PCOS患者体外受精周期r-FSH和HP-HMG促排卵临床结局的比较

目的:探讨多囊卵巢综合征(PCOS)患者体外受精(IVF)周期重组人卵泡刺激素(rFSH)与高纯度尿促性素(HP-HMG)促排卵临床结局的差异。方法:选择2012年1月~12月于我院进行IVF助孕的PCOS患者且符合纳入条件的211例,随机分为两组,并分别给予r-FSH(rFSH组,n=137)和HP-HMG(HP-HMG组,n=74)促排卵,比较两组促性腺激素(Gn)用量、Gn天数、临床妊娠率、种植率、HCG日生殖激素水平以及OHSS周期取消率。结果:HP-HMG组获卵数较r-FSH组明显减少(P=0.03),但其优质胚胎数增加(P=0.04),两组临床妊娠率和种植率差异无统计学意义(P=0.18,P=0.31),但HP-HMG组有增加趋势。HP-HMG组预防OHSS周期取消率较r-FSH组明显下降(P=0.04)。结论:HP-HMG能改善胚胎质量,降低OHSS发生率。     

国产注射用重组人卵泡刺激素在不同卵巢储备功能患者长方案控制性超促排卵中的疗效观察

目的探讨国产注射用重组人卵泡刺激素(rFSH)在不同卵巢储备功能患者长方案控制性促排卵中的效果。方法回顾性分析烟台毓璜顶医院生殖科自2016年1月至2018年1月行体外受精/卵胞浆内单精子注射-胚胎移植治疗的患者共1284例,所有患者均采用标准长方案促排卵,按其抗苗勒管激素(AMH)水平分为卵巢储备正常组(AMH 1.2～4.5μg/L,678例)及高反应组(AMH4.5μg/L,606例),每组患者按照启动日促性腺激素用药的不同分为国产rFSH组(卵巢储备正常组340例、高反应组330例)与进口rFSH两个亚组(卵巢储备正常组338例、高反应组276例),两两比较不同卵巢储备功能下两亚组患者促排卵后临床及实验室指标。结果不论卵巢储备功能正常或高反应,两亚组患者在促性腺激素(Gn)用量[(1983.15±510.00)U vs.(1913.32±422.12)U,P=0.053;(1816.86±506.37)U vs.(1786.63±453.90)U,P=0.44]、Gn天数[(8.96±1.33)d vs.(8.87±1.24)d,P=0.36;(9.45±1.51)d vs.(9.44±1.47)d,P=0.91]、注射用高纯度尿促性素用药量[(144.20±67.39)U vs.(143.42±56.73)U,P=0.86;(149.52±62.38)U vs.(160.21±84.87)U,P=0.09]、获卵数目[(8.14±3.57)个vs.(8.44±3.37)个,P=0.25;(11.47±4.74)个vs.(11.66±4.49)个,P=0.62]、MⅡ卵子率(82.08%vs. 82.01%,P=0.96;82.78%vs. 82.94%,P=0.90)、受精率(82.17%vs. 80.98%,P=0.30;80.75%vs. 82.16%,P=0.33)、卵裂率(94.55%vs. 93.92%,P=0.52;94.12%vs. 94.84%,P=0.49)、囊胚形成率(58.43%vs. 59.55%,P=0.69;61.14%vs. 63.09%,P=0.46)、临床妊娠率(59.49%vs. 56.54%,P=0.54;62.84%vs. 58.70%,P=0.57)、早期流产率(7.36%vs. 6.80%,P=0.42;11.30%vs. 11.11%,P=0.93)及中重度卵巢过度刺激综合征(OHSS)发生率(3.53%vs. 4.73%,P=0.71;7.58%vs. 9.06%,P=0.53)之间差异均无统计学意义,但国产rFSH组患者hCG日促黄体生成素(LH)水平均较进口rFSH组明显升高[(2.83±1.31)U/L vs.(2.49±1.14)U/L,P=0.007;(2.35±1.10)U/L vs.(2.11±0.94)U/L,P=0.005]。在卵巢储备正常组国产rFSH组hCG日E2浓度及1.6cm以上卵泡数更低,但优胚率显著增高(67.23%vs. 62.51%,P=0.038),差异有统计学意义。结论国产rFSH与进口rFSH长方案促排卵后具有相同的临床妊娠结局,但国产rFSH促排卵后hCG日LH浓度更高,卵巢储备正常患者应用国产rFSH后具有更高的优胚率。     

GnRH-a治疗难治性排卵障碍不孕患者的初步观察

目的探讨常规诱导排卵失败后应用促性腺激素释放激素激动剂(GnRH-a)诱导排卵的临床效果.方法对常规促排卵治疗(氯米芬和HMG)失败的13例排卵障碍不孕患者,其中多囊卵巢综合症(PCOS)5例,小卵泡排卵8例.采用GnRH-a+HMG治疗,并于周期第8天开始B超监测卵泡发育并测定尿LH,当卵泡平均径线达18 mm或尿LH(+)时,给HCG诱发排卵.结果13例患者采用GnRH-a+HMG治疗19个周期,均有优势卵泡发育,其中16个周期(84.2%)卵泡平均径线达18 mm时尿LH仍为(-),给HCG诱发排卵;3个周期提前出现LH峰,取消使用HCG.36.8%的周期为单卵泡发育,75.0%为＜3个优势卵泡,8.3%为4～10个,18.8%为＞10个.妊娠率58.3%,周期妊娠率41.2%,其中单胎4例,双胎2例,4胎1例;自然流产的发生率为14.3%.结论GnRH-a可增强PCOS患者对HMG的反应性,防止内源性LH峰早现,并有良好的妊娠率及妊娠结局,可望作为治疗PCOS及小卵泡排卵患者的二线药物;低剂量HMG可使75%的治疗周期中卵泡发育数＜3个.     

丙氨瑞林在诱导排卵中的应用

目的:探讨丙氨瑞林在对无排卵者诱导排卵中的应用。方法:回顾性分析WHO II型无排卵患者1155个周期,A组572个周期,月经周期d2开始使用hMG促排,至hCG日。B组583个周期,在A组方案基础上,d2开始肌注醋酸丙氨瑞林0.15mg/d至hCG日。二组均待有优势卵泡时注射hCG,指导同房或行IUI术,其后行黄体支持治疗。结果:A、B组患者的卵泡(直径≥16mm)数(2.7±2.3枚vs2.0±2.0枚)、排卵数(2.2±2.1vs1.8±1.8)、排卵日(12.2±2.5d vs12.5±2.1d)、hMG用量(10.8±2.3支,12.3±5.3支)、hCG日子宫内膜厚度(8.9±1.7mm vs9.3±1.7mm)、双胎妊娠率(16.6%vs13.7%)、三胎妊娠率(5.5%vs6.5%)和多胎妊娠率(22.1%vs20.2%)比较均无统计学差异,P>0.05;卵泡平均直径达到14mm日LH水平(7.5±3.9U/L vs4.1±3.9U/L)、周期取消率(17.8%vs2.6%)、流产率(26.8%vs4.6%)、轻度、中重度OHSS发生率(5.5%vs1.0%,0.5%vs0)、临床妊娠率(9.6%vs22.4%)间有显著性差异(P<0.05)。结论:hMG+丙氨瑞林诱导排卵方案与单用hMG比较,既能达到较好的临床妊娠率,又能降低周期取消率、流产率和OHSS的发生率。     

HP-hMG在卵巢次高反应患者体外受精周期中的临床应用效果

目的:探讨卵巢次高反应患者体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)周期应用高纯度尿促性素(HP-hMG,贺美奇)与重组人卵泡刺激素(r-FSH,果纳芬)促排卵的临床结局。方法:选择IVF-ET助孕的卵巢次高反应患者310例,随机分为A组和B组,分别给予r-FSH+HP-hMG(A组,n=124)和r-FSH(B组,n=186)促排卵,统计促性腺激素(Gn)总用量、Gn使用天数、获卵数、受精率、卵裂率、优质胚胎率、临床妊娠率以及因卵巢过度刺激综合征(OHSS)周期取消率及ET后OHSS发生率。结果:患者的基本情况组间无统计学差异(P0.05),B组Gn使用天数明显多于A组(P0.05),Gn总用量明显多于A组(P0.05),hCG注射日E_2、LH组间无统计学差异(P0.05),B组hCG注射日孕酮(P)值显著高于A组(P0.05);获卵数B组显著多于A组(P0.05),受精率、卵裂率、移植胚胎数组间无统计学差异(P0.05),但优质胚胎率B组却显著低于A组(P0.05),移植患者临床妊娠率组间差异无统计学意义(P0.05),A组仅稍高于B组。A组预防OHSS周期取消率较B组明显下降(P0.05),B组移植患者OHSS发生率略高于A组(P0.05)。结论:在卵巢次高反应患者人群中从启动日添加HP-hMG能改善胚胎质量,增加子宫内膜容受性,降低OHSS发生率。     

针灸联合宫内人工授精(IUI)治疗多囊卵巢综合征所致不孕——65例疗效观察

目的:观察针灸与药物促排卵配合宫腔内人工授精(IUI)治疗多囊卵巢综合征(PCOS)所致不孕的临床疗效。方法:125例PCOS患者随机分为2组:治疗组65例,在药物促排卵基础上于IUI术前、后加针灸治疗;对照组60例,在IUI术前单以药物促排卵治疗。结果:治疗组的周期排卵率为83.9%,妊娠率为36.9%,黄素化未破裂卵泡(LUF)发生率为4.1%,周期取消率为6.3%;对照组周期排卵率为69.9%,妊娠率为20%,LUF发生率为23.1%,周期取消率为21.4%,组间比较均有显著差异(P<0.05或P<0.01)。结论:针灸配合IUI治疗PCOS可有效提高临床妊娠率,降低了LUF及卵巢过度刺激综合征(OHSS)等并发症的发生率。     

来曲唑序贯氯米芬在多囊卵巢综合征患者中的应用

目的:探讨来曲唑(LE)序贯氯米芬(CC)对多囊卵巢综合征(PCOS)患者的促排卵效果。方法:分析PCOS患者共62例,72个促排周期。按促排卵方案分为LE序贯尿促性素(HMG)组和LE序贯CC组,比较两组单卵泡率、HCG日子宫内膜厚度、未成熟卵泡率、排卵率、卵泡过度刺激综合征(OHSS)发生率、临床妊娠率、多胎妊娠率及用药时间、费用的差异。结果:LE序贯HMG组和LE序贯CC组的单卵泡率分别为78.95%、88.24%,未成熟卵泡率为7.89%、2.94%,排卵率分别为89.47%、97.06%,OHSS发生率分别为5.26%、0,临床妊娠率分别为13.16%、11.76%,多胎妊娠率分别为5.26%、2.94%,差异均无统计学意义(P0.05),LE序贯HMG组HGC日子宫内膜厚度(10.27±1.92 mm)明显厚于LE序贯CC组(9.13±2.32 mm)(P0.05)。LE序贯CC组用药时间(10.00±0.00天)明显少于LE序贯HMG组(12.16±1.98天)(P0.05)。LE序贯HMG组的费用明显高于LE序贯CC组。结论:LE序贯CC与LE序贯HMG的排卵效果及妊娠率近似,OHSS发生率无明显差别,LE序贯CC用药时间更短,费用更低,但HCG日子宫内膜更薄,应用中应适当补充雌激素促进内膜生长。     

定坤丹联合氯米芬治疗多囊卵巢综合征伴不孕疗效观察

目的探讨定坤丹联合氯米芬治疗多囊卵巢综合征伴不孕的临床疗效。方法选择2015年12月至2016年8月河南中医药大学第一附属医院生殖医学科因排卵障碍致不孕的多囊卵巢综合征(PCOS)患者100例,按随机数字表法分为治疗组和对照组,每组各50例。治疗组采用氯米芬联合定坤丹治疗,以氯米芬治疗做对照。比较治疗后两组患者[月经第10天、人绒毛膜促性腺激素(h CG)日]的雌二醇(E2)水平与子宫内膜厚度、h CG日成熟卵泡数、排卵率、生化妊娠率、临床妊娠率。结果治疗后,治疗组月经第10天、h CG日E2水平[(607.92±11.75)pmol/L vs.(461.02±10.19)pmol/L,P=0.039;(1097.78±12.33)pmol/L vs.(899.10±12.80)pmol/L,P=0.000]与子宫内膜厚度[(6.10±0.84)mm vs.(5.28±0.83)mm,P=0.000;(9.28±0.73)mm vs.(5.74±0.72)mm,P=0.000]均大于对照组;两组双卵泡率、多卵泡率(36.0%vs.38.0%;4.0%vs.2.0%),差异均无统计学意义,治疗组单卵泡率、成熟卵泡率及排卵率均较对照组更高(58.0%vs.38.0%,P=0.045;98.0%vs.78.0%,P=0.002;91.5%vs.73.7%,P=0.028);治疗组生化妊娠率、临床妊娠率均优于对照组(8.0%vs.24.0%,P=0.029;42.0%vs.18.0%,P=0.009)。结论定坤丹联合氯米芬能明显改善多囊卵巢综合征伴不孕患者的临床疗效。     

降低hCG的剂量不影响控制性超促排卵中卵泡的最终成熟及随后冷冻胚胎移植的妊娠结局

目的:在卵巢中等反应和高反应患者中,比较2 000 IU、3 000 IU低剂量hCG与5 000 IU hCG在控制性超促排卵(COH)过程中诱导卵泡成熟及随后冷冻胚胎移植(FET)的妊娠结局。方法:回顾性分析2 166例接受IVF/ICSI治疗的患者的临床资料,根据hCG的剂量分为3组:2 000 IU(A组,n=722),3 000 IU(B组,n=722)和5 000 IU(C组,n=722),观察比较成熟卵母细胞的比例、受精率、临床妊娠率、累计妊娠率及卵巢过度刺激综合征(OHSS)的发生率等。结果:3组患者获得成熟卵母细胞比例(89.92%,91.40%,90.20%)和受精率(79.80%,80.07%,80.51%)均无统计学差异(P0.05)。A组hCG注射日E2水平、获成熟卵数及优质胚胎数均显著高于B组和C组。3组患者每次移植的临床妊娠率(45.95%,43.97%,44.25%)、继续妊娠率(43.17%,40.91%,42.53%)、种植率(30.74%,27.78%,29.86%)及每位患者的累计妊娠率(CPR)(58.31%,53.60%,54.85%)均无统计学差异。3组的OHSS发生率很低(0.00%,0.14%,0.28%)。结论:对于卵巢中等与高反应患者,2 000 IU hCG与5 000 IU hCG在诱导卵泡的成熟中发挥同样的效果,2 000 IU hCG不仅不影响妊娠结局,而且阻止了OHSS的发生。     

基因重组卵泡刺激素和高纯度尿促卵泡素对体外受精-胚胎移植中的治疗结局的影响

目的比较基因重组卵泡刺激素(rFSH)和高纯度尿促卵泡素(HP-uFSH)对体外受精-胚胎移植治疗过程及妊娠结局的影响。方法回顾性分析北京大学第三医院生殖医学中心自2012年1月至2013年6月行体外受精-胚胎移植(IVF-ET)治疗采用长方案的患者共5 608例,并将其按促性腺激素(Gn)启动日用药的不同分为rFSH与HP-uFSH组,比较两组之间在用药时间、用药量、人绒毛膜促性腺激素(hCG)注射日激素水平、获卵数、胚胎情况、妊娠结局及中重度卵巢过度刺激综合征(OHSS)发生率及活产率方面的差异。结果HP-uFSH组Gn用量及用药天数高于rFSH组,hCG注射日雌激素及黄体酮水平明显低于rFSH组,获卵数目、可移植胚胎数、优质胚胎数明显少于rFSH组,差异均具有统计学意义(P0.05);而在种植率、临床妊娠率、宫外孕发生率、流产率、活产率、中重度卵巢过度刺激综合征(OHSS)发生率方面,两组之间不存在统计学差异(P0.05)。结论在IVF治疗中,应用HP-uFSH促排卵作用相对较温和,但具有与rFSH等同的临床妊娠率及活产率。     

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study

Background and aim: There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS).

Methods: Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3?months. All patients got LTZ on day 3 for 5?d in combination with Hp-HMG, starting with 75?IU from cycle day 7 and maintained for up to 3?d. The maximum dose was 150?IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events.

Results: Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen.

Conclusions: LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.     

Comparison of different starting gonadotropin doses (50, 75 and 100?IU daily) for ovulation induction combined with intrauterine insemination

Purpose

To prevent multiple pregnancies the goal of ovulation induction by gonadotropins is to achieve only mono-follicular development. The most important issue is therefore to determine the starting dose. The aim of this study is to compare three different starting doses of follitropin beta to assess the lowest effective dose.

Methods

We evaluated 92 cycles with ovarian stimulation for patients with unexplained infertility, anovulatory disorder or mild male factor. We prospectively divided patients into 50, 75 and 100?IU groups based on patients’ response to clomiphene citrate treatment.

Results

We performed 87 intrauterine inseminations (95?% of cycles with ovulation induction). Five cycles were cancelled. We achieved 15 pregnancies; total pregnancy rate was 18?%. Pregnancy rate was 22, 10 and 28?% in 50, 75 and 100?IU follitropin beta groups. The average number of follicles was 2.0?±?0.8, 2.2?±?1.1 and 2.5?±?1.8 (ns), total dose of gonadotropins (IU) 483?±?192, 600?±?151 and 830?±?268 (p?Conclusions This study suggests that based on the dose which was chosen according to clomiphene citrate response, all treatment regimes were effective for ovulation induction. 50?IU of follitropin beta daily is the appropriate starting dose to support ovulation for clomiphene citrate-sensitive women. The disadvantage may be an increased risk of cycle cancellation due to low ovarian response. Daily doses 75 or 100?IU of rFSH increase total consumption of gonadotropins.     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

多囊卵巢综合征患者IVF-ET前达英-35预处理不同时间临床效果分析

目的:探讨不同的达英-35预处理时间对多囊卵巢综合征患者IVF-ET助孕结局的影响。方法:回顾性分析在我院接受IVF助孕的119个PCOS助孕周期。所有患者均接受达英-35预处理,根据达英-35预处理周期数分为A组(达英-35预处理时间≤3个月),B组(达英-35预处理时间>3个月),检测比较治疗前、后血清LH水平、睾酮水平、游离雄激素指数(FAI)、获卵数、空卵泡率、临床妊娠率、着床率、OHSS发生率等。结果:A、B组达英-35预处理前血清LH值分别为:5.96±3.03 IU/L、6.91±4.40 IU/L;FAI分别为:1.42±1.10、1.76±1.67,治疗后均明显下降,与治疗前比有显著统计学差异(LH:3.50±2.19 IU/L,3.78±0.21 IU/L,FAI:0.54±0.38,0.54±0.48,P<0.05);B组空卵泡率、OHSS发生率分别为17.4%、6.8%,均低于A组(30.2%,20.0%),受精率为83.5%,较A组(74.8%)高,差异均有统计学意义(P<0.05)。结论:IVF前达英-35预处理可以显著降低PCOS患者高LH、高雄激素水平;随着达英-35预处理时间延长,空卵泡率和OHSS发生率进一步下降,受精率得到改善。     

200 IU hCG替代hMG在晚卵泡期应用于控制性卵巢刺激的疗效观察

目的:探讨200 IU hCG在控制性卵巢刺激(COS)过程的晚卵泡期替代hMG对COS的疗效。方法:回顾性分析行体外受精/单精子卵胞质内注射-冻融胚胎移植(IVF/ICSI-FET)患者资料共154例,进行154个COS周期,根据晚卵泡期是否应用200 IU hCG分为:A组,COS完全应用hMG(65个周期);B组,COS的早卵泡期应用hMG,晚卵泡期则应用hCG(200 IU/d)替代hMG(89个周期)。后续166个周期进行FET,其中,A组70个周期,B组96个周期。统计分析COS周期的用药情况、IVF/ICSI-FET结局。结果:B组的hMG用药剂量和用药时间分别显著少于A组(1 361.0±494.6 IU vs 1 782.7±475.2 IU,P0.05;7.3±2.3 d vs 9.5±2.0 d,P0.05);B组的成熟卵母细胞数显著多于A组(15.2±6.6 vs 11.6±5.7,P0.05);冻融胚胎移植中A、B组的临床妊娠率(64.29%vs 64.58%,P0.05)及活产率(80.00%vs 79.03%,P0.05)比较无统计学差异。结论:200 IU hCG能够在COS的晚卵泡期替代hMG,能安全、有效地维持卵泡生长发育,并且减少Gn的用量,避免卵巢过度刺激综合征(OHSS)发生。     

Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study

The CONSORT dosing algorithm individualizes recombinant human FSH (r-hFSH) doses for assisted reproduction technologies, assigning 37.5 IU increments according to patient characteristics: basal FSH, body mass index, age and antral follicle count. A prospective, uncontrolled, international, 18-centre, pilot study of normo-ovulatory women aged 18-34 years inclusive undergoing a long agonist treatment protocol was performed. Follitropin alfa filled-by-mass (GONAL-f?) dose was assigned by the algorithm and was intended to be altered only for risk of ovarian hyperstimulation syndrome (OHSS). Primary end-point was number of oocytes retrieved. Dose groups containing ≥5 patients were analysed: 75 IU (n = 48), 112.5 IU in = 45), 150 IU (n = 34), 187.5 IU (n = 24), 225 IU (n = 10). Cancellations due to inadequate response were higher than expected in the 75 IU group (12/48). Overall, a median of 9.0 oocytes were retrieved (8.5, 8.0, 10.0, 12.0 and 8.0 in the 75, 112.5, 150, 187.5 and 225 IU groups respectively). Clinical pregnancy rates/cycle started were 31.3, 31.1, 35.3, 50.0 and 20.0%, respectively (overall, 34.2%). Two patients had severe OHSS. Use of the CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in this preliminary study. Adjustment of the algorithm could reduce cancellation rates.     

Relationship of baseline ovarian volume to ovarian response in World Health Organization II anovulatory patients who underwent ovulation induction with gonadotropins

OBJECTIVE: To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins. DESIGN: Retrospective data analysis of two prospective, randomized, multicenter studies. SETTING: Clinical development unit of biotechnology company. PATIENT(S): Four hundred sixty-five World Health Organization II anovulatory patients undergoing ovulation induction. MAIN OUTCOME MEASURE(S): Ovarian response to stimulation, ovulation (mid-luteal serum progesterone > 30 nmol/L), cancellation rate, pregnancy rate, and incidence of the ovarian hyperstimulation syndrome (OHSS) according to baseline ovarian volume (day 2-5) before stimulation. RESULT(S): Mean ovarian volume was 11.55 +/- 6.0 cm(3) (range, 0.8-49.3 cm(3)). Small ovarian volume was associated with lower rates of cycle cancellation owing to risk for OHSS (3 vs. 29 patients [2.8% vs. 9%]). Patients with small ovarian volume (<7.25 cm(3)) required fewer ampules of FSH (1373 IU vs. 1629 IU) and shorter duration of stimulation (16 vs. 18.1 days) and had higher ovulation rate than did patients with mid-range and larger ovarian volume (84.3% vs. 69.1% and 68.8%, respectively). The clinical pregnancy rate per cycle of hCG administration was similar in the three groups (25.8%, 28.1%, and 27.5%). CONCLUSIONS: World Health Organization II anovulatory women with medium-sized or large ovaries who are undergoing low-dose gonadotropin stimulation for ovulation induction may have higher risk for OHSS than do women with small ovaries. Women with small ovaries who meet criteria for administration of hCG respond better to ovulation induction and have a similar likelihood of conceiving compared with women with larger ovaries.     

Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy

This single centre randomized controlled trial was undertaken to compare the efficacy and safety of clomiphene citrate and low-dose recombinant FSH as first line pharmacological therapy for anovulatory infertility associated with polycystic ovary syndrome (PCOS). Seventy-six infertile patients with PCOS were randomized to receive clomiphene citrate (50-150 mg/day for 5 days) (clomiphene citrate group, n = 38) or recombinant human FSH (FSH group, n = 38) in a chronic, low-dose, step-up protocol (daily starting dose 75 IU) for up to three consecutive cycles. Ovarian response was monitored by transvaginal ultrasonography and human chorionic gonadotrophin (HCG) was given to trigger ovulation in all cycles with appropriate follicular development. The primary outcome measure was cumulative pregnancy after undergoing up to three treatment cycles. Secondary outcomes were cycle cancellation rate, ovulation rate per cycle, cumulative ovulation rate, pregnancy rate per cycle, incidence of OHSS, cumulative live birth rate, and multiple birth rate. One hundred and four clomiphene citrate cycles and 91 FSH cycles were evaluable. The relative risk and its 95% confidence interval were 1.17 (0.97-1.46) for HCG cycles with ovulation, 1.78 (0.92-3.54) for the pregnancy rate per woman, and 1.83 (0.79-4.40) for live births per woman in favour of FSH. The cumulative pregnancy rate after three treatment cycles was 43% with FSH and 24% with clomiphene citrate (P = 0.06). By logistic regression analysis, the factors predicting ovulation included female age, serum androstenedione and use of FSH. Predictors of pregnancy were duration of infertility and use of FSH. This randomized controlled trial suggests that low-dose recombinant FSH may be an effective alternative to clomiphene citrate in first-line treatment for anovulatory PCOS patients. Thus, further studies, possibly multi-centre, in order to avoid problems with patient recruitment, are warranted to confirm these results.     

Evaluation of a pen device for self-administration of recombinant human FSH in clomiphene citrate-resistant anovulatory women undergoing ovulation induction

This open-label multicentre study evaluated ease of use, safety, and efficacy of a pen device for self-administration of recombinant follicle-stimulating hormone (rFSH) in 43 subjects undergoing ovulation induction. Follitropin beta was administered subcutaneously with the Follistim Pen within 3 days of onset of menses. A 75 IU starting dose could be increased by 25 or 50 IU on days 8 and 15 if no ovarian response was observed. Human chorionic gonadotrophin (HCG; 10,000 IU) was administered when one follicle > or =18 mm or two to three follicles > or =15 mm were observed. Subjects received standardized instruction for the pen device and subject comprehension was recorded as subjects practised and prepared injections. Ease of use was also evaluated by questionnaire. Forty-four subjects enrolled; 43 were treated with rFSH and 41 were treated with HCG. The comprehension questionnaire revealed that during the mock injection, 100% of subjects properly loaded the cartridge into the pen device, while 95% selected the correct dose and 100% self-injected the medication prescribed. During the second actual injection, 100% of subjects comprehended these pen-related steps. The ease-of-use questionnaire showed that 100% of the subjects rated the overall experience of self-administering with the pen as 'very good' to 'good'. Mean duration and total amount of follitropin beta were 11.4 +/- 4.2 days and 1070.3 +/- 580.3 IU respectively. Ovulation rate was 95%. Biochemical and ongoing pregnancy rates per attempt were 34.9 and 30.2% respectively. Three subjects experienced serious adverse events [asthma; ovarian hyperstimulation syndrome (OHSS) and pain; OHSS]. In conclusion, the pen device provides an easy, safe, and effective way for women to self-administer follitropin beta during ovarian stimulation.