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.

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.

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.

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.

The association between fertility treatments and the incidence of paediatric cancer: A systematic review and meta-analysis.

BACKGROUND: It is important to explore the association between different fertility treatments and the incidence of paediatric cancer, as this will provide crucial guidance for clinical decision-making. Previous studies have explored the relationship between fertility treatments and different types of cancer in offspring, but the results are controversial. METHOD: Two authors searched PubMed, Embase, Web of Science and Cochrane databases independently to acquire qualified studies. Then, the same authors extracted data from these studies and analysed these data using RevMan 5.3. MAIN RESULTS: Eleven case-control studies and 16 cohort studies were included in this review and meta-analysis. The relative risk of association between in vitro fertilisation (IVF) and paediatric cancer incidence was 1.01 (95% confidence interval [CI]: 0.80-1.28) in cohort studies and 1.09 (95% CI: 0.74-1.58) in case-control studies. The relative risk of association between intracytoplasmic sperm injection (ICSI) and paediatric cancer incidence was 0.97 (95% CI: 0.80-1.17) in cohort studies. The relative risk of association between fertility drugs and paediatric cancer incidence was 1.07 (95% CI: 0.68-1.69) in cohort studies and 1.12 (95% CI: 0.90-1.41) in case-control studies. The relative risk of association between frozen embryo transfer and paediatric cancer incidence was 1.37 (95% CI: 1.04-1.81) in natural pregnancy controls and 1.28 (95% CI: 0.96-1.69) in fresh embryo transfer controls. CONCLUSION: There is no evidence that IVF, ICSI and fertility drugs are associated with an increase in paediatric cancer incidence in offspring; however, frozen embryo transfer is associated with an increase in paediatric cancer incidence in the offspring, but this finding needs further research and attention.

Endocrine approach in the treatment of obesity: Is there any space for the adiponectin action?

Adiponectin is a hormone secreted by adipose tissue, exerting many positive effects in the human body. Its action has been widely studied, placing it into the metabolic health beneficial products of the adipose tissue. Nevertheless, adiponectin has been shown to exert some extra beneficial non metabolic actions, as well. Adiponectin levels can be related to reduced incidence of cancer in obese patients. Moreover, adiponectin has been shown to be implicated in the positive fertility outcomes of women. Some new studies have also indicated that adiponectin has a potential effect in the control of appetite, which raises a question, whether adiponectin could be accredited to be useful in the endocrine evaluation of obesity. Could these additional non-metabolic actions prove its helpfulness?

Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.

Chemotherapy directly or indirectly affects organs in a short-term or continuous manner. Endocrine organs are especially sensitive to cancer treatment, leading to concerns among patients regarding their quality of life afterward. Side effects to the ovary include damage to the ovarian reserve, resulting in follicle loss, endocrine hormone deficiency, and infertility. It has been previously demonstrated that continuous treatment with 2 mg/kg cisplatin for 15 days can activate primordial follicles, suggesting that the response in the oocytes of primordial follicles was dependent on cisplatin concentration and administration frequency. However, our results demonstrate that continuous treatment with 2 mg/kg cisplatin for 15 days leads to the same consequence as with the continuous treatment of 5 mg/kg cisplatin: the death of oocytes in primordial follicles without indication of activation. Moreover, animals co-injected with melatonin and cisplatin did not display any significant differences from those treated with cisplatin only contrary to the known results. 6-hydroxymelatonin, a metabolite of melatonin, could not prevent follicle destruction, implying that melatonin does not confer the protection of ovarian follicles, either directly or indirectly. Altogether, our data support that fertoprotectants against cisplatin must target molecules that control cell death pathways in the oocytes of primordial follicles.

A review for physiological activities of EGCG and the role in improving fertility in humans/mammals.

Epigallocatechin-3-gallate (EGCG) is a secondary metabolite in green tea, which has various physiological activities, including antioxidant, antitumor, and antiviral activities. Studies have shown that EGCG has a preventive effect on infertility by protecting germ cells and oocytes from damage. EGCG functions mainly through the regulation of ROS (reactive oxygen species) levels, which affect the expression of catalase (CAT), superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2), and glutathione peroxidase (GPx), has positive influence on other enzyme activities in germ cells and oocytes, and actively alters antioxidant activities. These enzymes above can inhibit the activation of extracellular signal-regulated proteins (Erk), induce apoptosis, and control the production of ROS in tissue cells. Here, we present a comprehensive overview of the mechanisms underlying the main physiological activities of EGCG, including antioxidant, antitumor, and antiviral activities, and their potential roles in male and female reproductive systems and fertility. This paper discusses the mechanisms by which EGCG retards the infertility of germ cells and oocytes and provides a supportive recommendation for improving fertility in humans and animals. We hope it will provide useful references for related research in mammalian reproduction.

Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins.

OBJECTIVE: To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole. DESIGN: Prospective cohort study. SETTING: U.S. academic health centers. PATIENT(S): Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN). INTERVENTION(S): Longitudinal annual follow-up from birth to age 3. MAIN OUTCOME MEASURE(S): Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth. RESULT(S): One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items. CONCLUSION(S): Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.

Endometrial compaction before frozen euploid embryo transfer improves ongoing pregnancy rates.

OBJECTIVE: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs). DESIGN: An observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET. RESULT(S): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact. CONCLUSION(S): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.

Progesterone-based timed AI protocols for Bos indicus cattle II: Reproductive outcomes of either EB or GnRH-type protocol, using or not GnRH at AI.

The aim of these experiments was to study ovarian dynamics and fertility of Bos indicus beef cattle submitted to 7-d progesterone (P4)-based fixed-time AI (FTAI) protocols using different hormonal treatments. In Exp. 1, 2 yr old Nelore heifers (n = 973) were randomly assigned to one of four treatments: EB-0 (estradiol benzoate, EB on D0 and no GnRH at AI), EB-G (EB on D0 and GnRH at AI), G-0 (GnRH on D0 and no GnRH at AI), or G-G (GnRH on D0 and at AI). On D0, heifers received an intravaginal P4 implant (0.5 g) for 7 d and EB (1.5 mg) or GnRH (16.8 µg). On D7, the P4 implant was withdrawn and heifers received cloprostenol (PGF; 0.5 mg) and estradiol cypionate (EC, 0.5 mg). Heifers in G groups also received PGF and eCG (200 IU) on D6, whereas EB heifers received eCG on D7. At FTAI on D9, only EB-G and G-G groups received GnRH (8.4 µg). In Exp. 2, Nelore cows (n = 804) received the same treatments (EB-0, EB-G, G-0, or G-G) using a 1.0 g P4 implant, 2.0 mg EB, and 300 IU eCG. Effects were considered significant when P ≤ 0.05. After treatment on D0, G had more ovulations than EB in heifers (60.3 [287/476] vs. 12.7% [63/497]) and cows (73.7 [83/112] vs. 24.4% [28/113]). Luteolysis after D0 was greater in EB than G in heifers (39.2 [159/406] vs. 20.0% [77/385]) and cows (25.5 [14/55] vs. 1.6% [1/64]). Heifers in G had larger follicles (mm) than EB on D7 (10.3 ± 0.2 vs. 9.2 ± 0.2) and at AI (11.9 ± 0.2 vs. 11.3 ± 0.2). Cows had larger follicles in G than EB on D7 (11.0 ± 0.3 vs. 9.9 ± 0.3) but not at AI. More estrus was observed in G than EB for heifers (80.3 [382/476] vs. 69.6% [346/497]) and cows (67.6 [270/400] vs. 56.2% [227/404]). There was no interaction between D0 and D9 treatments on pregnancy per AI (P/AI) in heifers (EB-0: 56.7 [139/245], EB-G: 53.6 [135/252], G-0: 52.6 [127/241], and G-G: 57.5% [135/235]). However, cows from EB-G had greater P/AI than EB-0 (69.5 [142/204] vs. 60.2% [120/200]), whereas P/AI for G-0 (62.7% [127/203]) was similar to G-G (60.9% [120/197]). In heifers, there was no interaction of GnRH at AI with estrus, however, cows that did not display estrus had greater P/AI if they received GnRH at AI (GnRH = 59.1 [91/154] vs. No GnRH = 48.2% [78/162]). Thus, protocols initiated with EB or GnRH for Bos indicus heifers and cows had differing ovarian dynamics but similar overall fertility, enabling their use in reproductive management programs. Treatment with GnRH at time of AI increased fertility in some instances in Bos indicus cows but not in heifers.

New infertility therapy effects of polysaccharides from Althaea officinalis leaf with emphasis on characterization, antioxidant and anti-pathogenic activity.

Characterization, antioxidant, anti-pathogenic and infertility therapy effects of polysaccharides from Althaea officinalis (marshmallow) leaf (AOLPS) were investigated. AOLPS was fractionated using ion-exchange chromatography, affording fractions of AOLPS-1, AOLPS-2, AOLPS-3 and AOLPS-4. The fractions were mainly composed of d-galactopyranose (α-(1 â†’ 4)-glycosidic bond) with the average molecular weight of 1220, 2240, 998 and 2670 Da, respectively which means it was a pectin-like polysaccharide. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FT-IR) techniques were employed to characterize the structure of purified polysaccharides. Compared with AOLPS-1, AOLPS-2 and AOLPS-4, AOLPS-3 had higher potential as a natural antioxidant and antimicrobial. At the same time, the infertility therapy effects of four fractions of AOLPS were in the order AOLPS-3 > AOLPS-4 > AOLPS-1 > AOLPS-2. The experimental study provides strong evidence to exploit A. officinalis leaf in food and pharma manufacturing processes and presents new benefit of this plant in infertility therapy.

Use of fertility drugs in early-onset female cancer survivors-A Finnish register-based study on 8,929 survivors.

Advances in multimodality cancer treatments have increased the risk of long-term complications in early-onset cancer survivors. For female cancer survivors, these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of our study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A subclassification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95% CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counseling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years.

Fertility drugs and cutaneous melanoma risk: a French prospective cohort study.

Cutaneous melanoma has been suspected to be influenced by female sex hormones. A review of the literature in 2018 indicated that fertility drug (FD) use was associated with increased melanoma risk among parous women only. However, most studies so far were based on a retrospective design and the current evidence is unclear. We sought to prospectively investigate the associations between FD use and melanoma risk in women. E3N is a prospective cohort of 98 995 French women aged 40-65 years at inclusion in 1990. Information on use of FDs, including duration and time of administration, was assessed through self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and melanoma risk factors. Over 1990-2008, about 611 melanoma cases were ascertained among 86 653 women. Compared with never use, ever use of FDs was not associated with melanoma risk overall [hazard ratio (HR) = 1.15; 95% confidence interval (CI) = 0.75-1.74], or among parous women (HR = 1.08; 95% CI = 0.67-1.73). Among ever users of FDs, duration of use and age at first use were not associated with melanoma risk. Associations were similar after adjustment for UV exposure, although FD users were more likely to report tanning bed use than never-users (odds ratio = 1.50; CI = 1.01-2.22) in a subsample with recreational UV exposure data. Our data do not support an association between FD use and melanoma risk, but underlie the importance of taking into consideration potential confounding from sun exposure in future research.