Fertility-enhancing effects of inositol & vitamin C on cisplatin induced ovarian and uterine toxicity in rats via suppressing oxidative stress and apoptosis.

Cisplatin can lead to infertility due to its negative impact on the uterus and ovaries. This study aimed to explore the effects of Inositol and vitamin C on cisplatin-induced infertility. Forty-eight adult female Wistar rats were divided into eight groups (N = 6) and orally treated for 21 days. The treatments were as follows: negative control (saline), positive control (saline and cisplatin injected into the abdomen on day 15), T1-T3: rats given vitamin C (150 mg/kg), Inositol (420 mg/kg), and vitamin C + Inositol, respectively, along with cisplatin injected into the abdomen on day 15, T4-T6: rats given only vitamin C, Inositol, and vitamin C + Inositol, respectively. Vitamin C and Inositol enhanced cisplatin-induced histopathological improvements in the uterus and ovaries, raising progesterone and estradiol serum levels. Furthermore, the supplements enhanced ESR1 gene expression in the uterus and ovary, reducing uterine and ovarian apoptosis caused by cisplatin through modulation of caspase 3, 8, and Bcl-2 gene levels. These substances decreased ovarian and uterine malondialdehyde levels, boosted total antioxidant capacity and superoxide dismutase, and alleviated oxidative stress. The findings reveal that vitamin C and Inositol shield against cisplatin-related infertility by reducing oxidative stress and apoptosis in the uterus and ovaries.

Fertility protective effect of taxifolin in cisplatin-induced ovarian damage.

OBJECTIVE: The aim of our study was to investigate the protective effect of taxifolin on ovarian damage and reproductive dysfunction created by cisplatin administration. MATERIALS AND METHODS: A total of 36 albino Wistar female adult rats were equally divided into 3 groups as cisplatin administered only (CIS), taxifolin+cisplatin (T+C) and healthy control group (HG). Taxifolin 50 mg/kg was administered orally by gavage in the T+C (n=12) group. In the HG (n=12) and CIS (n=12) groups, the same volume of distilled water as a solvent was orally administered. One hour after administration of taxifolin or distilled water, animals in the T+C and CIS groups were injected with cisplatin at a dose of 2.5 mg/kg intraperitoneally. This procedure was repeated once a day for 14 days. Six animals from each group were sacrificed on day 15, and their ovaries were removed for histopathological and biochemical analysis. Ovarian tissue malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-kB), Tumor Necrosis Factor-α (TNF-α), Interleukin 1 beta (IL-1ß), and Interleukin-6 (IL-6) levels were measured. The remaining animals (n=6 in each group) were kept in the laboratory with mature male rats for two months to breed. RESULTS: CIS administration led to an increase in inflammatory molecules and membrane lipid peroxidation products, and decreased the synthesis of antioxidant molecules. Compared to the CIS group, the ovarian tissue MDA, NF-kB, TNF-α, IL-1ß and IL-6 levels were found to be significantly decreased in the T+C group (p<0.001 for all comparisons). On the other hand, the tGSH levels of the T+C group were significantly higher than the CIS group (p<0.001). Milder ovarian necrosis, fibrosis and follicle damage were detected in animals which were given taxifolin. Four out of the six rats (67%) treated with taxifolin gave birth within 27 days. CONCLUSIONS: We demonstrated, for the first time, that taxifolin ameliorates cisplatin-induced ovarian injury by decreasing MDA and proinflammatory cytokines and increasing the antioxidant enzyme. The fact that more than half of the animals receiving taxifolin became pregnant suggests that the cytoprotective effect of taxifolin is strong enough to preserve fertility.

Risk of colorectal cancer after use of fertility drugs-results from a large Danish population-based cohort of women with infertility.

OBJECTIVE: To study the association between use of fertility drugs and colorectal cancer among women with infertility. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): The study cohort was obtained from the Danish Infertility Cohort and consisted of all women with infertility aged 20-45 years living in Denmark during 1995-2017. INTERVENTION(S): Information on the use of specific types of fertility drugs, colorectal cancer diagnoses, covariates, and vital status were obtained from the Danish Infertility Cohort and Danish national registers. MAIN OUTCOME MEASURE(S): Cox proportional hazard models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer overall and rectal and colon cancer separately. RESULTS(S): Among 148,036 women in the final study cohort, 205 women were diagnosed with colorectal cancer. Ever use of clomiphene citrate (CC) was associated with a lower rate of colorectal cancer (unadjusted HR, 0.67; 95% CI, 0.51-0.89; adjusted HR, 0.68; 95% CI, 0.50-0.93). However, the lower rate was only seen among women who first used CC >8 years ago (unadjusted HR, 0.56; 95% CI, 0.41-0.76; adjusted HR, 0.52; 95% CI, 0.36-0.75). No marked associations were found between the use of any of other types of fertility drugs and colorectal cancer. The results for colon and rectal cancer analyzed separately were similar, except for a suggestion of a decreased risk of rectal cancer associated with the use of gonadotropins (adjusted HR, 0.46; 95% CI, 0.20-1.08). CONCLUSION(S): Among women with infertility, the use of most types of fertility drugs was not associated with colorectal cancer. However, CC may decrease the risk of colorectal cancer and gonadotropins might decrease the risk of rectal cancer, but we cannot rule out that these findings may be more related to the underlying conditions in these women or are chance findings. Consequently, the results from this study should be investigated further in large epidemiological studies.

Tumors of the central nervous system among women treated with fertility drugs: a population-based cohort study.

PURPOSE: To investigate the association between fertility drugs and tumors of the central nervous system (CNS). METHODS: This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995-2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. RESULTS: During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs. CONCLUSION: No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary.

Relation between Selenium and Female Fertility: A Systematic Review / Relação entre o selênio e a fertilidade feminina: Uma revisão sistemática

Abstract Objective To analyze the influence of selenium in female fertility. Data sourceA search was performed in the following databases: MEDLINE, Web of Science, Scopus, SciELO, LILACS, MDPI, ScienceDirect, and Europe PMC. The descriptors selected were "selenium" AND "female" AND "fertility". The search interval was from 1996 to 2021. Study selectionThe evaluation was performed independently by two reviewers, and a third reviewer confirmed the inclusion of papers in case of divergence between the first two reviewers. Papers were selected after the title and abstract were read, and those that met the eligibility criteria had the full text read. Data collectionThe following data was extracted: author, year of publication, country, type of study, objective, method, sample size, follow-up period, patients' mean age, inclusion and exclusion criteria, and concentration of serum and capillary selenium. The data was organized in chronological order of paper publication. Data synthesisThe number of papers identified totaled 3,800, out of which 7 were included in the systematic review. The studies indicated a positive correlation between serum selenium and antioxidant concentration in the follicular fluid, reduction in antithyroid antibodies, oocyte production and follicle number. Conclusion Selenium supplementation is promising in women with this micronutrient deficiency to promote improvement of the reproductive efficiency and prevent damage to the pregnancy. Further studies on this theme are still required.

Resumo Objetivo Analisar a influência do selênio na fertilidade feminina. Fonte dos dadosUma busca foi realizada nas seguintes bases de dados: MEDLINE, Web of Science, Scopus, SciELO, LILACS, MDPI, ScienceDirect e Europe PMC. Os descritores selecionados foram "selenium" AND "female" AND "fertility". O intervalo de busca foi de 1996 a 2021. Seleção dos estudosA avaliação ocorreu de maneira independente por dois revisores, sendo que um terceiro corroborou a eleição dos artigos em casos de divergência. Os estudos foram selecionados através da leitura do título e resumo, e aqueles que contemplaram os critérios de elegibilidade foram lidos na íntegra. Coleta dos dadosOs seguintes dados foram extraídos: autor, ano de publicação, país, tipo de estudo, objetivo, método, tamanho da amostra, tempo de acompanhamento, média de idade das pacientes, critérios de inclusão e exclusão, concentração de selênio sérico e capilar. Os dados foram organizados em ordem cronológica de publicação do estudo. Síntese dos dadosForam identificados 3.800 artigos e incluídos 7 estudos na revisão sistemática. Os resultados indicaram correlação positiva entre o nível de selênio sérico e a concentração de antioxidantes no fluido folicular; diminuição dos níveis de anticorpos antitireoidianos; produção de oócitos, e número de folículos. Conclusão A suplementação de selênio é promissora em mulheres com deficiência do micronutriente, a fim de promover melhora na eficiência reprodutiva e prevenir danos na gravidez. Salientou-se a necessidade de realização de mais estudos sobre o tema.

Phytochemical analysis and fertility enhancement effects of aerial parts of Fagonia arabica in male and female rats.

In this study, fertility enhancing effect of ethanol extract of aerial parts of Fagonia arabica was evaluated. 24 female and 12 male virgin Wistar rats (Average wt 150-250g) were selected. Dose was given daily for 23 days in 4 groups of animal. After 23 days, they were cohabitated for mating. Then dosing was continued for further 5 days. On 5th day of mating, sperm counting was done by observing vaginal smear under the microscope which showed fertility enhancement in male. Female were kept separately until delivery. The number of pubs born provided female fertility enhancement as compared to control. Average sperm count in 1 cm2 were counted in group A, B, C and control as 14.000±1.732, 12.000±1.000, 23.333±1.528 and 11.000±1.000 respectively. Number of pubs were counted in Group A, B, C and D as 8.667±2.082, 7.333±1.528, 7.333±1.528 10.000±2.000 and 5.333±0.577 respectively and fertility index was calculated for Group A, B and C as 62.516%, 37.502% and 87.512% respectively. Result showed that the orally administered dose of Fagonia arabica possess highly significant fertility enhancing activity in male and female rats after observing improvement in the sperm count and number of pubs as compared to control.

What is the fertility-enhancing effect of tubal flushing? A hypothesis article.

Hysterosalpingographies (HSGs) have formed an essential part of the fertility workup for more than a century. More recently, tubal flushing, especially with oil-based contrast, has been shown to significantly improve the natural conception rates. Critically, the mechanism of this fertility-enhancing effect during tubal flushing is still unclear. This article postulates hypotheses, based on published and own research, on the potential mechanisms and root cause of tubal flushing fertility enhancement. Possible explanations for the increased fertility rates, especially with oil-based contrast, are divided into the biochemical and interfacial effects derived from the contrast properties. The biochemical effects may include the immunological response of the endometrium or peritoneum, the impact on the endometrial opioid receptors or the iodine content. The interfacial effects may include improvement of interfacial factors due to the lubricant effect or dislodgement of mucus debris within the Fallopian tubes. Impact StatementWhat is already known on this subject? Tubal flushing during hysterosalpingographies (HSGs) increases natural conception rates, and using oil-based over water-based contrast increases that effect even further. However, the underlying mechanism of the observed fertility-enhancing effect is still poorly understood.What do the results of this study add? This article postulates different hypotheses on the potential mechanisms and root cause of the fertility enhancement from tubal flushing.What are the implications of these findings for clinical practice and/or further research? We suggest additional research on the different hypotheses, intending to determine which subfertile women will benefit most from tubal flushing using oil-based contrast and at which stage of their subfertility. Furthermore, we suggest research on administering tubal flushing with oil-based contrast, besides in HSG.

Fertility Effects on Blueberry Gall Midge (Diptera: Cecidomyiidae) in Wild Blueberry (Vaccinium angustifolium; Ericales: Ericaceae).

Blueberry gall midge, Dasineura oxycoccana (Johnson) (Diptera: Cecidomyiidae) is a pest in American cranberry, Vaccinium macrocarpon Aiton (Ericales: Ericaceae) and wild blueberry, Vaccinium angustifolium Aiton (Ericales: Ericaceae), and has been observed in areas of high soil and foliar nutrient levels. New management strategies, including fertilization, will need to be altered to sustain wild blueberry production under climate change and, in turn, may impact the occurrence of this pest. The purpose of this study was to measure the effect of diammonium phosphate (DAP) fertilizer application on density of infested stems and the combined effects of fertilizer application with and without infestation on wild blueberry systems. This study was conducted at two field sites in Jonesboro and Washington, ME during 2020 and 2021. Despite increases in habitat availability (blueberry cover) for the gall midge and greater infestation density, wild blueberry production benefited from DAP application. This was shown in the number of buds per stem at both sites, as well as in stem height, flowers, green fruit, blue fruit per stem, and total yield at the Washington site. Foliar nitrogen and phosphorus levels had a significant positive linear relationship with infestation density. Growers applying fertilizers should monitor blueberry gall midge field infestation levels due to our findings that DAP fertilizer impacted infestation density and the interaction of DAP fertilizer with infestation impacted wild blueberry production.

Infertility treatment associated with childhood asthma and atopy.

STUDY QUESTION: Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions? SUMMARY ANSWER: Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy. WHAT IS KNOWN ALREADY: Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments. STUDY DESIGN, SIZE, DURATION: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI). LIMITATIONS, REASONS FOR CAUTION: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association. WIDER IMPLICATIONS OF THE FINDINGS: Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Perspectivas de una producción sostenible en acuicultura multitrófica integrada (IMTA): una revisión / Prospects for sustainable production in integrated multitrophic aquaculture (IMTA): a review

RESUMEN La acuicultura tradicional se enfrenta a serios problemas medioambientales, particularmente por el uso de grandes volúmenes de agua, con las consecuentes descargas de efluentes ricos en nutrientes inorgánicos y partículas orgánicas. Un ejemplo claro de esto está en que del 20 al 30% del nitrógeno presente en la proteína del alimento suministrado es aprovechado por los peces, el restante 70-80% es desechado en el cuerpo de agua producto de la excreción y el alimento no consumido, lo que favorece la eutrofización de aguas receptoras y su entorno. Por lo anterior, se requiere el desarrollo de tecnologías y prácticas de producción innovadoras, responsables, sostenibles y rentables. Una de las alternativas que está generando interés, debido a sus implicaciones ambientales, económicas y sociales, es la producción en sistemas de acuicultura multitrófica integrada (IMTA). Este concepto se basa en la integración de diferentes niveles tróficos en un mismo sistema, lo que resulta en una conversión de los residuos de cultivo de unas especies en alimentos o fertilización para otras especies. Aplicada, la producción IMTA puede mejorar la sostenibilidad de la acuicultura al reducir el impacto de los efluentes y generar mayor rentabilidad económica, debido a la producción simultanea de dos o más productos finales y al uso mínimo de fertilizantes. El objetivo de la presente revisión es presentar los fundamentos básicos de los sistemas de IMTA, como una alternativa a los sistemas de producción en piscicultura.

ABSTRACT Traditional aquaculture faces serious environmental problems, particularly due to the use of large volumes of water, with the consequent discharge of effluents rich in inorganic nutrients and organic particles. A clear example of this is that only 20 to 30% of the nitrogen present in the protein of the supplied food is used by the fish. The remaining 70 to 80% is disposed of in the water body as a result of excretion and unconsumed food, favoring the eutrophication of receiving waters and their environment. Therefore, the development of innovative, responsible, sustainable, and profitable technologies and production practices is required. One of the alternatives that is generating interest due to its environmental, economic, and social implications is the production in integrated multitrophic aquaculture systems (IMTA). This concept is based on the integration of different trophic levels in the same system, which results in a conversion of the culture residues of some species into food or fertilization for other species. Applicated, the IMTA systems can improve the sustainability of aquaculture by reducing the impact of effluents, generating greater economic profitability due to the simultaneous production of two or more end products and minimal use of fertilizers. The objective of this review is to present fundamentals basic aspects of IMTA systems, as an alternative to fish farming production systems.

Assessment of Ferula hermonis Boiss fertility effects in immature female rats supported by quantification of ferutinin via HPLC and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula hermonis is a small shrub renowned for its aphrodisiac abilities. Middle East herbalists have utilized Ferula hermonis seed and root as an aphrodisiac folk medicine to treat women's frigidity and male erectile and sexual dysfunction. AIM OF THE STUDY: Assessment of follicle-stimulating hormone-like (FSH), luteinizing hormone-like (LH), and estrogenic activities of the methanolic extract (ME) of the roots of Ferula hermonis on female reproductive function. MATERIALS AND METHODS: The methanolic extract was prepared from the root of F. hermonis and studied at dose level 6 mg/kg in immature female rats for FSH-like, LH-like, and estrogenic activities. These activities were determined by analyzing gross anatomical features, relative organ weight, and serum level of FSH, LH, progesterone and estrogen hormones, and histopathological characteristics. Quantification of the main phytoestrogenic component ferutinin carried out by HPLC. In addition, molecular docking for the binding affinity of ferutinin inside active sites of both estrogen receptor alpha (ERα) and FSH receptor (FSHR) was performed to predict the potential role of ferutinin in regulating the female reproductive process. RESULTS: Ferula hermonis (ME) showed potent FSH-like, LH-like activities and moderate estrogenic effect at the dose of 6 mg/kg. The content of ferutinin in F. hermonis was estimated to be 92 ± 1.33 mg/g of the methanolic extract. Molecular docking of ferutinin with ERα and FSHR displayed strong interaction with target proteins. CONCLUSIONS: Based on results, it can be concluded that Ferula hermonis can be considered as a suitable female fertility improving agent.

Fertility drugs and incidence of thyroid cancer in a Danish nationwide cohort of 146 024 infertile women.

STUDY QUESTION: Do fertility drugs increase the risk of thyroid cancer among infertile women? SUMMARY ANSWER: The use of most types of fertility drugs was not associated with an increased risk of thyroid cancer. WHAT IS KNOWN ALREADY: The incidence of thyroid cancer is higher for women than men, especially during reproductive years, indicating that reproductive hormones may be involved in the development of thyroid cancer. Only a few previous studies have examined the association between the use of fertility drugs and incidence of thyroid cancer and the results are inconclusive. STUDY DESIGN, SIZE, DURATION: A retrospective, population-based cohort study including all 146 024 infertile women aged 20-45 years and living in Denmark in the period 1995-2017. The women were followed from the date of entry in the cohort (i.e. date of first infertility diagnosis) until the occurrence of thyroid cancer or any other cancer (except non-melanoma skin cancer), death, emigration, total thyroidectomy or the end of follow-up (31 December 2018), whichever occurred first. The median length of follow-up was 11.3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 167 women were diagnosed with thyroid cancer during the follow-up period. Information on the use of specific fertility drugs (clomiphene citrate, gonadotropins, hCGs, GnRH receptor modulators and progesterone), thyroid cancer, covariates and vital status was obtained from the Danish Infertility Cohort and various Danish national registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% CIs for thyroid cancer overall and for papillary thyroid cancer. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for the calendar year of infertility diagnosis, the highest obtained level of education, parity status, obesity or thyroid disease and mutual adjustment for other registered fertility drugs, no marked associations were observed between the use of clomiphene citrate, hCG, gonadotropins or GnRH receptor modulators and risk of overall or papillary thyroid cancer. However, ever use of progesterone was associated with an increased rate of both overall (HR 1.63; 95% CI 1.07-2.48) and papillary (HR 1.66, 95% CI 1.04-2.65) thyroid cancer after mutual adjustment for other specific fertility drugs. For most specific fertility drugs, we observed a tendency toward higher associations with thyroid cancer within the first 5 years after the start of drug use than after 5 years from the start of use. No marked associations were detected according to the cumulative dose for any of the specific fertility drugs. LIMITATIONS, REASONS FOR CAUTION: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of thyroid cancer cases. Although we were able to adjust for a number of potential confounders, residual and unmeasured confounding may potentially have affected the observed associations, as we could not adjust for some factors that may influence the association between fertility drugs and thyroid cancer, including age at menarche and BMI. WIDER IMPLICATIONS OF THE FINDINGS: Although this study, which is the largest to date, provides reassuring evidence that there is no strong link between the use of fertility drugs and thyroid cancer incidence, we observed a modest increased thyroid cancer incidence after the use of progesterone. However, we cannot rule out that this is a chance finding and the potential association between the use of progesterone and thyroid cancer should therefore be investigated further in large epidemiological studies. The results of the present study provide valuable knowledge for clinicians and other health care personnel involved in the diagnosis and treatment of infertility. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from the Jascha Foundation and the Aase and Ejner Danielsens Foundation. B.N. received honoraria and/or non-financial support by Gedeon Richter Nordics AB, IBSA Nordic APS and Merck KGAA. The remaining authors have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Anti-fertility effect of levonorgestrel and/or quinestrol on striped field mouse (Apodemus agrarius): evidence from both laboratory and field experiments.

The effect of combined levonorgestrel (P) and quinestrol (E) on the fertility of striped field mouse (Apodemus agrarius) has not been evaluated. We performed a series of experiments in both the laboratory and field to assess the effect of P and/or E on the fertility of A. agrarius. In the laboratory, to test the time-dependent anti-fertility effects of P and E, as well as their mixtures, 90 male striped field mice were randomly assigned to 6 treatment groups (n = 60), and a control group (n = 30). Mice in 3 treatment groups were administered 1 of the 3 compounds (1 mg⋅kg- 1 [body weight] EP-1, 0.34 mg⋅kg-1 E, 0.66 mg⋅kg-1 P) for 3 successive days (another half for 7 successive days) via oral gavage; mice were then sacrificed 15 and 45 days after initiating the gavage treatment. Our findings indicated that E and EP-1 treatment, but not P or control treatment, significantly decreased the sperm count in the caudal epididymis, as well as the weight of the testes, epididymides, and seminal vesicles. Additionally, fertile female mice mated with E- and EP-1-treated males produced smaller pups. These data indicate that E and EP-1 can induce infertility in male A. agrarius. In the field, the population density of A. agrarius was significantly influenced by EP-1, and the rodent density in the treatment group was lower than that in the control group. Overall, our results indicate that EP-1 is an effective contraceptive in A. agrarius, a dominant rodent species in the farmland.

Roles of melatonin in the field of reproductive medicine.

Melatonin, mostly released by the pineal gland, is a circadian rhythm-regulated and multifunctional hormone. Great advances in melatonin research have been made, including its role in rhythms of the sleep-wake cycle, retardation of ageing processes, as well as antioxidant or anti-inflammatory functions. Melatonin can scavenge free radicals such as reactive oxygen species (ROS), a key factor in reproductive functions. Melatonin plays an important role in oocyte maturation, fertilization and embryonic development as well. The concurrent use of melatonin increases the number of mature oocytes, the fertilization rate, and number of high-quality embryos, which improves the clinical outcome of assisted reproductive technology (ART). This review discusses the relationship between melatonin and human reproductive function, and potential clinical applications of melatonin in the field of reproductive medicine.

Phoenix dactylifera L. date tree pollen fertility effects on female rats in relation to its UPLC-MS profile via a biochemometric approach.

Date palm (Phoenix dactylifera L.) is among the most ancient cultivated crops, of special value owing to its fruits high nutritive and economic benefits. Asides, date palm pollen is a high energy material that has been used traditionally used for fertility enhancement. In this study, effects of date palm pollen crude extract and its fractions viz., petroleum ether, methylene chloride, ethyl acetate and n-butanol on the female reproductive system were evaluated for the first time in relation to its metabolite fingerprint. Fertility activity was evaluated in immature female rats by assessing their FSH-, LH- and estrogen- activities. To pinpoint active hormonal agents in crude pollen extract and fractions, UPLC- MS analysis was employed for metabolites profiling, and in correlation to extract/fraction bioassays using multivariate OPLS analysis. Results revealed that both polar n-butanol and non-polar petroleum ether fractions exhibited the strongest activities; with a significant increase in FSH (25.7 mIU/ml in n-butanol group), estradiol (414.7 pg/ml in petroleum ether group) and progesterone levels (122.4 pg/ml in n-butanol group). Correlation between UPLC-MS and fraction bioassays was attempted using multivariate OPLS analysis to reveal for bioactive hits in these fractions. This study provides the first report on the fertility effect of date palm pollen in female rats and in relation to its metabolite fingerprint.

Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study.

Objective: This study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis. Materials and Methods: This study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols. Results: In the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis. Conclusions: The ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

Use of Fertility Drugs and Risk of Malignant Melanoma: Results from a Large Danish Population-Based Cohort Study.

Fertility drugs have not definitively been linked to malignant melanoma. By the use of data from a large nationwide cohort of women aged 20.0-45.0 years and living in Denmark between January 1, 1995 and December 31, 2011, we assessed the association between the use of fertility drugs and the risk of malignant melanoma. Information on fertility status and the use of fertility drugs was obtained from the population-based Danish Infertility Cohort. Cox proportional hazard regression models were applied to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. The study population comprised 1,330,954 women, of whom 86,231 (6.5%) were treated with fertility drugs. During a median follow-up of 21.0 years, 6,139 women were diagnosed with malignant melanoma. Compared with fertile women, women with fertility challenges who had used any fertility drugs had an increased risk of malignant melanoma (hazard ratio = 1.14; 95% confidence interval = 1.02-1.27). Furthermore, the use of specific types of fertility drugs (clomiphene, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone preparations, and progesterone) was also associated with an increased risk of malignant melanoma, with hazard ratios ranging between 1.09 and 1.13; however, the association did not reach statistical significance. Our findings indicate that the use of fertility drugs was associated with a modestly increased risk of malignant melanoma.

Molecular Mechanism and Anti-Fertility Effect of Plant Complex Sterility Agent on Targeted Gene DPY19L2 in Rats.

BACKGROUND: Damage caused by rats is a serious hazard to the environment and crop irrigation. It not only results in great damage to the ecological environment, but also seriously affects the growth and yield of crops and forests. Controlling damage caused by rats is the primary task for improving the environment and maintaining ecological balance. METHODS: Basing on the related gene DPY19L2 in the maturation and development of seminal vesicles in rats, our study explored the effect of non-toxic and pollution-free plant complex sterility agent on rat fertility. RESULTS: The results showed that the plant complex sterility agent could effectively reduce the genital organ index of male rats, change the sperm morphology, reduce the testosterone content and sperm motility, inhibit the expression of spermatogenesis genes DPY19L2, SPATA16, SUN5, and ZPBP, and achieve the effective sterility control of rat pests. CONCLUSIONS: Plant complex sterility agent with high concentration can effectively target rat sperm gene DPY19L2 and realize effective sterility control of rat pests.

Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness.

Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.

How long does the fertility-enhancing effect of hysterosalpingography with oil-based contrast last?

RESEARCH QUESTION: Does the fertility-enhancing effect of tubal flushing during hysterosalpingography (HSG) with oil-based contrast change over time? DESIGN: This was a secondary analysis of the H2Oil (long-term follow-up) study, a multicentre randomized controlled trial evaluating the effectiveness of oil-based and water-based contrast during HSG. The main outcome was ongoing pregnancy. Cox proportional hazards models for time to ongoing pregnancy were fitted over 3 years of follow-up. RESULTS: Data on 1107 couples were available; 550 couples had oil-based contrast and 557 water-based contrast at HSG. Ongoing pregnancy rates after 3 years were 77% and 71%, respectively. Median follow-up was 9-10 months (5th-95th percentile: <1 to 36). The hazard ratio for ongoing pregnancy for oil versus water over 3 years of follow-up was 1.26 (95% confidence interval [CI] 1.10-1.45). The scaled Schoenfeld residual plots showed a decrease in hazard ratio that was linear with log-transformed time. After including an interaction with log-transformed time, the hazard ratio immediately after HSG was 1.71 (95% CI 1.27-2.31) and reduced to no effect (hazard ratio of 1) at approximately 2 years. There was no evidence for a change in hazard ratio over time in a subgroup of women who experienced pain during HSG. CONCLUSIONS: The hazard ratio for ongoing pregnancy of oil-based versus water-based contrast was 1.71 immediately after HSG, gradually decreasing and plateauing towards a hazard ratio of 1 (indicating no effect) after approximately 2 years. This supports the hypothesis that oil-based contrast might dislodge debris or mucus plugs from the Fallopian tubes, but this has yet to be definitively proved.