Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis

The effect of heparin on IVF outcome has been widely debated in the literature. A systematic review and meta-analysis of the published literature was conducted to evaluate the effect of heparin treatment on IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science and identified 10 relevant studies (five observational and five randomized) comprising 1217 and 732 IVF cycles, respectively. The randomized studies included small numbers of women and exhibited high methodological heterogeneity. Meta-analysis of the randomized studies showed no difference in the clinical pregnancy rate (RR 1.23, 95% CI 0.97–1.57), live birth rate (RR 1.27, 95% CI 0.89–1.81) implantation rate (RR 1.39, 95% CI 0.96–2.01) and miscarriage rate (RR 0.77, 95% CI 0.24–2.42) in women receiving heparin compared with placebo during IVF treatment. However, meta-analysis of the observational studies showed a significant increase in the clinical pregnancy rate (RR 1.83, 95% CI 1.04–3.23, P = 0.04) and live birth rate (RR 2.64, 95% CI 1.84–3.80, P < 0.0001). The role of heparin as an adjuvant therapy during IVF treatment requires further evaluation in adequately powered high-quality randomized studies.The effect of heparin on IVF outcome is widely debated. Despite the results of published studies being conflicting, it has been suggested that the use of heparin results in increased pregnancy rates following IVF treatment. We conducted a systematic and comprehensive of the published literature to evaluate the effect of heparin treatment on IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. We identified 10 studies from the literature and extracted the relevant data from the studies. Analyses of the data from randomized trials showed no improvement in the clinical pregnancy rate or the live birth rate in the group that received heparin. However, the studies included had small numbers of women and high methodological heterogeneity. The role of heparin in this context requires further evaluation in adequately powered randomized studies.     

Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome

Objective

To compare low-molecular-weight (LMW) heparin plus low-dose aspirin with intravenous immunoglobulin (IVIG) in the treatment of antiphospholipid antibody syndrome in women with recurrent spontaneous abortions before 10 weeks of gestation.

Method

This prospective, multicenter trial conducted between 2002 and 2006 included 85 patients aged 18-39 years. The women were allocated randomly to receive LMW heparin plus low-dose aspirin, or IVIG. Data were compared using the t test and Fisher exact test.

Results

The women treated with LMW heparin plus low-dose aspirin had a higher rate of live births than those treated with IVIG (P = 0.003). Of those who completed the study, 29/40 (72.5%) and 15/38 (39.5%), respectively, had live births. Intent-to-treat analysis revealed a significant difference between the 2 groups (OR 1.802; 95%CI, 1.14-2.84; P = 0.007).

Conclusions

LMW heparin plus low-dose aspirin resulted in a higher live birth rate than IVIG in the treatment of antiphospholipid antibody syndrome in women with recurrent abortion.     

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis

Purpose

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

Methods

Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.

Results

Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n?=?1429; control group n?=?1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.

Conclusion

The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

     

Clinical factors associated with pregnancy outcome in women with recurrent pregnancy loss

Abstract

The aim of this prospective cohort study was to evaluate clinical factors associated with pregnancy outcomes in women with recurrent pregnancy loss (RPL). Women with a history of two or more pregnancy losses underwent workups for clinical factors of RPL and their pregnancies were followed-up with informed consent. Two hundred eleven (81.5%) of 259 women with RPL became pregnant. The multivariable analyses demonstrated that age (p?<?.01, OR 0.9, 95%CI 0.97–0.83), uterine abnormality (p?<?.05, OR 0.3, 95%CI 0.11–0.8), and protein C (PC) deficiency (p?<?.01, OR 0.14, 95%CI 0.03–0.6) were independent factors for becoming pregnancy in women with RPL. The number of previous pregnancy loss (p?<?.01, OR 0.57, 95%CI 0.43–0.75) and natural killer (NK) cell activity ≥33% (p?<?.01, OR 0.31, 95%CI 0.13–0.73) were independent factors for live birth in the subsequent pregnancy. Advanced age, the presence of uterine abnormality, and PC deficiency were risk factors for reduced pregnancy rate in women with RPL. Increased number of previous pregnancy loss and high NK cell activity were risk factors for miscarriage in the subsequent pregnancy. These results involve important information and are helpful for clinical practitioners.     

Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis

Introduction: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide with a prevalence rate of approximately 6%. Although most cases of PPH have no identifiable risk factors, the incidence of PPH has been associated to the thromboprophylaxis in pregnancy with low molecular weight heparin (LMWH). Thus, the aim of the study is to evaluate the risk of PPH in cases of pregnant women exposed to LMWH.

Materials and methods: Electronic research was performed in OVID, Scopus, ClinicalTrials.gov, MEDLINE, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. We included randomized controlled trials, cohort and case-control studies of women who underwent thromboprophylaxis with LMWH during pregnancy compared to a control group (either placebo or no treatment). The primary outcome was the incidence of PPH. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI).

Results: Eight studies including 22,162 women were analyzed. Of the 22,162 women, 1320 (6%) were administered LMWH, 20,842 (94%) women formed the nonexposed group (control group). Women treated with LMWH had a higher risk of PPH (RR 1.45, 95%CI 1.02–2.05) compared to controls; there was no difference in mean of blood loss at delivery (MD ?32.90, 95%CI 68.72–2.93) and in risk of blood transfusion at delivery (RR 1.24, 95%CI 0.62–2.51), respectively.

Conclusions: Women who receive LMWH during pregnancy have a significantly higher risk of developing PPH. Women who receive LMWH during pregnancy have neither significantly higher mean blood loss at delivery nor higher risk of blood transfusion.     

Karyotype of first clinical miscarriage and prognosis of subsequent pregnancy outcome

Research questionIs the karyotype of the first clinical miscarriage in an infertile patient predictive of the outcome of the subsequent pregnancy?DesignRetrospective cohort study of infertile patients undergoing manual vacuum aspiration with chromosome testing at the time of the first (index) clinical miscarriage with a genetic diagnosis and a subsequent pregnancy. Patients treated at two academic-affiliated fertility centres from 1999 to 2018 were included; those using preimplantation genetic testing for aneuploidy were excluded. Main outcome was live birth in the subsequent pregnancy.ResultsOne hundred patients with euploid clinical miscarriage and 151 patients with aneuploid clinical miscarriage in the index pregnancy were included. Patients with euploid clinical miscarriage in the index pregnancy had a live birth rate of 63% in the subsequent pregnancy compared with 68% among patients with aneuploid clinical miscarriage (adjusted odds ratio [aOR] 0.75, 95% CI 0.47–1.39, P = 0.45, logistic regression model adjusting for age, parity, body mass index and mode of conception). In a multinomial logistic regression model with three outcomes (live birth, clinical miscarriage or biochemical miscarriage), euploid clinical miscarriage for the index pregnancy was associated with similar odds of clinical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage for the index pregnancy (32% versus 24%, respectively, aOR 1.49, 95% CI 0.83–2.70, P = 0.19). Euploid clinical miscarriage for the index pregnancy was not associated with likelihood of biochemical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage (5% versus 8%, respectively, aOR 0.46, 95% CI 0.14–1.55, P = 0.21).ConclusionPrognosis after a first clinical miscarriage among infertile patients is equally favourable among patients with euploid and aneuploid karyotype, and independent of the karyotype of the pregnancy loss.     

Benefits and risks of low molecular weight heparin use on reproductive outcomes: A retrospective cohort study

ObjectiveLow molecular weight heparin (LMWH) has been given to reproductive-age women with various indications. This study aims to assess the benefits and risks of such use.Materials and methodsWe retrospectively reviewed data (n = 204) between Jan 2016 and May 2019. Logistic regression analysis was conducted to evaluate the correlation between indications and reproductive outcomes.ResultsLMWH use had higher odds of live birth in women less than 30 years of age (OR: 4.98; 95% CI = 1.13–21.98; p = 0.034) and with protein S deficiency (OR: 3.90; 95% CI = 1.77–8.59; p = 0.001). For the subgroup of recurrent pregnant loss, LMWH use was only advantageous to women with protein S deficiency (OR: 2.45; 95%:1.01–5.97; p = 0.048). Risks such as preterm delivery, small-for-gestational-age, placental abruption, antepartum/postpartum hemorrhage were not significantly increased among subgroups. Women treated with LMWH and who had successful live births (n = 171) had a slightly increased risk of postpartum hemorrhage compared to controls (n = 8058) during this period in our institution (2.9% vs 1.2%, p < 0.001).ConclusionLMWH administration produces a higher chance of live-birth to women younger than 30 years of age or with protein S deficiency. However, risk of postpartum hemorrhage is increased.     

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles

ObjectiveEmbryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET).Materials and methodsThis retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis.ResultsTop-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33–1.89) and pregnancy complications (95% CI 0.12–7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05–1.22) and pregnancy complication (95% CI 1.01–1.29), respectively.ConclusionClinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.     

Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials

Objective: This study was designed to evaluate the efficacy of aspirin or heparin or both in the treatment for recurrent spontaneous abortion (RSA) in women with antiphospholipid antibody syndrome (APS).

Methods: Systematic searches for randomized clinical trials (RCTs) evaluating on live birth and preterm delivery, preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of RSA with APS patients receiving aspirin, and heparin therapy were carried out, from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative risk (RR) and its 95% confidence interval were calculated.

Results: Nineteen publications with randomized controlled trials were selected for this study, which included a total of 1251 pregnant patients with diagnosis of RSA with APS. With respect to live birth, it was remarkably improved in aspirin plus heparin or heparin alone group [RR?=1.23, 95% CI (1.12–1.36), p?p?=?.02]; aspirin alone group, however, there was no statistically significant difference compare to placebo [RR?=?0.97, 95% CI (0.80–1.16), p?=?.71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding. A beneficial therapeutic effect of heparin alone therapy was found on preventing preterm birth and low-dose aspirin plus heparin therapy was significant reduce the risk of preeclampsia.

Conclusion: An improvement of pregnancy outcomes in women with RSA and APS can be achieved by treatment strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin alone, by contrast, seemed inferior to other treatments in achieving more live birth.     

Ovulation induction in the new millennium: Recombinant follicle-stimulating hormone versus human menopausal gonadotropin

The renewed interest in luteinizing hormone (LH), together with limited and decreasing health resources, make essential the comparison of high-cost, recombinant follicle-stimulating hormone (rFSH) preparations (devoid of LH) and human menopausal gonadotropin (hMG) in terms of clinical efficacy. All published, randomized controlled trials (RCTs) comparing rFSH versus hMG under different protocols of stimulation were examined. Eight true RCTs were included in this meta-analysis, recruiting 2031 participants. Data for ongoing pregnancy/live birth rate, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) were extracted, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of a fixed-effects model. Data for the meta-analysis were combined using RevMan software (using the Mantel–Haenszel method). Pooling the results of these RCTs showed no significant difference between rFSH and hMG regarding the different outcomes: ongoing pregnancy/live birth rate, OR 1.18 (95% CI 0.93–1.50); clinical pregnancy rate, OR 1.2 (95% CI 0.99–1.47), miscarriage rate, OR 1.2 (95% CI 0.70–2.16); multiple pregnancy rate, OR 1.35 (95% CI 0.96–1.90); incidence of moderate/severe OHSS, OR 1.79 (95% CI 0.74–4.33). However, there was significant reduction in the amount of gonadotropins in favor of hMG over rFSH. There was no significant heterogeneity of treatment effect across the trials. In conclusion, there is no clinically significant difference between hMG and rFSH in in vitro fertilization/intracytoplasmic sperm injection cycles. Decision-makers should establish their choice of one drug over the other based on the most up-to-date evidence available.     

Use of embryo culture supernatant to improve clinical outcomes in assisted reproductive technology: a systematic review and meta-analysis

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22–0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77–1.36; two trials, 156 participants, I²?=?0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.     

低分子肝素预防子痫前期及其并发症的Meta分析

目的:分析评价对子痫前期(PE)高危妊娠妇女预防性应用低分子肝素(LMWH)的疗效及安全性。方法:检索PubMed、The Cochrane Library、Embase、CBM和CNKI等数据库,选择对PE高危妊娠妇女预防性应用LMWH的随机对照研究(RCTs),应用修改后Jadad量表进行质量评价,Stata12.0软件进行Meta分析。结果判定指标用相对危险度(RR)或标准化均数差(SMD)及其95%可信区间(95%CI)表示。结果:共纳入6篇RCTs,其中5篇为高质量文献,分成LMWH组(525例)与LMWH联合阿司匹林(ASA)组(363例)两个亚组。LMWH组与LMWH联合ASA组的Meta分析结果显示,对PE高危人群预防性应用LMWH可减少PE(6项研究888例,RR=0.34,95%CI为0.21～0.56和RR=0.53,95%CI为0.30～0.91)、5min Apgar评分7分(3项研究519例,RR=0.51,95%CI为0.32～0.83和RR=0.33,95%CI为0.18～0.57)、胎儿宫内生长受限(6项研究848例,RR=0.34,95%CI为0.21～0.55和RR=0.52,95%CI为0.31～0.89)、新生儿入住监护病房(3项研究494例,RR=0.52,95%CI为0.28～0.97和RR=0.37,95%CI为0.19～0.69)的发生率,适度增加出生体重、延长孕周,差异均有显著统计学意义(P0.05)。但对胎盘早剥、HELLP综合征、早产、胎死宫内与新生儿死亡方面无显著效果,且无增加产时出血风险。结论:LMWH预防PE及其并发症具有一定的疗效,临床应用安全,但仍需大样本、多中心的双盲RCTs以进一步证实其优越性。     

IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis

Purpose  To assess the efficacy of preimplantation genetic screening to increase ongoing pregnancy rates in couples without known genetic disorders. Methods  Systematic review and meta-analysis of randomized controlled trials. Two reviewers independently determined study eligibility and extracted data. Results  Ten randomized trials (1,512 women) were included. The quality of evidence was moderate. Meta-analyses using a random-effects model suggest that PGS has a lower rate of ongoing pregnancies (risk ratio=0.73, 95% confidence interval 0.62–0.87) and a lower rate of live births (risk ratio=0.76, 95% confidence interval 0.64–0.91) than standard in vitro fertilization/intracytoplasmic sperm injection. Conclusions  In women with poor prognosis or in general in vitro fertilization program, in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening for aneuploidy does not increase but instead was associated with lower rates of ongoing pregnancies and live births. The use of preimplantation genetic screening in daily practice does not appear to be justified. Capsule   Preimplantation genetic screening does not increase pregnancy rates in advanced maternal age, recurrent implantation failure, repeated miscarriages, or in general IVF population.     

Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta-analysis

Background

Recently, a relationship between recurrent pregnancy loss (RPL) and Apolipoprotein E (Apo E) gene polymorphisms has been proposed. In order to investigate the real association between Apo E polymorphisms and RPL, our meta-analysis was carried out.

Methods

We estimated the association with RPL risk under dominant and recessive models, in combination with the OR and RR with a 95 % confidence interval (CI), which was used to assess the association between RPL and Apo E polymorphisms.

Results

According to our criterion, there were 6 studies included. The dominant model used the E4/E3 group and the OR was 1.919 (95 %CI: 1.016–3.625, I² = 53.8 %), the RR was 1.308 (95 %Cl: 1.071–1.598) suggesting that carriers of the E4 allele would have a higher risk of causing spontaneous miscarriages. In addition, the OR was 0.727 (95 %CI: 0.566–0.932, I² = 0.0 %) and RR was 0.923 (95 %CI: 0.867–0.982) in a fixed model for E3/E3 homozygotes versus other genotypes, suggesting that the Apo E3 polymorphism could be a protective factor. The OR was 1.365 (95 % CI: 1.029–1.811, I² = 0 .0 %) in a fixed model comparing the E2 allele with the E3 allele, suggesting that Apo E2 polymorphisms may contribute to RPL as a risk factor. Furthermore, after conducting sensitivity analysis in the E4/E3 group, the results showed this to be consistent and the OR was 2.249 (95 %CI: 1.474–3.431).

Conclusions

There is a close association between RPL and Apo E gene polymorphisms. For RPL, the Apo E4 polymorphism could be a risk factor, the Apo E3 polymorphism may be a protective factor and the Apo E2 polymorphism may be another potential risk factor.     

Use of hyaluronic acid for sperm immobilisation and selection before intracytoplasmic sperm injection: A systematic review and meta-analysis

AIM: To appraise critically the published randomised controlled trials (RCTs) reporting on the effectiveness of using hyaluronic acid (HA) for sperm immobilisation and selection before intracytoplasmic sperm injection (ICSI). METHODS: Two authors used the PICO Method in order to perform a comprehensive literature search of the standard medical databases in June 2015. Data from the included studies was extracted independently by two authors using a predefined pro-forma. Review Manager (RevMan) was used to calculate the combined outcomes where multiple studies contributed with their results. Risk ratio (RR) with a 95%CI using the Mantel-Haenszel method was calculated for binary data variables. Heterogeneity was measured using the χ² test and quantified using I². In case of substantial heterogeneity (P < 0.10 for χ² test or I² > 50%) the combined outcome was calculated using the random effects model. The results from the meta-analysis were displayed as forest plots. The guideline of the Cochrane Collaboration was used to assess the risk of bias and it was illustrated as a risk of bias graph. RESULTS: The systematic literature search identified 166 different studies related to sperm immobilisation and selection for ICSI. Eleven RCTs involving 13719 oocyte intracytoplasmatic injections with sperm immobilised and selected using HA or polyvinylpyrrolidone (PVP) were included in this systematic review and meta-analysis. There was low heterogeneity among the included trials (χ² = 16.86, df = 11, P = 0.11; I² = 35%). There was no statistical difference between HA and PVP groups in terms of fertilisation rate (RR = 1.01; 95%CI: 0.99-1.03; z = 0.75; P = 0.45), good embryos rate (RR = 1.01; 95%CI: 0.96-1.06; z = 0.30; P = 0.76), live birth rate (RR = 1.15; 95%CI: 0.86-1.54; z = 0.92; P = 0.36), clinical pregnancy rate (RR = 1.04; 95%CI: 0.92-1.17; z = 0.62; P = 0.53) and implantation rate (RR = 1.17; 95%CI: 0.94-1.46; z = 0.40; P = 0.16). The quality of most of the included studies was moderate to poor because of unclear randomisation technique, inadequate allocation concealment and blinding. CONCLUSION: This systematic review and meta-analysis provides evidence of similar efficiency between using HA or PVP for sperm immobilisation and selection before ICSI.     

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p?=?.456 and 15/133 vs. 9/97, p?=?.624, respectively), nor to the secondary outcomes preset for this study (all p values?>.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.     

激动剂方案中添加重组LH对体外受精-胚胎移植妊娠结局影响的Meta分析

目的:评价激动剂方案中添加重组LH(rLH)的必要性。方法:计算机检索PubMed、Ovid、EMbase、Medline、Cochrane图书馆等中、外生物医学数据库。收集有关激动剂方案中是否添加rLH的随机对照试验。按Cochrane系统评价方法,评价所纳入研究的文献质量,并提取有效数据后采用RevMan5.1软件进行Meta分析。结果:纳入7个随机对照试验(RCT),共计1 741例患者,其中FSH+rLH组897例,FSH组844例。Meta分析结果显示:与FSH组比较,添加rLH对临床妊娠率(RR=0.99,95%CI=0.87~1.13,P=0.86)、活产率(RR=0.94,95%CI=0.76~1.16,P=0.57)、种植率(RR=1.00,95%CI=0.86~1.17,P=0.99)及流产率(RR=0.79,95%CI=0.52~1.22,P=0.29)无影响。但对于高龄患者,添加rLH降低了获卵数(WMD=-1.56,95%CI=-1.81~-1.32,P0.001)及MⅡ卵数(WMD=-1.40,95%CI=-1.79~-1.01,P0.001)。结论:与单独应用FSH相比,添加rLH对临床妊娠率、活产率、种植率及流产率无影响,但会减少高龄患者获卵数及MⅡ卵数。     

LEEP术治疗宫颈上皮内瘤变对妊娠母儿相关结局影响的Meta分析

目的：探讨宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）行宫颈环形电切术（loop electrosurgical excision procedure,LEEP）治疗对妊娠母儿相关结局的影响。方法：检索PubMed、Cochrane Library、CNKI、CBM、万方、维普等电子数据库发表的有关CIN行LEEP治疗对妊娠母儿结局影响的病例对照研究,采用Revman 5.3软件进行统计分析。结果：共纳入40篇病例对照研究,共9 002例病例,其中病例组4 196例、对照组4 806例。Meta分析结果显示,与对照组比较,CIN患者LEEP术后妊娠情况如下。（1）妊娠早、中期相关结局：流产（RR=1.34,９5%CI：1.14～1.57,P＜0.05）风险增加,而受孕率、引产率及异位妊娠率差异无统计学意义（均P＞0.05）;（2）妊娠晚期相关结局：① 孕产妇方面,早产（RR=1.60,95%CI：1.37～1.86,P＜0.05）、未足月胎膜早破（RR=2.72,95%CI：1.46～5.07,P＜0.05）风险明显增加,而胎膜早破、剖宫产、前置胎盘及产后出血的发生率差异无统计学意义（均P＞0.05）;② 围生儿方面,低出生体质量儿发生率（RR=1.35,95%CI：1.10～1.66,P＜0.05）增加,而胎儿窘迫、新生儿窒息及新生儿病死率差异无统计学意义（均P＞0.05）;③分娩方式及其并发症方面,LEEP术不增加急产、产钳与胎头吸引助产及宫颈裂伤的风险（均P＞0.05）。结论：LEEP术增加流产、早产、未足月胎膜早破及低出生体质量儿发生的风险。对于有生育要求的CIN患者,LEEP术前应充分告知妊娠不良结局的风险。     

Reproductive Outcomes Following Uterine Artery Occlusion at the Time of Myomectomy: Systematic Review and Meta-analysis

This investigation sought systematically to review and meta-analyze evidence on reproductive outcomes following uterine artery occlusion (UAO) at myomectomy. Databases searched included PubMed, EMBASE, Ovid MEDLINE, Web of Science, and ClinicalTrials.gov. Eligible studies included observational and randomized controlled trials in which patients underwent abdominal, laparoscopic, or robotic myomectomy and in which at least one measure of clinical pregnancy rate, live birth rate, or ovarian reserve was reported. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy rate, miscarriage rate, adverse pregnancy outcomes, and measures of ovarian reserve. Twelve articles involving 689 women were included in the systematic review. The intervention group underwent UAO at laparoscopic or abdominal myomectomy (UAO+M) (n = 470). The control group underwent myomectomy alone (n = 219). Seven articles involving 420 women were included in the meta-analysis (201 underwent UAO+M; 219 underwent myomectomy alone). Live births occurred in 54 of 201 (27%) women in the UAO+M group and in 74 of 219 (34%) women in the control group. Clinical pregnancies occurred in 73 of 201 (36%) women in the UAO+M group and in 102 of 219 (47%) control subjects. There was no difference in live birth rates (odds ratio 0.89; 95% CI 0.56–1.43; P = 0.51; 7 studies, 420 patients) or clinical pregnancy rates (odds ratio 0.81; 95% confidence interval 0.53–1.24; P = 0.33; 7 studies, 420 patients) between the UAO+M and control groups. Data on miscarriage rates, adverse pregnancy outcomes, and measures of ovarian reserve precluded meta-analysis. In conclusion, UAO at myomectomy is not associated with reductions in live birth or clinical pregnancy rates. Before routine use can be recommended in women desiring future fertility, more research is required on reproductive outcomes and effects on ovarian reserve.     

Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials

ObjectiveTo systematically evaluate the role of hyaluronic acid (HA) gel and its derivatives in the postoperative prevention of intrauterine adhesions (IUA) and to assess whether HA gel could improve the pregnancy rate.Data SourcesA structured search was performed in PubMed, Cochrane, Scopus, Web of Science, and Embase on February 2, 2022.Methods of Study SelectionWe chose medical subject headings and relevant terms from other articles for the database search. The following intervention was selected: HA gel or related derivatives vs placebo in randomized controlled trials (RCTs). The following outcomes were selected: the rate and severity of IUA after intrauterine operations and pregnancy rate. After the full-text screening, 12 articles were included in the final analysis. The study quality and risk of bias were assessed with the Cochrane tool (www.training.cochrane.org/handbook).Tabulation, Integration, and ResultsData from 12 articles on 1579 patients were extracted and analyzed by 2 independent reviewers. According to the meta-analysis, HA gel could decrease the risk of IUA (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.37–0.67; p = .005; I² = 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilatation and curettage (RR, 0.42; 95% CI, 0.30–0.59; p = .86; I² = 0) or hysteroscopic surgery (RR, 0.55; 95% CI, 0.38–0.80; p = .007; I² = 66%). The sensitivity analysis showed that heterogeneity could be improved significantly by removing one study. The severity of IUA (mean difference = –0.92; 95% CI, –1.49 to –0.34; p <.00; I² = 89%) was lower in the intervention group. Subgroup and sensitivity analyses did not significantly improve the heterogeneity. When the studies are classified by the volume of HA gel, 10 mL (RR, 0.40; 95% CI, 0.27–0.60; p = .96; I² = 0) and 5 mL (RR, 0.34; 95% CI, 0.14–0.82; p = .36; I² = 0) were effective in treating IUA. In contrast, HA gel <5 mL was not sufficient to prevent IUA (RR, 0.66; 95% CI, 0.43–1.01; p = .02; I² = 71%; p = .05). The pregnancy rate was also improved by the use of HA gel (RR, 1.39; 95% CI, 1.13–1.72; p = .37, I² = 0).ConclusionHA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A greater volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Moreover, HA gel can increase the pregnancy rate after intrauterine surgery. However, these conclusions should be interpreted with caution because of the inadequate quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are required to verify these conclusions in the future.