bioinformatic analyses were conducted to analyse the effects of SFRP4 on the transcriptome, and compare them to those of FSH or a constitutively active mutant of FOXO1. Additional granulosa cell cultures from wild-type or Sfrp4-null mice, some pretreated with pharmacologic inhibitors of specific signaling effectors, were used to examine the effects of FSH and/or SFRP4 on signaling pathways, autophagy and apoptosis by western blotting and TUNEL. Results Treatment of cultured granulosa cells with recombinant SFRP4 was found to decrease basal and FSH-stimulated mRNA levels of FSH target genes. Unexpectedly, this effect was found to occur neither via a canonical (CTNNB1-dependent) nor non-canonical WNT signaling mechanism, but was found to be GSK3β-dependent. Rather, SFRP4 was found to antognize AKT activity via a mechanism involving AMPK. This lead to the hypophosphorylation of FOXO1 and a decrease in the expression of a portion of the FSH and FOXO1 transcriptomes. Conversely, FSH-stimulated AMPK, AKT and FOXO1 phosphorylation levels were found to be increased in the granulosa cells of Sfrp4-null mice relative to wild-type controls. SFRP4 treatement of granulosa cells also induced autophagy by signaling via AKT-mTORC1-ULK1, as well as apoptosis. Conclusions This study identifies a novel GSK3β-AMPK-AKT signaling mechanism through which SFPR4 antagonizes FSH action, and further identifies SFRP4 as a novel regulator of granulosa cell autophagy. These findings provide a mechanistic basis for the phenotypic changes previously observed in Sfrp4-null mice, and broaden our understanding of the physiological roles of WNT signaling processes in the ovary.

Background: Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The present study aimed to elucidate the mechanisms whereby SFRP4 antagonizes FSH action. Methods: Primary cultures of granulosa cells from wild-type mice were treated with FSH and/or SFRP4, and effects of treatment on gene expression were evaluated by RT-qPCR and RNAseq. Bioinformatic analyses were conducted to analyse the effects of SFRP4 on the transcriptome, and compare them to those of FSH or a constitutively active mutant of FOXO1. Additional granulosa cell cultures from wild-type or Sfrp4-null mice, some pretreated with pharmacologic inhibitors of specific signaling effectors, were used to examine the effects of FSH and/or SFRP4 on signaling pathways, autophagy and apoptosis by western blotting and TUNEL. Results: Treatment of cultured granulosa cells with recombinant SFRP4 was found to decrease basal and FSH-stimulated mRNA levels of FSH target genes. Unexpectedly, this effect was found to occur neither via a canonical (CTNNB1-dependent) nor non-canonical WNT signaling mechanism, but was found to be GSK3β-dependent. Rather, SFRP4 was found to antognize AKT activity via a mechanism involving AMPK. This lead to the hypophosphorylation of FOXO1 and a decrease in the expression of a portion of the FSH and FOXO1 transcriptomes. Conversely, FSH-stimulated AMPK, AKT and FOXO1 phosphorylation levels were found to be increased in the granulosa cells of Sfrp4-null mice relative to wild-type controls. SFRP4 treatement of granulosa cells also induced autophagy by signaling via AKT-mTORC1-ULK1, as well as apoptosis. Conclusions: This study identifies a novel GSK3β-AMPK-AKT signaling mechanism through which SFPR4 antagonizes FSH action, and further identifies SFRP4 as a novel regulator of granulosa cell autophagy. These findings provide a mechanistic basis for the phenotypic changes previously observed in Sfrp4-null mice, and broaden our understanding of the physiological roles of WNT signaling processes in the ovary. [ABSTRACT FROM AUTHOR]

Objective: To compare two cancellation policies in controlled ovarian stimulation‐intrauterine insemination (COS‐IUI) cycles to lower the risk of multiple pregnancies (MP). Design: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS‐IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case‐by‐case and physician‐dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS‐IUI cycles, without any predefined cut‐off. Our main outcome measures were the MP rate (MPR) and the live‐birth rate (LBR). Results: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS‐IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02–2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16–1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001). Conclusions: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR. Synopsis: A cancellation strategy based on an algorithm allows reduction of the risk of multiple pregnancies without impacting the live birth rate. [ABSTRACT FROM AUTHOR]

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second—termed "mini-puberty"—in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of salmon gonadotropin releasing hormone analog (S-GnRH-A) and human chorionic gonadotropin (HCG) on the serum levels of gonadotropins (GtHs) and sex steroid hormones in Manchurian trout during sexual maturity. Females in the treatment group were injected with 20 µg/kg S-GnRH-A and 400 IU/kg HCG, whilst males were injected with half the amount. Blood samples were collected at 0, 5, 10, and 20 days post injection (dpi). The results showed an increase in female follicle-stimulating hormone (FSH) levels in the treatment group at 5 dpi, and from 5 dpi onwards, a difference was observed between the groups, with higher FSH levels in the treatment group compared to the control group. In males, FSH levels showed group differences at only 5 dpi (p < 0.05) and were higher in the treatment group. In females, luteinizing hormone (LH) peaked at 10 dpi in the treatment group, and there were differences between the two groups at 10 dpi and 20 dpi. In males, LH was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05). In females, estradiol (E2) was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05), whereas in males, the difference between the two groups was only observed at 5 dpi (p < 0.05). The female testosterone (T) level in the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), while T levels were significantly higher in the male treatment group than in the control group at 5 dpi (p < 0.05). The level of 17α–hydroxyprogesterone (17α-OHP) in the females of the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), and 17α-OHP levels were significantly higher in the male treatment group than in the control group at 10 and 20 dpi (p < 0.05). The fish were successfully spawned after S-GnRH-A and HCG injections, and brood amount, fertilization rate, and hatching rate were significantly increased (p < 0.05). This study provides a framework for a better understanding of the mechanisms of exogenous hormone-mediated control of reproduction in Manchurian trout. [ABSTRACT FROM AUTHOR]

Abstract Background The gonadotropins lutropin and follitropin stimulate steroid synthesis in the gonads during gonadal maturation by promoting oogenesis and spermatogenesis. Endocrine disruptors such as lindane (γHCH) can alter the reproductive stage so and could alter puberty by interfering with lutropin and follitropin signaling. γHCH was classified by World Health Organization as “moderately restricted”, and in 2009 it is production and agricultural use was prohibited, under the Stockholm Convention, however, its use as a pharmaceutical treatment against lice and scabies is still allowed (and mainly, for use by the health sector). This study aimed to examine the effects of single-dose exposure to γHCH in young mice (Mus musculus) on lutropin and follitropin concentration, and to correlate gonadal maturity status and phenotypic characteristics. Methods Young γHCH-treated mice (16 females and 16 males) received a single dose of 25, 10, 5, or 0 µg/ml γHCH per gram of body weight, ocular route. Once secondary sexual characteristics were observed, the gonads were dissected and examined using histological techniques and the ovarian follicles were classified as dependent and independent of gonadotropins; the testicles were classified as inactive, early and late spermatogenesis; and the blood was processed with the lutropin and follitropin ELISA kit. Results The results indicate significant differences in the concentration of lutropin and follitropin between males and females (Fisher p

Reproductive medicine is actively developing, and new methods, drugs, and protocols are being developed and introduced for the treatment of infertility. Assisted reproductive technologies (ART) are the most effective methods. In ART protocols, ovarian stimulation (OS) is based on gonadotropin use. The choice of the starting dose of gonadotropin is a critical factor in the successful OS and the effectiveness of ART programs. The article describes the development history of gonadotropins and provides current data on their use in ART programs. The use of biosimilars of follitropin alfa in OS is discussed, and the effectiveness of its Russian biosimilar is also addressed. TRANSLATE with x English Arabic Hebrew Polish Bulgarian Hindi Portuguese Catalan Hmong Daw Romanian Chinese Simplified Hungarian Russian Chinese Traditional Indonesian Slovak Czech Italian Slovenian Danish Japanese Spanish Dutch Klingon Swedish English Korean Thai Estonian Latvian Turkish Finnish Lithuanian Ukrainian French Malay Urdu German Maltese Vietnamese Greek Norwegian Welsh Haitian Creole Persian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

Polycystic ovary syndrome (PCOS) is a popular illness in women after puberty age. It’s described via overdone androgen production, and ovulation unrest while elevating metabolic syndrome. PCOS was usually diagnosed by Ultrasound or blood test to check the androgens and other hormone levels. There are many causes of having pathogenesis of POCS which was related to abnormalities in hormone levels, insulin resistance, obesity, and others. the symptoms of PCOS could include irregular periods, excess body hair, weight gain, oily skin, and infertility. Due to the variety of symptoms, the POCS has many different types of treatment options, for instant use of medications or lifestyle changes such as weight loss. Many medications are used to treat PCOS like organic compounds and have proven effective in treating PCOS as well as many metallic elements will aid medicinal chemists in planning, organizing, and implementing new approaches toward the discovery of novel drugs. One of the most important medications which were used to treat PCOS is clomiphene citrate and that is commonly used for the treatment of infertility. This review highlights to the causes and treatments of PCOS and gives many examples of recent research that uses drugs and metallic elements as a medication.

Background: The gonadotropins lutropin and follitropin stimulate steroid synthesis in the gonads during gonadal maturation by promoting oogenesis and spermatogenesis. Endocrine disruptors such as lindane (γHCH) can alter the reproductive stage so and could alter puberty by interfering with lutropin and follitropin signaling. γHCH was classified by World Health Organization as "moderately restricted", and in 2009 it is production and agricultural use was prohibited, under the Stockholm Convention, however, its use as a pharmaceutical treatment against lice and scabies is still allowed (and mainly, for use by the health sector). This study aimed to examine the effects of single-dose exposure to γHCH in young mice (Mus musculus) on lutropin and follitropin concentration, and to correlate gonadal maturity status and phenotypic characteristics. Methods: Young γHCH-treated mice (16 females and 16 males) received a single dose of 25, 10, 5, or 0 µg/ml γHCH per gram of body weight, ocular route. Once secondary sexual characteristics were observed, the gonads were dissected and examined using histological techniques and the ovarian follicles were classified as dependent and independent of gonadotropins; the testicles were classified as inactive, early and late spermatogenesis; and the blood was processed with the lutropin and follitropin ELISA kit. Results: The results indicate significant differences in the concentration of lutropin and follitropin between males and females (Fisher p < 0.05). The lutropin and follitropin levels showed a tendency to decrease in females, whereas, in males they tended to increase as the dose of γHCH increased. In females, it was observed that at the follitropin and lutropin decreased 42.3% and 83.7%, respectively at dose of 25 µg/ml; while in males, follitropin increased 51.9% at the dose of 25 µg/ml, and at the dose of 10 µg/ml lutropin increased by 242.5%. Contrary to that, gonadal maturity increased in females and decreased in males with increasing γHCH dose, disagreeing with the idea that gonadotropins coincide with the onset of puberty and gonadal maturity. Conclusions: The results allow us to infer that exposure to γHCH could promote non-monotonic responses; however, this does not seem to alter puberty in the doses and conditions of the present experiment. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadotropin-releasing hormone (GnRH), a critical regulator of pituitary gonadotropin secretion, plays a fundamental role in controlling physiological aspects of mammalian reproduction. GnRH is produced in the hypothalamus and regulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. GnRH analogs, including agonists and antagonists, have been developed for the reproductive management of animals. This review focuses on the functions of hypothalamic GnRH in reproductive processes and the enhancement of reproductive efficiency in farm animals. Various GnRH analogs have been synthesized to improve their potency and reproductive function. This review specifically highlights the application of GnRH in estrus synchronization to increase the reproductive efficiency of dairy cows. GnRH is essential for the regulation of mammalian reproductive processes. It regulates the production and release of pituitary gonadotropins, thereby influencing steroidogenesis and gametogenesis. While primarily produced in the hypothalamus, GnRH is also produced in peripheral organs, such as the gonads and placenta. GnRH analogs, including agonists and antagonists, have been synthesized for the reproductive management of animals and humans. This review focuses on the functions of hypothalamic GnRH in the reproductive processes of cattle. In addition to inducing the surge release of LH, the pulsatile secretion of GnRH stimulates the pituitary gland to release FSH and LH, thereby regulating gonadal function. Various GnRH-based products have been synthesized to increase their potency and efficacy in regulating reproductive functions. This review article describes the chemical structures of GnRH and its agonists. This discussion extends to the gene expression of GnRH in the hypothalamus, highlighting its pivotal role in regulating the reproductive process. Furthermore, GnRH is involved in regulating ovarian follicular development and luteal phase support, and estrus synchronization is involved. A comprehensive understanding of the role of GnRH and its analogs in the modulation of reproductive processes is essential for optimizing animal reproduction. [ABSTRACT FROM AUTHOR]

Chronic psychosocial stress can negatively affect the female reproductive system. Meanwhile, the effect of ovarian stimulation with gonadotropins during stress on the quality of oocytes remains poorly studied. This work was aimed to investigate the effects of chronic psychosocial stress on the quality of murine cumulus-oocyte complexes under the natural estrus cycle, as well as during the ovarian stimulation with exogenous gonadotropins, which is an important part of modern assisted reproductive technologies. Here we demonstrate that psychosocial stress does not affect the number of ovulating oocytes but deteriorates their quality, i.e. reduces the percentage of mature oocytes. In addition, stressed mice exhibited an enhanced accumulation of reactive oxygen species (ROS) in oocytes, accompanied by an increased apoptosis level in cumulus cells. Hormonal stimulation of the ovaries with gonadotropins alleviates the negative changes associated with psychosocial stress, normalizing ROS overproduction in oocytes and reducing apoptosis levels in cumulus cells. [ABSTRACT FROM AUTHOR]

Background: In otherwise normal boys with undescended testes, early orchidopexy is recommended to preserve fertility, to decrease the risk of testicular cancer, and to facilitate its detection. Indeed, compared to the general population, the risk of testicular cancer is increased two- to eight-fold in isolated cryptorchidism and usually occurs before the age of 40 years. By contrast, when cryptorchidism is associated with congenital hypogonadotropic hypogonadism, the risk of testicular cancer is unknown. Objective: The aim of this study was to determine the characteristics of testicular cancer when cryptorchidism is associated with congenital hypogonadotropic hypogonadism. Methods: We conducted a PubMed research without date limits including the following key words: hypogonadism, hypogonadotropic hypogonadism, testicular cancer, testicular germ cell tumors, undescended testis, Kallmann syndrome, FSH, AFP (α foeto protein), βHCG. Results: Only 3 patients with testicular cancer and congenital hypogonadotropic hypogonadism have been published in the past 4 decades and two were diagnosed at 50 and 64 years. Conclusion: Gonadotropin deficiency may protect against testicular cancer, and orchidopexy in this context may be deferred. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P  < 0.001), 0.767 for u24LH (P  < 0.001), and 0.753 for the u24LH/u24FSH ratio (P  < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER In-house #23-5214 registered study. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the bioequivalence in bovines in superovulatory, superstimulatory and fertility in an TFAI protocol between a single-chain equine chorionic gonadotropin produced by recombinant technology (eCG-like) and native eCG. In Experiment 1, a crossing over experimental design was used where 14 cows received 2,000 IU im of eCG or 2,000 IU im of eCG-like on Day 4 of a superovulatory protocol in two periods. The cyclicity, size of the preovulatory follicles (PF), the number of accumulated ovulations (AO) and the number of corpora lutea (CL) were determined by ultrasonography. Experiment 2 was performed to evaluate the pregnancy rate in beef cows, where 828 cows received a protocol based on P4 and estradiol, and on Day 8 (removal of the intravaginal device) they were assigned to receive 400 IU of eCG-like (n=278), 400 IU of native eCG (n=301) or remain as untreated controls (n=249). In Experiment 3, the percentage of pregnancy at TFAI in dairy cows (n=472) was evaluated, where the same TFAI protocol based on progesterone and estradiol was used, and on Day 8, the cows were assigned to receive 400 IU of eCG-like (n=187) or 400 IU of eCG (n=194) or remain control (n=91). In Experiment 1, there were no differences in the number of FPs, the number of AO, the number of CL. In Experiment 2, the pregnancy rate at IATF was 29.7%, being higher in the groups treated with eCG and eCG-like compared to the control: 31.6%, 32.4% and 24.5% respectively (P=0.0391). In Experiment 3, the follicular diameter on day 10 was greater in cows treated with eCG and eCG-like (P=0.0007) and the IATF pregnancy rate was 38.6% and was affected by the treatment (P= 0.0335). We conclude that single-chain eCG-like produced by recombinant technology demonstrated a similar biological response in cattle at the same dose as eCG, being the first report where bioequivalence has been demonstrated in cattle. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)? SUMMARY ANSWER Length of AGD seemed to differ in different groups of patients with cryptorchidism. WHAT IS KNOWN ALREADY AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer. STUDY DESIGN, SIZE, DURATION A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022). PARTICIPANTS/MATERIALS, SETTING, METHODS AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by 'The Infant Development and the Environment Study' (TIDES) and 'Cambridge Baby Growth Study', resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD. MAIN RESULTS AND THE ROLE OF CHANCE There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P  < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r  = 0.44), but not for boys with undescended testes (Spearman r  = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P  < 0.005) and (P  < 0.000001). LIMITATIONS, REASONS FOR CAUTION Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions. WIDER IMPLICATIONS OF THE FINDINGS The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in 'the masculinization programming window' in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and no competing interests are declared. TRIAL REGISTRATION NUMBER The trial was not registered in an ICMJE-recognized trial registry. [ABSTRACT FROM AUTHOR]

Objective: We examined how the sex steroids influence the synthesis of gonadotropins. Materials and Methods: The effects of sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) in pituitary gonadotroph cell model (LβT2 cells) in vitro and ovary-intact rats in vivo were examined. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats. Results: In LβT2 cells, E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle determined by vaginal smears was disrupted. P4 or DHT administration completely eliminated the estrous cycle. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in the anterior region of the hypothalamus that included the anteroventral periventricular nucleus. The expression of gonadotropin-releasing hormone (Gnrh) mRNA in the anterior hypothalamic region, where the preoptic area is located, appeared to be decreased by treatment with E2 and P4. Conclusion: Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland. [ABSTRACT FROM AUTHOR]

Short chain fatty acids (SCFA) have been linked to women's reproductive health, though to a lesser extent, alteration in the production of SCFA and SCFA-producing bacteria has been associated significantly with pregnancy-related complications, unfavourable pregnancy outcomes, menstrual anomalies, and gynaecological cancer.The female reproductive system is a delicate, intricate, hormone-dependent group of tissues required for the continuity of life and the species' survival. Reproductive health impacts the ovarian function to implantation and foetal development. Several environmental and physiological factors contribute to mammalian infertility concerns caused by a change in reproductive health status. Several lifestyle factors have been demonstrated to affect reproductive health, including age, body weight, smoking, alcohol consumption, work stress, exercise, diet, and nutrition. Nutrition influences puberty, the menstrual cycle, ovulation, conception, implantation and early foetal development. This review provides an overview of how intestinal derived SCFAs maintains female reproductive health summarizing the current knowledge and future perspectives. Microbial SCFAs improve human metabolism by interfering with, glucose homeostasis, appetite regulation and lipid metabolism. Also affect host immunity and intestinal barrier integrity via primary by inhibition of Histone deacetylases (HDAC) mechanism. Therefore, SCFAs exhibit anti-inflammatory, anti-obesity, immunoregulatory, anti-diabetes, anti-cancer, hepatoprotective, cardiovascular protective and neuroprotective properties.This review highlights recent findings on SCFA and gynaecological pathologies such as preeclampsia, gestational diabetes, pregnancy complications, polycystic ovary syndrome, bacterial vaginosis, and endometriosis to describe current knowledge of the relationship between SCFA and reproductive health and disease in women.

BACKGROUND: In this secondary analysis of the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) trial, we aimed to investigate if concurrent administration of letrozole vs. tamoxifen vs. no added treatment affects hormonal composition and size of stimulated ovarian follicles. METHODS: TALES is a randomized controlled trial of IVF stimulation for estrogen receptor (ER)-positive breast cancer patients stimulated with gonadotropins and administered concurrent tamoxifen 20 mg or letrozole 5 mg. We analyzed estradiol (E2), testosterone (T), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH). We used ANOVA/Kruskal-Wallis, logistic, and linear regression models to examine differences in follicular hormone levels, size, and mature oocyte yield between trial arm. RESULTS: We included data from total 246 follicles (94 letrozole, 82 tamoxifen, and 70 control) from 123 unique participants. E2 was lower (letrozole 187.4, tamoxifen 1026.0, control 821.5 ng/mL, p

Objective: To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins. Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. Setting: Multicenter randomized controlled trial. Patient(s): A total of 869 couples with unexplained infertility who underwent OS-IUI treatment cycles as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation study. Intervention(s): FPL was evaluated as a categorical variable defined by quintiles (q1: ≤11 days, q2: 12 days, q3: 13 days, q4: 14–15 days, and q5: ≥16 days). Main outcome measure(s): Clinical pregnancy, live birth rates, and ET. Result(s): Decreasing FPL quintiles did not reduce clinical pregnancy or live birth rates in unadjusted or adjusted models with all treatment groups combined or when stratified by the ovarian stimulation medication. All FPL categories had significantly thinner ET compared with the 5th quintile (≥16 days) among women treated with clomiphene citrate or letrozole. Similar but diminished associations were observed among women who underwent ovarian stimulation with gonadotropins, but the observed differences were limited to those with FPL of 12 days or shorter when compared with FPL ≥16 days. Conclusion(s): Although shorter FPL was associated with reduced ET, it was not associated with the outcomes of clinical pregnancy or live birth in women with unexplained infertility undergoing OS-IUI in all treatment groups combined. Similar patterns existed when analyses of clinical pregnancy and live birth rates were stratified by treatment. Clinical trial registration: NCT01044862.

Abstract Background Premature progesterone (P) rise during IVF stimulation reduces endometrial receptivity and is associated with lower pregnancy rates following embryo transfer (ET), which can influence provider recommendation for fresh or frozen ET. This study aimed to determine whether change in P level between in IVF baseline and trigger (𝚫P) is predictive of pregnancy outcome following fresh ET, and whether the ratio of gonadotropins influences P rise and, as a result, clinical pregnancy outcomes: clinical pregnancy rate (CPR) and live birth rates (LBR). Methods Retrospective cohort study at a single fertility center at an academic institution. The peak P level and 𝚫P were modeled in relation to prediction of CPR and LBR, and the ratios of hMG:rFSH were also modeled in relation to prediction of peak P level on day of trigger, 𝚫P, and CPR/LBR in a total of 291 patients undergoing fresh embryo transfer after controlled ovarian hyperstimulation-IVF (COH-IVF). Results 𝚫P correlates with CPR, with the most predictive range for success as 𝚫P 0.7–0.85 ng/mL (p = 0.005, 95% CI 0.635, 3.636; predicting CPR of 88.9%). The optimal range for peak P in regard to pregnancy outcome was 0.15–1.349 ng/mL (p = 0.01; 95% CI for coefficient in model 0.48–3.570). A multivariable logistic model for prediction of CPR and LBR using either peak or 𝚫P supported a stronger association between 𝚫P and CPR/LBR as compared to peak P. Furthermore, an hMG:rFSH ratio of > 0.6 was predictive of lowest peak P (p = 0.010, 95% CI 0.035, 0.256) and smallest 𝚫P (p = 0.012, 95% CI 0.030, 0.243) during COH-IVF cycles. Highest CPRs were observed within hMG:rFSH ratios of 0.3–0.4 [75.6% vs. 62.5% within and outside of the range, respectively, (p = 0.023, 95% CI 0.119, 1.618)]. Highest LBRs were seen within the range of 0.3–0.6 hMG:rFSH, [LBR of 55.4% vs. 41.4% (p = 0.010, 95% CI 0.176, 1.311)]. Conclusions Our data supports use of 𝚫P to best predict pregnancy rates and therefore can improve clinical decision making as to when fresh ET is most appropriate. Furthermore, we found optimal gonadotropin ratios can be considered to minimize P rise and to optimize CPR/LBR, emphasizing the importance of luteinizing hormone (LH) activity in COH-IVF cycles.

Background/Objectives: The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and their receptors are major regulators of reproduction in mammals and are absent in insects. We previously established transgenic Drosophila lines expressing a constitutively active human LH receptor variant (LHRD578Y) and the wild-type receptor (LHRwt; inactive in the absence of an agonist). That study showed that ubiquitously expression of LHRD578Y—but not of LHRwt—resulted in pupal lethality, and targeted expression in midline cells resulted in thorax/bristles defects. To further study the Drosophila model for an in vivo drug screening platform, we investigated here whether expressing LHRD578Y in the fly gonads alters reproduction, as shown in a transgenic mice model. Methods: The receptor was expressed in somatic cells of the gonads using the tissue-specific traffic jam-Gal4 driver. Western blot analysis confirmed receptor expression in the ovaries. Results: A fecundity assay indicated that the ectopic expression of LHRD578Y resulted in a decrease in egg laying compared to control flies carrying, but not expressing the transgene (~40% decrease in two independent fly lines, p < 0.001). No significant reduction in the number of laid eggs was seen in flies expressing the LHRWT (p > 0.05). The decreased egg laying demonstrates a phenotype of the active receptor in the fly gonads, the prime target organs of the gonadotropins in mammals. We suggest that this versatile Drosophila model can be used for the pharmacological search for gonadotropin modulators. Conclusions: This is expected to provide: (a) new mimetic drug candidates (receptor-agonists/signaling-activators) for assisted reproduction treatment, (b) blockers for potential fertility regulation, and (c) leads relevant for the purpose of managing extra gonadotropic reported activities.

The effect of 10% dietary flaxseed fed for 3 and 6 weeks on serum hormone levels of fattening gilts, the fatty acid (FA) follicular fluid (FF) composition of small and large antral follicles, and the steroidogenesis and IGF-I secretion by isolated small antral follicles and their response to regulatory hormones (LH, FSH, IGF-I) was studied using immunoassay and gas chromatography analyses. Both supplemental periods increased levels of P4 and IGF-I in blood serum. A shorter period inhibited steroidogenesis (P4, T, E2) and IGF-I secretion by small antral follicles, which was associated with decreased levels of monounsaturated FAs (MUFA) and preferred n-6 polyunsaturated FA (PUFA) metabolism. A longer period stimulated hormone secretion at elevated levels of saturated FAs (SFA) at the expense of MUFAs and PUFAs preferring the n-3 PUFA metabolism. Out of ovarian regulators, only LH and IGF-I were able to alter the secretion of steroids and IGF-I by small follicles of fattening pigs fed a basal diet. The effect of flaxseed on the secretion of follicular hormones after both supplemental periods was altered by all regulatory hormones in a dose-dependent manner. The level of SFAs and PUFAs in FF of large follicles increased with the length of flaxseed feeding, suggesting the suppression of ovulation. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome is a serious complication associated with assisted reproductive technology. This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent it and replaces the document of the same name last published in 2016. [ABSTRACT FROM AUTHOR]

Objective: Serum Anti‐Mullerian Hormone (AMH) concentrations have been proposed as a marker of spontaneous puberty and future fertility in Turner syndrome (TS). Gonadotropins during minipuberty may also provide a clue to ovarian function but there is insufficient data to inform utility in the routine clinical management of TS. Our objective was to describe the distribution of AMH in a cross‐sectional cohort of patients in a TS specialty clinic, and correlate with spontaneous puberty and karyotype, as well as gonadotropins during the minipuberty of infancy in a smaller subset of patients aged 2−9 months. Design: Retrospective chart review of patients seen in the TS clinic at Children's National Hospital from 1/1/2019 to 8/24/2022, to assess AMH and correlate with karyotype and spontaneous puberty. Results: Among 114 patients (median age 9.6 year, 0.08−22 year), AMH values were detectable in only (40/104) 38%, and higher mean AMH (2.7 ± 0.95 ng/mL) was seen in mosaic 45,X/46,XX karyotype compared to 45,X (0.03 ± 0.14 ng/mL) (p <.001), and structurally abnormal‐X karyotype (0.11 ± 0.5) (p =.0003). Mean AMH was higher (1.4 ± 1.6 ng/mL) among those with spontaneous menarche compared with spontaneous thelarche but no menarche. AMH was detectable in 2/10 during minipuberty in those with the lowest luteinizing hormone (LH). Conclusions: Our institutional data reflects a diverse cohort of patients seen in a TS specialty clinic in the United States, showing correlation of AMH with karyotype and spontaneous menarche, as well as description of gonadotropins during minipuberty highlighting their clinical relevance. Studies in larger, prospective longitudinal cohorts will help determine their predictive value and role in the care of TS. [ABSTRACT FROM AUTHOR]

Background: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus–pituitary–gonadotropic axis. Objectives: To assess the impact of the consumption of Δ‐9‐tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men. Materials and methods: The individuals in a Swiss cohort were divided according to their cannabis consumption. In the cannabis user group, we determined the delay between the last intake of cannabis and sample collection, the chronicity of use and the presence of cannabidiol in the consumed product. Urinary Δ‐9‐tetrahydrocannabinol metabolites were quantified via gas chromatography–mass spectrometry. Blood phytocannabinoids, endocannabinoids and male steroids were determined via liquid chromatography–mass spectrometry/mass spectrometry, and other hypothalamus–pituitary–gonadotropic axis hormones were determined via immunoassays. Semen parameters such as sperm concentration and motility were recorded using computer‐assisted sperm analysis. Results: Anandamide, N‐palmitoyl ethanolamide, androgens, estradiol and sex hormone binding globulin levels were all higher in cannabis users, particularly in chronic, recent and cannabidiol‐positive consumers. Gonadotropin levels were not significantly different in these user subpopulations, whereas prolactin and albumin concentrations were lower. In addition, cannabis users had a more basic semen pH and a higher percentage of spermatozoa with progressive motility. However, the two latter observations seem to be related to a shorter period of sexual abstinence in this group rather than to the use of cannabis. Conclusions: Because both cannabidiol and Δ‐9‐tetrahydrocannabinol are frequently used by men of reproductive age, it is highly relevant to elucidate the potential effects they may have on human reproductive health. This study demonstrates that the mode of cannabis consumption must be considered when evaluating the effect of cannabis on semen quality. [ABSTRACT FROM AUTHOR]

Objective Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. Design Systematic review and meta-analysis. Methods A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). Results After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. Conclusions This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost. SUMMARY ANSWER Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early. WHAT IS KNOWN ALREADY Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated. STUDY DESIGN, SIZE, DURATION Nationwide population-based cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18–49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1–3 months. Very early treatment dropout was analysed by multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring. LIMITATIONS, REASONS FOR CAUTION This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout. WIDER IMPLICATIONS OF THE FINDINGS Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The use of carp pituitary extract (CPE) in fish reproduction may have drawbacks, whereas analogues of mammalian (aGnRHm) or salmon (aGnRHs) gonadotropins containing dopamine inhibitor (DI) may off er greater advantages. The objective of this study was to evaluate the effect of different hormone inducers on the reproduction of Prochilodus brevis males. A total of 44 specimens of P. brevis were divided into six groups, namely, CPE 4.0 mg; saline solution 1.0 mL; aGnRHm+DI 0.3 mg and 0.5 mg; and aGnRHs+DI 0.25 mL and 0.35 mL kg-1 of live weight. The number of ejaculates, seminal volume, curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), sperm morphology and concentration, and membrane and DNA integrity were determined. Sample normality was examined using the Shapiro-Wilk test, and homogeneity using the Levene test. Analysis of variance (ANOVA) was conducted, followed by Tukey's test to compare means, with statistical significance set at p < 0.05. Notably, all fish induced with CPE 4.0 and aGnRHm+DI demonstrated ejaculation, yielding a greater seminal volume. Sperm concentration under aGnRHs+DI 0.35 exceeded that with aGnRHm+DI 0.3 and CPE 4.0. Regarding velocity, aGnRHm+DI 0.3 outperformed aGnRHs+DI 0.35 in VCL, while aGnRHm+DI 0.3 and 0.5 and aGnRHs+DI 0.25 led to higher VSL than aGnRHs 0.35. Additionally, VAP was elevated under aGnRHm+DI 0.3 and CPE, in contrast to aGnRHs+DI 0.35. Improved sperm morphology was observed with aGnRHm+DI 0.5 and aGnRHs+DI 0.25 compared to aGnRHm+DI 0.3. The remaining parameters did not differ significantly. [ABSTRACT FROM AUTHOR]

Background: Premature progesterone (P) rise during IVF stimulation reduces endometrial receptivity and is associated with lower pregnancy rates following embryo transfer (ET), which can influence provider recommendation for fresh or frozen ET. This study aimed to determine whether change in P level between in IVF baseline and trigger (횫P) is predictive of pregnancy outcome following fresh ET, and whether the ratio of gonadotropins influences P rise and, as a result, clinical pregnancy outcomes: clinical pregnancy rate (CPR) and live birth rates (LBR). Methods: Retrospective cohort study at a single fertility center at an academic institution. The peak P level and 횫P were modeled in relation to prediction of CPR and LBR, and the ratios of hMG:rFSH were also modeled in relation to prediction of peak P level on day of trigger, 횫P, and CPR/LBR in a total of 291 patients undergoing fresh embryo transfer after controlled ovarian hyperstimulation-IVF (COH-IVF). Results: 횫P correlates with CPR, with the most predictive range for success as 횫P 0.7–0.85 ng/mL (p = 0.005, 95% CI 0.635, 3.636; predicting CPR of 88.9%). The optimal range for peak P in regard to pregnancy outcome was 0.15–1.349 ng/mL (p = 0.01; 95% CI for coefficient in model 0.48–3.570). A multivariable logistic model for prediction of CPR and LBR using either peak or 횫P supported a stronger association between 횫P and CPR/LBR as compared to peak P. Furthermore, an hMG:rFSH ratio of > 0.6 was predictive of lowest peak P (p = 0.010, 95% CI 0.035, 0.256) and smallest 횫P (p = 0.012, 95% CI 0.030, 0.243) during COH-IVF cycles. Highest CPRs were observed within hMG:rFSH ratios of 0.3–0.4 [75.6% vs. 62.5% within and outside of the range, respectively, (p = 0.023, 95% CI 0.119, 1.618)]. Highest LBRs were seen within the range of 0.3–0.6 hMG:rFSH, [LBR of 55.4% vs. 41.4% (p = 0.010, 95% CI 0.176, 1.311)]. Conclusions: Our data supports use of 횫P to best predict pregnancy rates and therefore can improve clinical decision making as to when fresh ET is most appropriate. Furthermore, we found optimal gonadotropin ratios can be considered to minimize P rise and to optimize CPR/LBR, emphasizing the importance of luteinizing hormone (LH) activity in COH-IVF cycles. [ABSTRACT FROM AUTHOR]

Background The microbiome is still a new area of research in human health and disease, especially in reproductive health. The present article aims to aid the perception on reproductive tract microbiome that may enable better management of its dysbiosis causing reproductive dysfunctions. Main body In recent years, identification of microbiota in every part of human body has been eased by next-generation sequencing-based tools. It has been demonstrated that resident microbiota is vital for normal reproductive functions. The development of disease may result owing to changes in the microbiota brought about by internal or external factors. Female reproductive microbiota may be crucial in the success of assisted reproductive technologies such as embryo implantation and prenatal care. Though much has been learned about the vaginal microbiota, the uterine microbiome has gotten very little research attention. The impacts of well-known microorganisms including Chlamydia trachomatis, Mycoplasma tuberculosis, and Neisseria gonorrhoeae have been well documented, resulting in subclinical alterations that are considered risk factors for infertility and poor reproductive outcomes. Research on microbiota of male reproductive system is still in its early stages, and there are numerous questions concerning how inflammation and urogenital infections might impact male fertility. Certain microorganisms reportedly can directly affect spermatozoon function without even inducing oxidative stress or inflammatory cytokines, but via adhering to the spermatozoon or producing soluble factors capable of altering sperm motility and/or inducing apoptosis. Conclusion The presence of specific microbiota in the reproductive tract, regardless of their pathogenicity, or the alteration of the reproductive tract resident microbiota may pose issues with fertilization, implantation, pregnancy as well as embryo development. This may result in the failure of fertility treatments and a reduction in the number of live births. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOs) women usually exhibit a high luteinizing hormone (LH) and hypersensitivity to exogenous gonadotropins stimulation which is a tremendous risk to ovarian hyperstimulation syndrome (OHSS). Since the pathophysiology of PCOS is mysterious, an aetiological approach to the treatment is difficult and should be individually designed. These features affect the outcome of treatment including ovulation and success rate. Also, PCOS women who have difficulty conceiving, frequently experience substantial treatment burden, risk, and psychological distress. Recently, a renewed interest has emerged in patient-friendly, low-risk, and less costly IVF treatments. Our study proposed a new soft protocol in PCOS ovrian stimulation without prior pituitary desensitization followed by fresh embryo transfer. Patients and methods: a retrospective cohort study was conducted between January 2018 to December 2021, including 48 out of 325 women with PCOS who underwent gonadotropin-stimulated intrauterine insemination cycles but due to unexpectedly high response with risk of multiple pregnancies and OHSS, they had been shifted to a rescue IVF and fresh embryo transfer. The primary outcomes were biochemical pregnancy, implantation rate, clinical pregnancy, rate of miscarriage, OHSS, and multiple pregnancies. Secondary outcomes were the endocrinological profiles, gonadotropin dose, and duration of stimulation. This study aims to evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to "rescue" in vitro fertilization (IVF/fresh embryo transfer) regarding implantation rates, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS). Results This study used a low dose gonadotropin injections (2.1 ± 1.4) for an average duration of (9.1 ± 1.2) and showed a high success pregnancy rate: biochemical pregnancies (56.2%), implantation rate (50.2%), clinical pregnancy rate (49.9%), and miscarriage rate (8.5%). Multiple pregnancies occurred in (6.6%) and OHSS(4.4%) only in a mild form. Conclusion Our study revealed that ovarian stimulation without prior pituitary suppression in high responders was feasible to improve the implantation rate and alleviate profound OHSS without compromising the pregnancy outcomes. This encourages all fertility specialists to implement this new protocol with expected high responders as an alternative to the conventional cycle segmentation protocol: GnRH agonist-antagonist IVF/freeze-all strategy. [ABSTRACT FROM AUTHOR]

Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disorder affecting reproductive-aged women, characterized by clinical manifestations such as hyperandrogenism, menstrual irregularities, and polycystic ovaries. Despite its prevalence and impact on women's health, the pathogenesis of PCOS remains incompletely understood. This review provides a comprehensive critical appraisal of existing literature on PCOS pathogenesis, addressing knowledge gaps and highlighting its multifactorial nature. A systematic literature review identified relevant articles published up to the knowledge cutoff date in 2023, focusing on molecular, genetic, hormonal, and environmental factors contributing to PCOS pathogenesis. Electronic databases, including PubMed, MEDLINE, and Embase, were systematically searched using predefined terms. Eligible studies investigated molecular, genetic, hormonal, and environmental factors associated with PCOS pathogenesis. The critical appraisal revealed diverse studies enriching our understanding of PCOS. Molecular and genetic studies highlighted alterations in signaling pathways, hormonal dysregulation, and the role of insulin resistance. Environmental factors, including lifestyle and exposure to endocrine-disrupting chemicals, were implicated. Heterogeneity in study designs and methodologies underscored the need for standardized approaches to enhance comparability. This review synthesizes current evidence on PCOS critical appraisal and pathogenesis, emphasizing its multifaceted nature. Standardization of study designs and methodologies will facilitate future comparisons, enabling the development of targeted therapeutic interventions and personalized management strategies for women affected by PCOS.

The objective of this study was to investigate the effects of salmon gonadotropin releasing hormone analog (S-GnRH-A) and human chorionic gonadotropin (HCG) on the serum levels of gonadotropins (GtHs) and sex steroid hormones in Manchurian trout during sexual maturity. Females in the treatment group were injected with 20 µg/kg S-GnRH-A and 400 IU/kg HCG, whilst males were injected with half the amount. Blood samples were collected at 0, 5, 10, and 20 days post injection (dpi). The results showed an increase in female follicle-stimulating hormone (FSH) levels in the treatment group at 5 dpi, and from 5 dpi onwards, a difference was observed between the groups, with higher FSH levels in the treatment group compared to the control group. In males, FSH levels showed group differences at only 5 dpi (p < 0.05) and were higher in the treatment group. In females, luteinizing hormone (LH) peaked at 10 dpi in the treatment group, and there were differences between the two groups at 10 dpi and 20 dpi. In males, LH was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05). In females, estradiol (E2) was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05), whereas in males, the difference between the two groups was only observed at 5 dpi (p < 0.05). The female testosterone (T) level in the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), while T levels were significantly higher in the male treatment group than in the control group at 5 dpi (p < 0.05). The level of 17α–hydroxyprogesterone (17α-OHP) in the females of the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), and 17α-OHP levels were significantly higher in the male treatment group than in the control group at 10 and 20 dpi (p < 0.05). The fish were successfully spawned after S-GnRH-A and HCG injections, and brood amount, fertilization rate, and hatching rate were significantly increased (p < 0.05). This study provides a framework for a better understanding of the mechanisms of exogenous hormone-mediated control of reproduction in Manchurian trout.

Follicle stimulating hormone (FSH) is produced by the pituitary gland in a coordinated hypothalamic-pituitary-gonadal (HPG) axis event, plays important roles in reproduction and germ cell development during different phases of reproductive development (fetal, neonatal, puberty, and adult life), and is consequently essential for fertility. FSH is a heterodimeric glycoprotein hormone of two dissociable subunits, α and β. The FSH β-subunit (FSHβ) function starts upon coupling to its specific receptor: follicle-stimulating hormone receptor (FSHR). FSHRs are localized mainly on the surface of target cells on the testis and ovary (granulosa and Sertoli cells) and have recently been found in testicular stem cells and extra-gonadal tissue. Several reproduction disorders are associated with absent or low FSH secretion, with mutation of the FSH β-subunit or the FSH receptor, and/or its signaling pathways. However, the influence of FSH on germ cells is still poorly understood; some studies have suggested that this hormone also plays a determinant role in the self-renewal of germinative cells and acts to increase undifferentiated spermatogonia proliferation. In addition, in vitro, together with other factors, it assists the process of differentiation of primordial germ cells (PGCLCs) into gametes (oocyte-like and SSCLCs). In this review, we describe relevant research on the influence of FSH on spermatogenesis and folliculogenesis, mainly in the germ cell of humans and other species. The possible roles of FSH in germ cell generation in vitro are also presented.