国产曲普瑞林在体外受精-胚胎移植中垂体降调节效果的观察

<正>1984年Porter等[1]首次报道促性腺激素释放激素类似物(gonadotropin releasing hormone agonist,GnRH-a)用于体外受精-胚胎移植控制性促超排卵以来,GnRH-a与促性腺激素(Gn)联合促超排卵已广泛用于IVF-ET,尤以长方案应用最多。GnRH-a能有效地抑制内源性促黄体生成素(LH)峰出现,避免自发性排卵而获得较好的卵子质量与数量。但目前     

长方案降调节天数和LH水平对体外受精结局的影响

目的：探讨长方案使用促性腺激素（gonadotropin，Gn）前降调节天数和人绒毛膜促性腺激素（human chorionic gonadotropin，HCG）注射日黄体生成素（Iuteinizing hor-mone，LH）水平对体外受精结局的影响。方法：回顾分析2006年1月至12月482例采用促性腺激素释放激素（gonadotropin hormone releasing hormone，GnRH-α）长方案控制性超排卵的资料。结果：按长方案使用Gn前降调节的具体天数分组，发现相互间获卵数、受精率、卵裂率、临床妊娠率等无统计学差异。HCG注射日LH水平高低与受精率、卵裂率、胚胎利用率无显著关系。注射HCG日LH≤1mIU／ml组和1.1—2mlU／ml组获卵数显著高于其它各组（P〈0．05）。LH≤1mIU／ml组、1.1-2mlU／ml组和2.1-5mlU／ml组3组的优质胚胎率、胚胎种植率和累计妊娠率显著高于5.1-10mIU／ml组（P〈0．05）。结论：使用促性腺激素前降调节天数对体外受精结局没有显著影响。HCG注射日的LH水平≤5mlU／ml能获得好的优质胚胎率、胚胎种植率和妊娠率。     

减少GnRHa剂量对长方案促排卵卵巢反应性的影响

目的:探讨减少GnRHa剂量对长方案促排卵的卵巢反应性影响。方法:对37例采用长方案进行促排卵且第一周期未妊娠或流产的患者进行自身对照研究,第一个周期GnRHa用量为0.05mg/d,第二个周期GnRHa用量为0.03mg/d。结果:Gn使用天数、Gn用量、受精率第一、第二促排卵周期间无显著性差异(P>0.05)。获卵数、可移植胚胎数第二周期组较第一周期组显著增加(P<0.05)。结论:本研究认为在长方案促排卵过程中减少GnRHa的剂量可以增加获卵数,改善卵巢反应性,增加IVF妊娠率。     

短方案降调节hCG注射日前后血清雌孕激素水平变化及其比值对IVF/ICSI结局的影响

目的:探讨体外受精-胚胎移植(IVF-ET)中hCG注射日前后血清雌孕激素水平变化及其比值对妊娠结局的影响。方法:选取行短方案治疗的137例不孕症患者的临床资料,根据hCG注射日每成熟卵泡(B超下直径≥14 mm的卵泡)的E2水平分为3组,A1组E2水平<450 pg/ml,A2组E2水平450~600 pg/ml,A3组E2水平>600 pg/ml;据hCG注射日较前一日E2增幅程度不同亦分为3组,B1组增幅程度<20%,B2组增幅程度20%~30%,B3组增幅程度>30%;另外为探讨hCG注射日雌、孕激素比值对妊娠结局的影响,按hCG注射日E2/P值不同亦分为3组,C1组E2/P<3,C2组E2/P=3~5,C3组E2/P>5;对上述3组的临床资料进行回顾性分析。结果:A2组的临床妊娠率高于A3组,A1和A2组的胚胎种植率亦高于A3组,差异均有统计学意义(P<0.05);B1组的临床妊娠率明显高于B2和B3组,B1组的胚胎种植率亦高于B3组,差异均有统计学意义(P<0.05);C3组的临床妊娠率高于C1组,差异有统计学意义(P<0.05);C2、C3组的胚胎种植率明显高于C1组,差异有统计学意义(P<0.05)。结论:行IVF-ET患者的hCG注射日前后适合水平的血清雌、孕激素及其比值(E2水平在450~600 pg/ml,hCG注射日前后E2增幅<20%及E2/P>5)能获得较好的妊娠结局。     

降调节与非降调节激素替代内膜准备对冻融胚胎移植结局的影响

目的:比较3.75mg GnRHa降调节激素替代内膜准备方案与单纯激素替代内膜准备方案对冻融胚胎移植(FET)妊娠率的影响。方法:选取1225例(周期)行冻融胚胎移植患者,根据内膜准备方式分为激素替代周期组(A组)417例和降调节激素替代组808(B组)例。比较两组患者的种植率、妊娠率、流产率和生殖激素水平。结果:激素替代周期组和降调节激素替代组患者的种植率分别为33.6%和38.1%,临床妊娠率分别为52.3%和58.8%;两组的种植率和临床妊娠率比较差异均有统计学意义(P0.05)。降调节激素替代组的黄体酮注射日、ET前1日和ET后第3日LH低于A组,差异有统计学意义(P0.05)。两组患者的流产率和异位妊娠率比较,差异无统计学意义(P0.05)。结论:与传统激素替代内膜准备方案比较,3.75mg GnRHa降调节激素替代内膜准备方式可提高冻融胚胎移植妊娠率而不增加流产率。     

长方案垂体降调节对体外受精-胚胎移植结果的影响

目的:探讨长方案达到垂体降调节的时间长短是否会对控制性超促排卵(COH)和体外受精-胚胎移植(IVF-ET)的结果产生影响。方法:回顾性分析568个用长方案进行控制性超促排卵的IVF-ET周期,根据达到垂体降调节标准的时间长短分组:A组,14d达到降调节标准,419个周期;B组,14d达到降调节标准,149个周期,比较组间的促排卵情况及IVF-ET结果。结果:Gn用量、Gn用药天数、获卵数、注射hCG日子宫内膜厚度组间均无统计学差异(P>0.05),移植胚胎数、可移植胚胎数、种植率组间也均无统计学差异(P>0.05)。妊娠率A组略高于B组,但无统计学差异。A组降调后E2明显低于B组(P<0.05),受精率明显高于B组(P<0.05)。结论:长方案达到垂体降调节所需时间长短不影响COH结果及临床妊娠率,但较早达到降调节者临床妊娠率有增高趋势。     

GnRH-a降调节激素替代方案在IVF移植失败患者中应用的探讨

目的:探讨促性腺激素释放激素激动剂（GnRH-a）降调节激素替代方案在体外受精（IVF）移植失败患者中的适用指征,规范临床方案的选择。方法:选择2015年1月至2018年10月于江西省妇幼保健院行冻融胚胎移植周期的5467例患者,按照IVF移植失败0次、1次、2次及2次以上将患者分为4个层次,分别比较降调节激素替代方案组（GnRH-a组）与非降调节激素替代方案组（HRT组）的临床结局。最后通过多元Logistic回归控制混杂因素。结果:移植失败0、1次时GnRH-a组女方年龄显著高于HRT组（P<0.05）,失败2次患者HRT组继发不孕占比高于GnRH-a组（65.4%vs 57.4%）,差异有统计学意义（P<0.05）。临床结局比较中,GnRH-a组内膜厚度显著高于HRT组（P<0.05）,差异均有统计学意义（P<0.01）,失败0次患者GnRH-a组活产率显著低于HRT组（35.14%vs 47.62%,P<0.05）,差异有统计学意义。多元Logistic回归分析显示,对于移植失败>2次患者,调整女性年龄、移植胚胎数目、移植胚胎分期等混杂因素后,GnRH-a降调节方案较HRT方案活产率更高（调整OR=0.46,P=0.028）。结论:GnRH-a降调节方案可有效增加内膜厚度;对于移植失败0、1次患者,GnRH-a方案不增加活产率;对于移植失败2次患者,GnRH-a降调节方案有升高活产率的趋势,但尚需大样本研究验证;对于移植失败>2次患者,GnRH-a降调节方案对增加活产率有利。     

IVF/ICSI周期中不同移植方案的临床结局及经济学分析

目的:探讨IVF/ICSI周期中第三天可利用胚胎为5枚以上的患者选择不同移植方案的临床结局及经济学评价。方法:选取2014年1月至2015年12月于郑州大学第三附属医院生殖医学中心行IVF/ICSI-ET治疗不孕症的1400例周期,按移植方案分为3组:移植D3胚胎(A组,1109个周期),非选择性囊胚移植组(B组,160个周期),选择性(单)囊胚移植组(C组,131个周期)。分析各组的临床结局和经济学成本。结果:A组患者的获卵数和种植率均明显低于B组和C组,差异均有统计学意义(P0.05);3组患者的2PN受精率、卵裂率、可移植胚胎率、优质胚胎率、临床妊娠率和流产率比较,差异均无统计学意义(P0.05)。A组患者的多胎率明显高于B组和C组(P均=0.000),且B组明显高于C组(P=0.000)。C组患者移植的成本效果比最小。结论:3组移植方案的临床妊娠率相似;选择性单囊胚移植明显提高胚胎种植率,降低多胎率,治疗成本效果比最小,是相对最佳的移植方案。     

子宫内膜异位症患者IVF促排卵不同降调节方案的比较

目的:探讨子宫内膜异位症(EMs)患者合适的降调节方案。方法:收集因中-重度EMs接受IVF-ET治疗的139例不孕患者的资料,按不同的降调节方案分为超长方案(A组)、GnRHa长方案(B组)、GnRHa短方案(C组)3组,回顾性比较分析3组患者的治疗结局。结果:A组的促性腺激素(gonadotropic hormone,Gn)用量(尤其是hMG)显著多于B组和C组,差异有统计学意义(P<0.05);而冷冻周期率、临床妊娠率与种植率显著高于C组(P<0.05),与B组比较有上升趋势,但差异无统计学意义(P>0.05)。结论:EMs患者接受IVF/ICSI-ET治疗时,建议采用超长方案和常规长方案诱导排卵,以提高患者的临床妊娠率。     

促性腺激素释放激素激动剂降调节方案对子宫内膜容受性的研究进展

辅助生殖技术(ART)中,子宫内膜容受性(ER)是影响女性妊娠成功与否的重要因素。促性腺激素释放激素激动剂(GnRHa)在控制性卵巢刺激(COS)过程中得到广泛应用,GnRHa一方面解决了单纯促排卵导致的早发黄体生成激素(LH)峰造成卵子质量下降、周期取消率高的问题,另一方面能够通过调控激素及生物活性分子(雌、孕激素及其受体、整合素、转化生长因子等)的分泌、胞饮突的数量、HOXAl0等基因的表达影响ER,本文总结了GnRHa调节ER的机理,综述了不同的GnRHa降调节方案(GnRHa超长方案、GnRHa长方案、GnRHa短方案、GnRHa超短方案)对ER的影响,为临床上制定合理、科学的个体化GnRHa降调节方案提供参考。     

GnRH类似物－Buserelin在体外受精与胚胎移植超排卵（长方案）治疗中的作用

从１９９４年４月至１９９５年７月在体外受精与胚胎移植超排卵中，应用ＧｎＲＨ类似物－Ｂｕｓｅｒｅｌｉｎ及ＦＳＨ／ｈＭＧ长方案治疗９例（Ⅰ组）与单独用ＦＳＨ／ｈＭＧ１２例（Ⅱ组）进行比较。结果：Ⅰ组的ＦＳＨ／ｈＭＧ用量大，用药时间长，其受精率、卵裂率及妊娠数均高于Ⅱ组。卵巢过度刺激综合征（ＯＨＳＳ）发生率明显低于Ⅱ组。本文研究显示了Ｂｕｓｅｒｅｌｉｎ长方案治疗能明显提高体外受精与胚胎移植的效果。     

体外受精-胚胎移植短方案周期中移植胚胎数与临床妊娠结局的关系

目的:探讨体外受精-胚胎移植(IVF-ET)短方案周期中移植不同胚胎数对于临床妊娠率和多胎发生率的影响。方法:回顾性分析2002.01-2004.10期间进行第一次IVF-ET短方案周期治疗、年龄<35岁的患者1463例,将2002.01-2003.09间移植2个胚胎者为A组(n=84)、移植3个胚胎者为B组(n=716);2003.10-2004.10期间移植2个胚胎者为C组(n=663)。分析和比较3组的可移植胚胎数、胚胎种植率、临床妊娠率和多胎发生率等。结果:B组的可移植胚胎数(7.8±3.7)显著高于移植2个胚胎的A组(4.6±4.7)和C组(6.9±3.9),P均<0.05,胚胎种植率各组间无显著性差异(A:20.62%,B:14.88%,C:21.66%),P均>0.05。B组的临床妊娠率(42.96%)显著高于A组(25.93%)和C组(39.06%),P均<0.05;各组间的单胎妊娠率无显著性差异(A:27.19%,B:20.99%,C:29.42%,P均>0.05);A组(4.94%)和C组(10.06%)的多胎妊娠率均比B组(15.77%)显著降低,P<0.05。结论:IVF-ET短方案周期中,减少移植胚胎数可能会降低临床妊娠率,但移植2枚胚胎能够有效降低多胎妊娠的发生。     

Bilateral Ovarian Pregnancy After in Vitro Fertilization and Embryo Transfer in a Patient with Tubal Factor Infertility

Primary ovarian pregnancy is very rare event after natural pregnancy or assisted reproductive technology (ART) procedures. Although there are a few reports about unilateral ovarian pregnancy after in vitro fertilization and embryo transfer (IVF-ET), there has been no report about bilateral ovarian pregnancy. Moreover, it is difficult to diagnose an ovarian pregnancy following in vitro fertilization and embryo transfer because of enlarged ovary, fluid collection in pelvic cavity, and its low incidence. We present a case of a patient who underwent IVF-ET due to tubal factor infertility, but the patient developed bilateral ovarian pregnancy and was performed both ovarian wedge resection through laparotomy.     

Comparison of Clinical Outcome and Costs with CC + Gonadotropins and GnRHa + Gonadotropins During IVF/ICSI Cycles

OBJECTIVE: To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles. MATERIALS AND METHODS: Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates. RESULTS: Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p < 0.001). More ampoules of gonadotropins were used in the GnRHa group (24.0 +/- 0.3 vs 20.0 +/- 0.5, p < 0.001). Medication costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol. CONCLUSIONS: Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.     

Tubal Pregnancy Following Tubal Embryo Transfer into the Contralateral Fallopian Tube

Ectopic and heterotopic pregnancy may occur with increased frequency following assisted reproductive technology (ART) procedures. In addition, there may be unusual sites of implantation, which may cause atypical and confusing clinical manifestations. We present a case of tubal pregnancy after tubal embryo transfer (TET) to the contralateral fallopian tube. Four embryos were transferred to the left fallopian tube by laparoscopy, but the patient developed a right tubal pregnancy, possibly as a result of intrauterine or intra-abdominal migration of the embryo. ART patients must be followed closely soon after the procedure, and there should be a high index of suspicion for an unusual implantation site.     

Abdominal Ultrasound-Guided Embryo Transfer Improves Clinical Pregnancy Rates After In Vitro Fertilization: Experiences from 330 Clinical Investigations

Purpose: To investigate the effect of ultrasound-guided embryo transfer on the rate of implantation and clinical pregnancy.Methods: A prospective randomized trial was performed to compare ultrasound-guided embryo transfer with the traditional method. A total of 330 patients were randomly divided into two groups on the day of embryo transfer. For the cases (n = 178), ultrasound-guided was used; controls (n = 152) was performed using routine methods.Results: The rate of implantation and clinical pregnancy for the cases (19.6 and 37.1%, respectively) was significantly higher than for the controls (12.6 and 25%, respectively; p < 0.05).Conclusion: Ultrasound-guided embryo transfer can significantly increase the rate of implantation and clinical pregnancy, and should be recommended as a routine procedure in the process of in vitro fertilization and embryo transfer (IVF-ET).     

卵巢子宫内膜异位囊肿剥除术对IVF周期中卵巢反应性和妊娠结局的影响

目的：探讨卵巢子宫内膜异位囊肿剥除术后对体外受精（IVF）周期控制性超排卵中卵巢反应性和妊娠结局的影响。方法：选取体外受精．胚胎移植（IVF-ET）助孕且曾在腹腔镜下行卵巢子宫内膜双侧异位囊肿剥除术20例（25周期）患者及32例单侧异位囊肿剥除术（40周期）患者为研究对象,以同期因输卵管因素行IVF助孕的104例（129周期）患者作为对照组,收集卵巢反应性及妊娠结局相关指标,作回顾性病例对照研究。结果：3组在年龄、体质量指数、不孕年限、基础卵泡刺激素（FSH）水平、促性腺激素（Gn）天数、受精率和人绒毛膜促性腺激素（hCG）日雌二醇（E2）水平无统计学意义（P〉0．05）。3组妊娠率差异也无统计学意义（P〉0．05）,且单侧囊肿剥除组妊娠率最高（50．0％）。双侧囊肿剥除组获卵数、优质胚胎率及可冷冻的胚胎个数分别为[（4．95±3．46）个、（56．0±32．0）％、（1．40±1．96）个],明显低于单侧囊肿剥除组[（9．38±4．62）个、（70．1±20．2）％、（3．45±3．05）个]和输卵管组[（10．37±4．14）个、（85．1±19．9）％、（4．36±3．19）个],差异有统计学意义（P〈0．01）;其Gn总用量也明显高于输卵管组和单侧囊肿剥除组（P〈0．05）。单侧异位囊肿剥除术的手术侧卵巢的获卵数[（3．34±2．92）个]低于未手术侧卵巢[（6．06v2．27）个]（t=5．784,P〈0．01）。结论：卵巢子宫内膜异位囊肿剥除术可影响IVF周期中卵巢反应性,如导致Gn用量增加,获卵数、优质胚胎数和可冷冻胚胎个数减少,对IVF-ET有一定不良影响,而对IVF妊娠结局无明显影响。     

常规体外受精与卵胞浆单精子注射技术妊娠及分娩结果比较

目的通过比较接受常规体外受精技术(IVF)及卵胞浆单精子注射技术(ICSI)治疗后妊娠的病例,分析临床资料、妊娠及产科结局,从而评估其安全性。方法对中山大学附属第一医院1998年1月至1999年12月接受体外受精-胚胎移植治疗后妊娠的533例临床资料进行回顾性分析。结果ICSI组受精率明显高于IVF组,IVF和ICSI两组早期胚胎发育情况、产科结局、围生情况及出生后婴儿的健康情况差异无显著性意义。结论与常规IVF相比,ICSI并不增加胎儿畸形率及新生儿并发症,但仍需要长期的大量的随访以排除可能的危险性。     

来曲唑/FSH促排卵中GnRHa与hCG诱发卵泡成熟效果的比较

目的:比较曲普瑞林和hCG在来曲唑(LE)/FSH促排卵行IVF-ET治疗中诱发卵泡成熟的效果。方法:391个IVF-ET治疗周期随机分成促性腺激素激动剂(GnRHa)组(n=267)和hCG组(n=124),所有患者均采用LE/FSH促排卵方案,当主导卵泡平均直径达18～20mm时,GnRHa组患者采用达菲林0.1mg诱导卵泡成熟,hCG组采用hCG10000IU诱导卵泡成熟,比较组间的获卵数、MII卵率、受精率、卵裂率、优胚率、临床妊娠率和中-重度卵巢过度刺激综合症(OHSS)发生率。同时比较两组患者诱导日(d0)、取卵日(d2)、胚胎移植前日(d4)和胚胎移植后第4日(d9)的血清E2、P、LH水平。结果:hCG组Gn使用总量、MII卵率、卵裂率、中-重度OHSS发生率显著高于GnRHa组(P<0.05)。Gn使用天数、获卵数、受精率、种植率、临床妊娠率、流产率组间无统计学差异(P>0.05)。GnRHa组d0LH、d2LH、d9LH水平显著高于hCG组(P<0.05),而d2P、d4E2、d4P、d4LH、d9E2、d9P水平显著低于hCG组(P<0.05)。结论:在LE/FSH促排卵方案中可以用GnRHa替代hCG诱导卵泡成熟,而不影响IVF结局,并显著降低OHSS发生率。GnRHa诱导卵泡成熟的IVF周期其黄体期存在黄体功能不全,需适当补充外源性hCG加强黄体支持。     

The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET)

The use of gonadotropin releasing hormone agonists (Gn-RHa) has been shown to improve the response in patients classified as poor responders undergoing ovarian stimulation for in vitro fertilization/embryo transfer (IVF/ET). This study sought to determine whether GnRHa therapy would benefit patients undergoing IVF/ET who had been classified as good responders in prior attempts. Twenty-three patients who had completed a prior IVF/ET attempt but who failed to conceive underwent ovarian stimulation using a combination of GnRHa and human menopausal gonadotropin (hMG). Each patient's prior stimulation served as her control and consisted of clomiphene citrate (CC)/hMG in 18 patients and follicle stimulating hormone (FSH) and/or hMG in 5 patients. The numbers of oocytes retrieved, oocytes fertilized, embryos cleaved, and embryos transferred were all significantly greater in cycles treated with GnRHa/hMG compared to control cycles. The clinical pregnancy rate was 39% and the ongoing pregnancy rate was 26% during the cycle when GnRHa pretreatment was utilized. These data suggest that GnRHa therapy is of benefit even to those patients previously classified as good responders undergoing ovarian stimulation for IVF/ET.Presented at the 45th Annual Meeting of the American Fertility Society, November 1989, San Francisco, California.