移植前宫腔灌注人绒毛膜促性腺激素对于体外受精-胚胎移植妊娠结局影响的Meta分析

目的评价移植前宫腔灌注人绒毛膜促性腺激素(hCG)是否能影响体外受精-胚胎移植(IVF-ET)患者的妊娠结局。方法计算机检索Pub Med、EMBase、ISI Web of Science、Cochrane Library、中国知网全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方和维普等数据库,查找关于宫腔灌注hCG对于妊娠结局的影响的研究,检索年限自建库至2017年7月,对检索到的文献按照纳入和排除标准进行筛选、质量评价和数据提取,采用RevMan5.3软件进行数据分析。结果共纳入符合要求的12个随机对照研究,灌注组与对照组相比,临床妊娠率(OR=1.24,95%CI=1.08~1.43)和种植率(OR=1.21,95%CI=1.00~1.46)组间差异有统计学意义,活产率(OR=1.05,95%CI=0.81~1.36)和流产率(OR=1.02,95%CI=0.78~1.34)组间差异有统计学意义。其中移植卵裂期胚胎的患者,移植前宫腔灌注≥500 IU的hCG,与对照组相比,种植率(OR=1.61,95%CI=1.32~1.97)、临床妊娠率(OR=1.46,95%CI=1.26~1.70)和活产率(OR=1.52,95%CI=1.27~1.84)差异具有统计学意义。结论移植前宫腔灌注hCG能够改善不孕症患者胚胎移植的妊娠结局。     

宫腔灌注绒毛膜促性腺激素对反复着床失败后冻融胚胎移植妊娠结局的作用

目的:探讨胚胎反复着床失败(RIF)后冻融胚胎移植(FET)时行宫腔内灌注基因重组人绒毛膜促性腺激素(rh CG)对妊娠结局的影响。方法:选择既往胚胎RIF再次行FET的208个周期的患者资料进行回顾性分析。将其中FET日宫腔内灌注rh CG为研究组,另按1∶1选择匹配(年龄、既往ET失败次数、不孕类型)对照组。分析比较着床率、自然流产率、生化妊娠率、临床妊娠率、多胎妊娠率。结果:研究组着床率(22.92%)、生化妊娠率(5.77%)、自然流产率(17.78%)均略高于对照组(分别为16.88%、1.92%、16.13%),多胎妊娠率略低于对照组(15.56%vs 19.35%),但差异均无统计学意义(P0.05)。研究组和对照组均未观察到异位妊娠病例,研究组临床妊娠率显著高于对照组(43.27%vs 29.82%),差异有统计学意义(P0.05)。结论:FET日行宫腔内灌注rh CG可以提高RIF患者的临床妊娠率。     

A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures

Objective: To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs).

Methods: The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000?IU of hCG before embryo transfer (ET) (n?=?62). A placebo group (n?=?49) received an intrauterine injection of physiological saline before ET. A control group (n?=?50) did not receive an intrauterine injection. Clinical pregnancy rates, abortion rates, and ongoing pregnancy rates were compared between the three groups.

Results: The clinical pregnancy rates were 59.68%, 53.06%, and 32.00% in the hCG group, placebo group, and control group, respectively. The clinical pregnancy rates were significantly higher in the hCG and placebo groups than in the control group. There were no significant differences in the abortion rates among the three groups.

Conclusion: An intrauterine administration of hCG before FET significantly improved the pregnancy rates after TIFs. But local injury caused by the operation of intrauterine perfusion may play an important role in improving clinical pregnancy rates.     

Serum human chorionic gonadotropin measured 7 days following day 3 embryo transfer might predict pregnancy outcome in IVF

This prospective study investigated the predictive value of pregnancy outcomes with serum human chorionic gonadotropin (hCG) 7 days after day 3 embryo transfer (D3 ET), and whether estradiol (E2) and progesterone (P) improved the diagnostic efficiency. The study comprised 280 in vitro fertilization and embryo transfer (IVF-ET) cycles. Serum samples were obtained 7 days after D3 ET to measure hCG, E2, and P concentrations. Statistical analyses were conducted to evaluate the predictive value for pregnancy outcomes. We found significant differences in hCG level between pregnancy and non-pregnancy, viable and non-viable pregnancy, biochemical and viable pregnancy, as well as singleton and multiple pregnancy. An hCG cutoff value of 2.5?mIU/mL is predictive of pregnancy with a positive predictive value (PPV) of 95.9% and a negative predictive value (NPV) of 92.4%. An hCG value of 10.8?mIU/mL is predictive of a multiple pregnancy with an NPV of 98.1%. The area under the hCG curve between pregnancy and non-pregnancy was not improved by adding E2, P, or combined E2/P. Our results suggest a predictive value of pregnancy outcome with serum hCG drawn 7 days after D3 ET in IVF, and the diagnostic accuracy is not improved by adding measurements of E2/P.     

Timing of human chorionic gonadotropin (hCG) hormone administration in IVF/ICSI protocols using GnRH agonist or antagonists: a systematic review and meta-analysis

Objective: To evaluate the effect of altering the timing of human chorionic gonadotropin (hCG) administration on the clinical outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using gonadotropic hormone releasing hormone (GnRH) agonist or antagonist.

Methods: We systematically searched six databases. Randomized controlled trials (RCTs) of the effects of altering the timing of hCG administration on the clinical outcome of IVF and ICSI using GnRH agonist or antagonist were included. A meta-analysis was conducted following a quality evaluation performed with Cochrane Collaboration’s Review Manager (RevMan) 5.0.2.

Results: Seven RCTs and a total of 1295 participants were included. Significant difference was observed regarding estradiol and progesterone levels on the day of hCG administration and oocyte retrieval between early hCG and late hCG administration group and in favor of the latter. The fertilization rate was not statistically different between early and 24-h late hCG groups, but it is significantly higher in the 48-h late hCG group. The pooled results showed no significant differences in the ongoing pregnancy rate per oocyte pick-up, the miscarriage rate and the live birth rate.

Conclusion: The prolongation of follicular phase by delaying hCG administration could increase estradiol, progesterone levels and oocyte retrieval, which will not influence ongoing pregnancy rate per oocyte pick-up, miscarriage rate and live birth rate. Postponing hCG may enable increased flexibility of cycle scheduling to avoid weekend procedures.     

Bed rest following embryo transfer might negatively affect the outcome of IVF/ICSI: a systematic review and meta-analysis

The majority of patients undergoing in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment will reach the stage of embryo transfer (ET), but only a small proportion of transferred embryos implant. Bed rest following ET has been recommended as a way to prevent embryo expulsion by gravity. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) published prior to May 2014 reporting the effect of bed rest following ET, and irrespective of language, country of origin, blinding or sample size. Four RCTs, including 757 women met the inclusion criteria. Bed rest following ET did not improve clinical pregnancy and live birth rates, but reduced the implantation rate. The quality of the trials included was moderate because of attrition bias and possible reporting bias. The findings of this systematic review and meta-analysis are concordant with previously published literature and suggest that bed rest is not beneficial following ET. Moreover, it might negatively affect the outcome of IVF/ICSI cycles via stress/anxiety mechanisms.     

Effect of piroxicam administration before embryo transfer on IVF outcome: a randomized controlled trial

Two hundred women aged between 28 and 43 years, with infertility from tubal, male, endometriosis or unexplained factor were randomly allocated into treatment (100 patients) and control (100 patients) groups. On the day after oocyte retrieval, each patient began supplementation with progesterone 8% vaginal gel, once daily. The patients in the treatment group received a single oral dose of 10 mg of the non-steroidal anti-inflammatory drug piroxicam 1–2 h before embryo transfer. No statistically significant difference was found between the two groups in any of the analysed endpoints. The rate of positive β-human chorionic gonadotrophin test per transfer was 37% in the women treated with piroxicam and 47% in controls. The clinical pregnancy rate per transfer and implantation rate were 34% and 19.2% with piroxicam, 38% and 21.9% in controls. The miscarriage rate was 11.8% and 13.2%. No beneficial effect of piroxicam on pregnancy rates was found evaluating either different infertility causes or different ages. This study shows that the administration of a single dose of piroxicam before embryo transfer has no additional effect on pregnancy outcome in patients receiving adequate doses of progesterone for luteal phase supplementation after IVF or ICSI.     

Effects of embryo retention during embryo transfer on IVF outcomes

Journal of Assisted Reproduction and Genetics - To investigate embryo retention (ER) rate in embryo transfer (ET) cycles and its effects on reproductive outcomes in a large database. A matched...     

Effects of low-dose human chorionic gonadotropin on corpus luteum function after embryo transfer

This paper reports the effect of low-dose human chorionic gonadotropin (hCG) on the levels of serum hCG, progesterone, and estradiol, luteal-phase length, and conception in 20 patients undergoing in vitro fertilization and embryo transfer (IVF-ET). Alternate patients in a group of 20 received 1000 IU hCG on the day of embryo transfer and 3 days after. Six and 9 days from embryo transfer 2000 IU hCG was given. The remaining patients served as controls. No patients in the treated group and four in the control group became pregnant. The endocrine profiles with respect to hCG, progesterone, and estradiol levels were similar in the treated patients compared with pregnant patients in the control group. Treated patients had significantly longer (18.0±1.1 days) luteal phases compared with nonpregnant patients in the control group (12.5±1.2 days), indicating that low-dose hCG prolonged the life of the corpus luteum. It was concluded that while the administration of low-dose hCG prolonged the life of the corpus luteum, it did not apparently improve the conception rate.     

Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials

Purpose

To examine available data from randomized controlled trials to assess if the freeze-all embryo and subsequent frozen-thawed embryo transfer (FET) results in better clinical outcomes than fresh embryo transfer (ET).

Methods

Meta-analysis.

Results

We conducted an electronic literature search on PubMed and Embase databases and manually supplemented another 2 articles from relevant citations. Seven studies were finally included in the meta-analysis,including 1141 women who underwent fresh embryo transfer and 1079 who underwent frozen embryo transfer. The results of the meta-analysis suggested that the live birth rate [RR (95% CI) 1.18 (1.08–1.30), P?=?0.0003] and clinical pregnancy rate [RR (95% CI) 1.10 (1.02–1.19), P?=?0.02] were significantly higher in FET group. Miscarriage rate [RR (95% CI) 0.62 (0.48–0.80), P?=?0.0002], and moderate to severe OHSS occurrence rate [RR (95% CI) 0.22 (0.12 to 0.39), P?<?0.00001] were significantly lower in FET group. Differences of biochemical pregnancy rate, ongoing pregnancy rate and implantation rate between the two groups did not reach the statistical significance.

Conclusions

Our results suggest that the IVF/ICSI with FET is more efficient and less risky for OHSS compared with ET. However, we should comprehensively inform patients with advantages, disadvantages and potential risks related to embryo cryopreservation, and carefully assess their fertility conditions to make the most beneficial clinical decision.

     

Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI cycle outcomes in patients with history of poor fertilization

Purpose

The purpose of this study was to investigate the utility of a combined GnRH-agonist (GnRH-a) and human chorionic gonadotropin (hCG) trigger in improving ICSI cycle outcomes in patients with poor fertilization history after standard hCG trigger in prior ICSI cycles.

Methods

Retrospective cohort study. Patients with a fertilization rate of <20% in at least two prior ICSI cycles who subsequently underwent another ICSI cycle with hCG trigger were compared to those who underwent another ICSI cycle with a combined GnRH-a and hCG trigger. Oocyte maturity, fertilization, clinical pregnancy, and live birth rates were compared. A multiple linear regression model was used to explore the association between combined GnRH-a and hCG trigger (vs hCG trigger alone) and fertilization rate.

Results

A total of 427 patients with mean age of 37.3 ± 1.94 years and mean baseline fertilization rate of 17.9 ± 2.03% were included, of which 318 (74.5%) and 109 (25.5%) patients underwent a subsequent ICSI cycle with hCG and combined GnRH-a and hCG trigger, respectively. The baseline parameters of the male and female partner were similar. The mean fertilization rate in the combined trigger group was 16.4% (95% CI: 7.58–25.2%) higher than the hCG trigger group, even after adjustment for confounders. Patients in the combined trigger group had higher oocyte maturity (82.1 vs 69.8%), higher clinical pregnancy (27.5 vs 5.67%), and higher live birth rates (20.2 vs 3.46%) compared to the hCG trigger group.

Conclusions

Combined GnRH-a and hCG trigger in ICSI cycles increase oocyte maturity, fertilization, clinical pregnancy, and live birth rates in patients with a history of poor fertilization after standard hCG trigger alone.

     

Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal

One of the most problematic issues of assisted reproduction is the high incidence of multiple pregnancies, resulting from the transfer of more than one embryo. Particularly at risk are young women who have good quality embryos. The only strategy to reduce the incidence of multiple pregnancies, including twin pregnancies, after assisted reproduction is single embryo transfer (SET). In 1997, the present authors therefore introduced elective SET (eSET) in this particular target group. The proportion of eSET increased from 1.5 (1997-1998) to 17.5% (1999-2002) of all transfers. In 2002, 20% of all transfers were SET. Comparing these two periods, an overall pregnancy rate of 35 and 34% per transfer, respectively, was obtained, while the overall twinning rate dropped from 30 to 21%. The twinning rate dropped to 14% in 2002, and in the eSET group there was only one monozygotic twin. These results demonstrate that a decline in the twinning rate is feasible without a drop in overall pregnancy rates. Comparing eSET with elective double embryo transfer (eDET), it was found that ongoing pregnancy and implantation rates were the same in both groups, but the proportion of twins was clearly different. It was further observed that the mean birthweight of singleton children born after eSET was significantly higher than that after DET. This could reflect a better developmental or implantation potential of these embryos, but this finding remains to be confirmed.     

Blastocyst transfer and gender: IVF versus ICSI

Purpose  

To investigate the difference in sex ratio in our centre after day 5 embryo transfer among neonates delivered after fresh in vitro fertilization (IVF), fresh intra cytoplasmatic sperminjection (ICSI) and frozen embryo replacement (FER) compared to expected sex ratio in normal population.     

ABO血型系统对新鲜周期胚胎移植妊娠结局的影响

目的:研究接受新鲜周期胚胎移植的体外受精/卵胞浆内单精子注射(IVF/ICSI)助孕治疗的卵巢功能正常患者的ABO血型与妊娠结局之间的关系。方法:回顾分析2015年5月1日至2017年5月1日于郑州大学第三附属医院生殖中心行新鲜胚胎移植的2323例IVF/ICSI周期,根据血型分为A组(n=637)、B组(n=803)、O组(n=664)、AB组(n=219)。比较各组的一般情况及妊娠结局。应用二元逻辑回归分析患者血型与活产及临床妊娠结果的关系,同时控制混杂因素,估算优势比(OR)及95%置信区间(95%CI)。结果:ABO血型组间的临床妊娠率、活产率、早产率、流产率、OHSS发生率、孕龄及新生儿出生体重比较,差异均无统计学意义(P0.05)。年龄、BMI是临床妊娠的危险因素,OR(95%CI)分别为1.477(1.222～1.785)、1.255(1.057～1.490)。年龄是活产的危险因素,Gn总剂量、Gn天数是活产的保护因素,OR(95%CI)分别为1.380(1.145～1.662)、0.808(0.670～0.976)、0.763(0.614～0.946)。结论:卵巢功能正常接受新鲜周期胚胎移植的IVF/ICSI助孕患者的ABO血型与妊娠结局无关。考虑如年龄、BMI、卵巢刺激持续时间、促性腺激素剂量和移植日子宫内膜厚度等多种混杂因素后,结果不变。这些结果需更大规模的队列研究或前瞻性研究验证。     

Correlation of sperm DNA damage with IVF and ICSI outcomes: A systematic review and meta-analysis

PURPOSE: To assess the effects of sperm DNA damage, as determined by the TUNEL assay and the SCSA respectively, on the outcomes of IVF/ICSI treatment. METHODS: A Medline search (from Jan 1978 to Apr 2006) was performed, together with a manual search of the bibliographies of retrieved original papers and review articles. 8 articles met all inclusion/exclusion criteria, of which, 5 used the TUNEL assay and the other 3 used the SCSA. All these articles were included in separate meta-analysis. The meta-analysis was conducted using the RevMan software with fixed-effect model or random-effects model. RESULTS: As for articles using the TUNEL assay, the pooled results of IVF outcomes indicated that the clinical pregnancy rate (RR 0.68, 95% CI 0.54 to 0.85, P = 0.006), but not the fertilization rate (RR 0.79, 95% CI 0.54 to 1.16, P = 0.23) decreased significantly for patients with high degree of sperm DNA damage compared with those with low degree of sperm DNA damage. RRs of the ICSI outcomes indicated that there was no significant difference in either fertilization rate (RR 1.03, 95% CI 0.89 to1.18, P = 0.70) or clinical pregnancy rate (RR 0.76, 95% CI 0.55 to 1.04, P = 0.09) between these two groups. As for the SCSA papers, the pooled results showed no significant effects of sperm DNA damage on the clinical pregnancy rate after IVF (RR 0.58, 95% CI 0.25 to 1.31, P = 0.19) or ICSI (RR 1.18, 95% CI 0.81 to 1.74, P = 0.38). CONCLUSION(S): Our meta-analysis indicates that sperm DNA damage, as assessed by the TUNEL assay, significantly decreases only the chance of IVF clinical pregnancy, but not that of either IVF fertilization or ICSI fertilization or ICSI clinical pregnancy. Besides, our results also reveal that sperm DNA damage, when assessed by the SCSA, has no significant effect on the chance of clinical pregnancy after IVF or ICSI treatment.     

Single fresh blastocyst transfer or single cryopreserved-thawed blastocyst transfer: which is preferable for infertile patients in IVF/ICSI cycles? A meta-analysis

Purposes: Nowadays, an increasing number of studies have proposed single embryo transfer (SET), especially single blastocyst transfer (SBT). To compare the clinical outcomes of single fresh blastocyst transfer (BT) and single cryopreserved-thawed BT in patients undergoing in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles.

Methods: The PubMed, Embase, and Cochrane Library databases were searched from the start dates until February 2018. The primary outcomes were clinical pregnancy rate (CPR) and embryo implantation rate (IR). The secondary outcomes were multiple pregnancy rate (MPR), live birth rate (LBR), and miscarriage rate (MR). Using the Mantel–Haenszel random effects model to analyze summary risk ratio (RR) with 95% confidence intervals (CIs). Statistical heterogeneity scores were assessed with the standard Cochrane’s Q test and I² statistic.

Results: In total, eight studies (two prospective studies, six retrospective studies) were included in our analysis. There was no statistically significant difference regarding clinical pregnancy (RR?=?1.18, 95% CI?=?0.91–1.55) and embryo implantation (RR?=?1.04, 95% CI?=?0.77–1.41). Regarding secondary outcomes, there was no significant difference regarding miscarriage (RR?=?0.79, 95% CI?=?0.60–1.03) and multiple pregnancy (RR?=?1.23, 95% CI?=?0.75–2.04). However, single fresh BT is associated with an increased live birth (RR?=?1.28, 95% CI?=?1.05–1.57) compared with single cryopreserved-thawed BT.

Conclusions: In summary, this meta-analysis supports the hypothesis that single cryopreserved BT might not be the best choice compared with single fresh BT in patients undergoing IVF/ICSI cycles.     

Adenomyosis has no adverse effects on IVF/ICSI outcomes in women with endometriosis treated with long-term pituitary down-regulation before IVF/ICSI

Objectives

To establish the effect of adenomyosis on IVF/ICSI outcomes in infertile patients with endometriosis who were pretreated with long-term (≥3 months) GnRH-agonist prior to IVF/ICSI.

Study design

Retrospective study in 74 infertile patients with surgically proven endometriosis who were treated with IVF/ICSI between January 2002 and March 2007. The diagnosis of adenomyosis was based on transvaginal ultrasound criteria. All patients were pretreated with long-term (≥3 months) GnRH-agonist prior to IVF/ICSI.

Results

90.4% of the patients were diagnosed with endometriosis rASRM stages III-IV. Adenomyosis was demonstrated in 27% of them and was predominantly located in the posterior wall of the uterus. The following IVF/ICSI outcomes were found: a mean duration of GnRH-agonist use prior to IVF/ICSI of 5.35 months (3-26); a mean dosage of FSH used of 208 IU (75-450); the mean number of oocytes retrieved was 8.73 (1-30); the mean number of embryos obtained was 3.86 (0-16); the mean number of embryos transferred was 1.6; a mean fertilization rate of 43.6%; a mean implantation rate of 26.3%; a mean miscarriage rate of 24.3%; and a clinical pregnancy rate (fetal heart activity on ultrasound beyond 12 weeks of gestation) of 31.7%. No significant differences were found for any of the IVF/ICSI outcomes between women with and without adenomyosis.

Conclusions

Adenomyosis had no adverse effects on IVF/ICSI outcomes in infertile women with proven endometriosis who were pretreated with long-term GnRH-agonist.     

Human chorionic gonadotropin (hCG) plasma levels at oocyte retrieval and IVF outcomes

Purpose

The aim of our study was to ascertain the influence of hCG levels at oocyte pick-up on IVF outcomes, and their relationship with clinical parameters.

Methods

A prospective study was performed including 473 women undergoing IVF, aged under 40 years. Blood samples to analyze hCG levels were obtained at the time of follicular aspiration, 36 h after the administration of 250 μg of recombinant hCG.

Results

Neither the numbers of oocytes obtained or fertilized, nor the pregnancy rate, were correlated with hCG levels. Moreover, hCG values were very similar in women who did and did not become pregnant (123.3 ± 48.7 and 117.5 ± 44.7 mUI/mL). Cases in which no oocytes were recovered after follicular aspiration had similar hCG levels to those in which more than 1 oocyte was obtained. On the other hand, hCG levels were negatively related to body mass index, weight, and age.

Conclusions

These data indicate that after the administration of 250 μg of recombinant hCG, hCG levels are not responsible for failure to recover oocytes. Specifically, there was no correlation between plasma hCG levels and the number of oocytes obtained or other markers of IVF outcome. There was, however, an inverse relationship with BMI, body weight and age.