GnRH-a长方案和GnRH-ant方案在高龄患者IVF-ET中应用效果的比较

目的比较高龄患者应用促性腺激素释放激素激动剂（GnRH-a）长方案和促性腺激素释放激素拮抗剂（GnRH-ant）方案行体外受精-胚胎移植（in vitro fertilization-embryo transfer,IVF-ET）的疗效,探讨适合高龄患者控制性卵巢刺激的方案。方法回顾性分析2007年1月至2010年6月156例高生育年龄（35～40岁）不孕症女性在南方医科大学南方医院生殖医学中心行IVF-ET的临床资料,评估GnRH-a长方案和GnRH-ant方案的助孕效果。结果 GnRH-a长方案组和GnRH-ant方案组患者的促性腺激素（Gn）应用总量及hCG日孕激素（P）水平比较,差异无统计学意义（P〉0.05）;但两组在Gn应用时间、hCG日雌二醇（E2）水平、hCG日子宫内膜厚度、获卵数、成熟卵子数、受精数和2PN数比较,差异有统计学意义（P〈0.01）;同时,两组的hCG日黄体生成素（LH）水平比较,差异有统计学意义（P〈0.05）;GnRH-a长方案组的临床妊娠率和着床率显著高于GnRH-ant方案组（P〈0.001）。结论高生育年龄患者IVF-ET中应用GnRH-a长方案的助孕结局优于GnRH-ant方案。     

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。     

不同促排卵方法在卵巢储备功能下降患者中的应用

目的:探讨卵巢储备功能下降患者的促排卵优选方案。方法:GnRH-a/hMG/rFSH(Gn)长方案促排卵(A组)共39个周期,GnRH-a/hMG/rFSH(Gn)短方案促排卵(B组)46个周期,GnRH-A/hMG/rFSH(Gn)促排卵(C组)共35个周期,比较3组临床用药和临床结局情况。结果:A组Gn所用天数(12.4±1.51d)显著高于B组(9.5±1.7d)、C组(10.7±3.2),P<0.05,且Gn(75IU/支)所用支数(41.5±8.6支)也明显多于B组(34.7±9.7支)和C组(33.4±16.2支)(P<0.05)。B组Gn所用天数要少于C组(P<0.05),Gn所用总量与C组间无统计学差异(P>0.05)。hCG注射日的血清LH水平A组(1.20±1.02IU/L)显著低于B组(3.17±1.58IU/L)和C组(2.15±1.8IU/L)(P<0.05),B组与C组之间无统计学差异(P>0.05)。A组与C组注射hCG日的血清E2值(7958±4586pmol/L,6022±7852pmol/L)均低于B组(10145±5503pmol/L)(P<0.05)。3组种植率、临床妊娠率均无显著性差异。3组间hCG注射日内膜厚度、受精率、卵裂率均无统计学差异(P>0.05)。结论:短方案更适合于卵巢功能减退患者的促排卵治疗,长方案与GnRH-A方案促排卵也是可行方法。     

促排卵药物与妇科肿瘤相关性研究进展

近年来随着辅助生殖技术的应用和发展,促排卵药物的使用与妇科肿瘤的发生受到广泛关注,前者主要通过影响内源性雌激素、孕酮和促性腺激素水平影响卵巢,并会导致卵巢过度刺激、骨质疏松等不良事件.然而,促排卵药物与妇科肿瘤尤其是卵巢肿瘤发生的关系,国内外文献报道尚无统一结论.由于不孕症患者数量和促排卵药物使用的增加,明确这些药物的...     

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。     

促排卵药物与妇科肿瘤相关性研究进展北大核心CSCD

近年来随着辅助生殖技术的应用和发展,促排卵药物的使用与妇科肿瘤的发生受到广泛关注,前者主要通过影响内源性雌激素、孕酮和促性腺激素水平影响卵巢,并会导致卵巢过度刺激、骨质疏松等不良事件。然而,促排卵药物与妇科肿瘤尤其是卵巢肿瘤发生的关系,国内外文献报道尚无统一结论。由于不孕症患者数量和促排卵药物使用的增加,明确这些药物的长期影响特别是与妇科恶性肿瘤的关系非常重要。本文将对促排卵药物与妇科肿瘤发生、保护机制等进行讨论,以期为临床医生提供更直接有效的信息。     

控制性超排卵长、短方案在IVF-ET中的疗效比较

目的:比较促性腺激素释放激素激动剂(GnRHa)长、短方案控制性超排卵在体外受精-胚胎移植(IVF-ET)中的疗效。方法:将2001年7月-2002年4月因双侧输卵管梗阻IVF-ET的患者100人随机分为长方案组(50人)和短方案组(50人)进行超排卵。长方案组从使用促性腺激素(Gn)治疗前1月经周期黄体期(月经21天)使用GnRHa 0.3mg/d,至垂体完全降调节后加用Gn;短方案组从月经周期第2天开始用GnRHa0.1mg/d,同时加用Gn。当患者有3个以上卵泡直径>18mm时肌肉注射人绒毛膜促性腺激素(HCG),36小时后取卵行IVF,取卵48小时后行ET。结果:两组患者平均获卵数、受精率、卵裂率、优质胚胎率、移植胚胎数、临床妊娠率、胚胎种植率及流产率差异无显著性。而两者的Gn使用量有差别,短方案组少于长方案组,两组差异有显著性。两组用Gn第7天雌激素水平不同,短方案组明显高于长方案组,两者差异有显著性。结论:GnRHa长、短方案在IVF-ET中控制性超排卵效果相同,但所需Gn数量不同。     

IVF-ET中促性腺激素释放激素激动剂的超促排卵应用与剂量研究

促性腺激素释放激素激动剂(GnRH-a)是体外受精-胚胎移植(IVF-ET)技术中重要用药。GnRH-a与GnRH受体结合后,早期"突发"作用可刺激垂体促性腺激素急剧释放,持续应用后使垂体受抑制,内源性促性腺激素(Gn)水平下降,即所谓的降调节作用。利用这种生物学特性,GnRH-a联合Gn超促排卵可预防早发黄体生成素(LH)峰,避免卵泡过早黄素化。另外,GnRH-a代替人绒毛膜促性腺激素诱发排卵可降低卵巢过度刺激综合征(OHSS)发生率。探索既能有效抑制LH峰,又不使垂体过度抑制的GnRH-a有效低剂量对于超促排卵有重要意义。     

IVF中三种促超排卵方案效果的比较

目的：探讨IVF中最佳促超排卵方案。方法：将IVF对象随机分为3组。BFh组：23例126个周期,按BFh长方案（Buserelin／FSH／hCG）进行;Chh组：13例14个周期,以CC／hMG／hCG方案进行;Fhh组：55例57个周期,按FSH／hMG／hCG方案进行。结果：每周期平均促性腺激素（Gn）用量BFh组为18．62±5．95支;Chh组16．57±5．70支;Fhh组25．56±8．08支。每周期获成熟卵子数分别为10．23±5．80个;6．07±3．22个;10．96±6．45个。Gn用量BFh组与Chh组差异无显著性（P＞0．05）,但取到的卵子数,差异有显著性（P＜0．05）。BFh组与Fhh组比较,BFh组Gn用量少于Fhh组（P＜0．05）,但取到的卵子数差异无显著性（P＞0．05）,且BFh组无过早的LH峰出现,另二组则各有1例过早的出现内源性LH峰。结论：IVF中BFh方案是较为理想的促起排卵方案。     

血清性激素含量与体外受精-胚胎移植结局的关系分析

目的 探讨在控制性超排卵中血清性激素变化与妊娠结局的关系。方法 随机选择兰州大学第一医院辅助生殖医学中心2003—2004已接受试管婴儿技术治疗，采用黄体期长方案进行控制性超排卵临床妊娠病例147例，未妊娠140例，分析比较组间各项观察指标。结果 两组间患者降调节时间、促性腺激素（Gn）总量、募集卵泡数、获卵数、MII卵数差异均有显著性（P〈0．05），HCG注射日血清孕酮（P）值、血清雌二醇／孕酮（E2／P）比值差异有显著性（P〈0．05）；促性腺激素释放激素激动剂（GnRH—a，达菲林）用量、Gn天数差异无显著性（P〉0．05），降调节后血清黄体生成素（LH）、HCG注射日血清E2、取卵日血清E2、胚胎移植日血清催乳激素（PRL）水平差异无显著性（P〉0、05）。结论 在控制性超排卵治疗中，观察调控血清性激素含量至关重要。HCG注射日血清P值、E2／P比值是预测助孕结局的重要指标，血清E2／P值在1．32—6．11，血清P值在0．637—1.645μg/L时，临床妊娠率增加。     

卵巢慢反应患者控制性超促排卵相关因素分析:一项多中心回顾性研究

目的探讨控制性超促排卵(COH)过程中发生卵巢慢反应可能的相关因素。方法回顾性分析2014年1月—2016年1月期间于兰州大学第一医院、新疆佳音医院、青海省人民医院、银川市妇幼保健院、广西玉林市妇幼保健院进行促性腺激素释放激素激动剂(GnRH-a)长方案体外受精-胚胎移植(IVF-ET)的144例卵巢慢反应患者的临床资料,与132例卵巢正常反应患者(正常对照组)进行对比。结果与正常对照组相比,慢反应组患者体质量指数(BMI)、促甲状腺激素(TSH)较高,降调节及促排卵时间较长,促性腺激素(Gn)使用后7d平均卵泡直径偏小,雌二醇(E_2)、黄体生成素(LH)低,hCG注射日E_2低,IVF双原核(2PN)卵裂率较高,临床妊娠率低,差异均有统计学意义(P0.05)。患者年龄、不孕年限、基础卵泡刺激素(FSH)、LH、催乳素(PRL)、E_2、基础卵泡数、hCG注射日孕酮(P)、获卵率、胚胎质量、胚胎种植率、流产率、宫外孕率、继续妊娠率及取消移植率组间均无统计学差异(P0.05)。结论卵巢慢反应可能与患者BMI过高、甲状腺功能降低及GnRH-a过度抑制相关,较长的Gn天数仍可使慢反应患者获得较好的妊娠结局。     

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)     

Prolonging GnRH-agonist to achieve ovarian suppression does not compromise the results of a long protocol

Objectives

In the long gonadotropin-releasing hormone agonist (GnRHa) protocols, stimulation is delayed until complete pituitary-ovarian suppression has been achieved, which usually takes a minimum of 10 days. In women who do not achieve timely suppression we set out to evaluate if prolonging GnRHa affects the results of the IVF process.

Study design

We analyzed cycle and pregnancy outcome in 506 consecutive women undergoing IVF-ET after a standardized long GnRHa protocol, according to the time required to achieve ovarian suppression (i.e. estradiol < 40 pg/mL and no follicle >6 mm at ultrasound).

Results

Suppression was obtained after 14 GnRHa days in 383 (75.70%) women (Group 1) and 123 (24.30%) women (Group 2) required a mean ± SD (range) of 10 ± 4 (7-28) additional days to achieve complete suppression. Both groups were comparable for baseline clinical and biological characteristics. The rate of cancelled cycles due to poor ovarian response, the number of the oocytes retrieved, fertilization rates, the number and quality of the embryos cultured and transferred were similar in both groups, as well as the pregnancy, implantation and live birth rates. In Group 2, receiver-operator characteristics analysis showed that the probability of pregnancy was not related to the duration of GnRHa treatment.

Conclusions

In a standardized long GnRHa protocol, prolonging desensitization to achieve complete ovarian suppression does not affect the outcome.     

Controlled ovarian hyperstimulation interventions in infertile women aged 40 years or older undergoing in vitro fertilization

Background

The success of in vitro fertilization (IVF) treatment depends on adequate follicle recruitment following controlled ovarian hyperstimulation (COH). Women aged 40 years or older have a reduced ovarian reserve and various treatment protocols have been proposed that aim to increase their ovarian response.

Objectives

To compare the effectiveness of different COH treatment interventions in women undergoing IVF aged 40 years or older.

Search strategy

MEDLINE, the Cochrane Library, and the Chinese Biomedical database were searched for randomized controlled trials (RCTs).

Selection criteria

Only RCTs comparing one type of COH intervention with another in women undergoing IVF aged 40 years or older were included.

Data collection and analysis

Two authors independently searched the abstracts, identified relevant papers, assessed inclusion and trial quality, and extracted the relevant data.

Main results

Four trials involving 4 different comparison groups were included in the review and enrolled a total of 611 randomized subjects.

Conclusion

There was insufficient evidence to support the routine use of any particular COH intervention to manage infertile women aged 40 years or older undergoing IVF. More robust data from good quality RCTs with relevant outcomes are needed.     

Estradiol level on day 9 as a predictor of risk for ovarian hyperresponse during controlled ovarian hyperstimulation

Purpose : To investigate the estradiol (E₂) level in the mid-follicular phase during controlled ovarian hyperstimulation (COH) and evaluate it as a predictor of a high risk for ovarian hyperresponse. Methods : From January 1996 to October 2001, the records of a total of 146 patients undergoing 164 COH cycles were retrospectively reviewed. All patients received the long protocol of GnRH agonists from the previous mid-luteal phase and then hMG or FSH from day 3 of the menstrual cycle. The E₂ level was evaluated on day 9. Ovarian hyperresponse was defined as 1) an E₂ level on the day of hCG injection was >4000 pg/mL, or 2) the necessity for coasting during COH to decrease the risk of ovarian hyperstimulation syndrome (OHSS). Results : Of the 52 cycles in which day 9 E₂ level was >800 pg/mL, 29 (55.8%) fulfilled the criteria for ovarian hyperresponse. None of patients whose day 9 E₂ level was <300 pg/mL met the criteria for hyperresponse. The pregnancy rate in the groups with day 9 E₂ level <300 pg/mL was 42.9%; for an E₂ level = 300–800 pg/mL, 49.2%; and for an E₂ level >800 pg/mL, 32.7%. The corresponding implantation rates were 18.8, 28.0, and 17.0%. The E₂ level on day 9 did not correlate with clinical pregnancy rates or implantation rates. Conclusions : A high E₂ level in the mid-follicular phase was predictive of patients with a high ovarian response. An E₂ level on day 9 of menstrual cycle of >800 pg/mL suggests an increased risk for ovarian hyperresponse, and appropriate management should be instituted to decrease the risk of OHSS.     

The effect of multiple cycles in oocyte donors

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.