The incidence of monozygotic twinning in assisted reproductive technology: Analysis based on results from the 2010 Japanese ART national registry

Purpose

To assess the incidence of monozygotic twinning (MZT) among cases undergoing assisted reproductive technology (ART) treatment.

Methods

We performed a retrospective observational study and analyzed the data of patients who were registered in the national ART registry system of Japan from January to December 2010; only the data of patients with single embryo transfer (ET) were included.

Results

Of 30,405 pregnancies, 425 resulted in MZT following fresh and frozenthawed ET. The MZT incidence among women undergoing ART was 1.4 %. Multiple logistic regression analysis indicated that cases undergoing fresh and frozen-thawed ET, blastocyst transfer had a significantly increased MZT rate (P < 0.01). Assisted hatching (AH) and frozen-thawed ET and maternal age did not significantly affect the MZT incidence. Of 8510 fresh ET pregnancies, 104 resulted in MZT. Multiple logistic regression analysis indicated that blastocyst transfer significantly increased the MZT rate in cases undergoing fresh ET. Ovarian stimulation, intracytoplasmic sperm injection, AH, and maternal age did not significantly affect the MZT incidence.

Conclusions

Blastocyst transfer was associated with an increased MZT incidence. We have to be aware of the potential risk of MZT caused by blastocyst transfer. However, further studies are required to assess the correlation among specific AH types, embryo culture conditions, and MZT incidence.     

The effect of long zona dissection using ICSI pipettes for mechanical assisted hatching in vitrified-thawed blastocyst transfers

Objective

To investigate the effect of long zona dissection (LZD) compared with partial zona dissection (PZD) using ICSI pipettes for mechanical assisted hatching (AH) in vitrified-thawed blastocyst transfers.

Design

Prospective study.

Setting

University IVF clinic.

Patient(s)

A total of 120 women ≦ 38 years old undergone vitrified-thawed blastocyst transfers with LZD or PZD.

Intervention(s)

The culture of all pronucleate embryos to the blastocyst stage and the selection of blastocysts ≧ grade 3BB (Gardner and Schoolcraft score), followed by vitrified-thawed blastocyst transfers with LZD (n = 60) or with PZD (n = 60)

Main outcome measure(s)

Complete hatching rates, implantation rates, pregnancy rates.

Result(s)

At 5 h after thawing, complete hatching rates of blastocysts were significantly higher in LZD group compared with PZD group, 52.4 % vs. 31.8 % (P = 0.001). Implantation and clinical pregnancy rates were significantly higher in LZD group compared with PZD group, 40.9 % vs. 25.7 % and 63.0 % vs. 40.0 %, respectively (P = 0.010, P = 0.011).

Conclusion(s)

LZD using ICSI pipettes for mechanical AH improves significantly complete hatching, implantation and pregnancy rates in vitrified-thawed blastocyst transfers.     

Relationship between oxidative stress and clinical pregnancy in assisted reproductive technology treatment cycles

PurposeTo examine the relationship between serum total oxidant (TOS) and antioxidant (TAS) levels and clinical pregnancy in assisted reproductive technology (ART) cycles.MethodsPrior to and after oocyte pick-up (OPU) and embryo transfer (ET), blood samples were collected from gynecologically normal females (n = 70) who were enrolled for ART solely due to male factor infertility. TAS, TOS levels and oxidative stress indexes (OSI: TOS/TAS) in four phases of treatment cycle (pre and post OPU and ET) between clinically pregnant and non-pregnant patients were compared. Critical cut-off values of significantly different TAS, TOS levels and OSIes for clinical pregnancy were established.ResultsThe TAS levels in patients with clinical pregnancy were significantly higher in all of the four phases of the cycle. Post-OPU and pre-ET TOS levels were significantly higher in clinically pregnant patients. According to OSIes; only the pre-OPU OSI was significantly lower in clinically pregnant patients compared with non-pregnant ones. Moreover, the highest area under the ROC curve (AUC) from the seven different significant measurements [1) pre-OPU OSI, 2) pre-OPU TAS, 3) post-OPU TAS, 4) pre-ET TAS, 5) post-ET TAS, 6) post-OPU TOS, 7) pre-ET TOS] was related to pre-OPU OSI.ConclusionsIn ART cycles, women with a higher total antioxidant status prior to and after OPU and prior to and after ET have an increased probability of clinical pregnancy. Additionally; OSI before OPU was one of the most important determinants for clinical pregnancy, so the oxidant and antioxidant balance is as important as the antioxidant concentration alone.     

辅助生殖技术治疗后自然流产相关因素分析

目的 探讨辅助生殖技术（ART）治疗后自然流产的发生率及相关因素。方法 2003-01—2005-12对湘雅医院生殖医学中心接受ART治疗后的临床妊娠590例进行分析，了解体外受精-胚胎移植（IVF—ET）、单精子卵浆内显微注射（ICSI）、冻融胚胎移植（FET）的自然流产情况，比较未流产及流产组的既往自然流产史及多胎妊娠率，比较早期流产与晚期流产患者多胎妊娠率及行IVF前宫腔操作次数。结果 ART治疗后自然流产率为12．20％，IVF、ICSI及FET的自然流产率比较差异无显著意义（P〉0．05），而流产组有既往自然流产史者明显高于未流产组，流产组的多胎妊娠率低于未流产组，差异有显著性（P〈0．01）；晚期流产组多胎妊娠率及行IVF前宫腔操作次数明显高于早期流产组，差异有显著性（P〈0、01）。结论 行ART治疗的不孕患者如有多次宫腔操作史，后天性的宫颈管机械损伤不容忽视；当伴多胎妊娠时应考虑孕3～4个月行宫颈环扎术。     

The impact of assisted reproductive technology and chorionicity in twin pregnancies complicated by obstetric cholestasis

Objective: To assess in a cohort of twin pregnancies the prevalence of obstetric cholestasis (OC) and its correlation with the type of conception and chorionicity.

Methods: A retrospective cohort study including all the twin pregnancies delivered between 2005 and 2013 at our University Hospital was carried out. In the study population, the prevalence of OC was investigated in relationship to the impact of assisted reproductive technology (ART) and of chorionicity.

Results: Overall, 569 twin pregnancies were included in the study population. Among those complicated by OC, the rate of ART was 3-fold higher (OR 3.4, 95% CI 1.2–9.5, p?=?0.02), whereas the rate of dichorionicity did not differ significantly (OR 1.6, 95% CI 0.3–7.9, p?=?0.53).

Conclusion: The risk of developing OC seems to be significantly higher among twin pregnancies obtained after ART in comparison with those conceived spontaneously.     

Factors associated with subchorionic hematoma formation in pregnancies achieved via assisted reproductive technologies

To determine if certain clinical and/or embryologic factors are independently associated with the increased prevalence of subchorionic hematoma (SCH) among pregnancies achieved via in vitro fertilization (IVF) with fresh embryo transfer (ET). Retrospective chart review. In this retrospective study, data were abstracted from 210 autologous oocyte IVF clinical pregnancies that resulted from fresh ET at a single fertility center from January 2012 through December 2016. Clinical and embryology laboratory variables were analyzed as possible factors associated with the presence or absence of SCH in IVF pregnancies via bivariate associations and multivariable logistic regression analyses. Independent variables included prior uterine surgery versus no uterine surgery, peak estradiol, and progesterone levels, day 3 (n = 92) versus day 5 (n = 118) ET, and assisted hatching versus no assisted hatching. Among the day 5 ET subgroup of 118 patients, 117 had data for the variables inner cell mass (ICM) grading and trophectoderm (TE) because one day 5 ET was at the morula stage. We found a significant bivariate association between TE grading and SCH, where cases with TE grade “A” were significantly less likely to have SCH compared with cases with grades “B” or “C.” This significant difference remained when adjusting for the other factors considered in a multivariable logistic regression model for the probability of SCH. The data analyzed here suggest that a less-advanced trophectoderm grade may be a potential factor that is associated with the presence of SCH in pregnancies achieved via IVF.     

Obstetric and neonatal outcomes of twin pregnancies conceived by assisted reproductive technology compared with twin pregnancies conceived spontaneously: a prospective follow-up study

Objective

To compare the obstetric and neonatal outcomes of twin pregnancies conceived by assisted reproduction technology (ART) with spontaneously conceived (SC) twin pregnancies.

Study design

A prospective cohort study compared all dichorionic twin pregnancies in nulliparous women following fresh in vitro fertilization/intra-cytoplasmic sperm injection (ICSI) or ICSI cycles at Royan Institute (n = 320) with SC dichorionic twin pregnancies in nulliparous women at Arash Women's hospital (n = 170) from January 2008 to October 2010. These pregnancies were followed-up until hospital discharge following delivery. Obstetric and neonatal outcomes of SC and ART twin pregnancies were compared.

Results

Multivariate analysis, adjusted for maternal age and body mass index, revealed that the obstetric outcomes were similar in both groups. However, the risks of very preterm birth [odds ratio (OR) 5.2, 95% confidence interval (CI) 2.1–12.9], extremely low birth weight (OR 2.2, 95% CI 1.0–3.9), admission to a neonatal intensive care unit (OR 2.0, 95% CI 1.2–3.2) and perinatal mortality (OR 2.3, 95% CI 1.2–4.0) were higher in the ART group.

Conclusions

The maternal outcomes of ART dichorionic twins were comparable with those of SC twins. However, despite the same obstetric management, the rates of very preterm birth, extremely low birth weight, admission to a neonatal intensive care unit and perinatal mortality were significantly higher in the ART group.     

Prevention of multiple pregnancies in assisted reproduction

The incidence of multiple births has increased parallel with the success of assisted reproduction treatments (ART) mainly because of the multiple embryo transfer. As a response to the increased multiple birth rate, the number of embryos transferred was reduced in 1992–1994 from three or more to two in many European countries. After that, a dramatic drop in the number of triplet and higher-order pregnancies was seen, but the twin rate still remained high. According to the European registers by ESHRE, in 2001 still 34.4% of children conceived with ART originated from multiple pregnancies, of which 94% were twin pregnancies. Obstetric and perinatal complications affect twins more often than singletons, contributing to increased health risk of the mother of twins and the children born as twins. In addition to the medical complications, twin families are at a greater risk for psychosocial burden. From the health-economic point of view, cost impact for twins is threefold to that of singletons. Recently, the standards of success of infertility treatment have been widely debated in journals of reproductive medicine. The general conclusion from this debate is that both the delivery rate per treatment and the final outcome of the pregnancy should be considered when the success of ART is reported. The high iatrogenic twin rate resulting from ART still offers the infertility treatment providers a challenge to strive for minimizing the number of ART-related twins. The most efficient way to reduce twin rate in ART is single embryo transfer (SET). However, the worry about impairment of delivery rate if only one embryo is transferred has hampered the acceptance of SET. The four randomised controlled trials and some retrospective cohort studies published until now have confirmed the effectiveness of elective single embryo transfer (eSET) in reducing the twin rate below 10%. In addition, highly acceptable delivery rate is achieved with eSET. The final results of eSET are most obviously further improved by transfer of frozen-thawed embryos. The experience of eSET until now encourages mowing towards an individualised embryo transfer policy, where eSET is performed in good prognosis patients at high risk for a twin pregnancy when two embryos would be transferred. The aim of this article is to review studies about eSET as a method to prevent ART-related twin pregnancies and the ways used in nationwide implementation of eSET in Finland, Belgium and Sweden.     

Experience of using time lapse microscopy in the IVF program in patients with good ovarian reserve

Abstract

The aim of this study is to evaluate the outcomes of single embryo transfer in patients with good ovarian reserve in the IVF program using time-lapse microscopy. This is a retrospective cohort study in a private IVF center in Russia. Comparison was done between 90 IVF cycles using time-lapse (study group) and 113 IVF cycles using standard culture (control group). Within each group, subgroups were selected with selective transfer of one embryo for 5 days (5SET) and elective transfer of one embryo for 5 days (5eSET). The primary outcome of the study was pregnancy rate. Secondary outcomes were miscarriage rates, live birth. Pregnancy rate did not significantly differ between the groups – 64.2% in the study group and control group. In the study group, the delivery rate was 54% in the subgroup 5eSET and 51.1% in the subgroup 5SET (p?=?.940). In the control group, the type of the embryo transfer significantly influenced on the delivery rate: in the 5eSET subgroup the birth rate was 54.4%, and in the 5SET subgroup it was 34.3% (p?=?.055; by Fisher's exact method p?=?.052). There were no adverse effects of the intervention. Selection of a single blastocyst based on information derived from time-lapse monitoring can help embryo selection for transfer.     

冻融胚胎移植中辅助孵化对妊娠结局及安全性的影响

目的探讨在玻璃化冻融胚胎移植(FET)中,激光辅助孵化(AH)操作后对妊娠结局及母儿安全性的影响。方法回顾性分析2014年1月—2015年10月接受体外受精-胚胎移植(IVF-ET)失败后行FET患者的临床资料,根据患者年龄进行分组后比较AH操作后妊娠结局及母儿并发症的发生情况。结果在正常年龄组(38岁)的患者中,未行AH操作的对照组中胚胎种植率、临床妊娠率、活产率、多胎率均高于AH组,流产率低于AH组,并且差异有统计学意义(P0.05);在高龄(≥38岁)患者中,AH组的胚胎种植率、临床妊娠率较对照组有增高的趋势(P0.05);分娩周期中,AH组与对照组早产率、死胎率、母体并发症、新生儿男女比例、胎龄、出生体质量、新生儿缺陷率等均无统计学差异(P0.05)。结论对于正常年龄患者,卵裂期FET时不建议行AH操作;对于高龄患者,AH操作可提高胚胎种植率及临床妊娠率,但不能明显改善其妊娠结局;AH对母儿安全暂无不良影响。     

Effect of the site of assisted hatching on vitrified-warmed blastocyst transfer cycles: a prospective randomized study

Purpose

To assess the effect of assisted hatching (AH) site on the clinical outcomes in vitrified-warmed blastocyst transfer cycles.

Methods

A total of 160 women who underwent vitrified-warmed blastocyst transfer cycles were randomized to either the ICM group (AH performing at the site near the inner cell mess, ICM), or the TE group (AH performing at the site opposite to the ICM). AH with laser zona drilling was performed 20 or 30 min after thawing once the ICM can be detected. Clinical pregnancy rate, implantation rate, live birth rate and the occurrence rate of monozygotic twins (MZT) pregnancy after transfer of these two groups were compared.

Results

No significant difference was found in the clinical pregnancy rate (63.8 % vs. 67.5 %), implantation rate (51.7 % vs. 53.6 %) and live birth rate (57.5 % vs. 62.5 %) between the ICM group and the TE group. The occurrence rate of MZT was comparable between the two groups (3.9 % vs. 5.6 %).

Conclusions

The site of assisted hatching has no influence on the implantation, pregnancy and live birth rate in human vitrified-warmed blastocyst transfer cycles.     

Evaluating the factors associated with pregnancy loss in pregnant women undergoing assisted reproductive techniques

Introduction

Whenever assisted reproductive techniques (ART) leading to successful pregnancy (with live birth), they can be considered useful .This study is aimed at assessing the effect of risk factors associated with the pregnancy loss on pregnancy outcomes in pregnant women undergoing ART.

辅助生殖技术单胎妊娠结局分析

目的:研究辅助生殖技术(ART)与自然受孕两种不同受孕方式单胎妊娠的妊娠结局。方法:回顾分析2009年1月1日至2017年12月31日在广州医科大学附属第三医院住院分娩的妊娠≥20周的单胎妊娠病例资料。按受孕方法分为ART组及自然妊娠组,分析两组母儿结局,再按是否为高龄妊娠,比较ART组及自然妊娠组的母儿结局。结果:ART组孕妇的平均年龄、初产妇、定期产检、非足月胎膜早破(PPROM)、羊水量异常、子痫前期、妊娠期高血压、妊娠合并血小板减少症、妊娠期糖尿病、糖尿病合并妊娠、前置胎盘、胎盘植入/粘连、产后出血、剖宫产分娩、产钳/吸引产助产、人工剥离胎盘、药物/机械性引产、流产、胎儿窘迫及胎儿为男性发生率均高于自然妊娠组,ART组的住院天数更长,分娩孕周更低,转诊重症监护病房(ICU)、急性器官衰竭发生风险较低,ART组围产儿平均体重高于自然受孕组。高龄妊娠孕妇中,ART组的妊娠期糖尿病、剖宫产分娩发生风险增加。非高龄妊娠孕妇中,ART组子痫前期、妊娠期高血压、妊娠期糖尿病、糖尿病合并妊娠、流产、PROM、羊水量异常、前置胎盘、胎盘植入/粘连、产后出血、胎儿窘迫、人工剥离胎盘、药物/机械性引产发生风险增加。ART组较自然妊娠组钳产/吸引产风险均增加,产妇转诊ICU及非规律产检发生风险均降低,差异均有统计学意义(均P<0.05)。结论:ART受孕单胎妊娠并发症及新生儿不良结局发生率高于自然妊娠组孕妇,但其更注重孕期产检;在非高龄妊娠孕妇中,ART组母儿不良结局风险增加,而高龄妊娠孕妇中,ART组母儿不良结局风险增加不明显。     

辅助生殖技术后妊娠合并卵巢过度刺激综合征的诊治

卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)是辅助生殖技术最常见的并发症之一,妊娠可使病情加重,严重者甚至危及性命。因此,对妊娠合并卵巢过度刺激综合征需积极预防、严密监测、及时处理,避免其产生的严重后果。     

辅助生殖技术对子代印记基因影响的研究进展

辅助生殖技术(assisted reproductive technology,ART)是采用医学技术手段使不孕不育夫妇获得妊娠一系列技术的统称,与自然妊娠相比,在体内、体外环境等有所不同,配子及早期胚胎遭受医源性应激,致子代健康风险增加。目前普遍认为ART与配子及早期胚胎印记基因印迹改变相关,进而影响子代出生后远期健康。本文就ART对印记基因的影响进行综述,分别从配子、植入前胚胎、胎盘等方面进行论述,总结了ART与印记基因印迹异常的关系。