两种不同超促排卵方案在高龄患者中应用的比较

随着辅助生殖技术如体外受精-胚胎移植(IVF-ET)、卵母细胞浆内单精子显微注射(ICSI)等在治疗不孕不育中的应用,越来越多的不育夫妇得以生育.但是,高龄患者如何获得高质量、多数量的卵子和优质胚胎,进一步提高临床妊娠率,仍是生殖医学工作者关注的焦点.本研究通过对用两种超促排卵方案的136例高龄患者进行分析,比较了两者的Gn用药天数、剂量、获卵数、优质胚胎率及临床妊娠率,以探讨高龄患者的最佳超促排卵方案.     

改良长方案在初次拮抗剂方案助孕治疗失败患者中的应用

目的:比较改良长方案和拮抗剂方案在初次拮抗剂方案失败患者中的临床结局。方法:回顾分析初次拮抗剂方案失败行再次IVF/ICSI助孕治疗的169例患者,其中130例采用改良长方案治疗(研究组),39例采用拮抗剂方案治疗(对照组)。结果:两组患者的一般情况无明显差异(P0.05)。研究组的注射HCG日E2值、Gn用药时间和Gn剂量均显著高于对照组(P0.05),注射HCG日LH值显著低于对照组(P0.05)。研究组的临床妊娠率、种植率及活产率分别为55.2%、36.4%和46.4%,均显著高于对照组(27.3%、22.0%和21.2%)(P0.05)。结论:初次拮抗剂方案失败行再次助孕治疗的患者中,改良长方案可能通过改善子宫内膜的容受性,获得了较拮抗剂方案更好的妊娠结局。     

改良GnRH-a长方案在控制性促排卵中的应用

目的探讨改良GnRH—a/FSH/hMG联合长方案在控制性促排卵中的应用以及国产阿拉瑞林在此方案中的使用。方法以回顾性分析的方法对174例改良GnRH-a长方案和48例超短方案控制性促排卵的资料进行回顾性分析。结果 改良GnRH—a/FSH/hMG联合长方案在FSH/hMG用药天数、用药量、取卵数、移植数、冻存胚胎数、hCG丑内膜厚度、临床妊娠率、种植率、流产率、OHSS发生率等方面与短方案组相比差异均无显著性(P>0.05),其中流产率明显低于超短方案组。结论改良国产阿拉瑞林/FSH/hMG联合长方案是一种简单、经济、有效的控制性促排卵方案,值得在IVF—ET周期中推广。     

不同预处理促性腺激素拮抗剂方案在超促排卵中应用的临床分析

目的:探讨如何在体外受精-胚胎移植(IVF-ET)周期中更有效地运用拮抗剂方案。方法:回顾性分析319个使用拮抗剂方案进行IVF-ET无输卵管积液、无内膜息肉及无子宫解剖结构异常的新鲜移植周期。根据拮抗剂治疗前使用短效激动剂(n=125,A组)、口服避孕药(达英-35)(n=113,B组)和未处理组(n=81,C组)分组,比较各组患者的年龄、促性腺激素(Gn)使用天数和剂量、注射hCG日LH和E2水平、获卵数、优质胚胎率、临床妊娠率等。同时以261个促性腺激素激动剂长方案移植周期为对照组(D组)作进一步对比。结果:C组年龄(32.9±4.8岁)较其它组年龄明显偏大,P<0.05;A和B组Gn使用剂量大于C组,其中A组明显增多(P<0.01);A和B组hCG注射日LH水平均较C组明显低,其中A组LH值最低(P<0.01);A组获卵数最多(P<0.05);B组子宫内膜最薄(P<0.01)。3组的受精率、优质胚胎率均无统计学差异(P>0.05)。A组、B组和C组临床妊娠率分别为:32.8%、17.7%和37.0%,B组临床妊娠率显著低于A、C组(P<0.01)。C组、D组间临床妊娠率比较无统计学差异(37.0%vs 40.2%,P>0.05);C组Gn使用的时间和剂量均比D组明显减少(P<0.05)。结论:在IVF-ET中GnRH拮抗剂治疗前使用达必佳预处理未能提高妊娠率,使用过达因-35避孕的患者妊娠率明显下降,而未使用任何药物的患者接受GnRH拮抗剂超促排卵方案,能获得比较好的临床结局。     

拮抗剂方案黄体支持中添加GnRH-a对新鲜周期临床结局的影响

目的:比较拮抗剂方案中添加促性腺激素释放激素激动剂(GnRH-a)进行黄体支持对新鲜移植周期临床结局的影响,探讨更合适的黄体支持方案。方法:回顾性分析2018年1月至2021年12月在本院行体外受精或卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)助孕治疗,采用拮抗剂方案行新鲜周期移植的不孕症患者共674个周期的临床资料。根据黄体期是否添加GnRH-a进行黄体支持分为对照组和观察组,对照组给予常规的黄体支持,共348个周期;观察组在常规黄体支持的基础上,于取卵后多剂量间断给予GnRH-a 0.1 mg,共326个周期。比较分析两组患者的一般资料、促排卵情况及临床结局。结果:两组患者间的年龄、不孕年限、体质量指数(BMI)、基础卵泡刺激素(bFSH)、促性腺激素(Gn)天数及总量、绒促性素(HCG)日黄体生成素(LH)、雌二醇(E2)及孕酮(P)、获卵数、MII卵数、优质胚胎数、正常受精率、中重度卵巢过度刺激综合征(OHSS)发生率、流产率、活产率、多胎率、妊娠期并发症发生率、子代的出生体质量、早产率及出生缺陷率等比较差异均无统计学意义(P>0.05);观察组的着床率及临床妊娠率显著高于对照组(P<0.05)。多因素Logistic回归分析显示,年龄、移植胚胎数是临床妊娠率的影响因素(OR 0.958,95%CI 0.917～1.000;OR 1.857,95%CI 1.173～2.942)。结论:拮抗剂方案新鲜移植周期中,在常规黄体支持基础上,多剂量间断给予短效GnRH-a进行黄体支持可提高患者的着床率及临床妊娠率,可能成为拮抗剂方案新鲜周期移植后较合适的黄体支持方案。     

不同年龄段患者促性腺激素释放激素拮抗剂方案与激动剂长方案助孕结局比较

目的探讨不同年龄段患者促性腺激素释放激素拮抗剂(GnRH-ant)方案与促性腺激素释放激素激动剂(GnRH-a)长方案体外受精/单精子卵胞浆内注射-新鲜胚胎移植(IVF/ICSI-ET)周期及冷冻胚胎移植(FET)周期妊娠结局。方法回顾性分析南方医科大学南方医院生殖医学中心2010年4月1日至12月31日GnRH-ant方案组(A组)259个周期、同期黄体中期GnRH-a长方案组(B组)318个周期,并以38岁为界分为亚组A1(<38岁)、A2(≥38岁)和B1(<38岁)、B2(≥38岁)。在A1与B1组及A2与B2组中,比较A组与B组临床资料及妊娠结局。结果 A1组新鲜胚胎移植周期的促性腺激素(Gn)用量较B1组少,胚胎种植率及临床妊娠率均较B1组低;A1组卵巢过度刺激综合征(OHSS)发生率低于B2组,差异有统计学意义;两组活胎分娩率、流产率及早产率差异无统计学意义。A组与B组冷冻胚胎移植周期分年龄段比较,治疗结局差异均无统计学意义。A1组冷冻胚胎移植周期临床妊娠率明显高于新鲜移植。A2组新鲜移植与冷冻移植各项治疗结局差异无统计学意义。结论对<38岁患者,GnRH-ant方案虽然可减少Gn用药量以及降低OHSS发生率,但临床妊娠率比经典长方案低。在高龄患者中,拮抗剂方案也无明显优势。冷冻胚胎移植可改善临床妊娠率。拮抗剂或长方案的选择使用不影响妊娠后的远期结局。     

促性腺激素释放激素拮抗剂在辅助生殖技术中的应用

随着体外受精-胚胎移植(IVF—ET)，卵细胞浆内单精子注射(ICSI)等辅助生殖技术在治疗不孕不育中的广泛应用，越来越多的不孕夫妇获得生育，但是如何既要获得高质量、数目多的卵子，进一步提高临床妊娠率，又要减少卵巢过度刺激综合征(OHSS)和多胎妊娠等并发症，一直是大家所关     

促性腺激素释放激素拮抗剂的3种用药方案在体外受精-胚胎移植中的有效性对比

目的:探讨一种适合中国人群、有效的促性腺激素释放激素(GnRH)拮抗剂用药方案.方法:选择进行体外受精·胚胎移植(IVF-ET)治疗的患者102例共114周期,根据拮抗剂使用的不同方法分为3组.A组:从卵巢刺激第6天开始加用GnRH拮抗剂(Cetrotide,Serono),0.25 mg/d,至绒促性素(HCG)注射日.B组:当主导卵泡直径达12～14 mm时开始注射拮抗剂,0.25 mg/a,至HCG日.C组:当主导卵泡达14 mm时,一次性注射拮抗剂0.75 mg.结果:3组患者平均促性腺激素(Gn)用量及天数、各时段LH水平、获卵数、各型卵-冠-丘复合物数、受精率、卵裂率、着床率、临床妊娠率、流产率差异均无统计学意义(P>0.05),均未发生过早的LH峰及提前排卵情况,均无中、重度卵巢刺激综合征(OHSS)发生,但拮抗剂用量A组与B组、A组与C组差异有统计学意义(P<0.01),B组与C组差异无统计学意义(P>0.05).结论:在IVF卵巢刺激中,当主导卵泡直径达14 mm时一次性注射拮抗剂0.75 mg即可有效抑制LH峰,获得满意的临床效果.     

盆腔输卵管因素不孕且前次助孕失败患者再次冻融胚胎移植中应用GnRH-a的临床妊娠结局分析

目的:探讨盆腔输卵管因素不孕患者助孕失败后,在冻融胚胎移植(FET)中使用促性腺激素释放激素激动剂(GnRH-a)对妊娠结局的影响。方法:回顾性分析2015年1月至2018年1月在四川省人民医院因盆腔输卵管因素不孕行FET且前次助孕失败的患者319例,根据FET周期中是否使用GnRH-a分为对照组(n=135)和GnRH-a组(n=184),比较两组患者一般临床资料和妊娠结局,并采用Logistic回归模型分析临床妊娠和自然流产的相关影响因素。同时按照子宫内膜厚度是否>8 mm和是否高龄(≥35岁)对患者进行再次分层,比较分层后患者一般临床资料和妊娠结局。结果:(1)单因素分析提示GnRH-a组子宫内膜更厚,临床妊娠率和自然流产率更高(P<0.05),但活产率差异无统计学意义(P>0.05)。Logistic回归分析提示：FET内膜准备方案中使用GnRH-a不是临床妊娠的独立影响因素(OR 1.428,P=0.142),是自然流产的独立影响因素(OR 2.499,P=0.024)。(2)分层分析发现,与对照组比较,子宫内膜厚度>8 mm且年龄<35岁患者中,GnRH-a组临床妊娠率(64.28%vs.50.00%,P<0.05)和自然流产率(30.86%vs.14.29%,P<0.05)更高。结论:对于盆腔输卵管因素不孕且有助孕失败史的患者,GnRH-a未提高患者的活产率,且自然流产率增加。     

促性腺激素释放激素激动剂对重度子宫内膜异位症患者行体外受精-胚胎移植结果的影响

子宫内膜异位症(内异症)是育龄妇女的常见病，50％的患者合并不孕。体外受精一胚胎移植(IVF-ET)已成为内异症并发难治性不孕的主要治疗方法。促性腺激素释放激素激动剂(GnRH-a)治疗内异症及其相关症状的疗效，临床也已肯定。本研究探讨内异症患者行IVF-ET前予GnRH-a治疗，对IVF-ET效果的影响。     

Short-term use of gonadotropin-releasing hormone agonist (Leuprolide) for in vitro fertilization

A common problem encountered by in vitro fertilization (IVF) programs is the premature occurrence of the spontaneous lutenizing hormone (LH) surge during ovarian stimulation cycles. Administration of gonadotropin-releasing hormone agonists (GnRH-a) for 2 to 3 weeks produces a state of hypogonadotropic hypogonadism, thus allowing ovarian stimulation to proceed uncomplicated by a spontaneous LH surge. We have elected to treat seven patients with GnRH-a in a short-term protocol, with GnRH-a initiated on cycle day 3 along with exogenous gonadotropins. In this series, we found that the spontaneous LH surge was abolished, while ovarian responsiveness seemed to be improved. These results suggest that the initial surge of gonadotropins elicited by GnRH-a administration may enhance ovarian stimulation and that spontaneous LH surge is blocked when GnRH-a and exogenous gonadotropins are initiated concomitantly.     

Ovarian suppression with leuprolide acetate: Comparison of luteal,follicular, and flare-up administration in controlled ovarian hyperstimulation for oocyte retrieval

Adjunct use of leuprolide (LA) in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) was evaluated by three protocols: Group F(n=24) began LA on day 2 of the cycle and Group L(n=38) began LA on day 23 of the cycle until ovarian suppression, at which time hMG was added. Group FL (n=17) began LA on day 1 and hMG on day 3. Compared to FL, more ova were collected, more ova fertilized, and more pregnancies resulted per initiated cycle in groups achieving suppression before hMG stimulation. Fewer days were necessary to attain suppression for L vs F. After achieving suppression, patients were maintained on either 0.5 mg LA or 0.25 mg LA daily during hMG coadministration with similar results. Lower maintenance doses of LA during hMG did not decrease the amount of hMG needed but retained the benefits of LA. We recommend luteal initiation of LA to achieve suppression before hMG.Presented in part at the 45th Annual Meeting of the American Fertility Society, San Francisco, California, November 1989.     

A prospective randomized comparison between long and discontinuous-long protocols of gonadotropin-releasing hormone agonist for in vitro fertilization

Objective: To investigate the efficacy of a discontinuous-long protocol in an IVF program.

Design: Prospective randomized study.

Setting: University hospital.

Patient(s): One hundred thirty-seven IVF cycles of 92 patients in an outpatient IVF program from April 1995 to December 1995.

Intervention(s): In the discontinuous-long protocol group (n = 68), GnRH agonist (GnRH-a) was administered from the luteal phase until cycle day 7, when pure FSH administration was begun. In the long protocol group (n = 69), GnRH-a was administered until the day before hCG administration.

Main Outcome Measure(s): Serum LH and ovarian steroid hormone levels, and IVF outcome.

Result(s): The period and the total dosage of hMG were increased in the discontinuous-long protocol group. Although the fertilization rate was similar under both protocols, the number of embryos transferred was smaller and the cancellation rate was higher in the discontinuouslong protocol group because of the greater failure of oocyte retrieval and fertilization. Serum E₂ levels in the late follicular phase were lower in the discontinuous-long protocol group.

Conclusion(s): Early discontinuation of GnRH-a is not beneficial because of its adverse effects on follicular development.     

Ovarian stimulation for in vitro fertilization using pure follicle-stimulating hormone with and without gonadotropin-releasing hormone agonist in high-responder patients

There is a distinct pattern of response to gonadotropin stimulation in some patients marked by high peak estradiol (E₂) levels, multifollicular ovarians response, and elevated basal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios. We reviewed the stimulation profiles of five such high-responder patients who failed to conceive during in vitro fertilization with ovarian stimulation using pure FSH. All patients had baseline LH/FSH >1.5 and peak E₂>800 pg/ml. One cycle was canceled prior to hCG administration because of marked ovarian response (E₂>2500 pg/ml, multiple small follicles). In a subsequent cycle, all patients were pretreated with the gonadotropin releasing-hormone agonist (GnRHa) leuprolide acetete for 10–14 days prior to initiation of FSH for ovarian stimulation. Leuprolide was continued until the day of hCG administration. During cycles using GnRHa, there was a statistically significant decrease (P <0.05) in serum FSH on day 3 (<5 vs 8.3 mIU/ml), serum E₂ on day 3 (14.6 vs 34.6 pg/ml), and peak serum E₂ (1197.6 vs 1923.0 pg/ml). Patients during cycles with GnRHa had a greater number of preovulatory (8.6 vs 3.0) and total (12.4 vs 6.0) oocytes retrieved (P<0.05). The fertilization rate of preovulatory oocytes was also higher during cycles using GnRHa (83 vs 64%). Two pregnancies occurred in the cycles pretreated with GnRHa. These preliminary data indicate that in high-responder patients, a combination of GnRHa and pure FSH results in lower E₂ levels during the stimulation cycle and a greater number of total and mature oocytes retrieved and fertilized.     

Mild stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist and its influence on serum estradiol level and pregnancy rate

Aim:  The mild ovarian stimulation protocol for in vitro fertilization (IVF) is carried out to minimize adverse side-effects as well as cost. While performing mild ovarian stimulation with a gonadotropin-releasing hormone (GnRH) antagonist, the pregnancy rate was examined in cases that exhibited a serum estradiol (E2) drop down.
Methods:  In this study, 174 patients who requested mild ovarian stimulation for IVF began clomiphene citrate on day 3 and recombinant follicle-stimulating hormone (FSH) on day 5 of their menstrual cycles. A GnRH antagonist was administered when the dominant follicle reached a diameter of 14 mm. Serum luteinizing hormone and estradiol were measured at the time of GnRH antagonist administration and at the time of human chorionic gonadotropin (hCG) injection. Pregnancy rates and implantation rates were compared between 24 cycles in which the E2 level fell at the time of hCG injection and 150 cycles in which it did not fall.
Results:  The pregnancy rate in the cases in which the E2 level fell (25% decrease) at the time of hCG injection was significantly lower than it was in the cases in which it did not fall (16.7 vs 41.0%). The implantation rate for the cases in which the E2 level fell was also lower than that of the control group (7.0 vs 31.0%). There was no significant difference in the number of good-quality embryos between the two groups.
Conclusion:  When performing the mild ovarian stimulation protocol, serum E2 should be followed. It is prudent to avoid embryo transfer in the same cycle in cases that exhibit E2 drop down. (Reprod Med Biol 2008; 7 : 85–89)     

高剂量黄体生成素在卵泡期不同时段对体外受精-胚胎移植的影响

目的探讨在控制超排卵（controlled ovarian hyperstimulation，COH）用药中，高剂量黄体生成素（luteinising hormone，LH）在卵泡的不同时期对体外受精-胚胎移植（in—vitro fertilization and embryo transfer，IVF—ET）的影响。方法采用回顾性研究。常规方案实施IVF—ET的病人359例，按COH中卵泡刺激素（follicle—stimulating hormone，FSH）和LH的不同用量，以及用药时间分为3组：A组（n=252），FSH≥225u／d，且LH≤225u／d（对照组）。B组（n=43）为卵泡晚期高LH接触组，FSH〉225u／d，且取卵前3日内LH〉225u／d（高LH近期组）。C组（n=64）卵泡早、中期高LH接触组，FSH〉225u／d，且取卵前4日或以前LH〉225u／d，取卵前3日内LH〈225u／d（高LH远期组）。对各组受精率、胚胎植入率、临床受孕率、继续妊娠率进行比较分析。结果 A组的胚胎植入率、临床受孕率、继续妊娠率均高于B组（10：4％与7．0％，26．7％与18．4％，20．2％与9．5％，P〈0．05）；而与C组比较则差异无显著性（10．4％与9．5％，26．7％与23．6％，20．2％与18．6％，P〉0．05），但受精率差异显著（60．2％与50．4％，P〈0．05）。C组的胚胎植入率、临床受孕率与B组差异无显著性（9．5％与7．0％，23．6与18．4％，P〉0．05），但C组的继续妊娠率明显高于B组（18．6与9．5，P〈0．05）。结论降调节下COH应用LH〉225u／d时，可使IVF—ET的受精率下降。在卵泡晚期（取卵前3日内）高LH的不良影响较大，其植入率、临床受孕率、继续妊娠率均明显下降。     

Low dose gonadotropin-releasing hormone agonist treatments with early discontinuation for controlled ovarian hyperstimulation in an<Emphasis Type="Italic">in vitro</Emphasis> fertilization program

Aim:  The purpose of the present study was to investigate the applicability of a protocol for controlled ovarian hyperstimulation (COH) featuring early discontinuation of low dose gonadotropin-releasing hormone agonist (GnRHa) for ovulation induction for in vitro fertilization (IVF).
Methods:  Four hundred and eighty-seven women undergoing 555 IVF cycles were recruited into the study. Controlled ovarian hyperstimulation was achieved by using either a short protocol of low dose GnRHa (for 5 days only; groups 1 and 2) or a modified long protocol with early discontinuation of GnRHa (groups 3 and 4). Groups 1 and 3 received urinary follicle-stimulating hormone (FSH) and groups 2 and 4 received recombinant FSH. Oocyte retrieval was performed 34 to 36 h after human chorionic gonadotropin (hCG) injection, followed by embryo transfer 3 days later.
Results:  Luteinizing hormone (LH) levels on the hCG injection day were lower with the modified long protocol (groups 3 and 4) than with the short 5-day treatment (groups 1 and 2). There were higher LH levels in group 1 than in groups 2, 3 and 4, resulting in a worse fertilization rate and clinical pregnancy rate. There were no statistically significant differences between groups 2, 3 and 4 in the rates of fertilization, clinical pregnancy and delivery. A higher estradiol (E₂) level in group 3 than in groups 1, 2 and 4 resulted in a worse implantation rate.
Conclusion:  Early cessation of GnRHa may not induce a premature LH surge in controlled ovarian hyperstimulation, while a low dose also offers a useful alternative to a long protocol of IVF. Ovarian stimulation with recombinant follicle-stimulating hormone (rFSH) is considered to be favorable in this low dose GnRHa treatment. (Reprod Med Biol 2003; 2 : 25–30)