Outcomes from treatment of infertility with natural procreative technology in an irish general practice

Objectives: We evaluated outcomes in couples treated for infertility with natural procreative technology (NatProTechnology, NPT), a systematic medical approach for optimizing physiologic conditions for conception in vivo, from an Irish general practice. Methods: All couples receiving treatment from 2 NPT-trained family physicians between February 1998 and January 2002 were studied. The main outcome was live birth, and secondary outcomes included conceptions and multiple births. Crude proportions and adjusted life-table proportions were calculated per 100 couples. Results: A total of 1239 couples had an initial consult for NPT, of which 1072 had been trying for at least a year to conceive and initiated treatment. The average female age was 35.8 years, the mean duration of attempting to conceive was 5.6 years, 24% had a prior birth, and 33% had previously attempted treatment with assisted reproductive technology (ART). All couples were taught to identify the fertile days of the menstrual cycle with the Creighton Model FertilityCare System, and most received additional medical treatment, including clomiphene (75%). In life-table analysis, the cumulative proportion of first live births for those completing up to 24 months of NPT treatment was 52.8 per 100 couples. The crude proportion was 25.5. Younger couples and couples without previous ART attempts had higher rates of live birth. Among live births, there were 4.6% twin births. Conclusion: NPT provided by trained general practitioners had live birth rates comparable to cohort studies of more invasive treatments, including ART. Further studies are warranted to compare NPT directly to other treatments.     

Singleton Preterm Birth: Risk Factors and Association with Assisted Reproductive Technology

The objectives of this study were to determine risk factors for early (less than 34 weeks gestation) and late (34–36 weeks gestation) preterm singleton birth, by assisted reproductive technology (ART) status. We linked data from Massachusetts birth records and ART records representing singleton live births from 1997 through 2004. Using multinomial regression models, we assessed risk factors for early and late preterm birth by ART status. From 1997 to 2004 in Massachusetts, among non-ART births, risk factors for early and late preterm birth were similar and included women <15 and ≥35 years of age, those of non-white race or Hispanic ethnicity, those with ≤12 years of education, those with chronic diabetes, those with gestational diabetes, those with gestational hypertension, those who smoked during pregnancy, those who used fertility medications, and those who had not had a previous live birth. Among ART births, risk factors for early and late preterm birth differed and odds of early preterm birth were increased among women with ≤12 years of education while odds of late preterm birth were increased among women with gestational diabetes. Odds of both early and late preterm birth were increased among women of non-white race or Hispanic ethnicity and among women with gestational hypertension. Among non-ART births, increased risk for preterm birth was more strongly related to socioeconomic factors than among ART births. Medical conditions were associated with an increased risk for preterm birth regardless of women’s ART status. Efforts to prevent preterm births should focus on reducing modifiable risk factors.     

A primary care approach to the infertile couple

BACKGROUND: Approximately 20% of reproductive age couples have difficulty conceiving or maintaining an established pregnancy. The family physician is in a unique position to provide patient education, begin initial evaluation, make appropriate referrals, and offer ongoing counseling and support to couples who experience problems with fertility. METHODS: And extensive clinical review was conducted based on a MEDLINE search, the Cochrane database of systematic reviews, and other supporting evidence. RESULTS: Major physiologic influences affecting live birth rates include age, coital frequency, and duration of infertility. Male factor is associated with approximately 40% of these cases and should be addressed early in the evaluation. CONCLUSION: Many conditions once considered untreatable can now be routinely corrected. As managed care programs expand coverage to include infertility services, primary care providers will be asked to participate in the initial phase of this care. This article offers a practical approach.     

有生育要求的多囊卵巢综合征患者的治疗

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是无排卵性不孕常见的原因,有多种非药物性和药物性方法帮助有生育要求的PCOS患者排卵并怀孕。一线疗法包括改变生活方式和克罗米芬治疗。对于克罗米芬抵抗的PCOS患者可采用二线疗法:使用促性腺激素(Gonadotrophin,Gn)、腹腔镜下卵巢打孔术(laparoscopic ovarian drilling,LOD)或者胰岛素增敏剂。如果治疗无效或合并其他不孕因素,可采用三线疗法——辅助生殖技术(assisted reproductive technology,ART)。本文重点介绍每种疗法的特点和治疗进展,以便为PCOS患者制定更加个性化的治疗方案提供参考。     

供精人工授精临床结局影响因素分析

目的：探讨供精人工授精（AID）临床结局的影响因素。方法：回顾性分析2012年1月—2017年4月1 810对夫妇共4 067个AID周期的临床资料,分析女方年龄、女方不孕因素、治疗方案、授精时机及治疗周期数与临床结局的相关性。结果：①临床妊娠率、活产率随年龄增长均有下降趋势（均P＜0.05）。②女方合并排卵障碍、盆腔子宫内膜异位症术后及盆腔炎性疾病后遗症者AID临床结局与单纯男方因素者相比,差异均无统计学意义（均P＞0.05）。③自然周期、氯米芬、来曲唑及单纯促性腺激素（Gn）促排卵周期的临床妊娠率、宫内妊娠流产率和活产率差异均无统计学意义（均P＞0.05）;氯米芬和来曲唑促排卵周期的多胎妊娠率显著高于自然周期（均P＜0.001）。④无论自然周期还是促排卵周期,排卵前与排卵后授精的临床结局比较,差异均无统计学意义（均P＞0.05）。⑤前4个治疗周期随着治疗周期数的增加,累计妊娠率与累计活产率显著升高（均P＜0.05),第5个治疗周期开始累计妊娠率与累计活产率均无明显增长（均P＞0.05）。结论：女性年龄是影响AID临床结局的重要因素;未发现其他女性不孕因素及授精时机显著影响AID临床结局。实施3个或4个AID周期仍未孕者或女性年龄超过40岁建议行供精体外受精助孕。     

辅助生殖技术与出生缺陷

辅助生殖技术（ART）是否增加或引发出生缺陷目前尚无定论，但ART婴儿出生缺陷的原因可能是多因素的，与自然妊娠或许不同。目前研究主要关注于ART助孕过程如促排卵、胚胎培养液、培养时长等对子代的不利影响。ART与印迹疾病的风险近年来也受到很多关注。此外，引发不孕的疾病本身也可能导致出生缺陷。应当强调，大多数ART婴儿是健康的。未来应更好地探索ART出生缺陷的分子机制，改进现有ART治疗方法，降低出生缺陷的发生风险，提高出生人口的素质。     

1998年中国活产儿出生体重抽样的调查结果

目的 调查全国活产儿出生体重情况。方法 用分层抽样方法,对1998年7－10月期间在抽样地区出生的孕周≥28周的活产婴儿进行出生体重测查。结果 共测查活产儿22350人（男11584人,女10766人）,男女比例为1．08：1。多胎率和早产率分别是1．8％和3．5％。中国活产儿出生体重的分布特点表现为：城市（3031g）高于农村（3225g）,沿海、内地和边远地区活产儿出生体重（3262、3254、3115g）呈逐次下降趋势;农村一类县与城市接近,二、三和四类县的出生体重明显下降,四类县的出生体重较城市降低200g。结论 总体上,中国活产儿平均出生体重与发达国家水平相近,但不同经济水平地区间存在显著差别,尤其是经济和卫生保健状况相对落后的农村边远、贫困县是今后实施有效干预措施的重点地区。     

影响单囊胚移植临床妊娠及活婴出生的相关因素分析

欧洲人类生殖与胚胎协会在2002年对辅助生殖技术(assisted reproductive technology,ART)治疗效果提出了准确定义的衡量标准,即单个健康婴儿的出生。减少ART治疗中出现的严重并发症——多胎妊娠最有效的措施就是进行单囊胚移植(single blastocyst transfer,SBT)。从理论上讲,SBT可以杜绝双卵双胎的发生,但是无选择地对所有患者采取SBT策略,则可能会导致妊娠率和活产率降低,给患者带来更高的经济和时间成本以及精神压力。所以,对合适的患者进行选择性单囊胚移植(elective single blastocyst transfer,e SBT)有利于提高该部分患者的临床妊娠率及活婴出生率。分析影响SBT临床妊娠结局及活婴出生的相关因素,评估患者自身条件及预测SBT的成功概率,从而使患者更容易接受SBT,最终使其获得健康婴儿的出生。     

中国低出生体重儿抽样调查结果

目的　调查全国活产儿出生体重情况和低出生体重儿发生率。方法　采用分层抽样方法 ,对中国 11个省的 16个市、2 8个县 ,1998年 7～ 10月出生的孕周≥ 2 8周的全部活产婴儿进行出生体重测查。结果　共测查活产儿 2 2 35 0人 (男 115 84人、女 10 76 6人 )。多胎率和早产率分别为 1 8%和 3 5 %。城市、农村和全国加权低出生体重儿发生率分别为 4 2 0 %、6 2 6 %和 5 87%。低出生体重儿中 6 1 2 %为足月儿 (≥ 37周 ) ,在农村则占 71 6 %。城市和农村活产儿平均出生体重分别为 330 1g和 32 2 5g,城市显著高于农村。男婴和女婴活产儿平均出生体重分别为 32 80g、3173g ,接近WHO推荐的出生体重均值。沿海、内地、边远地区活产儿平均出生体重呈逐渐下降趋势。低出生体重儿早期新生儿死亡率在城市为 5 0 0‰ ,农村为 179 4‰ ,全国为 15 1 5‰ ,显著高于正常出生体重婴儿。结论中国活产儿平均出生体重和低出生体重的发生率与发达国家水平接近 ,但地区间差异有显著性。低出生体重的主要原因是宫内发育迟缓 ,低出生体重儿的早期新生儿死亡率显著高于正常体重儿 ,应采取干预措施。     

New Guinea sago gatherers

Records of fertility and infant mortality were collected from the twenty‐five women who had completed their reproductive cycle and who were part of a population living on the Wogamus River in the Upper Sepik region of New Guinea. The mean number of live births was 5.3. Infant and early childhood mortality was 43.2 per cent. Eleven per cent of infants are killed at birth, most of them females born too soon after an older sibling. Both infanticide and post‐partum taboos on sexual intercourse lasting at least two years are explicitly practiced to ensure the adequate nutrition of the older sibling. The pattern of family limitation is related to subsistence on wild food resources, including sago.     

辅助生殖技术予代的围生结局研究进展

辅助生殖技术（assisted reproductive technology,ART）作为不孕症治疗的有效方法正在被广泛应用。随着ART子代人数的增加,ART的安全性引起更多关注。多胎妊娠发生率的增加使ART子代伴有更多围生风险,但排除多胎妊娠后,ART单胎子代同自然妊娠子代比较仍具有稍高的早产率、低出生体质量率及先天畸形率等围生结局。其机制目前尚不明确,潜在的不孕背景、ART操作、促排卵可能是引起ART子代不良围生结局的原因。优生优育指导、必要的产前筛查及诊断有利于改善ART子代围生结局。综述ART子代围生结局研究进展,了解ART的安全性。     

辅助生殖技术子代的围生结局研究进展

辅助生殖技术（assisted reproductive technology,ART）作为不孕症治疗的有效方法正在被广泛应用。随着ART子代人数的增加,ART的安全性引起更多关注。多胎妊娠发生率的增加使ART子代伴有更多围生风险,但排除多胎妊娠后,ART单胎子代同自然妊娠子代比较仍具有稍高的早产率、低出生体质量率及先天畸形率等围生结局。其机制目前尚不明确,潜在的不孕背景、ART操作、促排卵可能是引起ART子代不良围生结局的原因。优生优育指导、必要的产前筛查及诊断有利于改善ART子代围生结局。综述ART子代围生结局研究进展,了解ART的安全性。     

41例染色体平衡易位携带者行体外受精/胞浆内单精子注射-胚胎移植后临床妊娠结局的研究

目的：探讨染色体平衡易位携带者行体外受精/胞浆内单精子注射-胚胎移植（IVF/ICSI-ET）治疗后的临床妊娠结局,为此类不孕症患者的辅助生殖治疗及遗传咨询提供指导。方法：回顾性研究41例携带染色体平衡易位的不孕症患者（观察组）及751例染色体正常不孕症患者（对照组）在行常规IVF/ICSI-ET治疗后的临床妊娠结局。结果：41例观察组患者中24例为常规IVF治疗周期,17例为ICSI治疗周期。41对不孕夫妇中28例为原发性不孕,11例有不良妊娠、生育史。2组患者女方年龄、获卵数、MⅡ卵数、移植胚胎数、临床妊娠率、晚期流产率、异位妊娠率、畸形胎儿率、死胎分娩率、活胎分娩率、每取卵周期活胎分娩率差异无统计学意义（均P＞0.05）;胚胎种植率对照组高于观察组、早期流产率观察组高于对照组,差异均有统计学意义（均P＜0.05）。41例观察组中有19对夫妇先后在27个移植周期中获得妊娠,并最终成功分娩了22个婴儿。结论：通过常规IVF/ICSI-ET治疗结合产前诊断技术,携带染色体平衡易位的不孕症患者可获得理想的临床妊娠结局,是一种相对有效、经济的治疗方法。     

Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.     

Rising multiple maternity rates and medical management of subfertility: better information is needed

Multiple maternity rates rose rapidly from the mid-1970s onwards in many Western countries. This has major public heath implications, as multiple pregnancies can lead to many problems for the mothers and their children. Ovarian stimulation and assisted reproductive technology (ART) play a major role in these trends but there are few data about them. Consistently defined multiple maternity rates, including twin and triplet maternity rates are needed annually for each country in order to monitor time trends and make international comparisons. In order to assess the contribution of ovarian stimulation and ART to trends in multiple maternities and to monitor their impact on pregnancy outcome, fuller and more consistent data are needed. These could be collected from ART centres and other care providers, or through medical birth registries or national surveys.     

体外培养与胚胎移植的策略选择

人类辅助生殖技术（ART）是目前解决不孕症最为有效的治疗方式之一。在ART治疗过程中,体外培养条件以及胚胎移植的策略是直接影响其临床活产率和单胎妊娠率的关键因素。体外培养条件主要包括温度、pH值、氧浓度、培养液的成分以及培养过程中不同阶段是否应该更换培养液等。胚胎移植的策略则包含胚胎移植数量的选择、卵裂期与囊胚期移植的选择以及优质囊胚指标的选择等。结合近期国外研究成果对体外培养条件以及胚胎移植的策略中仍然存在争议的一些问题进行了探讨和综述。     

Preterm singleton births--United States, 1989-1996

Preterm birth (birth at <37 completed weeks of gestation) is the second leading cause of neonatal mortality in the United States. Preterm birthrates differ by race; in 1996, black infants were 1.8 times more likely than white infants to be preterm. From 1989 through 1996, the overall rate of preterm birth (per 1000 live-born infants) increased 4%, and the rate of multiple births (e.g., twins, triplets, or other higher-order births) increased 19%. Multiple births are associated with preterm birth; trends in preterm births independent of the influence of multiple births have not been fully explored. To characterize race- and ethnicity-specific trends in preterm birth independent of multiple births, data from U.S. birth certificates for 1989-1996 were analyzed for singleton births only. This report summarizes the results of this analysis and indicates that although singleton preterm birthrates are stable overall, substantial changes in rates occurred in some racial/ethnic subgroups.     

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.