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ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.
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Objective:To explore the value of gonadotropin-releasing hormone (GnRH) antagonist in prostate cancer management.Methods:We retrospectively analyzed the data of 92 consecutive hormonal sensitive prostate cancer (HSPC) patients treated with GnRH antagonist from Jan 2019 to March 2022 in Fudan University Shanghai Cancer Center. The median (IQR) age at diagnosis was 70(65-76)years old. Median(IQR) serum prostate-specific antigen (PSA) level before treatment was 98.30 (32.50-436.75)ng/ml. The median (IQR) testosterone level was 12.30(1.51-18.44)nmol/L. Twenty-six(28.3%)cases were in M 0 stage, while 66(71.7%) were in M 1 stage at diagnosis. There were 67(72.8%)cases in ≥T 3 stage, and 54(58.7%)cases in N 1 stage.The Gleason score of 80(87.0%)cases was ≥8.The second generation androgen inhibitor was used in 58(63.0%)cases, and 21(22.8%)cases had specific gene mutation. Patients received a subcutaneously 240mg Degarelix in the first 28 days and 80 mg Degarelix following every 28 days. The pre-injection and 3 months post injection PSA and testosterone (T) level were collected. According to the proportion of patients with the largest decrease in PSA, the patients were divided into high response group (PSA decrease ≥99% after 3 months of use of Degarelix) and low response group (PSA decrease <99% after 3 months of use of Degarelix). Univariate and multivariate logistic analysis were used to analyze the risk factors affecting the treatment response of Degarelix. Results:Among the 92 prostate cancer patients, after 3 months Degarelix treatment, the median PSA value decreased to 0.64ng/ ml ( P <0.001), and the median testosterone value decreased to 0.45nmol/L ( P <0.001). After treatment, there were 48 cases in the high reaction group and 44 cases in the low reaction group. Before treatment, the median PSA in the high-response group was 100.00(67.11-444.25) ng/ml, higher than 88.50 (9.91-582.25) ng/ml in the low-response group, but not statistically significant ( P=0.077). The median testosterone level in the high response group was 13.82 (7.53-19.43) nmol/L, which was significantly higher than that in the low response group [4.61 (0.75-16.12) nmol/L, P =0.030]. After treatment, the median PSA in the high-response group was 0.22 (0.09-0.82) ng/ml, significantly lower than that in the low-response group [3.22 (0.19-15.88) ng/ ml, P<0.001]. The median testosterone value of the high reaction group was 0.40 (0.09-0.80) nmol/L and that of the low reaction group was 0.45 (0.02-0.65) nmol/L, which showed no significant difference ( P =0.826), and both reached the level of castration (<1.7nmol/L). Univariate analysis showed that age ≤ 65 years old was a good prognostic factor ( OR=0.333, 95% CI 0.119-0.810, P =0.017); T stage ( P =0.540), N stage ( P =0.363), M stage ( P =0.660), Gleason score ( P =0.834), application of second-generation antiandrogens ( P=0.238) and gene mutation ( P =0.525) were not related to Degarelix hyperresponsiveness. In multivariate analysis, age was the only independent favorite prognostic factors( OR=0.913, 95% CI 0.847-0.983, P=0.016). Conclusions:In the real world, GnRH antagonists significantly reduced the levels of testosterone and PSA in HSPC patients after 3 months of treatment regardless of TNM stage, Gleason score, and the second generation androgen inhibitor using.
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Objective: To investigate the effects of gonadotropin-releasing hor-mone-antagonist (GnRH-ant) on the proportion and toxicity of mice uterine nature killer (uNK) cells during implantation window. Methods: Sixteen C57BL/6 mice were randomly divided into GnRH-ant group and control group, with 8 mice in each group. From the 3rd day of the estrous cycle, GnRH-ant (1.5 μg/100 g) was injected intraperitoneally into the mice of the GnRH-ant group for 7 days continuously, and the control group was injected with the same volume of normal saline at the same time point. On the 7th day, the mice of the two groups were injected with human menopausal gonadotropin (40 U/100 g). The next day, they were injected with human chorionic gonadotropin (100 U/100 g) and sacrificed after 48 h. The uterus tissues were taken out for primary digestion to obtain single-cell suspension. Flow cytometry was used to analyze the proportion of uNK cells and the expression levels of toxicity molecules perforin (Pf) and granzyme B (Gz-B). Results: Compared with the control group, the proportion of uNK cells in GnRH-ant group increased (P=0.000), the proliferation level increased (P=0.000), the apoptosis level decreased (P=0.004), and the expression of toxicity molecules Pf (P=0.000) and Gz-B (P=0.034) were up-regulated. Conclusion: GnRH-ant may up-regulate the proportion of uNK cells and enhance their toxicity in the implantation window period of mice.
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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 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 33.89 years, 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% 3.2%) and similar spontaneous ovulation rate (0.6% 0.5%), clinical pregnancy rate (47.7% 45.9%) and live birth rate (37.5% 33.6%) following fresh embryo transfer ( > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% 0.1%, =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.
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OBJECTIVE: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). METHODS: Randomized patients in all three groups (early antagonist, n=14; conventional antagonist, n=11; long agonist, n=11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. RESULTS: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p=0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p=0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p=0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p=0.324). CONCLUSION: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.
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Feminino , Humanos , Gravidez , Transferência Embrionária , Fertilização in vitro , Hormônio Liberador de Gonadotropina , Incidência , Oócitos , Síndrome de Hiperestimulação Ovariana , Síndrome do Ovário Policístico , Taxa de Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. METHODS: This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. RESULTS: The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. CONCLUSION: The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.
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Gonadotropina Coriônica , Estruturas Embrionárias , Estrogênios , Fertilização in vitro , Hormônio Foliculoestimulante , Hormônio Liberador de Gonadotropina , Técnicas In Vitro , Nascido Vivo , Luteína , Luteinização , Oócitos , Indução da Ovulação , Taxa de Gravidez , ProgesteronaRESUMO
<p><b>Background</b>Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer (IVF-ET) with gonadotropin-releasing hormone (GnRH)-antagonist protocol. This study aimed to compare the effect between vaginal progesterone (VP) and intramuscular progesterone (IMP) with GnRH-antagonist protocol after IVF-ET.</p><p><b>Methods</b>A total of 1760 patients (18 years ≤ age ≤35 years) undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP (VP group) and 419 patients received IMP (IMP group) as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median (p25 and p75) and were compared using nonparametric Mann-Whitney U-test.</p><p><b>Results</b>Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% (χ = 8.287, P = 0.004). The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group (clinical intrauterine pregnancy rate 47.35% vs. 41.29%, χ = 4.727, P = 0.030; implantation rate 30.99% vs. 25.26%, χ = 14.546, P < 0.001). Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed.</p><p><b>Conclusion</b>: Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.</p>
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[Objective]To compare the clinical outcomes of fresh embryo transfer of the in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET)in different age groups as well as in different responders using gonadotropin-re-leasing hormone agonist(GnRH-a)long protocol or GnRH antagonist(GnRH-ant)protocol.[Methods]A retrospective analysis was performed on 737 IVF/ICSI cycles,including 386 cycles of GnRH-a long protocol(group A)and 351 cycles of GnRH-ant protocol (group B),from August 28,2015 to December 31,2016. Then all the cycles were divided into sub-groups by ages and retrieved oo-cyte numbers:group a1(15). The basic information of patients and clinical outcomes were compared.[Results](1)Comparable results were obtained from group A and group B in these following variables such as fertilization rate,normal fertilization rate,biochemical pregnancy rate and miscarriage rage. But the stimulation period,the total gonadotropin(Gn)dosage,estradiol(E2)level and endometrial thickness on the day of human chorionic gonadotropin(hCG)administration,number of oocytes retrieved and mature oocytes,ovarian hyperstimulation syn-drome(OHSS)rate,implantation rate and clinical pregnancy rate were significantly higher in group A than group B(P<0.05),and significantly higher cancellation rate of fresh embryo transfer was observed in group B(P<0.001).(2)When divided by ages,no mat-ter in sub-group a1 or sub-group a2,the implantation rate was slightly lower in GnRH-ant protocol than in GnRH-a long protocol, although they failed to reach significant difference(sub-group a1:32.6%vs 39.8%,P=0.067;sub-group a2:9.7%vs 17.9%,P=0.066). The clinical pregnancy rate was comparable using these two protocols in sub-group a1(54.8%vs 50.4%,P=0.429),but it was significantly lower by using GnRH-ant protocol than GnRH-a long protocol in sub-group a2(19.6%vs 39.1%,P=0.021).(3) When divided by numbers of oocytes retrieved,the implantation rate was significantly lower when using GnRH-ant protocol in sub-group b1(13.1%vs 26.0%,P=0.026),but we failed to observe significant differences in other two sub-groups. The clinical preg-nancy rates were comparable in all sub-groups ,whereas differed considerably in sub-group b1 (36.6% vs 19.3%,P = 0.056).[Conclusion]Overall,the implantation rate and clinical pregnancy rate were higher in GnRH-a long protocol than those in GnRH-ant protocol. Nevertheless,GnRH-ant protocol could reduce the dosage of Gn,shorten the treatment duration,and effectively reduce the occurrence of OHSS. There were similar pregnancy outcomes in two protocols for normal responders and high responders ,while for advanced patients or other poor responders,the implantation rate and clinical pregnancy rate were higher in GnRH-a protocol.
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OBJECTIVE: To evaluate whether letrozole incorporated in a gonadotrophin-releasing hormone (GnRH) antagonist multiple dose protocol (MDP) improved controlled ovarian stimulation (COS) and in vitro fertilization (IVF) results in poor responders who underwent IVF treatment. METHODS: In this retrospective cohort study, a total of 103 consecutive IVF cycles that were performed during either the letrozole/GnRH antagonist MDP cycles (letrozole group, n=46) or the standard GnRH antagonist MDP cycles (control group, n=57) were included in 103 poor responders. COS results and IVF outcomes were compared between the two groups. RESULTS: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the letrozole group than in the control group. Duration of GnRH antagonist administered was also shorter in the letrozole group. The number of oocytes retrieved was significantly higher in the letrozole group. However, clinical pregnancy rate per cycle initiated, clinical pregnancy rate per embryo transfer, embryo implantation rate and miscarriage rate were similar in the two groups. CONCLUSION: The letrozole incorporated in GnRH antagonist MDP may be more effective because it results comparable pregnancy outcomes with shorter duration and smaller dose of rhFSH, when compared with the standard GnRH antagonist MDP.
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Feminino , Humanos , Gravidez , Aborto Espontâneo , Aromatase , Estudos de Coortes , Implantação do Embrião , Transferência Embrionária , Fertilização in vitro , Hormônio Foliculoestimulante Humano , Hormônio Liberador de Gonadotropina , Oócitos , Indução da Ovulação , Resultado da Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the effect of the addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles for infertile patients undergoing IVF/ICSI. METHODS: One hundred and ten infertile patients, aged 28 to 39 years, were recruited for this prospective randomized study. They were randomly assigned to receive vaginal progesterone gel (Crinone) along with 4 mg estradiol valerate (group 1, n=55) or only Crinone (group 2, n=55) for luteal support. A GnRH antagonist multiple dose protocol using recombinant human FSH was used for controlled ovarian stimulation (COS) in all of the subjects. The COS results and pregnancy outcomes of the two groups were compared. RESULTS: Group 1 and 2 were comparable with respect to the patient characteristics. The COS and IVF results were also comparable between the two groups. There were no differences in the clinical pregnancy rate (PR) and multiple PR between the two groups. However, the embryo implantation rate were significantly higher in group 1 than that in group 2 (22.2% vs. 13.3%, p=0.035). The incidence of luteal vaginal bleeding (LVB) was significantly lower in group 1 (7.4% vs. 27.8%, p=0.010). CONCLUSION: The addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles reduces the incidence of LVB and increases the embryo implantation rate in infertile patients undergoing IVF/ICSI.
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Idoso , Feminino , Humanos , Gravidez , Implantação do Embrião , Estradiol , Fertilização in vitro , Hormônio Foliculoestimulante Humano , Hormônio Liberador de Gonadotropina , Incidência , Indução da Ovulação , Resultado da Gravidez , Taxa de Gravidez , Progesterona , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas , Hemorragia UterinaRESUMO
OBJECTIVE: To report the pregnancy which was made by in vitro fertilization using recombinant follicle stimulating hormone and gonadotropin releasing hormone antagonist. MATERIAL AND METHOD: Case report. RESULTS: Six oocytes were retrieved and all were fertilized by intracytoplasmic sperm injection. Six embryos were transferred and the pregnancy was confirmed. CONCLUSION: It is envisaged that the availability of recombinant gonadotropins and gonadotropin releasing hormone antagonists will ultimately lead to shorter, cheaper and safer treatments, using reduced dosages.
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Gravidez , Feminino , HumanosRESUMO
Objective To investigate the effect of human growth hormone antagonist (GHA) on diabetic nephropathy in mice. Methods Thirty nine C57BL male mice were divided into five groups: normal control, diabetic control, two GHA diabetic mice groups, human growth hormone (hGH) diabetic group. Diabetic mice were induced with Streptozotocin. hGH, GHA1 〔del(1 4), G120R, K168A, E174A, C182S, del(186 191) Cys 1〕 and GHA2 〔H21A, G120R, E174A〕, were respectively administered subcutaneously to diabetic mice for eleven weeks, the effects of them on body weight, urinary protein excretion and renal morphology in mice of all groups were observed. Results All diabetic mice showed growth retardation including hGH and GH antagonist groups when comparing with their nondiabetic mice. The results of kidney histology showed a significant increase in glomerular area 〔hGH:(4289?798)?m 2, DM:(4226?894)?m 2,GHA1:(3511?717)?m 2, GHA2:(3428?919)?m 2, Normal control:(3399?573)?m 2〕 and cell proliferation (hGH:37.4?5.5, DM:34.5?6.4, GHA1:31.1?6.5, GHA2:29.2?6.5, Normal control:29.0?6.0) in hGH and DM control groups compared with two GH antagonist groups and normal control group, but the expansion of mesangial area with increased extracellualar matrix existed in all diabetic mice, no significant difference was observed among diabetic groups. No statistical difference was found among diabetic groups in urinary protein excretion. Conclusion hGH may aggravate glomerular hypertrophy and mesangial cell proliferation in diabetic mice, and hGH antagonists are effective in preventing diabetic mice glomerular hypertrophy, mesangial cell proliferation and maintaining integrity of kidney normal morphology in diabetic mice.