Oocyte activation for women following intracytoplasmic sperm injection (ICSI).
Intracytoplasmic sperm injection (ICSI), a type of assisted reproductive technology (ART), is offered as a treatment option for male factor infertility. Over the years, the indications for ICSI have been expanded, despite uncertainty about its benefits and harms compared to the conventional method of achieving fertilisation. Artificial oocyte activation (AOA), which can be performed by chemical, electrical or mechanical intervention, has been employed during ART ICSI treatment where there has been a history of low fertilization rate or total fertilization failure, and it has been reported to improve reproductive outcomes. It is important to evaluate the clinical effectiveness and safety of AOA in women undergoing ART ICSI treatment.
To evaluate the benefits and harms of artificial oocyte activation in women affected by infertility undergoing intracytoplasmic sperm injection treatment.
We searched the following electronic databases: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO international Clinical Trials Registry Platform (8 August 2024). We also searched reference lists of relevant articles and contacted experts in the field.
Randomized controlled trials comparing artificial oocyte activation (AOA) (chemical, electrical or mechanical interventions) versus no intervention, placebo or another method of AOA in women undergoing ART.
We used methodological procedures as per Cochrane recommendations. We assessed the risk of bias in the included studies using ROB 2. The primary outcomes were live birth and miscarriage rates. We analyzed data using the risk ratio (RR) and a fixed-effect model. We assessed the certainty of the evidence by using GRADE criteria. We restricted the primary analyses to studies at low risk of bias.
We included a total of 20 studies, four of which were participant-based randomized trials with 743 participants. The remaining 16 were sibling-oocyte-model randomized studies. We based the main clinical findings of the current review on the participant-based RCTs, and we restricted our primary analysis to studies with a low risk of bias. Based on the one trial with 343 participants that we included in our primary analysis, the evidence is very uncertain about the effect of AOA on the live birth rate when compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.97, 95% CI 1.29 to 3.01; one trial; 343 participants). For a typical clinic with a live birth rate of 18% following ART, the addition of AOA may result in live birth rates between 24% and 55%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the miscarriage rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.99, 95% CI 0.48 to 2.04; one trial; 343 participants). If the miscarriage rate was 9% following ART, addition of oocyte activation may result in miscarriage rates between 4% and 18%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the clinical pregnancy rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.67, 95% CI 1.20 to 2.32; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the multiple pregnancy rate per participant compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.91, 95% CI 0.48 to 7.67; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the total fertilization failure rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.05, 95% CI 0.01 to 0.40; one trial; 343 participants). When we stratified our analysis according to various infertility factors, we found low-certainty evidence that in couples undergoing ICSI treatment who have had a history of low or no fertilization, AOA may help improve the live birth rate while making little or no difference to the miscarriage rate. Further research is needed to confirm or refute this finding. None of the trials reported congenital anomalies (birth defects) as an outcome. Lack of short- or long-term safety data is an important limitation of the review and of the trials in this field. We did not find any trials that compared two different methods of oocyte activation.
We are uncertain about the effect of AOA on the live birth and miscarriage rates in women undergoing ART ICSI. In the subpopulation of those who have had a previous history of low or no fertilization, AOA may result in an increase in the live birth rate when compared to conventional ICSI without AOA, while making little or no difference to the miscarriage rate. There was considerable variation in the protocols used for chemical AOA, which affects the generalizability of the findings. Due to the very low to low certainty of evidence, the results should be interpreted with caution.
Kamath MS
，Vogiatzi P
，Sunkara SK
，Woodward B
... -
《Cochrane Database of Systematic Reviews》
Antioxidants for female subfertility.
M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, https://doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, https://doi.org/10.1002/ijgo.12902; Gerli et al. 2007, https://doi.org/10.26355/eurrev_202309_33752, full text: https://europepmc.org/article/MED/18074942; Ismail et al. 2014, http://dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, https://doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, https://doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, https://doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings.
A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility.
To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women.
We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers.
We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility.
We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events.
We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency.
In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
Showell MG
，Mackenzie-Proctor R
，Jordan V
，Hart RJ
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
