Twisk M, Mastenbroek S, van Wely M, Heineman M J, Van der Veen F, Repping S
Academic Medical Center, Center for Reproductive Medicine, Meibergdreef 9 (H4-205), Amsterdam, Netherlands, 1105 AZ.
Cochrane Database Syst Rev. 2006 Jan 25(1):CD005291. doi: 10.1002/14651858.CD005291.pub2.
In both in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is generally based on morphological criteria. However, many women fail to achieve a pregnancy after transfer of good quality embryos. One of the presumed causes is that such morphologically normal embryos show an abnormal number of chromosomes (aneuploidies). In preimplantation genetic screening (PGS), embryos are analysed for aneuploidies and only embryos that are euploid for the chromosomes tested are transferred. This technique has been suggested and used to improve pregnancy rates for the following indications: (i) advanced maternal age, (ii) repeated IVF failure, (iii) repeated miscarriage and (iv) testicular sperm extraction (TESE)-ICSI. Although PGS is used more and more often, its effectiveness is still unclear.
To assess the effectiveness of PGS in terms of live births in women undergoing IVF or ICSI treatment.
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2005), MEDLINE (1966 to present) and EMBASE (1980 to present) (searched March 2005) and reference lists of articles. We also contacted authors for providing additional data when necessary.
Trials for all four suggested indications as mentioned above were sought. All relevant published randomised controlled trials were selected. They were eligible for inclusion if the comparison dealt with IVF/ICSI with PGS versus IVF/ICSI without PGS.
Relevant data were extracted independently by two authors. All trials were screened and analysed according to predetermined quality criteria. Validity was assessed in terms of method of randomisation, completeness of follow-up, intention-to-treat analysis and presence or absence of blinding. The primary outcome measure was live birth rate per woman. Secondary outcome measures were the proportion of women reaching embryo transfer, mean number of embryos transferred per transfer, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, ongoing pregnancy rate, proportion of women reaching embryo transfer after cryopreservation and proportion of women whose child has a congenital malformation.
Two randomised controlled trials met our predetermined eligibility criteria. These trials used PGS for advanced maternal age. The primary outcome of live birth rate per woman was not significantly different in the PGS and control groups, though data were only available from one study. The live birth rate was 11% (21 out of 199) in the PGS group, versus 15% (29 out of 190) in the control group (OR 0.65; 95% CI 0.36 to 1.19). For a control group rate of 15%, these data suggest a live birth rate using PGS of between 4% and 17%. Ongoing pregnancy rate was provided in both studies. This was not significantly different with a combined odds ratio of 0.64 (95% CI 0.37 to 1.09). For a control group rate of 20%, this suggests an ongoing pregnancy rate using PGS of between 8% and 21%.
AUTHORS' CONCLUSIONS: To date there is insufficient data to determine whether PGS is an effective intervention in IVF/ICSI for improving live birth rates. Available data on PGS for advanced maternal age showed no difference in live birth rate and ongoing pregnancy rate. However, only two randomised trials were found, of which one included only 39 patients. For both studies comments on their methodological quality can be made. Therefore more properly conducted randomised controlled trials are needed. Until such trials have been performed PGS should not be used in routine patient care.
在体外受精(IVF)和卵胞浆内单精子注射(ICSI)中,通常根据形态学标准来选择最具发育潜能的胚胎进行移植。然而,许多女性在移植优质胚胎后仍未能成功怀孕。一个推测的原因是,这些形态正常的胚胎存在染色体数目异常(非整倍体)。在植入前遗传学筛查(PGS)中,会对胚胎进行非整倍体分析,仅移植那些所检测染色体为整倍体的胚胎。这项技术已被提出并用于改善以下情况的妊娠率:(i)高龄产妇;(ii)反复IVF失败;(iii)反复流产;(iv)睾丸精子提取(TESE)-ICSI。尽管PGS的使用越来越频繁,但其有效性仍不明确。
评估PGS对于接受IVF或ICSI治疗的女性活产率方面的有效性。
我们检索了Cochrane月经紊乱与生育力低下研究组试验注册库、Cochrane对照试验中心注册库(CENTRAL)(Cochrane图书馆2005年第1期)、MEDLINE(1966年至今)和EMBASE(1980年至今)(2005年3月检索)以及文章的参考文献列表。必要时我们还联系了作者以获取额外数据。
寻找针对上述所有四种建议适应证的试验。选取所有相关的已发表随机对照试验。如果比较内容为采用PGS的IVF/ICSI与未采用PGS的IVF/ICSI,则这些试验符合纳入标准。
两位作者独立提取相关数据。所有试验均根据预先确定的质量标准进行筛选和分析。根据随机化方法、随访完整性、意向性分析以及是否设盲来评估有效性。主要结局指标是每位女性的活产率。次要结局指标包括达到胚胎移植的女性比例、每次移植平均移植胚胎数、临床妊娠率、多胎妊娠率、流产率、持续妊娠率、冷冻保存后达到胚胎移植的女性比例以及孩子患有先天性畸形的女性比例。
两项随机对照试验符合我们预先确定的纳入标准。这些试验将PGS用于高龄产妇。尽管仅有一项研究提供了数据,但PGS组和对照组每位女性的主要活产率结局并无显著差异。PGS组的活产率为11%(199例中有21例),而对照组为15%(190例中有29例)(比值比0.65;95%可信区间0.36至1.19)。对于对照组15%的比率,这些数据表明使用PGS的活产率在4%至17%之间。两项研究均提供了持续妊娠率。联合比值比为0.64(95%可信区间0.37至1.09),无显著差异。对于对照组20%的比率,这表明使用PGS的持续妊娠率在8%至21%之间。
迄今为止,尚无足够数据来确定PGS在IVF/ICSI中是否为提高活产率的有效干预措施。关于高龄产妇使用PGS的现有数据显示活产率和持续妊娠率并无差异。然而,仅找到两项随机试验,其中一项仅纳入了三十九名患者。对于这两项研究均可对其方法学质量进行评价。因此,需要开展更严格的随机对照试验。在进行此类试验之前,PGS不应常规用于患者治疗。