Exploration of standard dosage for GnRH antagonist protocol and dosage adjustments after premature luteinizing hormone surge

The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.

GnRHa黄体支持在IVF/ICSI-ET中的应用

目的探讨拮抗剂方案鲜胚移植黄体中期添加促性腺激素释放激素激动剂(GnRHa)对临床妊娠结局的影响。方法选取2020年1月至2023年2月行拮抗剂方案鲜胚移植IVF/ICSI 314例患者临床资料。在常规黄体支持基础上,根据添加不同剂量GnRHa,分为A组(0 mg,n=95)、B(在取卵后第6天皮下注射0.1 mg GnRHa,n=92)、C组(于取卵第2、5、8天单次皮下注射0.1 mgGnRHa,n=55)、D组(于取卵第2、4天单次皮下注射0.2 mg GnRHa,n=72),比较4组的妊娠结局。将314例分为临床妊娠组和非临床妊娠组,行单因素分析和logistic回归分析,探索影响ART妊娠结果的重要因素。结果4组患者年龄、不孕年限、体重指数(BMI)、抗苗勒管激素(AMH)、窦卵泡数(AFC)、获卵数、MⅡ数、2PN数、优质D3胚胎数差异均无统计学意义(P>0.05);A组临床妊娠率低于B、C、D组(P<0.05),4组种植率、早期流产率、多胎率差异无统计学意义(P>0.05)。Logistic回归分析发现,平均移植胚胎数、GnRHa黄体支持占比均与妊娠结局有相关性(P<0.05)。结论拮抗剂鲜胚移植黄体中期添加GnRHa可提高临床妊娠率,且安全的多剂量间断给药临床妊娠率方面效果更明显。平均移植胚胎数是影响临床妊娠结局的关键因素。

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with≥30 Follicles Measuring≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

Effect of estrogen pretreatment in GnRH antagonist protocol-Meta-analysis

Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of estrogen pre-treatment in antagonist prorocol were searched in PubMed,Web of Science,China National Knowledge Infrastructure,Wanfang Database.R software was used for meta-analysis.Results:Seven RCTs and two retrospective studies were included.In order to explore the source of heterogeneity,subgroup analysis was used,which was mainly conducted according to the ovarian response of the included population,which were divided into low responders,non-low responders and mixed responders.In the study about gonadotropin hormone(Gn)days,patients were divided into wash-out subgroup and non-wash-out subgroup according to drug use-pattern.Meta-results showed that the number of Gn days increased significantly in the non-wash-out subgroup(WMD=1.07,95%CI[0.83;1.31],I2=66%).The number of Gn days in the wash-out subgroup were not affected(WMD=-0.12,95%CI[-0.45;0.21],I2=0%).In the low-response subgroup,the number of oocytes retrieved(WMD=0.46,95%CI[-0.23;1.16],I2=81%),the fresh cycle clinical pregnancy rate(RR=0.77,95%CI[0.55;1.06],I2=73%)and the cycle cancellation rate(RR=0.80,95%CI[0.40;1.61],I2=83%)were not significantly changed with estrogen pre-treatment.In the non-low-response subgroup,the number of oocytes obtained(WMD=0.21,95%CI[-0.69;1.11],I2=2%),fresh cycle clinical pregnancy rate(RR=0.94,95%CI[0.77;1.14],I2=41%),live birth rate(RR=0.82,95%CI[0.62;1.08],I2=0%)and cycle cancellation rate(RR=0.89,95%CI[0.54;1.47],I2=2%)were not significantly changed with estrogen pre-treatment.Conclusions:Estrogen pre-treatment(with non-wash-out period)in antagonist protocol increases Gn days,dose not improve IVF outcomes in non-low responders and low responders.

Pregnancy outcomes following supplementation of single dose GnRH agonist to sustain the luteal phase in antagonist fresh embryo transfer cycles:A multicentric prospective cohort study

Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.

探讨GnRH拮抗剂方案的标准剂量及早发LH峰后的剂量调整

促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)拮抗剂方案已被广泛应用于控制性促排卵(controlled ovarian hyperstimulation,COH)的体外受精(in vitro fertilization,IVF)周期中,作为GnRH激动剂方案的有效替代治疗方法,适用于各种卵巢反应的不孕女性患者。尽管拮抗剂促排卵方案的临床应用已得到广泛认可,但其中仍有较大的优化空间。因此,本文将重点探讨GnRH拮抗剂方案的优缺点、最佳标准用量的选择以及出现早发黄体生成素(luteinizing hormone,LH)峰后拮抗剂用量的调整策略等问题,旨在为该方案的应用提供更为合理和科学的建议。

GnRHa激发试验与GnRH激发试验对性早熟诊断价值的比较研究

目的探讨比较促性腺激素释放激素类似物(GnRHa)激发试验与2 h促性腺激素释放激素(GnRH)激发试验对于性早熟的诊断价值。方法因乳房发育提前(<8岁)而就诊的女性儿童87例,随机分成GnRHa激发试验组(44例),GnRH激发试验组(43例),比较两者对性早熟的诊断价值。结果 GnRHa激发试验组44例,诊断中枢性性早熟(CPP)23例,单独性乳房早发育(PT)16例,外周性性早熟(PPP)5例;峰值主要出现在30 min,占90.9%。GnRH激发试验组43例,CPP 21例,PT 17例,PPP 5例;峰值主要30 min占60.5%。两组峰值时间差异有统计学意义(P<0.01)。结论 GnRHa激发试验对于儿童性早熟鉴别诊断有很好的应用价值。

GnRHa和rHCG诱导卵泡成熟在加强黄体支持治疗的拮抗剂方案中的疗效对比研究

目的 比较在加强黄体支持治疗的拮抗剂促排卵方案中使用促性腺激素释放激素激动剂（GnRHa）、重组绒毛膜促性腺激素（rHCG）诱导卵泡成熟治疗的安全性和有效性。方法回顾性分析2011年1月-2013年4月在新疆医科大学第一附属医院生殖医学科因输卵管因素行GnRH拮抗剂方案治疗的162个IVF周期，依据HCG日最终诱发卵泡成熟药物的不同分为两组：A组皮下注射GnRHa0．2mg诱导卵泡成熟，共74个周期（其中71个周期进行了新鲜胚胎移植）；B组皮下注射rHCG250p-g诱导卵泡成熟，共88个周期（其中82个周期进行了新鲜胚胎移植）。两组常规于用药后35～36h取卵并于当日行IVF受精。所有患者自取卵日起每日常规肌注黄体酮60mg、口服地屈孕酮20mg支持黄体功能，A组患者于取卵后第2天、第4天加用HCG2000U肌注加强黄体支持。取卵后3d在超声引导下移植胚胎1～3枚。比较两组的获卵率、MⅡ 卵子率、受精率、优质胚胎率、临床妊娠率、周期取消率及OHSS发生率。结果两组获卵率、MⅡ卵子率、受精率、优质胚胎率、临床妊娠率差异无统计学意义（P〉0．05），A组周期取消率和OHSS发生率低于B组，差异有统计学意义（P〈0．05）。结论在加强黄体支持的GnRH拮抗剂促排卵方案中使用GnRHa诱导卵泡成熟可获得与rHCG相仿的获卵率、胚胎质量和临床妊娠率，但其可降低周期取消率和中重度OHSS发生率，故应用GnRHa诱导卵泡成熟是安全、有效的治疗选择。

拮抗剂方案中GnRHa扳机与hCG扳机联合应用的效果观察

目的探讨拮抗剂方案中促性腺激素释放激素激动剂(GnRHa)扳机与人绒毛膜促性腺激素(hCG)扳机联合应用的效果。方法选取在我院生殖中心进行体外受精/卵胞浆内单精子(IVF/ICSI)注射且正常卵巢储备采用的60例患者,两组均采用拮抗剂方案治疗,根据扳机方式不同分为A组(n=30)和B组(n=30)。A组采用GnRHa+hCG方案,B组采用hCG方案,比较两组胚胎质量及妊娠结局。结果A组的获卵数、D3Ⅰ级胚胎率明显高于B组(P<0.05)。A组的临床妊娠率、活产率明显高于B组(P<0.05)。结论与单独使用hCG扳机相比,拮抗剂方案中GnRHa扳机与hCG扳机联合应用可明显提高胚胎质量,改善妊娠结局,值得临床推广。

长效GnRH激动剂与GnRH拮抗剂促排卵方案在反复种植失败患者中的临床应用

目的 比较卵泡期长效促性腺激素释放激素(GnRH)激动剂方案和GnRH拮抗剂方案应用于反复种植失败(RIF)患者的临床效果。方法 回顾性分析2017年6月至2020年3月在中山大学附属第六医院生殖医学中心行体外受精/卵胞浆内单精子注射(IVF/ICSI)治疗的RIF患者的临床资料。根据促排卵方案进行分组,并通过倾向性评分1∶1匹配选择数据,最终纳入594例患者,长效激动剂组(采用长效GnRH激动剂方案促排卵)297例,拮抗剂组(采用GnRH拮抗剂方案促排卵)297例。比较两组患者的一般资料、促排卵及胚胎发育情况、鲜胚移植及冻融胚胎移植妊娠结局。结果 两组患者的年龄、不孕年限、基础激素水平等一般资料比较均无显著性差异(P>0.05)。拮抗剂组HCG日LH水平显著高于长效激动剂组(P<0.05),HCG日子宫内膜厚度、Gn总量、Gn天数、获卵数则显著低于长效激动剂组(P<0.05)。长效激动剂组新鲜周期的临床妊娠率、活产率显著高于拮抗剂组(P<0.05),两组患者冷冻周期的妊娠结局无显著性差异(P>0.05);但长效激动剂组的累计活产率显著高于拮抗剂组(P<0.05)。结论 卵泡期长效激动剂方案促排卵后行新鲜周期移植的助孕策略可以显著改善RIF患者的妊娠结局,值得优先考虑。

Flexible GnRH Antagonist Protocol versus Progestin-primed Ovarian Stimulation (PPOS) Protocol in Patients with Polycystic Ovary Syndrome: Comparison of Clinical Outcomes and Ovarian Response

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.

Effect of CD14/TLR4 antagonist on GnRH/LH secretion in ewe during central inflammation induced by intracerebroventricular administration of LPS

Background: Immune stress induced by lipopolysaccharide(LPS) influences the gonadotropin-releasing hormone(GnRH)/luteinizing hormone(LH) secretion. Presence of LPS interacting Toll-like receptor(TLR) 4 in the hypothalamus may enable the direct action of LPS on the GnRH/LH secretion. So, the aim of the study was to investigate the influence of intracerebroventricular(icv) injection of TLR4 antagonist on GnRH/LH secretion in anestrous ewes during LPS-induced central inflammation. Animals were divided into three groups icv-treated with: Ringer-Locke solution, LPS and TLR4 antagonist followed by LPS.Results: It was demonstrated that TLR4 antagonist reduced LPS-dependent suppression of GnRH gene expression in the preoptic area and in the medial basal hypothalamus, and suppression of receptor for GnRH gene expression in the anterior pituitary gland. It was also shown that TLR4 antagonist reduced suppression of LH release caused by icv injection of LPS. Central administration of LPS stimulated TLR4 gene expression in the medial basal hypothalamus.Conclusions: It was indicated that blockade of TLR4 prevents the inhibitory effect of centrally acting LPS on the GnRH/LH secretion. This suggests that some negative effects of bacterial infection on the hypothalamic-pituitary-gonadal axis activity at the hypothalamic level may be caused by central action of LPS acting through TLR4.

Comparison between a GnRH Agonist and a GnRH Antagonist Protocol for the Same Patient Undergoing IVF

In order to compare GnRH agonist with antagonist protocol for the same patient during controlled ovarian stimulation cycles, the in vitro fertilization and embryo transfer （IVF-ET） outcome was retrospectively studied in 81 patients undergoing 105 agonist protocols and 88 antagonist protocols. The results showed that there was no statistically significant difference in duration of ovarian stimulation, number of ampoules, oocytes retrieved, serum estradiol （E2） and progesterone （P） levels, thickness of endometrium, the zygote- and blastocyst-development rate between GnRH agonist and antagonist protocols （P〉0.05）. High quality embryo rate was higher in antagonist protocols, but there was no significant difference between two protocols. Implantation rate and clinical pregnant rate were significantly higher in antagonist protocol （15.82% and 30.26%, respectively） than in agonist protocol （5.26% and 10.64% respectively （P〈0.05）. It was concluded GnRH antagonist protocol probably improved the outcome of pregnancy of older patients with a history of multiple failure of IVF-ET in a GnRH protocol.

取卵后使用GnRH拮抗剂防治卵巢过度刺激综合征的临床研究

目的评价取卵后使用促性腺激素释放激素拮抗剂(GnRH-ant)防治中/重度卵巢过度刺激综合征(OHSS)的应用价值。方法收集2019年10月至2022年10月在郑州大学第二附属医院生殖中心接受拮抗剂方案助孕因OHSS高风险行全胚冷冻的160例患者作为研究对象,根据取卵术后使用的药物不同分为GnRH-ant组(n=80)与对照组(n=80);对照组采用常规治疗及取卵术后第2天开始给予低分子肝素钙治疗5 d,而GnRH-ant组在对照组治疗的基础上于取卵术后当日开始给予GnRH-ant治疗3~7 d。比较两组患者的一般资料、促排卵情况、OHSS相关临床和实验室指标及临床结局,并采用Spearman相关性分析探讨GnRH-ant组患者各临床指标与中/重度OHSS的关系。结果GnRH-ant组的获卵数、2PN胚胎数及冷冻胚胎数均显著高于对照组(P<0.05);GnRH-ant组取卵后提前来月经的患者比例显著高于对照组(P<0.05);GnRH-ant组穿刺放腹水比例、中/重度OHSS发生率及取卵后2~5 d雌二醇(E 2)、白细胞计数(WBC)、血红蛋白(Hb)、红细胞比容(HCT)、血管内皮生长因子(VEGF)、血浆纤维蛋白原(FIB)均显著低于对照组(P<0.05)。Spearman相关性分析结果显示,GnRH-ant组患者的中/重度OHSS发生与取卵后GnRH-ant总剂量呈负相关(r=-0.224,P<0.05),与获卵数呈正相关(r=0.252,P<0.05)。结论取卵后使用GnRH-ant可以加速黄体溶解并显著降低OHSS高危患者E 2及VEGF水平,降低中/重度OHSS发生风险,并能改善患者的凝血功能,降低血栓风险。

Comparison of the Predictive Value of Antral Follicle Count, Anti-Müllerian Hormone and Follicle-Stimulating Hormone in Women Following GnRH-Antagonist Protocol for Intracytoplasmic Sperm Injection

Background: Prediction of ovarian response is one of the prerequisites for women undergoing intracytoplasmic sperm injection (ICSI) treatment prior to the first controlled ovarian stimulation (COS) cycle. Predictive factors may be variable in patients pre-treated with oral contraceptives (OC) for scheduling purposes. Objective: To evaluate antral follicle count (AFC), anti-müllerian hormone (AMH) and basal follicle stimulating hormone (FSH) for predicting ovarian responses in patients under controlled ovarian hyperstimulation randomized to receive either oral contraceptives (OC) or no treatment (non-OC) prior to their first controlled ovarian stimulation (COS) cycle. Study Design: One hundred infertile women randomized to receive OC treatment or no treatment, prior to their first COS cycle;were stimulated with Gonadotropin Releasing Hormone (GnRH) antagonist protocol. During the early follicular phase (day 2) of the two subsequent cycles (cycle A & cycle B) sonographic (AFC, ovarian volume) and endocrine data (AMH, basal FSH) were recorded. Transvaginal ultrasound was performed for all patients to monitor the ovarian response. Total number of oocytes retrieved and number of generated embryos were recorded and patients were categorized according to retrieved oocytes as poor (oocytes 12). Result(s): AFC, AMH and basal FSH were lower in users than in non-users of hormonal contraception. Poor responders showed less number of oocytes retrieved and had lower AFC and AMH but a higher basal FSH level was recorded in both groups (OC and non-OC). Conclusion: The better predictive value of AMH or AFC, as a single test or in combination will prevent cycle cancellations due to too low or too high ovarian response. AMH in OC group is not affected by OC pretreatment and is superior to other parameters, while AFC is superior to AMH and basal FSH in non-OC group.

GnRH Antagonist Protocol: Is It Effective for Expected Poor Ovarian Responders with Tubal Factor Undergoing IVF?

Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: A total of 341 IVF-ET cycles were retrospectively identified. The following inclusion criteria were applied: age ≥ 40 years and patients with tubal factors. The cycles were divided into two groups: a GnRH antagonist group (157 cycles) and a GnRH agonist group (184 cycles). Results: The duration of stimulation and the total doses of gonadotropin in the GnRH agonist group were significantly more than those in the GnRH antagonist group (P < 0.05). There were significant differences in LH and P values on the hCG measurement days between the two groups (0.91 ± 1.17 vs. 4.82 ± 4.69 U/L and 0.69 ± 0.42 vs. 1.03 ± 0.50 ng/mL, P < 0.05). The implantation rate of the GnRH antagonist group was 12.24%, which was slightly higher than that of the GnRH agonist group (10.10%, P = 0.437). The clinical pregnancy rate of the two groups showed no statistical differences (23.36% vs. 23.03%, P = 1.000). Conclusion: For expected poor ovarian responders, the GnRH antagonist protocol was, to some extent, superior to the GnRH agonist protocol in terms of the implantation and clinical pregnancy rates.

GnRH Antagonist Protocol: Is It Optimal for All Patients of Different Ages Undergoing <i>In Vitro</i>Fertilization and Embryo Transfer?

Background: To assess the effect of these two protocols in patients of different ages. Methods: 1923 in vitro fertilization and embryo transfer (IVF-ET) cycles were divided into two groups: a GnRH-ant protocol group and GnRH-a long protocol group, and then every group were subdivided into four age ranges. The general materials and IVF outcomes were compared. Results: The incidence of OHSS fluctuated from 0% to 2.37% with GnRH-ant protocol, which was significantly lower than another (P P Conclusion: The antagonist protocol should be considered in patients with a high ovarian response (e.g., PCOS patients) to avoid OHSS. Older patients (>35 years) could be treated with the antagonist protocol.

Impact of Serum Progesterone Levels in GnRH Antagonist Assisted Reproduction Cycles on Pregnancy Outcomes: A Prospective Cohort Study

Background: With controlled ovarian hyperstimulation (COH) with gonadotrophin releasing hormone (GnRH) antagonists, sometimes it is associated with incomplete luteolysis leading to elevated serum progesterone in early follicular phase. Persistence of this elevation might reduce the chance for clinical pregnancy. Objective: To assess the effect of elevated early and late follicular progesterone (P) levels during gonadotrophins releasing hormone (GnRH) antagonist cycles on pregnancy outcome. Design: Prospective single center study. Setting: North-western Military hospital, Kingdom of Saudi Arabia. Patients: 302 in vitro fertilization/intra-cytoplasmic sperm injection (IVF-ICSI) patients. Intervention(s): Recombinant follicle stimulating hormone (r-FSH), (150 - 300 IU) started daily from cycle day 2;GnRH antagonist treatment started on day 6 of the cycle. The serum progesterone (P) measured twice on cycle day 2 and human chorionic gonadotrophin (hCG) day. Main Outcome Measures: Clinical pregnancy and live birth rates per started cycle. Results: The incidence of elevated serum P on day 2 was (5.3%) and on hCG day was (17.5%), statistically significant differences in clinical pregnancy rate (32.3% versus 13.0%) and in live birth rate (23.4% versus 11.1%) were present between the normal and high serum progesterone groups on hCG day, but these differences were not statistically significant in the groups of elevated basal progesterone. Conclusion: Follicular phase progesterone rise either on day 2 or the day of hCG trigger was associated with lower clinical pregnancy and live birth rates. This impact was more prominent with trigger day elevation.

Anti-Müllerian hormone and antral follicle count predict ovarian response in women less than 45 years following GnRH antagonist multiple-dose protocol

Objective:To speculate which of the following parameters:antral follicle count(AFC),anti-Müllerian hormone(AMH),follicle-stimulating hormone(FSH)and age can be used as a predictor of ovarian response to gonadotropin-releasing hormone(GnRH)antagonist stimulation multiple-dose protocol in women under 45 years,and to determine the cutoff value of these parameters and their correlations for predicting low and high ovarian response.Methods:This prospective study included 462 women with the mean age of(29.3±6.5)years.All women were subjected to the GnRH antagonist stimulation multiple-dose protocol.On the second day of the menstrual cycle,ultrasonography was conducted to determine AFC in both ovaries.Peripheral blood samples were collected to evaluate the level of estradiol,FSH,luteinizing hormone,prolactin,thyroid-stimulating hormone,and AMH.The women were divided into three groups:low response(AHH<1 ng/mL,n=173),normal response(AMH=1.0-3.5 ng/mL,n=175),and high response(AMH>3.5 ng/mL,n=114).Results:A significant decrease was found in the age and FSH level in the high response group compared to other groups(P<0.001).Conversely,a significant increase was shown in AMH,estradiol on human chorionic gonadotropin(hCG)day,AFC,mature oocytes,fertilized oocytes,and embryos transferred in the high response group compared to the other two groups(P<0.001).The receiver operating characteristic(ROC)curves demonstrated that AFC and AMH had the highest accuracy,followed by basal FSH level and age in the prediction of low ovarian reserves(P<0.001)with cutoff values of≤4.50 and≤0.95 for AFC and AMH,respectively.Moreover,the ROC analysis showed that AFC had the highest accuracy,followed by AMH level and age in the prediction of high ovarian reserves with a cutoff value of≥14.50,≥3.63,and≤27.50 years,respectively(P<0.01).A significant decrease was observed in women's age,estradiol level,and oocyte fertilization rate in pregnant women compared to non-pregnant women(P<0.001).Additionally,significant negative correlations were found between the AFC,the number of mature oocytes,fertilized oocytes,embryos transferred,and the age of pregnant women(P<0.001).Conclusions:AFC and AMH predict low and high ovarian response to GnRH antagonist stimulation multiple-dose protocol in women under 45 years.

Switching of GnRH Agent from Agonist to Antagonist in Patients with Castration-Resistant Prostate Cancer

Objectives: To evaluate the efficacy of alteration from gonadotropin-releasing hormone (GnRH) agonist to antagonist in patients with castration-resistant prostate cancer (CRPC). Methods: Fourteen patients with CRPC were switched from GnRH agonist to GnRH antagonist. CRPC was defined as 3 consecutive rises of PSA values under androgen deprivation therapy despite a testosterone level at the castration level. No patient underwent a change in oral anti-androgen agent or any additional therapy. Patients who showed increase of the PSA value within 10% or showed decrease in the PSA value compared to the baseline were defined as responders. We measured serum PSA, testosterone, follicular stimulating hormone (FSH), and leutenizing hormone (LH) at the time of alteration and 3 months after alteration. Results: The mean age at diagnosis was 74.8 ± 6.3 years with a mean initial PSA level of 537.3 ± 999.1 ng/mL. The mean age at alteration to GnRH antagonist was 81.4 years with a mean PSA level of 28.6 ng/mL. Two out of 14 patients (14%) were judged as responders based on PSA after alteration to GnRH antagonist, although they did not show any further reduction of the serum testosterone level (remain less than 0.03). Six patients showed further reduction of the serum FSH level after alteration;however, they showed no PSA response (from 46.4 ± 42.6 to 69.4 ± 70.3). Conclusions: The switch from GnRH agonist to GnRH antagonist affected 14% of the patients (2 out of 14 patients) with CRPC at 3 months based on PSA. Larger and longer-term studies are required to determine the efficacy of alteration to GnRH antagonist in patients with CRPC.