Clinical and neonatal outcomes of intrauterine insemination with frozen donor sperm

This retrospective study evaluated the association between frozen donor sperm used for intrauterine insemination and clinical and neonatal outcomes, including 304 singleton pregnancies resulting from artificial insemination by the husband (AIH) and 173 singleton pregnancies resulting from artificial insemination by a donor (AID). The clinical outcomes for AID showed no increased risk of abortion, ectopic pregnancy or pregnancy complications compared to those for AIH. There were no differences in gender, gestational age or prematurity of live births between the two groups. However, the birthweight of live births from AID was significantly higher than that from AIH. Moreover, the AID group exhibited no increased risk of stillbirths or fetal defects compared to the AIH group. These results indicate that frozen donor sperm did not increase the occurrence of adverse clinical and neonatal outcomes when compared to sperm from the husband.

Abbreviations: AID: artificial insemination by a donor; AIH: artificial insemination by the husband; ART: assisted reproduction technology; FET: frozen embryo transfer; IVF: in vitro fertilization; ICSI: intracytoplasmic sperm injection; IUI: intrauterine insemination; LBW: low birth weight     

冻融胚胎移植周期中不同辅助生殖技术助孕方式和移植不同发育阶段胚胎对出生性别比的影响

目的:探讨冻融胚胎移植（frozen-thawed embryo transfer, FET）周期中不同辅助生殖技术（assisted reproductive technology, ART）助孕方式和移植不同发育阶段胚胎对新生儿性别的影响。方法:回顾性队列研究分析2010年4月至2018年10月期间于广州市妇女儿童...     

卵胞浆内单精子显微注射子代临床随访研究

目的 了解卵胞浆内单精子显微注射(ICSI)子代围产期并发症、出生缺陷和生长发育等状况.方法 对中山大学附属第一医院生殖医学中心经ICSI技术治疗妊娠成功的575例ICSI子代进行临床随访分析,内容包括孕母妊娠期并发症、子代新生儿期并发症、围产期出生缺陷和以后发现的出生缺陷以及体重、身长/高增长状况等.结果 多胎妊娠ICSI子代早产、低出生体重儿发生率较单胎妊娠子代高;孕母妊娠高血压综合征和ICSI子代新生儿窒息、呼吸窘迫综合征、感染性疾病的发生率在多胎妊娠子代中发生率也较高(P＜0.05).11例死亡的ICSI子代中,10例在新生儿期死亡,均为早产儿;1例单胎足月儿2岁死于肝母细胞瘤.多胎妊娠ICSI子代围产期出生缺陷的发生率较一般人群调查的发生率高(P＜0.05).大部分ICSI子代1～3岁的体重、身长/身高能达到同龄儿童标准范围.结论 ICSI子代围产期并发症较高发生率与多胎妊娠密切相关.     

Early Autism Spectrum Disorders in Children Born to Fertile,Subfertile, and ART-Treated Women

Introduction

We examined the prevalence of autism spectrum disorders (ASDs) in Massachusetts (MA) comparing children born via assisted reproductive technology (ART) and children born to women with indicators of subfertility but no ART (Subfertile), to children born to women with neither ART nor indicators of subfertility (Fertile). We assessed the direct, indirect, and total effects of ART and subfertility on ASD among singletons.

Methods

This study included 10,147 ART, 8072 Subfertile and 441,898 Fertile MA resident births from the MA Outcome Study of ART (MOSART) database linked with Early Intervention program participation data. ART included fresh in vitro fertilization (IVF), fresh intracytoplasmic sperm injection (ICSI), and frozen embryo transfer. We estimated the prevalence of ASD by fertility group. We used logistic regression to assess the natural direct effect (NDE), natural indirect effect (NIE) through preterm birth, and total effects of each fertility group on ASD.

Results

The NDE indicated that, compared to the Fertile group, the odds of ASD were not statistically higher in the ART (OR_NDE 1.07; 95% CI 0.88–1.30), Subfertile (OR_NDE 1.11; 95% CI 0.89–1.38), IVF (OR_NDE 0.91; 95% CI 0.68–1.22), or ICSI (OR_NDE 1.13; 95% CI 0.84–1.51) groups, even if the rate of preterm birth was the same across all groups. The total effect (product of NDE and NIE) was not significant for ART (OR_{Total Effect} 1.08; 95% CI 0.89–1.30), Subfertile (OR_{Total Effect} 1.11; 95% CI 0.89–1.38), IVF (OR_{Total Effect} 0.92; 95% CI 0.69–1.23), or ICSI (OR_{Total Effect} 1.13; 95% CI 0.84–1.52).

Conclusion

Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.

     

Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a method of assisted reproductive technology that involves the selection of a single sperm cell and the manual injection of this cell into the egg. The lack of relevant experimental studies, the nature of the technology involving non-natural selection of the fertilizing sperm, and possible damage to the egg have caused concern that ICSI could increase the risk of birth defects. Data from available cohort studies comparing ICSI with standard in vitro fertilization (IVF) should be combined to evaluate the risks involved with ICSI. METHODS: We reviewed more than 2500 titles and abstracts containing keywords related to ICSI and identified 22 scientific articles with data on birth defects among ICSI-births. A total of four peer-reviewed, non-overlapping prospective cohort studies provided reliable and comparable data on birth defects both for children conceived by ICSI and children conceived by standard IVF. These studies included a total of 5395 children born after ICSI. RESULTS: The pooled estimate of the risk of a major birth defect was a 1.12-fold increase after ICSI when compared with standard IVF (risk ratio = 1.12, 95% confidence interval (CI): 0.97-1.28, P = 0.12). There was no marked heterogeneity of risk ratios between these studies (P = 0.10). We found no significantly increased risks after ICSI for any of the categories cardiovascular defects, musculoskeletal defects, hypospadias, neural tube defects, or oral clefts. CONCLUSIONS: Our analysis does not indicate that the ICSI-procedure represents significant additional risks of major birth defects in addition to the risk involved in standard IVF. The data was limited, particularly on risks of specific categories of defects.     

From the Centers of Disease Control and Prevention. Use of assisted reproductive technology--United States, 1996 and 1998

Since 1983, when the first infant was conceived from in vitro fertilization (IVF) in the United States, the use of IVF and related procedures (assisted reproductive technology [ART]) has increased substantially. In 1998, an estimated 0.7% of the 3.9 million births were the result of ART. ART patients are more likely to deliver multiple infants than women who conceive without treatment, and these multiple-infant births are associated with increased risks for pregnancy complications, premature delivery, low birth-weight infants, and long-term disability among surviving infants. This report examines state-specific use of ART in 1996 and 1998 and provides data on ART live-born and multiple-infant birth rates in 1998. Findings indicate that the use of ART is increasing in most states and that more than half the infants born as a result of these procedures are multiple births. These high-risk births contribute disproportionately to health-care costs and might negatively affect maternal and child health outcomes, particularly in states where large numbers of ART procedures are performed.     

子宫纵隔不孕症患者行宫腔镜子宫纵隔切除术后IVF/ICSI结局分析

目的：探讨宫腔镜子宫纵隔切除术（transcervical resection of septum,TCRS）对子宫纵隔不孕症患者行体外受精（in vitro fertilization,IVF）/卵细胞质内单精子注射（intracytoplasmic sperm injection,ICSI）结局的影响。方法：回顾性分析并比较2013年1月—2020年7月在南京大学医学院附属鼓楼医院生殖医学中心进行IVF/ICSI的183例子宫纵隔不孕症患者的治疗结局。其中156例行TCRS后IVF/ICSI(TCRS组),而27例患者拒绝TCRS直接行IVF/ICSI（未行TCRS组）。结果：共有247个移植周期,其中新鲜胚胎移植周期100个,临床妊娠率64.0%,活产率49.0%;冻融胚胎移植周期147个,临床妊娠率51.0%,活产率40.1%。新鲜胚胎移植周期和冻融胚胎移植周期中TCRS组与未行TCRS组的胚胎种植率、临床妊娠率、流产率、早产率、活产率及单胎妊娠新生儿出生体质量比较,差异均无统计学意义（均P>0.05）。新鲜胚胎移植周期中,与TCRS组比较,未行TCRS组的双胎妊娠率高（...     

体外受精/胞浆内单精子注射子代围生期结局的回顾性分析

目的：回顾性分析体外受精（IVF）/胞浆内单精子注射（ICSI）子代的围生期结局。方法：分析2012年1月—2013年12月在南京医科大学附属苏州医院接受辅助生殖技术（ART）治疗鲜胚和冻胚移植840个活产周期的临床资料和围生期结局。结果：双胎妊娠出生体质量[（2 536.84±417.23）g vs. （3 314.67±466.56）g]和分娩孕周[（36.78±1.74）周 vs.（39.31±1.45）周]均低于单胎妊娠,差异有统计学意义（P＜0.05）;双胎妊娠早产发生率（45.66% vs. 3.70%）、低出生体质量儿发生率（41.32% vs. 2.41%）、剖宫产率（97.26% vs. 81.64%）高于单胎妊娠,差异有统计学意义（P＜0.05）。冻胚移植单胎妊娠出生体质量[（3 358.96±458.34）g vs. （3 249.11±474.28）g]和剖宫产率（85.97% vs. 74.58%）高于鲜胚移植,差异有统计学意义（P＜0.05）。结论：IVF/ICSI技术获得的双胎妊娠较单胎妊娠不良围生期结局更多;在单胎妊娠中冻胚移植出生体质量和剖宫产率高于鲜胚移植。     

植入前遗传学诊断研究进展

近年来 ,随着辅助生殖技术如体外受精 胚胎移植技术 ,显微操作技术如卵胞浆内单精子注射技术的发展 ,因其携带遗传性缺陷的风险和生殖细胞畸变的比率明显高于正常人群 ,故在此基础上发展了植入前遗传学诊断技术。目前 ,此项技术已在国内外各生殖中心迅速开展 ,现对其研究进展作一综述。     

In-vitro-Fertilisation und intrazytoplasmatische Spermieninjektion

Since the delivery of the first baby conceived via in vitro fertilization (IVF) in 1978, IVF has become a standard procedure in sterility treatment. In Germany, 78,000 IVF/intracytoplasmic sperm injection (ICSI) cycles are performed annually with a delivery rate per embryo transfer of about 20?%. The cumulative delivery rate after three trials is more than 50?%. The main medical problems are the high rates of multiple pregnancies of more than 20?%, which carry an increased risk for mothers (preeclampsia) and children (preterm delivery, lung immaturity, brain problems). Also singleton babies after IVF are more often too small (small for gestational age, SGA) and delivered preterm. As a result, proper counselling is necessary. New laboratory methods have increased the success rate. Cryopreservation techniques such as vitrification are standard for freezing oocytes, pronuclear-stage oocytes and embryos if they are not needed during the current treatment cycle. Continuous observation of embryos by time-lapse imaging helps to identify the best embryos for transfer. The current legislation in the German embryo protection act (Embryonenschutzgesetz) is the main problem. It is unclear how many fertilized oocytes can be cultured to achieve a transfer of one to three embryos. The prohibition of oocyte donation and surrogacy are not comprehensible from a medical, psychological, and ethical point of view. Reimbursement of publicly insured patients is restricted in comparison with other European countries. Married couples receive half of the payment for three IVF/ICSI cycles; non-married couples receive no payment at all.     

Comparison between paraffin and mineral oil covering on early human embryo culture: a prospective randomized study

The oil overlay in microdrop culture systems prevents medium evaporation, helps to maintain appropriate pH and osmotic conditions and protects from microbial contamination. In the present study, we prospectively compared covering by Ovoil?, a paraffin oil, and LiteOil®, a mineral oil, on the in vitro development of human embryos and their suitability for transfer/freezing at day 3 and live birth rate. One hundred and one patients undergoing in vitro fertilization (IVF) treatment by intracytoplasmic sperm injection (ICSI) were enrolled in our study. After ICSI, 1237 oocytes were 1:1 randomly allocated into 2 groups according to the type of overlaying oil: Ovoil? (616 oocytes) or LiteOil® (621 oocytes). Fertilization rate was assessed around 18 hours post-insemination (hpi) and embryos were checked for early cleavage at 25 hpi. Embryo morphology was recorded on days 2 and 3. A total of 437 (Ovoil?) and 438 day 3 embryos (LiteOil®) were analyzed. There were no differences between the two groups in terms of fertilization rate and occurrence of early cleavage. The proportion of top quality embryos (41.7% vs. 41.2%) and the final utilization rates (92.2% vs. 92.0%) were similar in Ovoil and LiteOil groups, respectively, at day 3. Live birth rate per transfer was essentially the same with Ovoil? overlay (26.9%) when compared to LiteOil® (26.2%). Live birth rate in patients who simultaneously received embryos from both overlay types was 17.2%. Despite the different characteristics of these two oils regarding hydrocarbon saturation, packing and temperature storage, Ovoil? and LiteOil® can be used in parallel in the same IVF protocol.

Abbreviations: ART: assisted reproductive technologies; hpi: hours post-insemination; hSA: human serum albumin; HTF: human tubal fluid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MII: metaphase II; MEA: mouse embryo assay; RT: room temperature.     

Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews

Several systematic reviews have been published recently on birth outcomes of infants conceived through assisted reproductive technologies (ART), compared with infants conceived spontaneously. These outcomes include perinatal mortality, preterm birth, low birthweight and birth defects. Methodological limitations of many of the individual studies (including small sample size, potential for bias in ascertainment of outcomes and considering singletons and multiples together) were obviated in these reviews by excluding studies where methods were considered inadequate, by conducting meta-analyses using data from all methodologically sound studies (small and large) and by examining singletons separately. Overall, the reviews indicate few differences between outcomes in ART twins compared with twins conceived spontaneously. However, in singleton ART infants, there are around two-fold increases in risk of perinatal mortality, low birthweight and preterm birth, about a 50% increase in small for gestational age and a 30-35% increase in birth defects, compared with singletons conceived spontaneously. Couples considering ART should be counselled about the increased risk of adverse outcomes. Epidemiologists, in conjunction with clinical and laboratory colleagues, should now focus on large, methodologically sound studies with long-term follow up that seek to identify the reasons for these increased risks and their long-term consequences, whether they are associated with particular technologies and causes of infertility, and how they might be reduced.     

Children after in vitro fertilization. An overview of the literature.

This paper provides an overview of the effects of in vitro fertilization (IVF) on the children born from it. One of the main problems with IVF to date remains the high incidence of multiple pregnancies, which carry an inherent higher risk of preterm delivery and, therefore, of increased morbidity and mortality in newborns. Further, singleton pregnancies and twin pregnancies from IVF compared to control singleton or twin pregnancies appear to be at higher risk of preterm birth and low birth weight. Whether this is an effect of the procedure per se or is related to maternal factors, or a combination of both, remains to be studied. The risk of congenital malformations does not, with the available data, seem to be elevated. As of now, it remains unclear whether embryo freezing is a safe procedure. Psychomotor development of children born through IVF does not seem to be disturbed. Until further and more extensive studies are conducted, it remains unclear whether IVF poses long-term risks for the children.     

Contribution of assisted reproductive technology and ovulation-inducing drugs to triplet and higher-order multiple births--United States, 1980-1997

In the United States, pregnancies associated with assisted reproductive technology (ART) or ovulation-inducing drugs are more likely to result in multiple births than spontaneously conceived pregnancies (1). In addition, triplet and higher-order multiple births are at greater risk than singleton births to be preterm (< or = 37 completed weeks' gestation), low birthweight (LBW) (i.e., < or = 2500 g), or very low birthweight (i.e., < 1500 g), resulting in higher infant morbidity and mortality (2). Because preterm and LBW infants often require costly neonatal care and long-term developmental follow-up, the continuing increase in triplet and higher-order multiple births causes concern among health-care providers and policymakers (3). This report provides estimates of the contribution of ART and ovulation-inducing drugs to these birth outcomes for 1996 and 1997, and summarizes trends during 1980-1997, which indicate that the ratio of triplet and higher-order multiple births has more than quadrupled and that a large proportion of this increase can be attributed to ART or the use of ovulation-inducing drugs.     

辅助生殖技术助孕后子代出生缺陷风险:基于队列研究的Meta分析

目的评估辅助生殖技术(assisted reproductive technology,ART)助孕对子代出生缺陷的影响。方法检索从建库到2018年8月在PubMed、Embase、Cochrane图书馆、Sinomed、CNKI、万方、维普数据库中满足预先纳入标准的队列研究,使用I2统计和Q-检验评估研究之间的统计异质性,使用固定效应模型或随机效应模型估计总体组合的风险。结果本次最终纳入60项研究进行Meta分析,评估ART助孕后的子代730756名和自然受孕(spontaneously conceived,SC)的子代26185008名的出生缺陷风险。与SC子代相比,ART助孕后的子代出生缺陷风险高[RR=1.42,95%CI(1.30-1.56)]。排除异质性大的1项研究后,余下59项研究在限定部分条件后,其出生缺陷风险的变化如下,泌尿生殖器畸形[RR=1.49,95%CI(1.40-1.59)],单胎畸形[RR=1.43,95%CI(1.30-1.58)],亚洲地区[RR=1.52,95%CI(1.28-1.80)],基于临床的研究[RR=1.36,95%CI(1.21-1.60)],小样本量的研究[<500,RR=1.52,95%CI(1.35-1.72)],分层分析后,ART助孕后的子代出生缺陷风险高于SC子代。结论ART助孕子代出生缺陷风险高于SC组,因此在ART助孕后必须进行严格产前筛查,以避免严重畸形儿的出生。     

辅助生殖技术中基因印迹分析

人类辅助生殖临床数据已经显示,辅助生殖技术（ART）与自发流产、早产和围生期死亡、低体质量儿以及一些印迹疾病有关。在配子及胚胎早期发育过程中,基因印迹需经历印迹擦除、重建和维持过程,其中任何一个环节出错都可能导致胚胎发育缺陷,甚至死亡。ART恰施于这一表观遗传重编程的关键时期。因此,这些异常结局可能与ART导致的印迹基因的异常表达有关。而ART中主要的治疗手段有促排卵、体外受精、胞浆内单精子注射（ICSI）和体外培养。这些操作通过干扰基因印迹的重建和维持,影响基因表达和表型,进而影响配子和早期胚胎的发育,从而影响子代的生长发育潜能。     

不同体外受精方式对胚胎玻璃化冷冻复苏的影响

目的:观察常规体外受精和卵胞浆内单精子注射两种不同体外受精方式对胚胎玻璃化冷冻复苏的影响。方法:将移植冷冻复苏胚胎的患者(均为玻璃化法)分为两组。IVF组:新鲜周期采取常规体外受精方式而获得的胚胎;ICSI组:新鲜周期采取卵胞浆内单精子注射方式受精而得到的胚胎;比较两组的不孕类型、不孕原因以及冷冻复苏周期的复苏率、着床率、临床妊娠率和流产率等。结果:IVF组和ICSI组的复苏率、着床率、临床妊娠率差异无统计学意义(P>0.05),ICSI组的流产率明显高于IVF组但差异无统计学意义(P>0.05),IVF组和ICSI组原发不孕所占比例、继发不孕所占比例差异有统计学意义(P<0.05),IVF组和ICSI组男方因素不孕所占比例、输卵管因素不孕所占比例差异有统计学意义(P<0.05)。结论:ICSI不影响胚胎玻璃化冷冻周期的复苏率、着床率及临床妊娠率,ICSI后胚胎玻璃化冷冻复苏流产率有升高的趋势,ICSI体外受精方式主要用于原发不孕患者以及男方因素导致的不孕患者。     

正常人群与不孕人群妊娠并发症及围生结局的比较

目的:探讨不孕夫妇的不孕背景对妊娠并发症及围生结局的影响。方法:对2014年6月—12月在南京医科大学附属苏州医院(本院)入院待产的1 000名产妇进行自制问卷调查。其中备孕时间超过1年、单胎且未行辅助生殖技术(ART)者136名作为不孕症史组;备孕时间未超过1年、单胎、且与不孕症史组的年龄、产次、分娩方式严格按照1∶2匹配的272名产妇为正常对照组;在本院生殖中心行体外受精/胞浆内单精子注射(IVF/ICSI)治疗同期本院分娩的114名产妇为ART组。比较各组的妊娠并发症及围生结局。结果:不孕症史组低出生体质量儿发生率高于正常对照组,差异有统计学意义(11.03%vs.5.15%,P0.05);ART组与不孕症史组、正常对照组比较围生结局差异均无统计学意义(P0.05)。3组妊娠并发症发生率比较差异均无统计学意义(P0.05)。结论:不孕夫妇的不孕背景可能影响了新生儿低出生体质量的发生率。     

Preconception Care and Treatment with Assisted Reproductive Technologies

Couples with fertility problems seeking treatment with assisted reproductive technologies (ART) such as in vitro fertilization should receive preconception counseling on all factors that are provided when counseling patients without fertility problems. Additional counseling should address success rates and possible risks from ART therapies. Success rates from ART are improving, with the highest live birth rates averaging about 40% per cycle among women less than 35 years old. A woman’s age lowers the chance of achieving a live birth, as do smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine leiomyoma, or male factor infertility. Singletons conceived with ART may have lower birth weights. Animal studies suggest that genetic imprinting disorders may be induced by certain embryo culture conditions. The major risk from ovarian stimulation is multiple gestation. About one-third of live-birth deliveries from ART have more than one infant, and twins represent 85% of these multiple-birth children. There are more complications in multiple gestation pregnancies, infants are more likely to be born preterm and with other health problems, and families caring for multiples experience more stress. Transferring fewer embryos per cycle reduces the multiple birth rate from ART, but the patient may have to pay for additional cycles of ART because of a lower likelihood of pregnancy.

     

State-Specific Trends in Preterm Delivery: Are Rates Really Declining Among Non-Hispanic African Americans Across the United States?

Objectives: This study sought to examine state-specific trends in preterm delivery rates among non-Hispanic African Americans and to assess whether these rates are influenced by misclassification of gestational age. Methods: The sample population consisted of singleton non-Hispanic White and non-Hispanic African–American infants born in 1991 and 2001 to U.S. resident mothers. For both time periods, state-specific and national preterm delivery rates were calculated for all infants, stratified by infant race/ethnicity. Next, birth-weight distributions within strata of gestational age were studied to explore possible misclassifications of gestational age. Lastly, state-specific and national preterm delivery rates among infants who weighed less than 2,500 g were separately computed. Results: National analyses showed that the frequency of preterm delivery increased by 15.8% among non-Hispanic Whites but declined by 10.3% among non-Hispanic African Americans over the same period. For both subgroups, a bimodal distribution of birth weights was apparent among preterm births at 28–31 weeks of gestation. The second peak with its cluster of normal-weight infants was more prominent among non-Hispanic African Americans in 1991 than in 2001. After excluding preterm infants who weighed 2,500 g or more, the national trends persisted. State-specific analyses showed that preterm delivery rates increased for both subgroups in 13 states during this period. Of these 13, 6 states had a number of non-Hispanic African–American births classified as preterm that were apparently term births mistakenly assigned short gestational ages. Such misclassification was more frequent in 1991 than in 2001 and inflated 1991 rates. Conclusion: There is heterogeneity in state-specific preterm delivery rates. Such differences are often overlooked when aggregate results are presented.