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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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 , 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
9.
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
10.
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
11.
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
12.
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
13.
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
14.
Vitam Horm ; 107: 155-175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29544629

RESUMO

Ovarian follicular cell undergoes extensive proliferation and differentiation during the period that the follicle evolved from the primordial state to its ovulatory phase and then corpus luteum status. During this process, different and various levels of steroid hormones in follicular fluid, or obtained from circulation and adjacent cells as granulosa and theca cells, or from environment and diet will all affect the process of follicular growth and development. Differential steroid hormones might have differential effects on ovarian folliculogenesis via the effect on granulosa cell growth and follicular fluid formation that involves cell proliferation, apoptosis, and angiogenesis within the follicle. In this chapter we further discuss the role of various steroid hormones such as estrogens, progesterone, and androgens on ovarian follicular growth and development. Various stages of follicle development that might be disturbed by the steroid hormones are also discussed in this chapter.


Assuntos
Androgênios/farmacologia , Estrogênios/farmacologia , Fármacos para a Fertilidade Feminina/farmacologia , Fase Folicular/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Ovário/efeitos dos fármacos , Progestinas/farmacologia , Androgênios/metabolismo , Animais , Apoptose/efeitos dos fármacos , Corpo Lúteo/citologia , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/crescimento & desenvolvimento , Corpo Lúteo/fisiologia , Estrogênios/metabolismo , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Fase Folicular/metabolismo , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/metabolismo , Ovário/citologia , Ovário/crescimento & desenvolvimento , Ovário/fisiologia , Progestinas/metabolismo
15.
Vitam Horm ; 107: 27-66, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29544634

RESUMO

Gonadotropin-releasing hormone (GnRH) is recognized as the central regulator of the functions of the pituitary-gonadal axis. The increasing knowledge on the mechanisms controlling the development and the function of GnRH-producing neurons is leading to a better diagnostic and therapeutic approach for hypogonadotropic hypogonadisms and for alterations of the puberty onset. During female life span, the function of the GnRH pulse generator may be affected by a number of inputs from other neuronal systems, offering alternative strategies for diagnostic and therapeutic interventions. Moreover, the identification of a GnRH/GnRH receptor system in both human ovary and endometrium has widened the spectrum of action of the peptide outside its hypothalamic functions. The pharmacological use of GnRH itself or its synthetic analogs (agonists and antagonists) provides a valid tool to either stimulate or block gonadotropin secretion and to modulate the female fertility in several reproductive disorders and in assisted reproduction technology. The use of GnRH agonists in young female patients undergoing chemotherapy is also considered a promising therapeutic approach to counteract iatrogenic ovarian failure.


Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Modelos Biológicos , Células Neuroendócrinas/fisiologia , Ovário/fisiologia , Precursores de Proteínas/metabolismo , Receptores LHRH/agonistas , Reprodução , Animais , Endométrio/efeitos dos fármacos , Endométrio/crescimento & desenvolvimento , Endométrio/fisiologia , Endométrio/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Fármacos para a Fertilidade Feminina/uso terapêutico , Preservação da Fertilidade/tendências , Hormônio Liberador de Gonadotropina/química , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Infertilidade Feminina/terapia , Ciclo Menstrual/efeitos dos fármacos , Células Neuroendócrinas/citologia , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/fisiopatologia , Gravidez , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/patologia , Insuficiência Ovariana Primária/fisiopatologia , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/química , Puberdade/efeitos dos fármacos , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Receptores LHRH/uso terapêutico , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
16.
Vitam Horm ; 107: 67-87, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29544643

RESUMO

The expression of luteinizing hormone receptor (LHR) in the mammalian ovary is regulated in response to changes in the secretion of follicle-stimulating hormone and luteinizing hormone by the anterior pituitary, at least in part, through posttranscriptional mechanisms. The steady-state levels of LHR mRNA are maintained by controlling its rate of degradation by an RNA-binding protein designated as LHR mRNA-binding protein (LRBP). LRBP forms a complex with LHR mRNA and targets it for degradation in the p bodies. miR-122, an 18 nucleotide noncoding RNA, regulates the expression of LRBP. Thus, the levels of miR-122 determine the cellular levels of LHR mRNA expression. This phenomenon has been examined during the induction of LHR mRNA expression that occurs during follicle maturation in response to rising levels of FSH. In this situation, miR-122 and LRBP levels decrease as LHR mRNA expression undergoes downregulation in response to preovulatory LH surge. miR-122 expression as well as LRBP levels show robust increases. The mechanism of induction of LRBP by miR-122 has also been discussed.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Ciclo Menstrual , MicroRNAs/metabolismo , Modelos Biológicos , Ovário/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores do LH/metabolismo , Animais , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Ciclo Menstrual/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Interferência de RNA , Estabilidade de RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/agonistas , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Receptores do LH/agonistas , Receptores do LH/antagonistas & inibidores , Receptores do LH/genética , Transdução de Sinais/efeitos dos fármacos
17.
Anim Reprod Sci ; 192: 200-205, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29550272

RESUMO

The aim of this study was to evaluate the effectiveness of a protocol based on GnRH and PGF2α to synchronize the emergence of a new wave of ovarian follicular development in llamas and, therefore, when a new dominant follicle develops. Llamas (n = 18) were assigned to growing, mature or regressing follicle groups according to the phase of the follicular wave at the beginning of treatment. The protocol was initiated with a GnRH analogue (GnRHa) injection on Day 0 followed 7 days later with a d-cloprostenol injection and a second GnRHa injection on Day 10. Ovulation rate after the first GnRHa treatment, day of new follicle emergence, mean plasma progesterone concentration and percentage of animals with a newly developed dominant follicle ≥ 7 mm on Day 10 were evaluated. Ovulation rate after the first GnRHa was less in the regressing than mature and growing follicle groups and new follicular wave emergence occurred earlier in the regressing follicle group than in the other two groups. Mean plasma progesterone concentration in females that had ovulations after the first GnRHa injection was similar. The percentage of animals that had a new follicle ≥ 7 mm on Day 10 was not different among groups and the overall percentage was 66.6%. The total synchronization rate for development of a new wave of follicular development on Day 10 was greater in females having ovulations after the first GnRHa injection than in those that did not have ovulations. In conclusion, the protocol used in the present study was useful for synchronizing ovarian follicular development in 66% of the llamas regardless of the phase of the follicular wave development at the beginning of treatment.


Assuntos
Busserrelina/farmacologia , Camelídeos Americanos/fisiologia , Cloprostenol/farmacologia , Folículo Ovariano/crescimento & desenvolvimento , Animais , Busserrelina/administração & dosagem , Cloprostenol/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Luteolíticos/administração & dosagem , Luteolíticos/farmacologia , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ovulação/fisiologia
18.
J Reprod Dev ; 64(2): 135-143, 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29398684

RESUMO

The objective of this study was to investigate cyclical changes in endometrial thickness in relation to progesterone (P4) and estradiol-17ß (E2) concentrations during natural and induced estrus in 15 cows. In the prostaglandin (PG) F2α-induced estrus group, ultrasonography (USG) at 6-h intervals was used to determine endometrial thickness 48-24 h before the PGF2α treatment until 24 h after ovulation (ovulation = Day 0). In the natural estrus group, USG was performed every 48 h from Day 3 to Days 15-18 after the first ovulation, and then every 6 h until 24 h after ovulation. Endometrial thickness was standardized using Day 13 as a reference day. Blood was collected during every USG examination and plasma P4 and E2 concentrations were determined. Endometrial thickness of the induced estrus group (n = 11) was greater than that of the natural estrus group (n = 9) between 60 and 12 h before ovulation (P < 0.05). In the natural estrus group, prior to an increase in endometrial thickness, a decrease in P4 and an increase in E2 were detected. In the induced estrus group, based on the time of ovulation, an increase in endometrial thickness was detected at the same time of a decrease in P4 before an increase in E2. These results suggest that decreases in P4 concentrations may be a cue to changes in endometrial thickness, while increases in E2 concentrations appear to sustain and/or enhance these changes.


Assuntos
Endométrio/efeitos dos fármacos , Estradiol/sangue , Sincronização do Estro , Estro/sangue , Progesterona/sangue , Animais , Comportamento Animal/efeitos dos fármacos , Bovinos , Indústria de Laticínios , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Dinoprosta/análogos & derivados , Dinoprosta/farmacologia , Endométrio/diagnóstico por imagem , Endométrio/fisiologia , Ciclo Estral/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Japão , Lactação , Tamanho do Órgão/efeitos dos fármacos , Progesterona/administração & dosagem , Progesterona/farmacologia , Ultrassonografia/veterinária
19.
Eur J Obstet Gynecol Reprod Biol ; 222: 119-125, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29408742

RESUMO

STUDY OBJECTIVES: To investigate the effect of N312S polymorphism in the LHCGR gene as a predictive pharmacogenetic marker on clinical and embryological parameters and determining the need of r-hLH supplementation combine with r-hFSH in patients undergoing ART treatment. STUDY DESIGN: In a cross-sectional study, a retrospective analysis of women (n = 553), who underwent controlled ovarian stimulation treatment protocol was conducted during the years 2012-2014. R-hFSH (Gonal-F, Merck Serono) was administered to all patients undergoing ART cycle after initiating long luteal gonadotrophin-releasing hormone (GnRH) agonist down-regulation. R-hLH was supplemented based on P.C. Wong criteria. N312S genotype was determined using sequencing methodology. The mean r-hFSH, r-hLH doses, total number of oocytes, cleavage rates of embryos and clinical pregnancy were recorded. The association between the r-hLH supplementation and LHCGR N312S polymorphism and clinical pregnancy rates was determined using regression analysis by SPSS. RESULTS: 19.7% of women were homozygous for A allele encoding asparagine (N/N), 45.7% were heterozygous (N/S) and 34.6% were homozygous (S/S) for G allele encoding serine. Women heterozygous (N/S) or homozygous (S/S) for serine showed a higher requirement for r-hLH (OR, 95% p-trend = <0.0001) compared to those homozygous for asparagine (N/N). Homozygous G allele was also associated with higher daily and total r-hLH dose per treatment cycle p-trend = <0.0001. Though, the total no of oocytes (14.87 ±â€¯4.95 vs 12.98 ±â€¯5.39 and 13.58 ±â€¯5.45), Gr-I quality embryos (2.61 ±â€¯1.81 vs 2.18 ±â€¯1.96 and 1.98 ±â€¯2.05) were significantly higher in women homozygous for A allele compared to women with heterozygous and homozygous for G allele, clinical pregnancy rates were significantly more in women with for G allele after excluding patients with PCOS and endometriosis conditions (P < 0.04). CONCLUSION: The present findings reveal that women heterozygous and homozygous for G allele required higher doses of r-hLH supplementation and these women were shown to have higher clinical pregnancy rates.


Assuntos
Resistência a Medicamentos/genética , Hormônio Liberador de Hormônio do Crescimento/agonistas , Infertilidade Feminina/terapia , Hormônio Luteinizante/farmacologia , Indução da Ovulação , Polimorfismo de Nucleotídeo Único , Receptores LHRH/genética , Adulto , Substituição de Aminoácidos , Estudos de Coortes , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/metabolismo , Fármacos para a Fertilidade Feminina/farmacologia , Fertilização In Vitro , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante/farmacologia , Estudos de Associação Genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Humanos , Índia , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Hormônio Luteinizante/administração & dosagem , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Farmacogenética/métodos , Receptores LHRH/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Estudos Retrospectivos
20.
J Anim Sci ; 96(1): 236-249, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29408965

RESUMO

This experiment evaluated the impacts of estrus expression and intensity, estimated by physical activity during a timed-AI protocol, on reproductive performance of Bos indicus-influenced beef cows. A total of 290 lactating, primiparous, and multiparous nonpregnant Nelore × Angus cows received a 2 mg injection of estradiol benzoate and an intravaginal progesterone (P4) releasing device (CIDR) on d -11, a 12.5 mg injection of PGF2α on d -4, CIDR removal in addition to 0.6 mg injection of estradiol cypionate and 300 IU injection of eCG on d -2, and timed-AI on d 0. Cows were fitted with a pedometer behind their left shoulder on d -4. An estrus detection patch was attached to the tail-head of each cow on d -2. Pedometer results were recorded on d -2 and 0. Estrus expression was defined as removal of >50% of the rub-off coating from the patch on d 0. Net physical activity during estrus was calculated by subtracting total steps from d -4 to -2 (nonestrus basal activity) from total steps from d -2 to 0 (proestrus + estrus period) of each cow. Cows that did not express estrus were classified as NOESTR. Cows that expressed estrus were ranked by net physical activity; those above the median were classified as HIESTR and the remaining cows as LWESTR. Ovarian ultrasonography was performed on d 0 and 7. Blood was collected on d 0, 7, 20, and 30. Pregnancy status was verified by ultrasonography on d 30. Only data from cows responsive to the estrus synchronization protocol were utilized (NOESTR, n = 59; LWESTR, n = 100; HIESTR, n = 98). Diameter of dominant follicle on d 0, corpus luteum volume on d 7, and plasma P4 concentrations on d 7 were greater (P ≤ 0.05) in HIESTR vs. LWESTR and NOESTR and also greater (P ≤ 0.05) for LWESTR vs. NOESTR. Plasma P4 concentrations on d 0 were greater (P < 0.01) in NOESTR vs. HIESTR and LWESTR and similar (P = 0.93) between HIESTR and LWESTR. Whole blood mRNA expression of myxovirus resistance 2 on d 20 was greater (P ≤ 0.05) in HIESTR vs. LWESTR and NOESTR, and similar (P = 0.72) between LWESTR and NOESTR. Pregnancy rates were less (P ≤ 0.04) in NOESTR vs. HIESTR and LWESTR (52.4%, 68.9%, and 73.5%, SEM = 7.2), and similar (P = 0.57) between HIESTR and LWESTR. Hence, expression of estrus during a timed-AI protocol improved ovarian dynamics and pregnancy success, whereas estrus intensity modulated key biological markers associated with fertility but not pregnancy rates in B. indicus-influenced cows beef cows.


Assuntos
Bovinos/fisiologia , Sincronização do Estro/métodos , Estro/efeitos dos fármacos , Inseminação Artificial/veterinária , Administração Intravaginal , Animais , Dinoprosta/administração & dosagem , Dinoprosta/farmacologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Inseminação Artificial/métodos , Folículo Ovariano , Gravidez , Progesterona/administração & dosagem , Progesterona/sangue , Progesterona/farmacologia
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