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1.
Zhonghua Fu Chan Ke Za Zhi ; 55(1): 9-14, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32074767

RESUMO

Objective: To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS). Methods: A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured. Results: There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05). Conclusion: Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.


Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Infertilidade Feminina/terapia , Letrozol/uso terapêutico , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação , Estradiol/sangue , Feminino , Fertilização In Vitro , Humanos , Fase Luteal , Hormônio Luteinizante/sangue , Progesterona/sangue
2.
N Engl J Med ; 382(4): 328-340, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971678

RESUMO

BACKGROUND: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hidrocarbonetos Fluorados/uso terapêutico , Leiomioma/complicações , Menorragia/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Densidade Óssea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fogachos/induzido quimicamente , Humanos , Hidrocarbonetos Fluorados/efeitos adversos , Menorragia/etiologia , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1207-1212, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801718

RESUMO

OBJECTIVE: To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles. METHODS: We retrospectively analyzed 2572 GnRH-ant cycles of in vitro fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared. RESULTS: Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 vs 33.89 years, P < 0.001) and a lower body mass index (21.57 vs 21.84 kg/m2, P=0.024). After adjustment for age and body mass index of the patients, no significant differences were found between the two groups in the levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), progesterone (P) levels either at the baseline or on the day of hCG triggering, or in the number of oocytes retrieved (P > 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% vs 3.2%) and similar spontaneous ovulation rate (0.6% vs 0.5%), clinical pregnancy rate (47.7% vs 45.9%) and live birth rate (37.5% vs 33.6%) following fresh embryo transfer (P > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% vs 0.1%, P=0.006). CONCLUSIONS: Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.


Assuntos
Fertilização In Vitro , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Hormônio Luteinizante/fisiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Hormônio Luteinizante/sangue , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento
4.
Histochem Cell Biol ; 152(6): 423-437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630211

RESUMO

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/farmacologia , Oócitos/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/química , Camundongos , Camundongos Endogâmicos BALB C , Oócitos/metabolismo , Puberdade/metabolismo
5.
Taiwan J Obstet Gynecol ; 58(4): 471-476, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307735

RESUMO

OBJECTIVE: To study the impact of stimulation duration on intracytoplasmic sperm injection (ICSI) - embryo transfer (ET) outcome in poor and normal responders during controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol. MATERIALS AND METHODS: This is a retrospective cohort study. There were 1481 women undergoing ICSI-ET cycles. Women with ovum pick-up number ≤3 were defined as poor responders (n = 235), and those with a number ≥4 were normal responders (n = 1246). RESULTS: The mean stimulation duration was shorter in poor responders with pregnancy group as compared with normal responders with pregnancy group (7.8 ± 2.2 vs. 9.2 ± 1.6 days, p < 0.01). Poor responders with a shortest stimulation duration (≤6 days) appeared a higher live birth rate (≤6 days: 33.3%, 7-8 days: 20.0%, 9-10 days: 15.9%, and ≥11 days: 11.1%, p = 0.18). Normal responders with a shortest stimulation duration (≤6 days) appeared a lowest live birth rate (≤6 days: 28.6%, 7-8 days: 35.8%, 9-10 days: 33.6%, and ≥11 days: 29.3%, p = 0.61). Oocyte maturation rate was significantly lower at stimulation durations ≤6 days group (≤6 days: 67%, 7-8 days: 80%, 9-10 days: 85%, and ≥11 days: 87%, p = 0.02) in normal responders. CONCLUSION: In ICSI-ET cycles, stimulation duration appears to have different impact on oocyte maturation, clinical pregnancy rates and live birth rates in both poor and normal responders.


Assuntos
Transferência Embrionária/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Ciclo Menstrual/efeitos dos fármacos , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto , Estudos de Coortes , Transferência Embrionária/efeitos adversos , Feminino , Fertilização In Vitro/efeitos adversos , Fertilização In Vitro/métodos , Seguimentos , Hormônio Liberador de Gonadotropina/administração & dosagem , Hospitais Universitários , Humanos , Ciclo Menstrual/fisiologia , Recuperação de Oócitos/métodos , Oócitos/efeitos dos fármacos , Gravidez , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Taiwan , Fatores de Tempo
6.
Cell Tissue Res ; 378(2): 359-370, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256286

RESUMO

Prostaglandin D and the associated prostaglandin D synthases (PGDS) and receptor (DP) are considered to be involved in spermatogenesis. However, the interplay of the PGDS-DP system in male reproduction is far from being understood. The expression of PGDS lipocalin (L) and hematopoietic (H) type and DP was studied in the GnRH agonist-downregulated canine testis (week, w 0) and during recrudescence of spermatogenesis after implant removal (w 3, 6, 9, 12). H-PGDS, L-PGDS and DP were present in the adult (CG), juvenile (JG) and downregulated canine testis at the mRNA level. PGDS immunohistochemistry revealed positive staining in the cytoplasm of Leydig cells (LCs) of all samples i.e., no difference between groups. mRNA expression (ratio) of L-, H-PGDS and DP did not differ between groups w 0-12 and CG. In contrast, significant differences were found for L-PGDS (p = 0.0388), H-PGDS (p < 0.001) and DP (p < 0.001) for the groups at downregulation (w0, suprelorin group, SG, profact group, PRG) compared with the control groups (JG, CG). L-PGDS expression was lowest in JG, whereas H-PGDS was significantly lower in CG compared with JG and at downregulation (p < 0.001 to p < 0.01). The highest ratio for H-PGDS and DP was observed in the dogs treated with buserelin acetate (PRG). Our data show that the PGDS-DP system is expressed in juvenile and adult canine testes and that downregulation of the testicular endocrine and germinative function significantly affects H-PGDS, L-PGDS and DP mRNA expression indicating a role in the regulation of spermatogenesis.


Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Espermatogênese/fisiologia , Testículo/metabolismo , Animais , Cães , Masculino
7.
Chin Med J (Engl) ; 132(12): 1448-1453, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31205103

RESUMO

BACKGROUND: There is no absolute consensus for the best time for triggering. The aim of this study was to investigate the effect of different proportion of dominant follicles (PDF) on the human chorionic gonadotropin (HCG) day for the clinical outcomes in patients with polycystic ovary syndrome (PCOS) of different ovarian stimulation protocols. METHODS: A total of 371 cycles of the gonadotropin-releasing hormone (GnRH) agonist long protocol and 347 cycles of GnRH antagonist protocol from January 2014 to December 2016 were included in this retrospective study. Based on the PDF on the day of the HCG administration, the included patients were divided into three groups: Group A (low PDF), PDF <20%; Group B (medium PDF), 20%≤ PDF ≤40%; Group C (high PDF), PDF >40%. The measurements regarding ovarian stimulation characteristics, fertilization rate, top quality embryo rate, clinical pregnancy rate, and ovarian hyperstimualtion syndrome (OHSS) rate were compared in different PDF groups with different protocols. RESULTS: In both the GnRH antagonist protocol and GnRH agonist long protocol, the characteristics such as mean age, anti-Mullerian hormone, antral follicle count (AFC), and body mass index were comparable between groups. The number of oocytes retrieved decreased statistically significantly as the PDF and rate of matured oocytes increased. In the GnRH agonist long protocol, the rate of normally fertilized oocytes was highest in Group A (59.74 ±â€Š31.21 vs. 49.70 ±â€Š37.95, 49.67 ±â€Š36.62; F = 3.743, P = 0.025). There were no significant differences in the rate of top-quality embryos and the clinical pregnancy rate between the groups. The clinical pregnancy rate was similar in the three groups (63.6%, 62.5%, 67.5%, respectively, χ = 0.989, P = 0.911). The moderate and severe OHSS rate increased statistically significantly when the PDF increased, which was highest in group C (1.4%, 3.1%, 6.7%, respectively, χ = 12.014, P = 0.017). In the GnRH antagonist protocol, there were no significant differences in the rate of top-quality embryos, the rate of normally fertilized oocytes, the clinical pregnancy rate, and the moderate and severe OHSS rate between the groups. The clinical pregnancy rate in Group C was higher than that in Group A (57.9% vs. 46.6%, χ = 10.850, P = 0.093). CONCLUSIONS: In the GnRH antagonist protocol, PDF on the HCG day of less than 20% may be unfavorable to the clinical pregnancy rate in PCOS. In the GnRH agonist long protocol, delaying the HCG trigger timing has no good effect on clinical pregnancy and the risk of OHSS might increase in patients with PCOS.


Assuntos
Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Gonadotropina Coriônica/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
8.
J Urol ; 202(6): 1199-1208, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31188734

RESUMO

PURPOSE: Androgen deprivation therapy may increase the risk of cardiovascular disease. Limited data suggest that GnRH (gonadotropin-releasing hormone) antagonist may be associated with a lower risk of cardiovascular disease than GnRH agonist. MATERIALS AND METHODS: We performed a phase II, randomized, open label study in men with prostate cancer and preexisting cardiovascular disease who were randomized to receive GnRH agonists or antagonists for 1 year. The primary outcome was endothelial function measured by the EndoPAT 2000 device (Itamar Medical, Caesarea, Israel). The predefined secondary outcome was a new cardiovascular event. Patients were followed for the development of cardiovascular disease, defined as death, myocardial infarction, a cerebrovascular event, percutaneous angioplasty with coronary stent insertion or hospitalizations due to cardiac events. RESULTS: A total of 80 patients were enrolled in study, including 41 and 39 who received GnRH antagonist and agonist, respectively. Patients in each arm had similar baseline characteristics. We did not detect a difference in the primary end point (endothelial function) between the groups (mean ± SD reactive hyperemia index 2.07 ± 0.15 vs 1.92 ± 0.11, p=0.42). However, during the trial period a new cardiovascular event (the secondary end point) developed in 15 patients. Of cases new major cardiovascular and cerebrovascular events developed in 9, including death in 2, myocardial infarction in 1, a cerebrovascular event in 2 and percutaneous angioplasty with coronary stent insertion in 4. Of the patients 20% randomized to GnRH agonist experienced a major cardiovascular and cerebrovascular event compared to 3% of those on GnRH antagonist (p=0.013). The absolute risk reduction in major cardiovascular and cerebrovascular events at 12 months using GnRH antagonist was 18.1% (95% CI 4.6-31.2, p=0.032). CONCLUSIONS: To our knowledge this is the first prospective study to test cardiovascular outcomes among patients with prostate cancer who received androgen deprivation therapy. No differences in the primary end point were noted between the study arms. However, the secondary end point revealed that patients treated with GnRH agonist experienced significantly more major cardiovascular and cerebrovascular events than those treated with GnRH antagonist. These phase II results suggest that in patients with prostate cancer who have preexisting cardiovascular disease selecting the androgen deprivation therapy modality may differentially affect cardiac outcomes.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/complicações , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Incidência , Masculino , Projetos Piloto , Estudos Prospectivos , Neoplasias da Próstata/complicações
9.
Curr Med Sci ; 39(3): 431-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209815

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Antagonistas de Hormônios/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Progestinas/administração & dosagem , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Estradiol/sangue , Feminino , Fertilização In Vitro/métodos , Expressão Gênica , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Masculino , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/diagnóstico , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Taxa de Gravidez , Progestinas/efeitos adversos , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento
10.
Curr Med Sci ; 39(3): 437-441, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209816

RESUMO

This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (n=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), follicle-stimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, MII rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<0.01). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.


Assuntos
Preparações de Ação Retardada/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Aborto Espontâneo/diagnóstico , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Estradiol/sangue , Feminino , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante/sangue , Expressão Gênica , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/metabolismo , Infertilidade Feminina/fisiopatologia , Masculino , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento
11.
Drug Des Devel Ther ; 13: 1855-1863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239640

RESUMO

Purpose: The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. Patients and methods: We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). Results: We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. Conclusion: We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.


Assuntos
Endométrio/efeitos dos fármacos , Doenças das Tubas Uterinas/tratamento farmacológico , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/farmacologia , Proteômica , Adulto , Algoritmos , Análise por Conglomerados , Endométrio/patologia , Doenças das Tubas Uterinas/patologia , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos
12.
Medicine (Baltimore) ; 98(19): e15492, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083186

RESUMO

OBJECTIVE: The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care. PERSPECTIVE: The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol. SETTING: This retrospective study was conducted from January 2014 to August 2017 at an academic hospital. METHODS: A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment. RESULTS: The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ±â€Š9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ±â€Š8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ±â€Š10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ±â€Š2,147.71 ¥ and 12,753.67 ±â€Š1,905.02 ¥. CONCLUSIONS: The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients <29 years old and the GnRHa protocol for patients >30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.


Assuntos
Análise Custo-Benefício , Transferência Embrionária/economia , Transferência Embrionária/métodos , Fertilização In Vitro/economia , Fertilização In Vitro/métodos , Adulto , Fatores Etários , Protocolos Clínicos , Árvores de Decisões , Economia Hospitalar , Feminino , Fármacos para a Fertilidade Feminina/economia , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Governo , Antagonistas de Hormônios/economia , Antagonistas de Hormônios/uso terapêutico , Humanos , Infertilidade Feminina/economia , Infertilidade Feminina/terapia , Seguro Saúde/economia , Estudos Retrospectivos
13.
Fertil Steril ; 112(2): 298-304.e3, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30992150

RESUMO

OBJECTIVE: To evaluate the efficacy of elagolix, an oral GnRH antagonist, for the reduction of fatigue in women with moderate or severe endometriosis-associated pain. DESIGN: Randomized, double-blind, multicenter, placebo-controlled phase III trial. SETTING: Clinics. PATIENT(S): A total of 860 women treated with elagolix or placebo. INTERVENTION(S): Women received either elagolix at 150 mg daily (QD) orally, elagolix at 200 mg twice daily (BID) orally, or placebo. MAIN OUTCOME MEASURE(S): Change from baseline to month 1, 3, and 6 visits, in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire T-scores. RESULTS(S): At baseline, 54%-74% of women with moderate to severe pain associated with endometriosis reported having fatigue-related issues "quite a bit" or "very much," depending on the question asked. Fatigue extent was reduced to 29%-43% and 14%-29% for women treated with elagolix at 150 mg QD and 200 mg BID, respectively, at 6 months, compared with 35%-50% with placebo. The resultant decrease in fatigue T-scores was significant after elagolix treatment compared with placebo at 6 months, with changes of -2.21 and -5.90 with elagolix at 150 mg QD and 200 mg BID, respectively. Significant reduction in fatigue scores were observed among patients reporting clinically meaningful response "reduction" in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia (-7.31, -6.62, and -4.31, respectively) compared with nonresponders. CONCLUSION(S): In women with moderate to severe endometriosis related pain, elagolix significantly reduces fatigue levels.


Assuntos
Endometriose/tratamento farmacológico , Fadiga/tratamento farmacológico , Hidrocarbonetos Fluorados/uso terapêutico , Dor Pélvica/tratamento farmacológico , Pirimidinas/uso terapêutico , Doenças Uterinas/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Endometriose/complicações , Fadiga/etiologia , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Humanos , Pessoa de Meia-Idade , Medição da Dor , Dor Pélvica/etiologia , Dor Pélvica/patologia , Placebos , Índice de Gravidade de Doença , Resultado do Tratamento , Doenças Uterinas/complicações , Adulto Jovem
14.
Eur J Obstet Gynecol Reprod Biol ; 236: 133-138, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30909009

RESUMO

OBJECTIVE: This non-interventional study aimed to validate a pre-specified anti-Müllerian hormone (AMH) cut-off of 15 pmol/L (2.10 ng/mL) for the prediction of hyper-response to controlled ovarian stimulation (COS) using the fully automated Elecsys® AMH immunoassay. STUDY DESIGN: One hundred and forty-nine women aged <44 years with regular menstrual cycles underwent COS with 150 IU/day follicle-stimulating hormone in a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Response to COS (poor vs normal vs hyper-response) was defined by number of oocytes retrieved and occurrence of ovarian hyper-stimulation syndrome (OHSS). RESULTS: Significant differences were seen between response classes for the number of follicles prior to follicle puncture (p < 0.001), the number of retrieved oocytes (p < 0.001) and the occurrence of OHSS (p < 0.001), which were all highest in hyper-responders. The area under the receiver operating characteristic curve for AMH to predict hyper-response was 82.1% (95% confidence interval [CI]: 72.5-91.7). When applying the AMH cut-off of 15.0 pmol/L, a sensitivity of 81.3% (95%CI: 54.4-96.0) to predict hyper-response and a specificity of 64.7% (95%CI: 55.9-72.8) to identify poor/normal responders was reached. CONCLUSION: The Elecsys® AMH assay can reliably predict hyper-response to COS in women undergoing a GnRH antagonist treatment protocol.


Assuntos
Hormônio Antimülleriano/sangue , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Indução da Ovulação/métodos , Adulto , Feminino , Fertilização In Vitro/métodos , Humanos , Recuperação de Oócitos , Folículo Ovariano , Resultado do Tratamento
15.
Fundam Clin Pharmacol ; 33(4): 479-499, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30776136

RESUMO

One of the more recently investigated adverse long-term side effects of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is cardiovascular disease (CVD). Studies suggest lower risk of CVD following GnRH antagonists (degarelix) than GnRH agonists. This protocol describes precise codes used to extract variables from five European databases for a study that compares risk of CVD following GnRH agonists and antagonists for PCa. PCa men on primary GnRH agonists or antagonists were identified from the UK THIN (The Health Improvement Network) database, National Health Service (NHS) Scotland, Belgian Cancer Registry (BCR), Dutch PHARMO Database Network and French National Database (SNIIRAM). Cohort entry was defined as date of treatment initiation. CVD event was defined as any first incident or fatal CVD after cohort entry. Readcodes in THIN and ICD codes in NHS Scotland, BCR, PHARMO and SNIIRAM were used to extract variables. Risk of Bias in Non-randomised studies of Interventions (ROBINS-I) tool was used to assess the potential risk of biases in this study. 51 572 men with a median follow-up time of 2 years started on GnRH agonists and 2 417 men with a median follow-up time of 1 year started on GnRH antagonists between 2010 and 2017 in the UK, Scotland, Belgium, the Netherlands and France. Data from five countries improved the study power and internal validity required to compare risk of CVD between GnRH agonists and antagonists, the latter being a fairly new drug with limited data in individual countries.


Assuntos
Doenças Cardiovasculares/epidemiologia , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Fatores Etários , Bases de Dados Factuais/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Masculino , Estadiamento de Neoplasias , Oligopeptídeos/efeitos adversos , Projetos de Pesquisa , Fatores de Risco , Medicina Estatal , Fatores de Tempo
16.
Obstet Gynecol ; 133(3): 423-433, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30741797

RESUMO

OBJECTIVE: To investigate the noninferiority of relugolix compared with leuprorelin acetate in reducing heavy menstrual bleeding associated with uterine leiomyomas. METHODS: In a double-blind, double-dummy trial, premenopausal women with uterine leiomyomas and heavy menstrual bleeding defined as a pictorial blood loss assessment chart score of at least 120 were randomized in a 1:1 ratio to relugolix (40 mg, oral, once daily) or leuprorelin acetate (1.88 mg or 3.75 mg, monthly injection) for 24 weeks. The primary endpoint was the proportion of patients with a total pictorial blood loss assessment chart score of less than 10 for weeks 6-12. Secondary endpoints included myoma and uterine volumes, and hemoglobin levels. A sample size of 144 patients per group (n=288) was estimated to provide at least 90% power to demonstrate noninferiority (prespecified noninferiority margin -15%; one-sided 0.025 level of significance). RESULTS: From March 2016 to September 2017, 281 patients were randomized (relugolix, n=139, leuprorelin n=142). Demographic and baseline characteristics were well balanced; mean pictorial blood loss assessment chart score was 254.3 in the relugolix group and 263.7 in the leuprorelin group. The proportion of patients with total pictorial blood loss assessment chart score of less than 10 for weeks 6-12 was 82.2% in the relugolix group and 83.1% in the leuprorelin group, demonstrating noninferiority of relugolix compared with leuprorelin (relugolix-leuprorelin difference -0.9%; 95% CI: -10.10 to 8.35; prespecified noninferiority margin -15%; P=.001). Reductions in myoma and uterine volumes and increases in hemoglobin levels were comparable in the two groups. Relugolix was associated with an earlier effect on menstrual bleeding than leuprorelin (pictorial blood loss assessment chart score of less than 10, 64.2% vs 31.7% [relugolix-leuprorelin difference 32.5%; 95% CI: 20.95-44.13%] for weeks 2-6 and pictorial blood loss assessment chart score of 0, 52.6% vs 21.8% [30.7%; 95% CI: 19.45-42.00%] for weeks 2-6) and faster recovery of menses after treatment discontinuation (relugolix median [Q1, Q3], 37 days [32.0, 46.0]; leuprorelin median, 65 days [54.0, 77.0]). Adverse events and bone mineral density loss were similar between relugolix and leuprorelin treatment groups. CONCLUSION: In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6-12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02655237; JAPIC Clinical Trial Information, JapicCTI-163128. FUNDING SOURCE: Takeda Pharmaceutical Company Limited and an affiliate of NovaQuest Capital Management LLC.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Leiomioma/tratamento farmacológico , Leuprolida/uso terapêutico , Menorragia/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Pirimidinonas/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Administração Oral , Adulto , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Método Duplo-Cego , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hemoglobinas/metabolismo , Humanos , Injeções , Leiomioma/complicações , Leiomioma/patologia , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Menorragia/etiologia , Pessoa de Meia-Idade , Tamanho do Órgão , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Índice de Gravidade de Doença , Carga Tumoral , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia , Útero/patologia
17.
J Gynecol Obstet Hum Reprod ; 48(5): 341-345, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30794953

RESUMO

OBJECTIVE: to evaluate the effect of the addition of low dose human chorionic gonadotropin (hCG) to human menopausal gonadotropin (HMG) throughout the early follicular phase in controlled ovarian stimulation (COS) conducted with two difference regimens. Gonadotropin-releasing hormone (GnRH) antagonist and short GnRH-agonist protocol were applied in two in vitro fertilization (IVF) clinics. METHODS: Clinical study conducted during the period 2014-2016 in two IVF clinics in a cohort of 240 women. In the first group 1 (124 women), a GnRH antagonist protocol with HMG and addition of low dose (100IU/day) h CG was applied. The other group 2 consisted of 116 women who underwent a short GnRH- agonist protocol with HMG and addition of low dose (100IU/day) h CG. RESULTS: Multiple logistic regression analysis was performed. The group 2 found to be associated with greater number of follicles and oocytes. The pregnancy rates were 12.1% and 26.7% in group 1 and group 2, respectively (p=0.004). For patients over 40 years, the number of follicles and oocytes retrieved were significant higher in group 2.The pregnancy rate in group 2 was higher than in group 1 (21, 6% vs 5%, p=0.017). CONCLUSIONS: Advanced age women are likely to achievepregnancy using the GnRH Short than GnRH antagonist, when HMG/hCG is used, while HMG-hCG gonadotropins have the same potentialas Recombinant follicle stimulating hormone (rFSH)-hCG used in GnRH short protocol.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Fertilização In Vitro , Taxa de Gravidez , Adulto , Busserrelina/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fase Folicular , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Menotropinas/administração & dosagem , Oócitos , Indução da Ovulação , Gravidez
19.
Gynecol Endocrinol ; 35(5): 368-369, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30614333

RESUMO

This study aims to report a case of early, severe ovarian hyperstimulation syndrome (OHSS) following GnRH agonist trigger for final oocyte maturation despite luteal support with a GnRH agonist. Contrary to the claim that luteal support using a GnRH agonist eliminates the risk for OHSS in high-risk patients, this report alerts practitioners to the risk of severe OHSS development despite GnRH agonist luteal support in patients receiving GnRH antagonist protocol with GnRH agonist triggering and cautions the practitioners to consider other measures of OHSS prevention.


Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Fase Luteal , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Adulto , Transferência Embrionária , Feminino , Fertilização In Vitro/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Síndrome de Hiperestimulação Ovariana/etiologia , Indução da Ovulação/métodos , Gravidez , Resultado do Tratamento
20.
Gynecol Endocrinol ; 35(6): 481-484, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30600726

RESUMO

The study aimed to assess the impacts and the targets of progesterone (P4) and estradiol (E2) levels on IVF outcomes in GnRH antagonist protocols. The study was retrospective and concerned patients for their first fresh embryo transfers, after stimulation by a recombinant FSH (rFSH)-GnRH antagonist protocol, between September 2012 and July 2017 in the Toulouse University Hospital. Multivariable analysis, taking into account female age and the ovarian stimulation index, showed that E2 levels had no impact on IVF outcomes, while high P4 levels (>1.10 ng/mL) were associated to low pregnancy rate. The P4 concentrations were significantly negatively correlated to the percentage of top embryos and to the implantation rate. Therefore, the deleterious effect of high levels P4 could to act mainly by impairing embryo quality, which questions the place of the freeze-all strategy in these cases.


Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/uso terapêutico , Fase Folicular/sangue , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Indução da Ovulação/métodos , Progesterona/sangue , Adulto , Transferência Embrionária , Feminino , Fertilização In Vitro/métodos , Humanos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
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