微刺激全部胚胎冷冻方案在常规体外受精-胚胎移植失败的卵巢低反应患者中的应用

目的探讨微刺激全部胚胎冷冻方案在常规体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)方案失败的卵巢低反应(POR)患者中的应用价值。方法对196例IVF/ICSI-ET应用常规促排卵方案因POR放弃周期或移植失败后改用微刺激方案的402个周期进行回顾性分析,比较前、后2次不同促排卵方案的临床和实验室指标。结果 402个微刺激周期中32个周期取消,周期取消率为7.96%,370个周期获得卵母细胞,平均获卵数(2.2±1.5)个,共233个周期有胚胎冷冻,胚胎冷冻率为57.96%,共194个周期进行了ET,临床妊娠74例,早期自然流产6例,起始周期累积妊娠率为37.75%(74/196),冻融胚胎移植(FET)周期临床妊娠率为38.14%(74/194),其中≤37岁组FET周期的临床妊娠率(50.89%)明显高于37岁组(20.73%)(P0.05)。微刺激方案的临床和实验室指标均显著优于常规长方案。结论微刺激全部胚胎冷冻方案对常规方案IVF/ICSI-ET治疗失败的POR患者具有疗程短、刺激剂量小,获卵率高、可利用胚胎率高、周期取消率低等特点,对于该类患者再次助孕可考虑微刺激方案。     

微刺激方案在常规IVF-ET治疗失败后卵巢低反应患者中的应用

目的:探讨微刺激方案在IVF-ET过程中对卵巢低反应患者的应用价值。方法:对56例卵巢低反应患者应用常规促排卵方案进行112个IVF周期治疗失败后改用微刺激方案的201个周期进行回顾性分析,比较使用这2种方案的治疗效果及临床结局,同时比较微刺激方案中使用与未使用GnRH-拮抗剂的临床数据与治疗结局。结果:112个常规促排卵周期中6个周期取消。106个周期取卵,95个周期获得卵母细胞,平均获卵数3.7±1.5个。共91个周期进行胚胎移植,均未获得妊娠。201个微刺激周期中17个周期取消,184个取卵周期中163个周期获得卵母细胞,平均获卵数3.4±1.4个。共160个周期进行胚胎移植,临床妊娠18例,双胎妊娠2例,流产3例,胚胎种植率为5.9%(20/336),起始周期临床妊娠率为9.8%(18/184),移植周期临床妊娠率为11.3%(18/160),累计继续妊娠率为26.8%(15/56)。比较前、后2种方案,常规促排卵方案中刺激时间为12.0±1.4 d,Gn使用总量为3 780±1 350 IU,远多于微刺激方案中的8.0±1.2 d和650±120 IU(P<0.05),而hCG注射日E2值(860±36 pg/ml vs 756±28 pg/ml)、平均获卵数(3.7±1.5 vs 3.4±1.4)、受精率(68.5%vs 64.5%)、优质胚胎率(56.7%vs 47.7%)2种方案均无显著性差异(P>0.05)。微刺激周期中使用拮抗剂组较未使用拮抗剂组周期取消率降低(4.5%vs 22.0%),hCG注射日LH值降低(2.3±1.1 U vs 7.8±2.4 U)(P<0.05),优质胚胎率(53.7%vs 25.7%)、胚胎着床率(6.5%vs3.9%)及临床妊娠率(12.3%vs 6.7%)均有增高的趋势,但差异均无统计学意义(P>0.05)。结论:微刺激方案对卵巢反应不良患者具有简便、疗程短、患者心理负担轻、医疗风险小等特点,值得推广应用,并建议联合拮抗剂使用。     

未成熟卵母细胞体外培养在体外受精中对卵巢低反应性者的补救性应用

目的:探讨未成熟卵母细胞体外培养(IVM)在体外受精(IVF)中对卵巢低反应性者的补救性治疗效果。方法:30例行IVF时表现为卵巢低反应者(实验组)在B超引导下经阴道行卵泡穿刺术,取卵后对不同期未成熟卵母细胞行IVM,再行胞浆内单精子注射(ICSI)受精;对成熟卵母细胞则进行常规受精,胚胎形成后行移植术。取同期进行ICSI周期治疗的63例作为对照组。结果:应用IVM行IVF-ET补救治疗的30个周期中有29个周期获胚胎移植,临床妊娠9例(31%),胚胎种植率18.47%,但该组未成熟卵培养成熟后的受精率、卵裂率均低于对照组;总妊娠率及胚胎种植率比常规ICSI组低。结论:IVM技术联合IVF为卵巢低反应性者提供了一种有效的补救措施,明显减少了IVF周期的取消率,提高了妊娠机会。     

两种控制性超促排卵方案在卵巢低反应患者中的临床研究

目的:探讨标准长方案与拮抗剂方案控制性超促排卵(COH)周期在卵巢低反应(POR)患者中的临床效果。方法:通过对POR患者行体外受精-胚胎移植(IVF-ET)的191个周期进行回顾性分析,其中GnRH-a长方案85个周期(A组),拮抗剂方案106个周期(B组),比较组间的临床资料及助孕结局。结果:A组的hCG注射日内膜厚度、获卵数、MII卵子数、可移植胚胎数、活产分娩率均高于B组,差异有统计学意义(P0.05);A组的优质胚胎数、胚胎种植率、移植周期妊娠率均高于B组,A组的周期取消率、流产率均低于B组,但差异均无统计学意义(P0.05)。结论:标准长方案对卵巢低反应患者有较好的治疗效果;标准长方案可提高患者获卵数、可移植胚胎数、活产分娩率。     

体外受精-胚胎移植(IVF-ET)输卵管积水预处理后冻融胚胎解冻移植结局分析

目的:探讨体外受精-胚胎移植(IVF-ET)中输卵管积水患者积水处理(单侧或双侧输卵管切除/结扎)后冻融胚胎移植结局和影响因素。方法:回顾分析2012年6月~2014年6月在兰州大学第一医院生殖医学专科医院因输卵管积水行IVF-ET的117例患者的临床资料。117例患者中,取卵后因积水返流宫腔行全胚冷冻取消移植者69例,不良结局者48例。比较行输卵管积水处理后的117例患者(研究组)和因输卵管因素行冻融胚胎解冻移植(FET)的212例患者的妊娠结局。结果:研究组117例患者中111例行积水单侧或双侧结扎/切除,6例行输卵管栓塞,FET 115例后妊娠70例,妊娠率60.87%,早期流产8例,流产率11.42%,宫角妊娠2例。对照组212例完成206个解冻移植周期,妊娠114例,妊娠率55.33%,早期流产12例,早期流产率10.52%,异位妊娠3例,异位妊娠率2.63%。两组的受精率、可利用胚胎率、临床妊娠率等无统计学差异(P0.05)。结论:体外受精-胚胎移植(IVF-ET)取卵后输卵管积水切除或结扎或栓塞后行冻融胚胎解冻移植,可获得良好的妊娠结局。     

行体外受精-胚胎移植的40岁以上妇女妊娠结局分析

目的 探讨行体外受精-胚胎移植(IVF-ET)40岁以上妇女的结局及其影响因素.方法 采用回顾性分析方法,收集2001年3月至2006年3月于广东省妇幼保健院行IVF-ET治疗不孕症的40岁以上妇女82例,共93个周期,从中找出不同年龄妇女进行IVF-ET的临床结局及其影响因素.结果 82例患者共行93个超促排卵周期,其中取消周期11个,取消率11.83%;行新鲜胚胎移植74个周期,临床妊娠率25.68%,着床率10.87%,流产率36.4%;40岁、41岁、42岁、43岁及以上组临床妊娠率分别为32.14%、36.36%、25.00%和0;前3组的流产率分别为44.44%、25.00%和50.00%;与短方案组比较,长方案组促性腺激素(Gn)刺激时间、用量明显增多,获胚胎数和移植胚胎数更多(P＜0.05),但两组临床妊娠率、着床率和流产率差异并无显著意义;42岁及以下妇女当获卵数超过4个,妊娠率明显增加.结论 40岁以上妇女行IVF-ET妊娠率和着床率均明显降低,并且流产率升高.对于40岁以上妇女,一定数量的卵子可能提高IVF成功率.     

高效孕激素下超促排卵和微刺激方案在卵巢功能减退患者中应用效果分析

目的探讨高效孕激素下超促排卵(PPOS)和微刺激两种方案在卵巢功能减退患者(DOR)中的促排卵效果和全胚冷冻后行冻融胚胎移植(FET)的临床妊娠结局的差异。方法对2015年12月至2016年7月在郑州大学第二附属医院行体外受精-胚胎移植(IVF-ET)辅助生殖技术的431例卵巢储备功能下降患者的资料进行回顾性分析,其中PPOS方案组209例,微刺激组222例,比较两组的促排卵实验室结局和全胚冷冻后FET的妊娠结局。采用多因素Logistic回归校正混杂因素后比较两种促排卵方案的临床妊娠率。结果 PPOS组扳机日促黄体生成素(LH)水平低于微刺激组[3.63(2.40,5.46)U/L vs.7.07(4.04,11.92)U/L,P0.05],PPOS组取消取卵率低于微刺激组(1.44%vs.7.21%,P0.05),PPOS组获卵数、可利用胚胎数和优质胚胎数均高于微刺激组(P0.05)。全胚冷冻后行复苏移植,PPOS组临床妊娠率(29.17%)和胚胎着床率(14.63%)略高于微刺激组(19.70%和12.59%,P0.05)。多因素Logistic回归分析结果显示:PPOS方案可以获得更高的临床妊娠率(OR=6.79,95%CI 1.15~40.06,P=0.035)。结论对于DOR患者,PPOS方案较微刺激方案可减少取消取卵率,并可获得更多的获卵数、可利用胚胎数和优质胚胎数,累积胚胎提供更多移植机会。PPOS方案可作为DOR患者行IVF-ET辅助生殖技术时促排卵方案的一种选择。     

体外受精—胚胎移植后异位妊娠58例分析

目的:探讨体外受精-胚胎移植(IVF-ET)后异位妊娠(EP)的高危因素。方法:对接受体外受精胚胎移植(IVF-ET)助孕后发生异位妊娠病例的助孕指征、助孕方式等进行回顾性分析。结果:2009年1月至2010年12月佛市妇幼保健院行体外受精胚胎移植(IVF-ET)2445个周期,1153个周期临床妊娠,发生率47.16%,异位妊娠58个周期,发生率为5.03%。年龄、促性腺激素总量、取卵数、移植胚胎个数及优质胚胎率与本次助孕后异位妊娠的发生无关(P>0.05)。49例患者助孕指征为输卵管因素和/或盆腔粘连,占84.48%。2种助孕方式(IVF-ET,ICSI)比较,总妊娠率差异无统计学意义(P>0.05),2种助孕方式异位妊娠率比较,差异亦无统计学意义(P>0.05)。结论:输卵管因素是异位妊娠发生的高危因素,与年龄、促性腺激素总量、取卵数、移植胚胎个数、优质胚胎率、助孕方式无关。     

不同促排卵方案在卵巢低反应患者中的应用

目的:探讨不同促排卵方案在接受体外受精-胚胎移植(IVF-ET)的卵巢低反应患者中的应用价值。方法:对87例卵巢低反应患者采用不同方案进行IVF/ICSI-ET共200个周期的临床资料进行回顾性分析,其中短方案者50个周期(A组),拮抗剂方案者39个周期(B组),微刺激方案者93个周期(C组),自然周期方案者18个周期(D组)。比较分析各组的促排卵结局。结果:4组间周期取消率无统计学差异,hCG注射日LH水平A组低于其他3组,E2水平高于其他3组,与C、D组比有统计学差异(P<0.05),优势卵泡数及平均获卵数D组低于其他3组,而正常受精率高于其他3组,与A、B组比有统计学差异(P<0.05),hCG注射日内膜厚度、P值、MⅡ卵率、可利用胚胎率、临床妊娠率C组临床妊娠率略高,但各组间差异均无统计学意义(P>0.05)。结论:对卵巢低反应患者微刺激方案在IVF-ET促排卵中相对其他方案有更好的临床效果。     

卵巢反应与IVF-ET妊娠结局的关系

在IVF-ET中,控制性超促排卵(controlled ovrian hyperstimulation,COH)后的卵巢反应是影响妊娠结局的重要因素。卵巢反应低下,获卵数少,可导致供移植胚胎数目减少,甚至无胚胎移植,从而周期取消率增高,临床妊娠率降低。卵巢反应过高,获卵数过多,会造成卵子质量下降,子宫内膜容受性受损,着床率降低,卵子利用效率下降及合并症的发生,最终影响临床妊娠率。在最佳的卵巢反应下获得适当的卵子数,有利于改善妊娠结局。     

In vitro fertilization following natural cycles in poor responders.

This prospective study was designed to examine the feasibility of natural cycle in vitro fertilization (IVF) in poor responders, and the clinical factors that may predict successful outcome. Twenty-two poor responders underwent IVF treatment with 44 unstimulated cycles. The results of the natural cycles were compared with those of the 55 low-response stimulated cycles of these patients during the 12 months prior to the study. Eighteen (82%) patients had at least one oocyte retrieved, while nine (41%) had at least one cycle with embryo transfer. Two (9%) patients each gave birth to a healthy term baby. These results are comparable with those of the stimulated cycles. Serum early follicular follicle stimulating hormone (FSH) level was found to be the only reliable predictor of oocyte recovery and overall outcome in each specific natural cycle. However, because of great variability in basal FSH levels among different cycles of the same patient, this is not a reliable predictor of outcome in future cycles. We conclude that poor responders are a unique group of patients who may benefit from natural-cycle IVF treatment.     

An 18-month survey of infertility treatment by in vitro fertilization,gamete and zygote intrafallopian transfer,and replacement of frozen-thawed embryos

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N=793) or ultrasonically guided (N=342) ovum pickup, gamete intrafallopian transfer (GIFT;N=284), or zygote intrafallopian transfer (ZIFT;N=15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure onethird of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.     

Embryo transfer and luteal support in natural cycles

Embryo transfer policy and luteal supplementation was reviewed, comparing literature data and the results from the Maribor IVF Centre. A retrospective analysis of 1024 cycles in patients undergoing IVF, intracytoplasmic sperm injection (ICSI) or testicular sperm aspiration in unstimulated cycles was carried out using four different approaches for cycle monitoring. This showed that the most successful protocol for monitoring was administration of human chorionic gonadotrophin (HCG) when serum oestradiol was >0.49 nmol/l and follicle diameter was at least 15 mm. The implantation rate per transferred embryo was higher when a blastocyst was transferred (42.8%) rather than a day-2 embryo (23.5%) in the same monitoring protocol. Analysis of the influence of patient age on the success of oocyte retrieval, oocyte fertilization, embryo transfer rate and delivery rate demonstrates that patient age does not influence the rate of positive oocyte retrieval or fertilization rate as much as it influences pregnancy rate per embryo transfer. The delivery rate per cycle was dramatically influenced by age in patients over 38 years. There is no clear evidence in the literature as to whether luteal phase support is necessary in natural cycles for IVF/ICSI. Comparing the data, a higher pregnancy rate was observed if HCG was administered after embryo transfer.     

Intracytoplasmic sperm injection as a treatment for unexplained total fertilization failure or low fertilization after conventional in vitro fertilization

OBJECTIVE: To determine whether IVF or intracytoplasmic sperm injection (ICSI) should be the choice of treatment in case of a previous IVF attempt with unexplained total fertilization failure or low fertilization (<25%). DESIGN: Prospective study. SETTING: Leiden University Medical Center. PATIENT(S): Thirty-eight couples undergoing IVF and ICSI on sibling oocytes after a first IVF attempt with total fertilization failure or with low fertilization (<25%). INTERVENTION(S): Performing IVF and ICSI on sibling oocytes. MAIN OUTCOME MEASURE(S): Fertilization and (ongoing) pregnancy rate. RESULT(S): A total of 271 oocytes were collected in 24 oocyte retrievals in the total fertilization failure group. Hundred nine oocytes were randomly allocated to IVF and 12 were fertilized (11%); 162 sibling oocytes were allocated to ICSI and 78 were fertilized (48%). In 8 of the 24 patients fertilization occurred after IVF. The pregnancy rate after transfer of 1 IVF and 1 ICSI embryo (n = 3) was 67% and after the transfer of 2 ICSI embryos (n = 21) this was 52%. In the low fertilization group 169 oocytes were collected in 14 oocyte retrievals. Seventy-two oocytes were randomly allocated to IVF and 16 were fertilized (22%). Ninety-seven sibling oocytes were allocated to ICSI and 58 were fertilized (60%). In 7 of 14 patients fertilization occurred after IVF. The pregnancy rate after the transfer of 1 IVF and 1 ICSI embryo (n = 5) was 80% and after the transfer of 2 ICSI embryos (n = 9) this was 33%. CONCLUSION(S): Performing ICSI on some oocytes of a cohort may avoid total fertilization failures both in patients with a history of total fertilization failure and in patients with a history of low fertilization, as the percentage of fertilization is higher after ICSI compared to IVF and the recurrence of total fertilization failure and low fertilization is high after IVF treatment.     

Programming in vitro fertilization for a 5- or 3-day week

OBJECTIVE: To schedule oocyte retrievals on either 5 or 3 days per week in in vitro fertilization (IVF) cycles. DESIGN: Human chorionic gonadotropin (hCG) administration was delayed by at least 24 hours in patients undergoing superovulation to avoid egg collections on weekends (group 1). Encouraged by the results, a further prospective study in which oocyte retrievals were programmed for only 3 days a week was undertaken (group 2). SETTING: Hammersmith Hospital, a tertiary referral unit. PATIENTS: All patients undergoing IVF treatment were included. MAIN OUTCOME MEASURES: To schedule oocyte retrievals on either 5 or 3 days per week. RESULTS: Only 4.0% of egg collections (12/303) occurred on weekends compared with 12.6% (22/175) before delaying hCG. In group 2 (n = 215), only four egg collections (2.1%) had to be performed out of schedule. Delaying administration of hCG had no detrimental effects. CONCLUSIONS: Delayed administration of hCG allows scheduling oocyte retrievals on either 5 or 3 days per week, leading to a substantial decrease in out-of-hours oocyte retrievals, reducing cycle costs, and facilitating efficiency. The method is applicable to assisted reproduction specialized units as well as district general hospitals that use gonadotropin-releasing hormone analogs in their superovulation regimens before IVF, gamete intrafallopian transfer, or intrauterine insemination.     

常规IVF中受精失败相关因素及后续处理结果分析

目的:分析常规IVF受精失败原因,以进一步提高IVF受精率。方法:回顾性分析常规IVF中受精率低下或受精失败患者的各种因素及后续处理结果。结果:438个常规IVF取卵周期中,受精率≤25%的周期30个(A组)(6.85%)。其中12个周期第1日行补救性ICSI或重复IVF,最终共20个周期进行了胚胎移植,但均未获得临床妊娠。与受精率正常的周期(B组)相比,A组精子密度、活率、a级精子比例、前向运动精子比例(PMS)及分离后的精子活率、PMS比例、精子密度等均显著降低(P均<0.05)。组间的获卵数无明显差别,但A组MI期及GV期卵的数量明显高于B组(P<0.01)。其他受精失败因素包括对精子因素导致受精失败的7例在随后的周期进行ICSI,5例获得临床妊娠。结论:受精失败的原因是多方面的,但精液各参数下降及卵子发育不成熟是其主要原因;第1日行补救性ICSI或重复IVF的妊娠结局差;对于精子因素造成的受精失败,在以后的周期中行ICSI能获得理想的结果。     

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs.

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin superovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program. Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7-10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39). A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively. GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.     

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization–embryo transfer programs

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin super-ovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program.

Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7–10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39).

A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively.

GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.     

The outcome of continued treatment of luteinizing hormone-surged cycles in in vitro fertilization with the use of human menopausal gonadotropin

Over a 2-year period 75 patients were treated for 109 cycles with human menopausal gonadotropin for in vitro fertilization. The occurrence of endogenous luteinizing hormone (LH) surges was monitored by daily blood sampling. Forty-six cycles (42%) showed an endogenous LH surge. Instead of canceling the treatment cycle as other programs do, we proceeded to oocyte collection when the surge was detected. Human chorionic gonadotropin was administered routinely to the "surge" patients as soon as the LH surge was determined. The oocyte collection was carried out around 24 hours after the "surge" blood had been drawn, although the beginning of the endogenous LH surge was unable to be pinpointed. Significantly more immature oocytes, lower fertilization rate, and lower cleavage rate were seen in the "surge" patients than in the "nonsurge" patients. In five "surge" cycles laparoscopy for oocyte collection was canceled, but none was canceled because of premature ovulation detected by the immediately preoperative ultrasonography. In four "surge" cycles no potentially fertilizable egg was recovered. This was not significantly different from that of the "nonsurge" group. The pregnancy rate of the "surge" group (4/41 or 9.8% per laparoscopy and 4/34 of 11.8% per embryo transfer) was not statistically different from that of the "nonsurge" group (7/61 or 11.5% per laparoscopy and 7/56 or 12.5% per embryo transfer). This study presents the possibility of proceeding to oocyte collection, fertilization, embryo transfer, and pregnancy in patients with endogenous LH surge in in vitro fertilization procedures with the use of human menopausal gonadotropin treatment.