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1.
BMC Pregnancy Childbirth ; 21(1): 348, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934703

RESUMO

BACKGROUND: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS. METHODS: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group. RESULT(S): No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol. CONCLUSION(S): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration. TRIAL REGISTRATION: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.


Assuntos
Infertilidade Feminina/terapia , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Gonadotropina Coriônica/administração & dosagem , Feminino , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Infertilidade Feminina/fisiopatologia , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Pamoato de Triptorrelina/administração & dosagem , Adulto Jovem
2.
BMC Pregnancy Childbirth ; 21(1): 363, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957886

RESUMO

BACKGROUND: Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of this retrospective study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate. METHOD: We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population (n = 1210) and a selected "top cycle" population (n = 677), after blastocyst transfer on day 5 or cleaved embryo transfer on day 3. The selected couples had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the progesterone to oocyte index (POI), the progesterone:estradiol ratio (P:E2 ratio), and the progesterone to follicle (> 14 mm) index (PFI). RESULTS: In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p <  0.01); the same was true for the birth rate (32.1 and 22.8%, respectively, p <  0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate, and 33.9 and 34.9% for the birth rate). The serum progesterone levels on the eve of the trigger day and on the day itself were significantly lower in the pregnant women (p <  0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other researchers. The POI and the PFI appear to have predictive value for cleaved embryos transfers. CONCLUSIONS: Blastocyst transfers were associated with higher clinical pregnancy and birth rates than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.


Assuntos
Blastocisto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Fertilização In Vitro , Progesterona/sangue , Adulto , Feminino , Humanos , Masculino , Indução da Ovulação , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , Fatores de Tempo
3.
AAPS PharmSciTech ; 22(3): 118, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782790

RESUMO

The present study was designed to develop an efficient, safe, and patient-friendly dosage form, for oral delivery of alfa-choriogonadotropin, used in the treatment of female reproductive infertility. Silica-coated, saturated fatty acid (dipalmitoylphosphatidylcholine (DPPC))-engineered, nanolipidic vesicular (NLVs) system was developed for systemic delivery of therapeutic peptide, alfa-choriogonadotropin, through oral route. DPPC-based NLVs were formulated using the technique of thin-film hydration and were coated with silica to form a homogeneous surface silica shell. The formulated silica-coated NLVs were evaluated for physicochemical and physiologic stability under simulated conditions and were optimized based on physicochemical parameters like particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, and in vitro release profile. Silica-coated, DPPC-based NLVs imparted physicochemical stability to entrapped alfa-choriogonadotropin against the biological environment prevailing in the human gastrointestinal tract (GIT). In vivo, subchronic animal toxicity studies were performed to assess the safety of the designed dosage form. Results of in vitro characterization and in vivo pharmacokinetic studies of fabricated formulation revealed that the silica-coated, DPPC-based NLV formulation was not only stable in human GIT but was also as efficacious as a marketed parenteral formulation for the systemic delivery of alfa-choriogonadotropin. In vivo toxicity studies revealed that silica-coated NLVs did not alter hematological and serum biochemical parameters. The histopathological studies also depicted no macroscopic changes in major organs; thus, the developed formulation was proven to be nontoxic and equally efficient as a marketed parenteral formulation for the delivery of alfa-choriogonadotropin with added benefits of possible self-medication, more patient acceptability, and no chances of infection.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/química , Ácidos Graxos/química , Lipídeos/química , Substâncias para o Controle da Reprodução/administração & dosagem , Substâncias para o Controle da Reprodução/química , Dióxido de Silício/química , 1,2-Dipalmitoilfosfatidilcolina/química , Administração Oral , Animais , Gonadotropina Coriônica/toxicidade , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Substâncias para o Controle da Reprodução/toxicidade
4.
Life Sci ; 275: 119351, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737084

RESUMO

AIM: Endometrial exosomes carry bioactive agents to uterine epithelial cells and trophectoderm to promote implantation. On the other hand, intrauterine administration of human chorionic gonadotropin (hCG) could improve endometrial receptivity. Therefore, we investigated the delivery of hCG to the endometrial cells by uterine exosomes to increase endometrial receptivity. MAIN METHODS: Exosomes were isolated from uterine fluid and characterized by dynamic light scattering, transmission electron microscopy, and western blotting. The freeze-thaw cycle and sonication methods were used to load hCG into the exosomes. The drug release pattern and uptake of exosomes into the endometrial cells were evaluated. Finally, the influence of hCG loaded-exosomes on the expression of several endometrial receptivity markers was evaluated. KEY FINDINGS: The isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8 nm and zeta potential of -9.75 mV. The average loading capacity of exosomes for hCG was 710.05 ± 73.74 and 245.06 ± 95.66 IU/mg using the sonication and freeze-thaw cycle methods, respectively. The effect of hCG loaded-exosomes on the endometrial receptivity was greater than the hCG or exosomes alone. We found that hCG upregulated LIF and Trophinin and downregulated Muc-16 and IGFBP1 genes. Interestingly, the effect of hCG on the expression of LIF and Muc-16 was significantly intensified when used in the form of hCG loaded-exosomes. SIGNIFICANCE: These findings strengthen our hope in using uterine fluid-derived exosome as an effective carrier for proteins or other therapeutic agents to effective delivery into endometrial cells.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Endométrio/metabolismo , Exossomos/metabolismo , Útero/metabolismo , Western Blotting , Células Cultivadas , Implantação do Embrião , Exossomos/ultraestrutura , Feminino , Humanos , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma
5.
BMC Pregnancy Childbirth ; 21(1): 16, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407250

RESUMO

BACKGROUND: This study aimed at determining the predictive value of human chorionic gonadotropin and progesterone levels on pregnancy outcomes in patients receiving in vitro fertilization due to fallopian tube associated infertility. METHODS: We retrospectively analyzed the clinical data of 854 cycles due to fallopian tube associated infertility in vitro fertilization fresh embryo transfer. The clinical data had been collected from January 2010 to December 2018 and was divided into 7 groups depending on the progesterone level on human chorionic gonadotropin administration day. Live birth rates and observation trends were calculated. The receiver operating characteristic curve was established to determine the optimal cutoff value for progesterone, which was used to further divide the data into 3 groups; Group 1 (progesterone ≦ 1.0 ng/ml), Group 2 (1.0 ng/ml ≤ progesterone ≤ 1.25 ng/ml), and Group 3 (progesterone ≥ 1.25 ng/ml). We then compared the ovulation results and clinical outcomes among the 3 groups. RESULTS: There were no significant differences in age, infertility years, gonadotropin dosage, gonadotropin days, Luteinizing hormone level on human chorionic gonadotropin day, 2 pronuclear fertilization rates, clinical pregnancy rates, live birth rates, full-term birth rate, and preterm birth rates among the three groups. However body mass index (p = 0.001), basal luteinizing hormone (p = 0.034), estrogen peak (p < 0.001), number of oocytes obtained (P < 0.001) were significantly different. CONCLUSIONS: Progesterone level on human chorionic gonadotropin day does not affect the clinical pregnancy rate and live birth rates after in vitro fertilization. However, progesterone levels between 1.0 and 1.25 ng/ml may lead to good clinical pregnancy outcomes.


Assuntos
Doenças das Tubas Uterinas/complicações , Fertilização In Vitro , Infertilidade Feminina/terapia , Resultado da Gravidez , Progesterona/sangue , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Feminino , Humanos , Infertilidade Feminina/etiologia , Nascido Vivo , Gravidez , Taxa de Gravidez , Curva ROC , Estudos Retrospectivos
6.
J Anim Sci ; 98(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32901281

RESUMO

Bovine twin birth is associated with detriments, including increased embryo/fetal losses, malpresentation, and dystocia. Incidence of these is lessened in bilateral compared with unilateral twin pregnancy. This study was undertaken to assess the use of follicular ablation by aspiration to create bilateral twin pregnancies in females with genetic potential for ~3.5 ovulations per cycle (Trio allele carriers). In experiment 1, carriers (n = 30) and noncarriers (n = 10) were synchronized for ovulation and timed artificial insemination (TAI). Follicles (>5 mm) in excess of one per ovary were aspirated ~16 h preceding TAI. Follicle count for females with follicles on only one ovary was reduced to two. Blood was sampled 2 wk post-TAI to assess progesterone (P4) concentrations; embryo count was determined by ultrasound 6 wk post-TAI. Circulating P4 concentration post-TAI was significantly (P < 0.001) associated with both genotype and subsequent pregnancy status (pregnant noncarriers: 7.06 ± 0.68 ng/mL; pregnant carriers: 5.54 ± 0.55 ng/mL; nonpregnant noncarriers: 5.22 ± 1.05 ng/mL; nonpregnant carriers: 3.13 ± 0.42 ng/mL). Experiment 2 was undertaken to offset the negative effects of follicular aspiration on subsequent P4 concentration observed in experiment 1. Carriers (n = 38) and noncarriers (n = 32) were submitted to TAI and follicle ablation as described for experiment 1. Additionally, accessory corpora lutea (CL) were induced in carriers by the administration of human chorionic gonadotropin (carriers) at day 6 post-TAI. Consequently, P4 concentration post-TAI was significantly (P < 0.05) associated with subsequent pregnancy status (pregnant: 8.48 ± 0.61 ng/mL; nonpregnant: 6.70 ± 0.63 ng/mL) but not with genotype (carrier: 8.01 ± 0.59 ng/mL; noncarrier: 7.17 ± 0.64 ng/mL). Embryo number was greater in carriers (exp. 1: 1.64 ± 0.81; exp 2: 1.45 ± 0.09) vs. noncarriers (1.00 ± 0.00, both experiments). Single, twin, and triplet pregnancies occurred in carriers in experiment 1, whereas multiples in experiment 2 were limited to twin pregnancies. Genotype effects on pregnancy rate were not significant (P > 0.10) in either experiment. Results suggest that follicular ablation to create bilateral twin pregnancies in Trio carriers is feasible but requires the induction of accessory CL to offset the negative effects of follicular aspiration on subsequent P4 concentration and associated fertility outcomes.


Assuntos
Bovinos/genética , Fertilidade/genética , Ovulação/genética , Progesterona/análise , Alelos , Animais , Bovinos/fisiologia , Gonadotropina Coriônica/administração & dosagem , Corpo Lúteo/efeitos dos fármacos , Sincronização do Estro/efeitos dos fármacos , Feminino , Genótipo , Heterozigoto , Humanos , Inseminação Artificial/veterinária , Tamanho da Ninhada de Vivíparos , Folículo Ovariano/efeitos dos fármacos , Gravidez , Taxa de Gravidez
7.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1137-1144, July-Aug. 2020. tab, ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-1131517

RESUMO

Utilizaram-se quatro garanhões nos meses de janeiro, abril, julho e outubro de 2016, em dois protocolos, em que: GI (n=4; 5mL de solução salina, i.v.) e GII (n=4; 5000UI de hCG, i.v.) e subdividiram-se esses protocolos em ciclos (C1 e C2), seguindo o esquema crossover, sendo: CI=animais 1 (GI) e 2 (GII), avaliados nos dias D1, D3 e D5, e animais 3 (GI) e 4 (GII), em D2, D4 e D6; CII= animais 1 (GII) e 2 (GI), em D1, D3, D5, e animais 3 (GII) e 4 (GI), em D2, D4 e D6. Realizou-se o tratamento em D1 e D2 de cada ciclo e a ultrassonografia testicular no modo color Doppler e Doppler espectral, uma hora antes de cada coleta de sêmen e imediatamente após. Avaliou-se: número de reflexo de Flehmen, de montas sem ereção, início da monta, tempo de reação à ereção e total da monta e análises de qualidade seminal. Estatisticamente foram utilizados os testes de qui-quadrado e ANOVA. Não houve diferenças estatísticas (P>0,05) entre os parâmetros analisados. Concluiu-se que uma única dose de 5000UI de hCG em garanhões não causou alterações significativas nos parâmetros avaliados em diferentes estações do ano.(AU)


Four stallions were used in January, April, July and October 2016 in two protocols: GI (n=4; 5ml saline, iv) and GII (n=4; 5000 hCG, iv), and these protocols were subdivided into cycles (C1 and C2) following the cross over scheme, as follows: CI=animal 1 (GI) and 2 (GII) evaluated on days D1, D3 and D5 and animal 3 (GI) and 4 (GII) at D 2, D 4 and D 6; CII=animal 1 (GII) and 2 (GI) at D1, D3, D5 and animal 3 (GII) and 4 (GI) at D2, D4 and D6. Treatment was performed on D1 and D2 of each cycle and testicular ultrasound in color Doppler and spectral Doppler mode, one hour before each semen collection and immediately after. We evaluated: Flehmen's reflex number, mounts without erection, start of the mount, reaction time to erection and total mount and seminal quality analyzes. Statistically, the Chi-square and ANOVA tests were used. There were no statistical differences (P>0.05) between the analyzed parameters. It was concluded that a single dose of 5000IU hCG in stallions did not cause significant changes in the parameters evaluated in different seasons of the year.(AU)


Assuntos
Animais , Masculino , Testículo/diagnóstico por imagem , Gonadotropina Coriônica/administração & dosagem , Cavalos/fisiologia , Estações do Ano , Ultrassonografia Doppler em Cores/veterinária
8.
J Vet Sci ; 21(3): e48, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476321

RESUMO

BACKGROUND: Mature oocytes at the metaphase II status (MII-stage oocytes) played an important role in assisted reproductive technology in non-human primates. OBJECTIVES: In order to improve the proportion of MII-stage oocytes retrieval, three different superovulation protocols were performed on 24 female cynomolgus monkeys. METHODS: All the monkeys received once-daily injection of follicle-stimulating hormone (25 international unit [IU]) on day 3 of the menstruation, 3-day intervals, twice daily for 8-12 days until the time of human chorionic gonadotropin (1,500 IU) injection, on the 14-17th day of menstruation collecting oocytes. The difference between protocol I and protocol II was that 0.1 mg the gonadotropin-releasing hormone agonist was injected on day 1 of the menstruation, while the difference between personalized superovulation protocol and protocol II was that oocytes could be collected on the 14-17th day of menstrual cycle according to the length of each monkey. RESULTS: The total number of oocytes harvested using the personalized superovulation protocol was much higher than that using protocol I (p < 0.05), and the proportion of MII-stage oocytes was significantly greater than that from either superovulation protocol I or II (p < 0.001 and p < 0.01 respectively), while the proportion of immature oocytes at the germinal vesicle was less than that from superovulation protocol I (p < 0.05). CONCLUSIONS: The personalized superovulation protocol could increase the rate of MII-stage oocytes acquired, and successfully develop into embryos after intracytoplasmic sperm injection, and eventually generated fetus.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Feto/fisiologia , Macaca fascicularis/fisiologia , Oócitos/fisiologia , Injeções de Esperma Intracitoplásmicas/veterinária , Superovulação/fisiologia , Animais , Gonadotropina Coriônica/farmacologia , Feminino , Feto/embriologia
9.
J Sex Med ; 17(4): 645-657, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32171629

RESUMO

BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder characterized by absent or incomplete puberty and infertility, and heterogeneous responses are often observed during treatment. AIM: To investigate the role of CHH-associated variants in patients with CHH with poor responses to human chorionic gonadotropin (hCG). METHODS: This retrospective study investigated 110 Chinese male patients with CHH undergoing genetic analysis and hCG treatment. CHH-associated rare sequence variants (RSVs) were identified by using a tailored next-generation sequencing panel and were interpreted in accordance with the American College of Medical Genetics and Genomics criteria. Clinical characteristics were recorded, and Kyoto Encyclopedia of Genes and Genomes analysis was conducted to assess pathways enriched in protein networks implicated in poor responses. OUTCOMES: The outcomes include testicular volume, serum hormonal profiles, parameters of semen analysis, pathogenicity classification, and pathway enrichment. RESULTS: Among the 110 patients, 94.55% achieved normal serum testosterone and 54.55% achieved seminal spermatozoa appearance (SSA). PLXNB1, ROBO3, LHB, NRP2, CHD7, and PLXNA1 RSVs were identified in patients who had an abnormal serum testosterone level during treatment. In spermatogenesis, the number of CHH-associated RSVs was not significantly strongly associated with delayed SSA. After pathogenicity classification, pathogenic/likely pathogenic (P/LP) RSVs were identified in 30% (33/110) of patients. Patients with P/LP RSVs showed delayed SSA compared with noncarriers, and P/LP PROKR2 RSVs showed the strongest association (48, 95% CI: 34.1-61.9 months, P = .043). Enriched pathways implicated in delayed SSA included neuroactive ligand-receptor interaction; Rap1, MAPK, PI3K-Akt signaling; and regulation of actin cytoskeleton. CLINICAL IMPLICATIONS: Male patients with CHH harboring P/LP PROKR2 RSVs should be aware of a high probability of poor responses to hCG; If these patients desire fertility, it might be better to recommend hCG/human menopausal gonadotropin, hCG/recombinant follicle-stimulating hormone, or pulsatile GnRH administration before treatments start or as early as possible. STRENGTHS & LIMITATIONS: Strengths are the standardized regimen and extensive follow-up (median time of 40 months). However, included patients in the study voluntarily chose hCG treatment because of the burden of drug cost and/or little fertility desire. Therefore, human menopausal gonadotropin or follicle-stimulating hormone was not added to this cohort. Our observed correlations should be further verified in patients with CHH undergoing other treatments. CONCLUSION: Among all P/LP RSVs, P/LP PROKR2 RSVs might correlate with poor responses in CHH under hCG treatment; our study supports the pathogenicity assessment of American College of Medical Genetics and Genomics criteria in genetic counseling, to improve management of patients with CHH. Chen Y, Sun T, Niu Y, et al. Correlations AmongGenotype and Outcome in Chinese Male Patients WithCongenital Hypogonadotropic Hypogonadism Under HCG Treatment. J Sex Med 2020;17:645-657.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Hipogonadismo/tratamento farmacológico , Espermatogênese , Adolescente , Adulto , Estudos de Coortes , Genótipo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade/etiologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Retrospectivos , Adulto Jovem
10.
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
11.
J Assist Reprod Genet ; 37(1): 33-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758513

RESUMO

PURPOSE: High progesterone is associated with low implantation rate. Our previous study demonstrated that DNA methylation in endometrium was increased in women with high progesterone in IVF cycles. However, the DNA methylation status is still not yet confirmed, and how it affects endometrial receptivity in high progesterone is still unknown. Current study investigated the effects of high progesterone on DNA methylation and gene expression of adhesion molecules on endometrium during implantation window. METHODS: A cohort study included 20 women with high progesterone (HP) and 20 with normal progesterone (NP) on the day of human chorionic gonadotropin (hCG) administration after controlled ovarian hyperstimulation in IVF cycle. Endometrial tissues were collected on the 7th day after hCG administration. Immunohistochemical staining of DNA methyltransferases (DNMT1 and DNMT3B) and adhesion molecules (MUC1, CDH1 and CTNNB1) were performed. Methylation of MUC1, CDH1, and CTNNB1 promoter regions was detected by Sequenom MassARRAY or bisulfite sequencing PCR. RT-qPCR was used to quantify mRNA expression levels, and correlation of methylation and gene expression level of the adhesion molecules were determined. RESULTS: DNMT3B, but not DNMT1, in nucleus of luminal and glandular epithelial cells in HP group was significantly higher than that in NP group. Promoter regions of CDH1 and CTNNB1, but not MUC1, in endometrium of HP group were hypermethylated. Protein and mRNA expression of MUC1, CDH1, and CTNNB1 in endometrium of HP group was significantly lower than that in NP group. Level of DNA methylation was negatively correlated with the gene expression of CDH1 and CTNNB1, but not MUC1. CONCLUSIONS: DNA hypermethylation and low expression of adhesion molecules on endometrium were associated with high progesterone during implantation window, which may contribute to the underlying epigenetic mechanism in the failure of IVF treatment.


Assuntos
Moléculas de Adesão Celular/metabolismo , Metilação de DNA , Implantação do Embrião/genética , Endométrio/metabolismo , Fertilização In Vitro/métodos , Infertilidade Feminina/metabolismo , Progesterona/farmacologia , Adulto , Moléculas de Adesão Celular/genética , Gonadotropina Coriônica/administração & dosagem , Estudos de Coortes , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/genética , Indução da Ovulação/métodos , Progestinas/farmacologia
12.
J Dairy Sci ; 103(2): 2006-2018, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785879

RESUMO

One strategy for improving fertility in cattle is administration of GnRH or human chorionic gonadotropin (hCG) during the luteal phase, which increases progesterone (P4) secretion and delays luteolysis. To provide an overview of how GnRH or hCG treatment between 4 and 15 d after artificial insemination (AI) improves pregnancy per AI (P/AI) in cows, a meta-analysis was performed on 107 different trials from 52 publications. Data from 18,082 treated cows and 18,385 untreated controls were meta-analyzed. The meta-analysis explained the relative risk for P/AI with GnRH or hCG treatment under various circumstances. The results did not show any difference in P/AI between cows treated with hCG and cows treated with GnRH. Compared with no treatment, treatment with GnRH or hCG improved the chances of P/AI in cows with very poor (<30%) and poor (30.1 to 45%) fertility, whereas treatment did not benefit cows with very good fertility (>60.1%). Moreover, treatment with GnRH and hCG improved the chances of P/AI in primiparous cows. The improvement was much better in primiparous cows with very low fertility. Treatment with buserelin at a dose above 10 µg and with hCG at a dose above 2,500 IU was associated with increased chances of P/AI compared with lower doses. Treatment with GnRH 10 d after AI was also associated with increased chances of P/AI compared with earlier treatment. The present meta-analysis showed that the use of GnRH and hCG after AI should be focused on cows expected to have low or moderate fertility. Day and dose of treatment have to be considered as well.


Assuntos
Busserrelina/administração & dosagem , Bovinos/fisiologia , Gonadotropina Coriônica/administração & dosagem , Fertilidade/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/administração & dosagem , Animais , Indústria de Laticínios , Feminino , Humanos , Inseminação Artificial/veterinária , Fase Luteal , Luteólise/efeitos dos fármacos , Gravidez , Progesterona/metabolismo , Fatores de Tempo
13.
Theriogenology ; 141: 168-172, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542520

RESUMO

This study evaluated embryo production after superovulation (SO) with a reduced number of FSH applications and increased eCG dose in 26 Bos taurus × Bos indicus donors. On Day 0, donors received an intravaginal device (CIDR) with 1.9 g of progesterone plus 2.5 mg of estradiol benzoate and 50 mg of progesterone via IM. On Day 4, donors were randomly allotted to one of three SO treatments: 1) 455 IU of Folltropin +400 IU of eCG (n = 9), 2) 350 IU of Folltropin +600 IU of eCG (n = 9), and 3) 500 IU of Pluset + 600 IU of eCG (n = 8). In treatment 455 IU of Folltropin +400 IU of eCG, donors received eight IM Folltropin injections in decreasing dose 12 h apart from Day 4 to Day 7. On Day 6, at the same time as the Folltropin, donors received via IM 25 mg of dinoprost tromethamine (PGF2a). On Day 7, the CIDR was removed, and together with the Folltropin, donors received 200 IU of eCG via IM. In treatment 350 IU of Folltropin +600 IU of eCG, donors received four IM Folltropin injections in decreasing dose 12 h apart on Days 4 and 5. On Day 6, donors received via IM 600 IU of eCG in the morning and two doses of 25 mg of PGF2a 12 h apart. On Day 7, the CIDR was removed. Donors from treatment 500 IU of Pluset +600 IU of eCG received four IM Pluset injections in decreasing dose 12 h apart on Days 4 and 5. On Day 6, donors received via IM 600 IU of eCG in the morning and two doses of 25 mg of PGF2a 12 h apart. On Day 7, the CIDR was removed. In the morning of Day 8, donors from the three treatments received 0.25 mg of GnRH via IM. Artificial insemination was performed on Day 8 (pm) and Day 9 (am). Embryos were collected on Day 15. Variables evaluated were number of CL before embryo collection, number of structures recovered, transferable embryos, degenerate embryos and unfertilized oocytes, recovery rate, and viability rate. There was no difference in any variable among treatments (P > 0.05). In conclusion, replacement of four Folltropin or Pluset injections from a conventional eight FSH-injection SO protocol, by a single injection of 600 IU of eCG, is a good alternative to reduce donor handling without decreasing yield of transferable embryos.


Assuntos
Bovinos/embriologia , Gonadotropina Coriônica/farmacologia , Hormônio Foliculoestimulante/farmacologia , Superovulação/efeitos dos fármacos , Animais , Gonadotropina Coriônica/administração & dosagem , Técnicas de Cultura Embrionária , Feminino , Fertilização In Vitro , Hormônio Foliculoestimulante/administração & dosagem , Doadores de Tecidos
14.
J Vet Med Sci ; 82(2): 209-211, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31875577

RESUMO

Serum anti-Müllerian hormone (AMH), a marker of equine cryptorchidism, is detectable in intact and cryptorchid stallions but not in geldings because it is secreted from Sertoli cells. A 4-year-old uncastrated Thoroughbred racehorse had no visible testes; therefore, the horse was considered a bilateral cryptorchidism. However, the serum AMH was undetectable (<0.08 ng/ml). Human chorionic gonadotrophin (hCG) stimulating test result indicated that the horse was a gelding. The results of sex chromosomal analysis and sequence analysis of SRY gene suggested that the horse was a genetically-intact stallion (X/Y). Only one small degenerative testis was present in the abdominal cavity. The reasons of undetectable serum AMH levels and negative response to hCG stimulation might be low numbers of Sertoli and Leydig cells. This study reports a case of serum AMH-undetectable cryptorchid stallion.


Assuntos
Hormônio Antimülleriano/sangue , Criptorquidismo/veterinária , Doenças dos Cavalos/congênito , Animais , Gonadotropina Coriônica/administração & dosagem , Genes sry , Doenças dos Cavalos/genética , Cavalos , Masculino , Cromossomos Sexuais
15.
Reprod Domest Anim ; 55(1): 54-63, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661568

RESUMO

Two experiments were done using a two-by-two design to determine the effects of season and superstimulatory protocol on embryo production in wood bison. In Experiment 1 (in vivo-derived embryos), ovarian superstimulation was induced in female bison during the ovulatory and anovulatory seasons with either two or three doses of FSH given every-other-day (FSH × 2 vs. FSH × 3, respectively). Bison were given hCG to induce ovulation, inseminated 12 and 24 hr after hCG, and embryos were collected 8 days after hCG (n = 10 bison/group). In Experiment 2 (in vitro embryo production), ovarian superstimulation was induced in female bison during the ovulatory and anovulatory seasons with two doses of FSH, and in vivo maturation of the cumulus-oocyte complexes (COC) was induced with hCG at either 48 or 72 hr after the last dose of FSH. COC were collected 34 hr after hCG, and expanded COC were used for in vitro fertilization and culture. In Experiment 1, the number of follicles ≥9 mm, the proportion of follicles that ovulated, the number of CL, and the total number of ova/embryos collected did not differ between seasons or treatment groups, but the number of transferable embryos was greater (p < .05) in the ovulatory season. In Experiment 2, no differences were detected between seasons or treatment groups for any end point. The number of transferable embryos produced per bison was greatest (p < .05) using in vitro fertilization and was unaffected by season (1.5 ± 0.2 and 1.1 ± 0.3 during anovulatory and ovulatory seasons, respectively), in contrast to in vivo embryo production which was affected by season (0.1 ± 0.01 and 0.7 ± 0.2 during anovulatory and ovulatory seasons, respectively). Results demonstrate that transferable embryos can be produced throughout the year in wood bison by both in vivo and in vitro techniques, but the efficiency of embryo production of in vivo-derived embryos is significantly lower during the anovulatory season.


Assuntos
Bison/fisiologia , Transferência Embrionária/veterinária , Fertilização In Vitro/veterinária , Técnicas de Maturação in Vitro de Oócitos/veterinária , Animais , Bison/embriologia , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Células do Cúmulo/fisiologia , Transferência Embrionária/métodos , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Foliculoestimulante/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Masculino , Oócitos/fisiologia , Indução da Ovulação/veterinária , Estações do Ano , Superovulação/efeitos dos fármacos
16.
Nihon Hinyokika Gakkai Zasshi ; 111(1): 30-33, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33473092

RESUMO

A 32-year-old Japanese man was referred to our hospital with a chief complaint of the delayed puberty with having been aware of it since he was in his teens. Physical examination demonstrated the small penis, the impalpable left testis, and the atrophic right testis in the scrotum. Abdominal magnetic resonance imaging showed the left testis of 8 mm in the external inguinal ring. Endocrinological blood tests revealed that testosterone and luteinizing hormone were 0.34 ng/mL and 1 mIU/mL, respectively, leading to a diagnosis of the left cryptorchidism with hypogonadotropic hypogonadism. The hCG therapy was initiated, resulting in the increased volume and spontaneous descent into the scrotum of the left testis after 6 months of the treatment. The hCG therapy could be an alternative treatment for surgery for cryptorchidism with hypogonadism in adults.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Criptorquidismo/tratamento farmacológico , Criptorquidismo/etiologia , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Adulto , Biomarcadores/sangue , Criptorquidismo/diagnóstico , Humanos , Hipogonadismo/diagnóstico , Hormônio Luteinizante/sangue , Imageamento por Ressonância Magnética , Masculino , Testosterona/análogos & derivados , Testosterona/sangue , Resultado do Tratamento
17.
Anim Reprod Sci ; 211: 106209, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31785631

RESUMO

In seasonally anestrous goat does, ovulations can be induced by combining a treatment regimen including progestagen, eCG and prostaglandins. Nonetheless, ovulations occur only once and then does return to a seasonally anestrous state. This study was performed to determine whether the presence of a sexually active buck can stimulate a second ovulation after induced luteolysis using prostaglandins following the first ovulation. Three groups of seasonally anestrous does were treated to induce ovulations using an intra-vaginally inserted sponge containing a progestin combined with eCG and prostaglandin administrations. Goats that had ovulations were treated with a prostaglandin 11 days after progestin sponge removal. After the prostaglandin injection, does continued to be isolated from bucks (n = 8), were penned with a control buck (n = 9), or were penned with a sexually active buck (n = 10). The proportion of goats having ovulations after imposing the ovulation-induction protocol was greater than 80% and did not differ among treatment groups (P >  0.05). The proportion of does having ovulations after injecting prostaglandins was greater when does were penned with a sexually active buck (8/10) than does penned with a control buck (0/9) or that were isolated from bucks (0/8; P < 0.05). It is concluded that in seasonally anestrous goat does induced to have ovulations using a hormonal treatment regimen, the presence of a sexually active buck can induce a second ovulation when there is an induced luteolysis.


Assuntos
Gonadotropina Coriônica/farmacologia , Acetato de Fluorogestona/farmacologia , Cabras/fisiologia , Ovulação/fisiologia , Prostaglandinas/farmacologia , Estações do Ano , Animais , Gonadotropina Coriônica/administração & dosagem , Feminino , Acetato de Fluorogestona/administração & dosagem , Masculino , Ovulação/efeitos dos fármacos , Indução da Ovulação/veterinária , Fotoperíodo , Prostaglandinas/administração & dosagem , Comportamento Sexual Animal
18.
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
19.
Eur J Obstet Gynecol Reprod Biol ; 243: 133-138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704529

RESUMO

OBJECTIVE: To investigate whether intrauterine perfusion of hCG before embryo transfer (ET) is effective in women experienced two or more implantation failures. STUDY DESIGN: Systematic review and meta-analysis. In the current meta-analysis, Pubmed, EMBASE and The Cochrane Library were searched for trials which compared the efficacy of intrauterine perfusion of hCG with no perfusion of hCG in women undergoing in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or frozen embryo transfer (FET) before ET. The primary outcomes are the clinical pregnancy rate (CPR) and live birth rate (LBR). RESULTS: Six trials consisted of 1432 women were eligible for quantitative analysis. CPR (including 6 trials consisted of 1432 women) and LBR (including 3 trials consisted of 870 women) were significantly improved in the hCG group compared to the control group, with a CPR of 41.8 % vs. 31.2 % (RR 1.30, 95 % CI 1.14∼1.50, P < .001), an LBR of 27.8 % vs. 18.0 % (RR 1.52, 95 % CI 1.18∼1.96, P = .001). CONCLUSION: Intrauterine perfusion of hCG is effective in improving clinical pregnancy rate and live birth rate in women who experienced two or more implantation failures, which might provide a potential therapeutical intervention for recurrent implantation failure (RIF). Although promising, further evidence from multicenter, randomized controlled trials are needed to confirm the conclusion from the current meta-analysis.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Nascido Vivo , Taxa de Gravidez , Substâncias para o Controle da Reprodução/administração & dosagem , Implantação do Embrião , Feminino , Fertilização In Vitro/métodos , Humanos , Gravidez , Falha de Tratamento , Resultado do Tratamento
20.
Proc Natl Acad Sci U S A ; 116(41): 20267-20273, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31570579

RESUMO

The ovulatory homolog model of female orgasm posits that the neuro-endocrine mechanisms underlying female orgasm evolved from and are homologous to the mechanisms mediating copulation-induced ovulation in some mammals. This model predicts that pharmacological agents that affect human orgasm, such as fluoxetine, should also affect ovulation in animals with copulation-induced ovulation, such as rabbits. We tested this prediction by treating rabbits with daily doses of fluoxetine for 2 wk and found that fluoxetine treatment reduces the number of ovulations postcopulation by 30%. In a second experiment we tested whether this result was mediated by an effect on the brain or via peripheral serotonin functions. We treated animals with fluoxetine and induced ovulation with a single injection of human chorionic gonadotropin. In this experiment ovulation rate was nominally reduced by only 8%, which is statistically not significant. We conclude that the effect of fluoxetine on copulation-induced ovulation rate supports the ovulatory homolog model of female orgasm, suggesting that female orgasm has very deep evolutionary roots among the early eutherian mammals.


Assuntos
Evolução Biológica , Gonadotropina Coriônica/farmacologia , Fluoxetina/farmacologia , Ovulação/efeitos dos fármacos , Animais , Gonadotropina Coriônica/administração & dosagem , Copulação/fisiologia , Feminino , Fluoxetina/administração & dosagem , Masculino , Ovulação/fisiologia , Coelhos , Substâncias para o Controle da Reprodução/administração & dosagem , Substâncias para o Controle da Reprodução/farmacologia , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/farmacologia
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