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1.
Reprod Domest Anim ; 55(3): 374-383, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930759

RESUMO

The aim of this study was to assess the efficacy of different doses of buserelin acetate and another GnRH agonist, triptorelin acetate, in saline solution in a single subcutaneous injection, to induce ovulation of growing pre-ovulatory follicle in mare and compare it with the classical treatment of a single injection of hCG. The study is split into 3 experiments over different breeding seasons in the same stud with a random distribution of treatment. The first one was to compare the injection of 6 mg of buserelin with 1,500 IU of hCG; the second one consisted of comparing different doses of buserelin (6 mg and 3 mg); and the third one compared three different doses of buserelin (3, 2 and 1 mg), 0.1 mg of triptorelin with 1,500 IU of hCG as a control group. The results of all experiments showed the same efficacy between all treatments with mares ovulating between 24 and 48 hr after injection: experiment 1: hCG (78% n = 41) and buserelin 6 mg (90% n = 50); experiment 2: buserelin 6 mg (78,1% n = 192) and buserelin 3 mg (78% n = 341); and experiment 3: hCG (87% n = 106), buserelin 3 mg (84,7% n = 137), buserelin 2 mg (82,7% n = 104), buserelin 1 mg (87% n = 54) and triptorelin 0.1 mg (84,7% n = 72). In conclusion, this study contributes to erasing the dogma that has been established since 1975 that a single injection in solution without any long-acting excipient of a GnRH agonist cannot induce ovulation in the mare. This study also shows that a injection of 0.1 mg of triptorelin in solution is a good alternative for ovulation induction and is comparable to small doses of buserelin acetate in solution (1 mg) and 1,500 IU of the gold standard trigger hCG, mainly in countries where human formulation of buserelin is not available.


Assuntos
Busserrelina/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Cavalos/fisiologia , Indução da Ovulação/veterinária , Pamoato de Triptorrelina/farmacologia , Animais , Cruzamento , Busserrelina/administração & dosagem , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Injeções Subcutâneas/veterinária , Indução da Ovulação/métodos , Pamoato de Triptorrelina/administração & dosagem
2.
Anim Reprod Sci ; 211: 106234, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31785632

RESUMO

Two experiments evaluated the effects of injectable trace minerals (ITM) administered 11 d before artificial insemination (AI) on body weight (BW), body condition score (BCS), ovarian structures, pregnancy rate, and antioxidant response of Nellore cows. In Experiment 1, 20 multiparous cows were assigned to one of two treatments: subcutaneous injection (6 mL/cow; 11 d before AI) of saline solution or ITM (60, 10, 5, and 15 mg/mL of Zn, Mn, Se and Cu, respectively) and BW, BCS, ovarian structures and blood were evaluated. In Experiment 2, 1,144 multiparous cows were assigned to same treatments described in Experiment 1 and pregnancy rate on d 30 was evaluated. In Experiment 1, ITM did not affect (P ≥  0.23) BW, dominant follicle size, ovulation rate, and plasma concentrations of haptoglobin, ceruloplasmin and progesterone (P4). The ITM treatment tended to increase (P =  0.06) cow BCS and reduce (P ≤  0.06) corpus luteum (CL) diameter and volume. Furthermore, ITM treatment tended to increase (P =  0.06) plasma concentrations of SOD and increased (P =  0.007) GSH-Px compared with saline injection. In Experiment 2, ITM treatment tended (P =  0.06) to increase pregnancy rate of cows with BCS ≤ 5.0 but not cows with BCS > 5.0 (P =  0.99). The ITM treatment did not alter BW, plasma P4, and acute phase response, but enhanced plasma concentrations of antioxidant enzymes, and tended to enhance BCS and pregnancy rates to AI of cows with BCS ≤ 5.0, even though there was a smaller corpus luteum size.


Assuntos
Bovinos , Inseminação Artificial/veterinária , Oligoelementos/administração & dosagem , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Gravidez , Progesterona/administração & dosagem , Progesterona/farmacologia , Reprodução/efeitos dos fármacos , Substâncias para o Controle da Reprodução/administração & dosagem , Substâncias para o Controle da Reprodução/farmacologia
3.
Rev Assoc Med Bras (1992) ; 65(9): 1144-1150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618328

RESUMO

OBJECTIVE: In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS: A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS: The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION: The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Muco do Colo Uterino/efeitos dos fármacos , Clomifeno/farmacologia , Quimioterapia Combinada , Endométrio/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Proteína de Ligação a Elemento Regulador de Esterol 1/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto Jovem
4.
Anim Reprod Sci ; 210: 106193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31635779

RESUMO

The objective of this study was to determine effects of a novel seminal supplement, SuinFort, on fertility of multiparous sows. For 2 years, a total of 1159 sows were assigned to be artificial inseminated (AI) either with semen supplemented with the additive (2 IU oxytocin, 5 µg lecirelin, 2 mM caffeine, n = 830 AI) or with no supplementation (Control, n = 2422 AI). The supplement was included 15 min before insemination. Supplementation with SuinFort resulted in greater fertility both by increasing farrowing rate 87.2% ± 0.7 to 90.7% ± 1.0 (P < 0.001) and litter size from 13.8 ± 0.1 to 14.4 ± 0.1 (P < 0.001). To test if there was a direct effect of SuinFort on spermatozoa, an in vitro experiment was conducted using semen doses from 10 boars. Semen was stored at 15 °C and on days 1, 2 and 3 were aliquoted to a control and SuinFort-supplemented group, incubated at 37 °C and analyzed for sperm quality at 15 min and 2 h. For aliquots with SuinFort, there was a small decrease in semen quality. In conclusion, the administration of a combination of oxytocin, lecirelin and caffeine to boar semen 15 min prior to AI, positively affects sow fertility. Considering that in vitro effects on sperm quality were small, it is likely that SuinFort affects fertility by modulating uterine function. Supplementation of semen with SuinFort, therefore, has potential for increasing pork production efficiency as a result of increased reproductive efficiency after AI of sows.


Assuntos
Fármacos para a Fertilidade Feminina/farmacologia , Inseminação Artificial/veterinária , Sêmen , Suínos/fisiologia , Animais , Cafeína/administração & dosagem , Cafeína/farmacologia , Criopreservação/veterinária , Quimioterapia Combinada , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Masculino , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Ocitocina/administração & dosagem , Ocitocina/farmacologia , Gravidez , Análise do Sêmen , Preservação do Sêmen/veterinária
5.
Anim Reprod Sci ; 210: 106191, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31635781

RESUMO

A 2-year experiment was conducted to determine the effect of a single injection of prostaglandin after initiation of the breeding season on ewe estrous synchronization. Rambouillet ewes (n = 101; Year 1 = 52; Year 2 = 49) assigned to one of three treatments: untreated (CON); 12-d CIDR insert (CIDR); or 1 injection of prostaglandin at d 2.5 (1 PG) after rams were placed with ewes. Rams were placed with ewes at the time of CIDR removal (d 0) and remained with ewes during a 35-d breeding season. Both the CIDR- (94%) and 1 PG (73.5%) treatment groups had a larger number (P ≤ 0.01) of ewes bred in the first 5 d of the breeding season compared to ewes of the control (33%) group. As expected, CIDR-treated ewes had a shorter time to mating, than 1 PG-treated ewes and ewes of the control group had a longer interval to mating than both CIDR- and 1 PG-treated ewes (P ≤ 0.01). The number of lambs born per ewe and kg of lamb weaned per ewe was not different (P ≥ 0.31) among treatment groups. Additionally, there was no difference (P =  0.78) in net profit per ewe among treatment groups. Based on these data, utilizing a single injection of PG 2.5 d after initiation of the breeding season resulted in similar pregnancy rates at d 5 of the breeding season when compared with CIDR-treated ewes indicating the potential utilization of the 1PG protocol in a confinement setting as a viable method for estrous synchronization.


Assuntos
Sincronização do Estro/métodos , Fármacos para a Fertilidade Feminina/farmacologia , Ovinos/fisiologia , Criação de Animais Domésticos/economia , Animais , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/economia , Masculino , Gravidez
6.
Endocr Regul ; 53(3): 146-153, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517633

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.


Assuntos
Ovário/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Síndrome do Ovário Policístico/patologia , Testosterona/sangue , Ulmus/química , Animais , Modelos Animais de Doenças , Etanol/química , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Infertilidade Feminina/sangue , Infertilidade Feminina/patologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/patologia , Fitoterapia , Síndrome do Ovário Policístico/sangue , Ratos , Água/química
7.
Reprod Biol ; 19(3): 245-254, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383475

RESUMO

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H2O2) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H2O2. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2'-7'-dichlorodihydrofluorescein diacetate fluorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H2O2. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.


Assuntos
Células da Granulosa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Tiorredoxinas/metabolismo , Adulto , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Estrogênios/sangue , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Foliculoestimulante Humano/farmacologia , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Tiorredoxinas/genética , Adulto Jovem
8.
Medicine (Baltimore) ; 98(27): e16213, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277129

RESUMO

RATIONALE: The borderline form of empty follicle syndrome (EFS) is a phenomenon where only a few mature or immature oocytes are retrieved despite adequate response to controlled ovarian hyperstimulation (COH). It is a rare phenomenon with an unclear underlying mechanism, and there is currently no effective treatment. PATIENT CONCERNS: The patient received 3 assisted reproductive technology cycles, and although her follicular development and estrogen levels were normal during COH, the outcome with respect to the oocytes obtained was unsatisfactory. DIAGNOSES: Borderline form of EFS. INTERVENTIONS: In the context of undergoing GnRH-antagonist protocol, we implemented a double-trigger with human chorionic gonadotropin (hCG) after 6 hours of gonadotropin-releasing hormone agonist (GnRH-a) administration. OUTCOMES: Eleven oocytes were obtained (M I × 3, M II × 8), which underwent in vitro fertilization (IVF). After 18 hours, 7 oocytes showed normal fertilization, with 2 embryos formed 72 hours later (embryo rating, 6C II × 1, 9C II × 1); the embryos were then frozen. LESSONS: Oocyte maturation and ovulation are time-dependent processes, and that different patients require different lengths/intervals of time for treatment. Therefore, the borderline form of EFS, in general, may be treatable, and our novel trigger method provides a new treatment option for such patients in the future.


Assuntos
Gonadotropina Coriônica/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Liberador de Gonadotropina/agonistas , Síndrome de Hiperestimulação Ovariana/terapia , Indução da Ovulação/métodos , Adulto , Feminino , Fertilização In Vitro , Humanos , Recuperação de Oócitos , Gravidez , Substâncias para o Controle da Reprodução/farmacologia
9.
Eur J Contracept Reprod Health Care ; 24(3): 209-215, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066303

RESUMO

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus-pituitary-ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal. Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention. Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9-12), E2WD 13 (12-13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4-9), E2WD 10.5 (10-12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7-8)] but not E2WD [10.5 (8-11)]. Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes.


Assuntos
Muco do Colo Uterino/efeitos dos fármacos , Colo do Útero , Anticoncepcionais Orais Hormonais/farmacologia , Estradiol/farmacologia , Leuprolida/farmacologia , Progestinas/farmacologia , Adulto , Estudos Cross-Over , Estradiol/administração & dosagem , Estradiol/sangue , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Humanos , Muco , Noretindrona/sangue , Noretindrona/farmacologia , Projetos Piloto , Progesterona/sangue , Adesivo Transdérmico , Adulto Jovem
10.
Fertil Steril ; 111(4): 641-649, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30929721

RESUMO

The advent of third party parenting ushered in the era of artificial stimulation of the endometrium. Initially intended only for patients with ovarian failure, exogenous induction of endometrial receptivity was quickly shown to be as good as natural endometrial preparation, with the advantage that the timing of embryo transfer could be controlled. It is perhaps surprising that even though the ovary produces a variety of steroids, that estradiol (E2) and progesterone (P) alone would be needed to achieve optimal receptivity; no other substance has ever been shown to improve on the basic regimen of E2 and P. A variety of routes of administration are available for both E2 and P and physiologic (or supraphysiologic) serum or endometrial tissue levels of both can be achieved. The optimal duration of E2 stimulation and the timing of the onset of P administration continue to be debated, but it appears that imitating the sequence that normally occurs in nature leads to optimal results. The poorly responsive endometrium and cases of recurrent implantation failure remain a challenge, but the clear majority of patients can successfully achieve pregnancy as long as embryos of adequate quality are transferred.


Assuntos
Implantação do Embrião/fisiologia , Transferência Embrionária/métodos , Endométrio , Luteinização , Técnicas de Reprodução Assistida , Mães Substitutas , Criopreservação , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/fisiologia , Estradiol/farmacologia , Estradiol/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Luteinização/efeitos dos fármacos , Luteinização/fisiologia , Gravidez , Taxa de Gravidez
11.
Arch Virol ; 164(1): 225-234, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30357482

RESUMO

Dengue virus (DENV) infections are a major cause of morbidity and mortality in tropical and subtropical areas. Several compounds that act against DENV have been studied in clinical trials to date; however, there have been no compounds identified that are effective in reducing the severity of the clinical manifestations. To explore anti-DENV drugs, we examined small molecules that interact with DENV NS1 and inhibit DENV replication. Cyclofenil, which is a selective estrogen receptor modulator (SERM) and has been used clinically as an ovulation-inducing drug, showed an inhibitory effect on DENV replication in mammalian cells but not in mosquito cells. Other SERMs also inhibited DENV replication in mammalian cells, but cyclofenil showed the weakest cytotoxicity among these SERMs. Cyclofenil also inhibited the replication of Zika virus. A time-of-addition assay suggested that cyclofenil may interfere with two stages of the DENV life cycle: the translation-RNA synthesis and assembly-maturation stages. However, the level of intracellular infectious particles decreased more drastically after treatment with cyclofenil than the viral RNA level did, indicating that the assembly-maturation stage might be the main target of cyclofenil. In electron microscopy analysis, many aggregated particles were detected in DENV-infected cells in the presence of cyclofenil, supporting the possibility that cyclofenil impedes the process of assembly and maturation of DENV.


Assuntos
Antivirais/farmacologia , Ciclofenil/farmacologia , Vírus da Dengue/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Sobrevivência Celular , Chlorocebus aethiops , Ciclofenil/administração & dosagem , Relação Dose-Resposta a Droga , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Células Vero , Replicação Viral/efeitos dos fármacos
12.
J Endocrinol Invest ; 42(5): 549-555, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30284220

RESUMO

PURPOSE: To investigate the effects of metabolic abnormalities, hyperandrogenemia and ovulation induction by clomiphene/acupuncture on liver function parameters among women with polycystic ovary syndrome (PCOS). METHODS: This is a secondary analysis of a randomized controlled trial. All 1000 subjects were diagnosed as PCOS by modified Rotterdam criteria. Liver function parameters, metabolic panel and hormone profile were measured at baseline and after treatment. The relationship between liver parameters with metabolic, hormonal parameters and ovulation induction was examined. RESULTS: PCOS women with metabolic syndrome had higher liver enzyme levels but lower bilirubin and bile acid levels than without. PCOS women with hyperandrogenemia had higher liver enzyme, bilirubin levels than without. Correlation analyses showed that worsening of metabolic parameters was associated with higher liver enzyme levels but lower bilirubin and bile acid levels, while increased androgen levels were associated with higher liver enzyme, bilirubin and bile acid levels. Ovulation induction with clomiphene citrate could decrease bilirubin and bile acid levels, while acupuncture had no obvious effect on liver function. CONCLUSIONS: Among PCOS women, metabolic abnormalities and hyperandrogenemia impaired different liver function parameters. Clomiphene could decrease the bilirubin and bile acid levels while acupuncture had no obvious effect on liver function.


Assuntos
Clomifeno/farmacologia , Hiperandrogenismo/complicações , Fígado/fisiopatologia , Síndrome Metabólica/complicações , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Terapia por Acupuntura , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Seguimentos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/patologia , Prognóstico , Estudos Prospectivos
13.
Hum Fertil (Camb) ; 22(1): 33-38, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28738699

RESUMO

Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman's r = -0.308), the number of collected oocytes (r = -0.451), the number of mature oocytes (r = -0.526), the number of fertilized oocytes (r = -0.439) and the number of viable embryos (r = -0.443, all statistically significant at p < 0.02 level). No such associations were found with caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.


Assuntos
Caspase 3/metabolismo , Hormônio Liberador de Gonadotropina/análogos & derivados , Células da Granulosa/enzimologia , Nafarelina/farmacologia , Oócitos/fisiologia , Indução da Ovulação/métodos , Caspase 3/genética , Gonadotropina Coriônica/farmacologia , Estudos de Coortes , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Oócitos/metabolismo
14.
Theriogenology ; 125: 64-70, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30390480

RESUMO

The main objective of this study was to evaluate the effect of intramuscular (I.M.) administration of different doses of kisspeptin (Kp) on the pattern of luteinizing hormone (LH) release in Bos taurus and Bos indicus prepubertal heifers. Holstein heifers weighing 215.1 ±â€¯38.6 kg (n = 24; aged 5-8 mo) and Gyr heifers weighing 215.4 ±â€¯31.4 kg (n = 24; aged 6-10 mo) were enrolled in this study. The animals were confirmed as non-cyclical by absence of a corpus luteum (CL) as determined by ultrasound scanning of the ovaries and low circulating P4 concentrations (<1.0 ng/mL) evaluated at a 10-day interval (on day -10 and day 0). For each genetic group, heifers were randomly assigned to one of four treatments: Kp at 2.5 µg/kg body weight (Kp2.5), Kp at 5.0 µg/kg (Kp5), Kp at 10 µg/kg (Kp10), or gonadotropin-releasing hormone (GnRH) agonist (0.01 mg of buserelin acetate per heifer), all administered by I.M. injection. All animals responded to the treatments with an LH surge (P < 0.01). There was an effect of breed (P < 0.01) on induced LH release, with Holstein heifers having a greater area under the curve for LH (AUC; P < 0.01) and greater LH peak amplitude (P < 0.01) than Gyr heifers. Nevertheless, greater AUC for LH occurred in Kp10 heifers for both breeds. There was no effect of breed on LH AUC or LH peak amplitude after GnRH agonist treatment. For both breeds, heifers treated with Kp displayed an earlier (P < 0.01) LH peak with a reduced amplitude of the LH peak (P < 0.01) and reduced LH AUC (P < 0.01) compared to heifers treated with GnRH agonist. Thus, both zebu and taurus immature heifers treated with I.M. Kp injection responded with a rapid and dose-dependent LH surge, although even large doses of the native Kp-10 did not mimic the magnitude or duration of the LH surge produced by the GnRH agonist. The early onset of the LH surge after Kp treatment and the short duration suggest that the effects of Kp were likely due to pituitary rather than hypothalamic action. Finally, there seems to be a greater responsiveness to Kp in Bos taurus than in Bos indicus prepubertal heifers, although LH release after GnRH agonist treatment was similar for the two breeds.


Assuntos
Bovinos/fisiologia , Kisspeptinas/farmacologia , Hormônio Luteinizante/metabolismo , Maturidade Sexual/fisiologia , Animais , Busserrelina/administração & dosagem , Busserrelina/farmacologia , Bovinos/genética , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Injeções Intramusculares , Kisspeptinas/administração & dosagem , Distribuição Aleatória , Especificidade da Espécie
15.
Drug Des Devel Ther ; 13: 4461-4470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32099323

RESUMO

Purpose: Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear. Patients and methods: This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle. Results: A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9-11 and trigger day (all P<0.001), and the dose of hMG was significantly lower (1710.7±431.6 vs 1891.3±402.2 IU, P<0.001). No significant between-group differences were found in the number of viable embryos (5.3±3.1 vs 5.0±4.1, P=0.139) and live birth rate per FET cycle (43.5% vs 47.7%, P=0.383). None of the participants experienced moderate-to-severe ovarian hyperstimulation syndrome in either group. Conclusion: Our results showed that the application of DYG in PPOS protocol could achieve comparable oocyte retrieval and pregnancy outcomes to MPA, but significantly reduce the consumption of gonadotropins in PCOS women for IVF treatment.


Assuntos
Didrogesterona/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Fertilização In Vitro/efeitos dos fármacos , Acetato de Medroxiprogesterona/farmacologia , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Progestinas/farmacologia , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Retrospectivos , Adulto Jovem
16.
JBRA Assist Reprod ; 22(4): 355-362, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30264948

RESUMO

OBJECTIVE: Minimal stimulation IVF is a treatment option that uses clomiphene citrate (CC). We sought to evaluate how CC impacts endometrial thickness during minimal stimulation IVF cycles. METHODS: We retrospectively analyzed a cohort of 230 cycles in 119 poor ovarian response patients. The IVF cycles were studied in three groups: 130 minimal stimulation cycles, 29 mild stimulation cycles, and 30 conventional high dose gonadotropin releasing hormone (GnRH) antagonist cycles. Thirty-three minimal stimulation IVF patients had 41 frozen embryo transfers (FET) which allowed us to study whether the CC effects were prolonged. RESULTS: Endometrial thickness in the minimal stimulation group was significantly lower than the mild and conventional stimulation groups (7.3±2.2mm versus 11.4±3.3mm versus 12.9±3.8mm, respectively, p<0.0001). In patients who underwent minimal stimulation IVF followed by FET, significantly thicker endometrial thickness was achieved during their FET cycles as compared to their minimal stimulation cycles (7.95±2.1mm versus 10.3±1.8mm, p<0.0001). CONCLUSION: We concluded that endometrial thickness is impacted during minimal stimulation IVF cycles. Since negative effects on endometrial thickness are not observed in the patients' subsequent FET cycle, a freeze-all approach is justified to mitigate adverse endometrial effects of CC in minimal stimulation IVF cycles.


Assuntos
Clomifeno/farmacologia , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/farmacologia , Indução da Ovulação/métodos , Clomifeno/uso terapêutico , Criopreservação , Transferência Embrionária , Endométrio/diagnóstico por imagem , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Fertilização In Vitro , Humanos , Reserva Ovariana , Estudos Retrospectivos
17.
Curr Med Sci ; 38(4): 626-631, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30128871

RESUMO

The clinical outcomes of five groups of infertility patients receiving frozen-thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone (GnRH) agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups: tubal infertility, polycystic ovary syndrome (PCOS), endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention: group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B (control group) was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively (P<0.05). The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%,respectively (P<0.05). The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist cotreatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.


Assuntos
Técnicas de Cultura Embrionária/métodos , Transferência Embrionária/métodos , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Infertilidade/terapia , Leuprolida/uso terapêutico , Adulto , Criopreservação/métodos , Transferência Embrionária/efeitos adversos , Estrogênios/sangue , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Liberador de Gonadotropina/sangue , Humanos , Infertilidade/classificação , Infertilidade/etiologia , Leuprolida/administração & dosagem , Leuprolida/farmacologia , Masculino , Gravidez , Resultado da Gravidez , Gravidez Ectópica/epidemiologia , Progesterona/sangue
18.
Eur J Obstet Gynecol Reprod Biol ; 228: 27-31, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29908374

RESUMO

OBJECTIVES: Matrix metalloproteinase-9, Nitric oxide and inflammation plays a role in the pathogenesis of poly cystic ovary syndrome (PCOS). Even though these parameters are altered in PCOS, the effect of clomiphene citrate on them has not been studied till date. The present study was done to assess the effect of clomiphene citrate on matrix metalloproteinase-9, nitric oxide and interleukin-10 levels in women with PCOS. STUDY DESIGN: 72 women diagnosed with PCOS were enrolled in the study. Matrix metalloproteinase-9, nitric oxide and interleukin-10 levels were compared at baseline and after three weeks following Clomiphene citrate treatment. RESULTS: Clomiphene citrate increases both nitric oxide (p = 0.03) and interleukin-10 (p < 0.001) levels and reduces matrix metalloproteinase-9 levels (p < 0.001) in women with PCOS. It also improves the ovulation rate (52.8%) and clinical pregnancy rate (19.4%) in PCOS. Also there was a significant reduction in matrix metalloproteinase-9 levels in both the ovulatory (p < 0.001) and conceived groups (p = 0.024) compared to non ovulatory and non conceived group. There was no difference in nitric oxide and interleukin-10 levels in ovulatory and conceived groups compared to non ovulatory and non conceived group. CONCLUSION: We conclude that clomiphene citrate increases the levels of nitric oxide and interleukin-10 and decreases the matrix metalloproteinase - 9 levels and improves the ovulation rate and clinical pregnancy rate in PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Interleucina-10/sangue , Metaloproteinase 9 da Matriz/sangue , Óxido Nítrico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Clomifeno/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Seguimentos , Humanos , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Gravidez , Taxa de Gravidez , Adulto Jovem
19.
J Assist Reprod Genet ; 35(6): 1047-1052, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29633146

RESUMO

PURPOSE: Mild controlled ovarian hyperstimulation (COH), combined with oocyte retrieval (OR) under local anaesthesia (LA), may provide low-impact IVF. Since a single injection of corifollitrophin alfa (CFA) provides 7 days of COH, we hypothesised that clomiphene-citrate (CC) followed by CFA may provide adequate COH response from one single FSH injection. Therefore, the aim was to assess IVF outcomes after a novel clomiphene citrate/CFA (CC/CFA) protocol, compared to women undergoing standard rFSH COH protocols (good prognosis comparative cohort:GPCC) in a 1:2 matched design. MATERIALS AND METHODS: In this pilot study of 25 patients (ANZCTR id:ACTRN12612000740897, MINIVA:Minimal_Stimulation_in_IVF), we examined the effectiveness of oral clomiphene (100 mg-days 2-6) followed by CFA in a GnRH antagonist protocol producing a single injection COH stimulation regime. All OR were conducted under LA pre-ovarian block. Cycle outcomes were compared to a matched good prognosis comparative cohort (GPCC) undergoing standard rFSH COH. RESULTS: Mild stimulation was achieved with less oocytes being collected compared to the GPCC (6.4 ± 0.7 vs. 10.7 ± 0.9, p < 0.001), resulting in a reduced number of good quality embryos available for transfer/cryopreservation (3.7 ± 0.6 vs. 5.7 ± 0.5, p = 0.01). While embryo quality was similar between the two groups, endometrial thickness was significantly lower in the group receiving CC/CFA. Pregnancy rates were significantly lower in the CC/CFA cohort compared to GPCC (31.8 vs. 57.1%, p = 0.04) and 44% of CC/CFA participants required supplemental rFSH in order to achieve the hCG trigger criteria. CONCLUSION: Sequential clomiphene CFA protocol does not appear to be an optimal regime for low impact IVF treatment as it does not provide adequate COH from a single CFA injection and results in lower fresh embryo transfer pregnancy rates and fewer embryos for cryopreservation.


Assuntos
Clomifeno/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Fertilização In Vitro/efeitos dos fármacos , Hormônio Foliculoestimulante Humano/farmacologia , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Adulto , Transferência Embrionária , Feminino , Humanos , Projetos Piloto , Gravidez , Taxa de Gravidez , Estudo de Prova de Conceito
20.
Gynecol Endocrinol ; 34(9): 775-780, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29510649

RESUMO

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/ß-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.


Assuntos
Clomifeno/farmacologia , Endométrio/efeitos dos fármacos , Letrozol/farmacologia , Síndrome do Ovário Policístico/metabolismo , Proteínas Wnt/metabolismo , Proteína Wnt3/metabolismo , Adulto , Hormônio Antimülleriano/sangue , Endométrio/metabolismo , Estradiol/sangue , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Humanos , Progesterona/sangue , Adulto Jovem
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