米非司酮黄体期用药对垂体－肾上腺轴的影响

征集健康育龄妇女９例于连续若干周期的黄体晚期单次口服米非司酮，剂量分别依次为２５ｍｇ、１００ｍｇ、４００ｍｇ和６００ｍｇ，并于服药前以及服药后４、８、１２、２４、４８、７２、９６和１２０ｈ采血，以测定血清ＡＣＴＨ和皮质醇。另征集健康育龄妇女１５例，随机分成三组（组Ⅰ～Ⅲ），分别在黄体早、中、晚期给于米非司酮２５ｍｇｑ１２ｈ×６，在ｄ１～ｄ７期间每天采血以测定血清ＡＣＴＨ、皮质醇和米非司酮水平。结果显示米非司酮２５ｍｇ和１００ｍｇ单次口服对ＡＣＴＨ、皮质醇水平及其昼夜分泌节律并无明显影响，可是一次口服高剂量（４００ｍｇ和６００ｍｇ）后，ＡＣＴＨ和皮质醇上午分泌水平增加，昼夜变化幅度明显减少。米非司酮多次用药（２５ｍｑｑ１２ｈ×６）期间，每天上午ＡＣＴＨ和皮质醇几乎无明显变化，黄体期早、中、晚期服药的对象，其血药浓度、ＡＣＴＨ与皮质醇水平均无明显差异。本研究提示对于非妊娠妇女，米非司酮以剂量－依赖的方式显示其抗糖皮质激素活性，只有一次口服大剂量米非司酮才会明显影响其ＡＣＴＨ与皮质醇的昼夜分泌节律。黄体期不同的生殖激素状态对口服米非司酮后的药物吸收及其抗糖皮质激素活性无明显影响。     

米非司酮对早孕妇女内分泌的影响

共征集２４名停经≤４９ｄ、要求中止妊娠的健康妇女，分４组，各组依次口服米非司酮５０ｍｇ（组Ⅰ）、５０ｍｇＱ１２ｈ×６（组Ⅱ）、２００ｍｇ（组Ⅲ）和６００ｍｇ（组Ⅳ），首次服药后７２ｈ行人流术（组Ⅰ）或阴道内放置卡前列甲酯栓（ＰＧ０５）１ｍｇ（组Ⅱ～Ⅳ）。结果显示各组之间临床效果及临床经过差异均无统计学意义（Ｐ＞０．０５）。血清β－ｈＣＧ、Ｅ２Ｐ变化趋势亦基本一致。β－ｈＣＧ在用药前２４ｈ内上升５０％～１００％（Ｐ＜０．０１），服药后至孕囊排出前仍呈上升趋势，口服首剂米非司酮后，各组Ｅ２水平亦持续高于服药前，而Ｐ水平则缓慢下降。妊娠中止后，上述三种激素急剧下降。服药期间，各组ＰＲＬ和皮质醇明显上升，孕囊排出后前者下降缓慢，而后者下降迅速，ＡＣＴＨ、Ｔ３、Ｔ４和ＴＳＨ变化均无统计学意义。本研究结果表明来非司酮（５０ｍｇＱ１２ｈ×６，２００ｍｇ和６００ｍｇ）抗早孕时无明显量效关系；其主要作用部位似不在卵巢和绒毛；但对垂体一肾上腺轴有一定影响，尤其是大剂量时；对垂体一甲状腺轴影响不明显；ＰＲＬ水平变化似为药物直接作用所致，其临床意义尚待进一步研究。     

米非司酮用于紧急事后避孕的临床观察

征集３１５例健康妇女，将其分成Ａ、Ｂ两组，Ａ组房事后７２ｈ内单次口服米非司酮１５０ｍｇ；Ｂ组：２５ｍｇ。结果Ａ、Ｂ两组实际妊娠率分别为２．４８％、１．８２％，两组间无显著差异，与预期妊娠率（１２．１９％、１１．７１％）相比有显著差异。服药后第一次月经，在卵泡期服药者月经周期延长，Ａ组，３３．９％，Ｂ组；２６．９％。黄体期服药者月经周期准时或提早，Ａ组：７１．２％，Ｂ组：７７．１％，两组之间无差别。Ａ、Ｂ两组月经量正常者分别为８１％、９３％，经期均无改变，显示了米非司酮作为事后避孕药对月经无明显影响。可选择小剂量２５ｍｇ作为事后避孕药。     

不同剂量米非司酮和米索前列醇终止早孕的临床研究

将６００例停经＜４９天要求终止妊娠的早孕妇女随机分为三组。组１：３０１例，应用米非司酮，总剂量１５０ｍｇ，首次剂量５０ｍｇ，以后每１２小时口服２５ｍｇ，共口服４次，于开始服药第三天口服米索前列醇６００μｇ；组２：１５０例，应用米非司酮，剂量服法同组１，于第三天阴道放置卡孕栓１ｍｇ；组３：１４９例，单次口服米非司酮２００ｍｇ，用药第三天口服米索前列醇６００μｇ。观察各组完全流产率与副反应。三组完全流产率分别为９５．３％，９７．３％与９５．４％；不全流产率为３．０％，２．０％与２．６％，三组比较，差异无显著性。副反应情况，约８０％的妇女有下腹痛，但组２腹泻与呕吐的发生率及严重程度比组１、３明显为高（Ｐ＜０．００１）。提示：米索前列醇配伍两种剂量米非司酮终止早孕的完全流产率与卡孕栓相同。米索前列醇具有可以口服、不需低温保存、副反应轻等优点。     

黄体期应用米非司酮对卵巢功能的影响

本研究旨在比较黄体期不同阶段应用米非司酮对黄体功能、卵泡发育、排卵和阴道出血类型的影响以探讨其生育调节的作用机理。１５名采取屏障避孕的健康育龄妇女，随机分成三组（组Ⅰ～Ⅲ），分别在黄体早、中、晚期给予米非司酮口服２５ｍｇｑ１２ｈ×６。每例对象在对照周期、服药周期和随访周期均接受采血，测定其血清ＦＳＨ、ＬＨ、ＰＲＬ、Ｅ２和Ｐ的水平，记录其阴道出血量及时间。结果显示服药后阴道出血类型和激素水平的变化因服药时机而异。服药时间距ＬＨ峰愈近，则诱发阴道出血所需时间愈长，两者是显著负相关（ｒ＝－０．８７，Ｐ＜０．００１）。黄体早期用药（组Ⅰ）对黄体功能及出血类型无明显影响。黄体中期用药（组Ⅱ）者中，３例孕酮水平提前下降，服药周期缩短，提示黄体过早溶解；另２例在月经预期来潮之前亦有一次阴道出血，但其孕酮水平并未随之下降，提示黄体未提前萎缩。黄体晚期用药（组Ⅲ）对服药周期无明显影响；但是在随访周期，２例对象卵泡发育缓慢，排卵明显延迟，并且其黄体期也缩短。     

米非司酮单独或合并双炔失碳酯用于紧急避孕的临床比较研究

探讨低剂量米非司酮单独或合并双炔失碳酯应用于紧急避孕的临床效果。将避孕失败或无保护性生活后９６ｈ内就诊的２６０例健康妇女随机分为４组,组Ⅰ（６５例）：单次口服米非司酮２５ｍｇ;组Ⅱ（６５例）：单次同时口服米非同酮２５ｍｇ,双炔失碳酯７．５ｍｇ;组Ⅲ（６５例）：单次同时口服米非司酮１０ｍｇ,双炔失碳酯５ｍｇ;组Ⅳ（６５例）：单次口服米非司酮１０ｍｇ。结果显示各组均有一例妊娠,失败率均为１．５４％,避孕有效率４组依次为７６．１５％、７９．３６％、８１．９４％、８１．９５％,各组间差异无显著性（Ｐ＞０．０５）。服药后月经周期改变少,且与服药时间有关,副反应发生比例低。表明单次服用低剂量米非司酮２５ｍｇ或１０ｍｇ都可作为有效紧急避孕方法,米非司酮与双炔失碳酯合用未显示出协同作用。     

不同剂量米非司酮及合并双炔失碳酯用于紧急避孕的多中心随机临床研究

目的了解在无保护性交后９６小时内应用不同剂量米非司酮及与双炔失碳配伍用于紧急避孕的效果及其副反应。方法将无保护性交后９６小时内的２４００例健康育龄妇女随机分为４组（每组６００例）,分别予单次口服２５ｍｇ米非司酮、２５ｍｇ米非司酮加７．５ｍｇ双炔失碳酯、１０ｍｇ米非司酮加５ｍｇ双炔失碳酯及１０ｍｇ米非司酮。按Ｄｉｘｏｎ法推算避孕有效率。结果除２例接纳错误和１１例失访外,２３８７例妇女的总预期妊娠数为１７１．９例,实际妊娠３２例。４组的避孕有效率分别为８０．９％、８５．３％、９０．６％和６７．３％。１０ｍｇ米非司酮配伍５ｍｇ双炔失碳酯的避孕失败率０．７％,显著低于单次口服１０ｍｇ米非司酮者（２．２％）（Ｐ＜０．０５）。４组的诱导性出血发生率分别为９．２％、４．９％、３．４％和６．７％,配伍双炔失碳酯后诱导性出血发生率明显低于单次口服米非司酮者（Ｐ＜０．０１）。结论２５ｍｇ米非司酮或者１０ｍｇ米非司酮合并５ｍｇ双炔失碳酯为安全有效的紧急避孕方案,无严重副反应及对月经周期的明显干扰     

米非司酮合并米索前列醇房事后避孕临床多中心研究

在黄体早、中、晚期应用米非司酮合并米索前列醇与单用米非司酮进行房事后避孕临床多中心比较性研究。５４１名自愿接随机序号参加本研究的健康、月经规律妇女，组Ⅰ口服米非司酮２５ｍｇ，ｑ１２ｈ共４次，第三天上午加服米索前列醇０．４ｍｇ，妊娠率为０．４％。组Ⅱ单服米非司酮２５ｍｇ，ｑ１２ｈ，共４～６次，妊娠率为３％。二者差异有显著性（Ｐ＜０．０５）。两者引起出血类型和时间均与正常月经相似，且无明显副反应发生，错过了服用传统房事后避孕药时，采用本研究的方法可不考虑性生活时间、次数。这种方法提供了一种新型有效避孕方法。     

米非司酮用于子宫肌瘤患者治疗及避孕的研究

目的：探讨子宫肌瘤患者应用米非司酮治疗和避孕的效果。方法：将１１４例随机分为两组。第１组（６８例）,子宫＜妊娠７周大。在月经第８至１５天给予米非司酮２５ｍｇ／ｄ,第１６至２３天,每天给予甲地孕酮１ｍｇ合并乙炔雌二醇０．０２５ｍｇ。３个月经周期为一疗程,停药２个周期后继续用药。第２组（４６例）,子宫相当妊娠７～１２周大,每天服用米非司酮１０ｍｇ,１２周为一疗程,在２次转经后继续服用。用阴道超声了解治疗前和２个疗程后肌瘤的变化,服药期间不用其它方法避孕。结果：服药组无意外妊娠发生。２个疗程后,两组肌瘤平均体积均较前显著缩小（Ｐ＜０．０１）。血清ＰＲＬ、ＡＣＴＨ、皮质醇和肝肾功能均正常。结论：长期间断序贯应用米非司酮和甲地孕酮加乙炔雌二醇和米非司酮１０ｍｇ连续应用１２ｗ的方案,可成为子宫肌瘤患者及避孕和治疗的方法,且无明显副作用。     

不同剂量米非司酮及合并双炔失碳酯用于紧急避孕的多中心随 …

目的 了解在无保护性交后９６小时内应用不同剂量米非司酮及与双炔失碳配伍用于紧急避孕的效果及其副反应。方法 交无保护性交后９６小时内的２４００例健康育龄妇女随机分为４组,分别予单次口服２５ｍｇ米非司酮、２５ｍｇ米非司酮加７．５ｍｇ双炔失碳碳酯、１０ｍｇ米非司酮加５ｍｇ双炔失碳酯及１０ｍｇ米非司酮。按Ｄｉｘｏｎ法推算避孕有效率。结果 除２例接纳错误和１１例失访外,２３８７例妇女的总预期妊娠数为１７１．     

Differences in female and male perception of information and decision-making in single-embryo transfer in in vitro fertilization in Sweden

Purpose The aim of this study was to evaluate the information and the factors that contribute to the decision to accept and choose single embryo transfer (SET) in females and males. Materials and methods Fifty-four females and males undergoing SET were interviewed separately using a structured questionnaire. Results The women were significantly more satisfied with the information than the men (odds ratio 3.3), but the decision to accept SET was nevertheless more difficult for women (OR 3.1). Only one-third of both female and males were aware of the increased maternal risks with twin pregnancies. There was a tendency that the women who accepted SET had previous children, shorter duration of infertility, and were younger. Cryopreservation of embryos and a good pregnancy chance were important irrespective of gender. Conclusion The female needs more support to choose SET. The male needs better information and further involvement in decision-making. The females were more aware of the fetal risks, but the awareness of the increased maternal risks with twin pregnancies was low. The female need more support to accept and choose single embryo transfer, compared to the male and information should in some areas be directed differently to females and males.     

Non-persistent pesticides in breast milk in an agricultural area in Turkey

Background: Organophosphates, pythyreoids, carbamate pesticides and fungicides are heavily used in agriculture. They may have dangerous effects on newborn health especially on immune system and growth via prenatal transmission by placenta or postnatal transmission by breastfeeding.

Methods: In 2015, 144 non-persistent pesticides in 64 milk samples of 32 mothers were studied by OuEChERS method in liquid chromatography/tandem mass spectrometer in neonatal Intensive Care Unit in Adana, a city in Cukurova region which is an important agricultural area in Turkey.

Results: Pesticides were detected in milk samples of 11 mothers (34.3%) and 21 (32.8%) of milk samples. In five mothers, fungicides (in 5/10 samples propicanozole-PP, in 4/10 samples bromucanozole-BM), in five mothers, organophosphates (in 10/10 samples primyphosphomethyl-PPM), in one mother, both organophosphates and fungicide (in 1/2 samples PPM and in 1/2 samples buprimate) were detected. However, the estimated daily intakes (EDI) were less than acceptable daily intakes (ADI) for PPM, PP and BM, respectively.

Conclusions: Although pesticides levels in human milk did not exceed the ADIs, we suggest monitoring pesticides in human breast milk especially for newborn health.     

Ovulation induction in in vitro fertilization

The main goal of an in vitro fertilization (IVF) program is to maximize the number of women who become pregnant in any treatment cycle. In order to achieve pregnancy, many steps should be successfully accomplished. The number of mature oocytes that are retrieved and fertilized in a treatment cycle has the major impact on the success rate of the IVF program. The chances of achieving conception increases dramatically when the number of embryos replaced into the uterus increases^1-3. Hence, most IVF treatment programs currently use some combination of ovulation induction agents in order to stimulate and aspirate as many follicles as possible.     

Heterogeneity in alpha-thalassemia interactions in Malays, Chinese and Indians in Malaysia

AIM: Interactions between different determinants of alpha-thalassemia raises considerable problems, particularly during pregnancies where antenatal diagnosis is necessary. This study aims to determine the different types of deletional alpha-thalassemia and Hemoglobin Constant Spring (HbCS), and their frequency in Malays, Chinese and Indians in Malaysia. METHODS: DNA from 650 pregnant women from the Antenatal Clinic of the University of Malaya Medical Center in Kuala Lumpur, Malaysia who showed mean cell volume < or =89 fL and/or mean cell hemoglobin < or =28 pg were analyzed for the double alpha-globin gene South-East Asian deletion (--SEA), the -alpha3.7 and -alpha4.2 single alpha-globin gene deletions and HbCS. RESULTS: One hundred and three (15.8%) of the pregnant women were confirmed as alpha-thalassemia carriers: 25 (3.8%) were alpha-thalassemia-1 carriers with the --SEA/alphaalpha genotype, 64 (9.8%) were heterozygous for the -alpha3.7 rightward deletion (-alpha3.7/alphaalpha), four (0.6%) were heterozygous for the -alpha4.2 leftward deletion (-alpha4.2/alphaalpha), nine (1.4%) were heterozygous for HbCS (alphaCSalpha/alphaalpha) and one (0.2%) was compound heterozygous with the -alpha3.7/alphaCSalpha genotype. The double alpha-globin gene --SEA deletion was significantly higher in the Chinese (15%) compared to the Malays (2.5%) and not detected in the Indians studied. The -alpha3.7 deletion was distributed equally in the three races. HbCS and -alpha4.2 was observed only in the Malays. CONCLUSION: The data obtained gives a better understanding of the interactions of the different alpha-thalassemia determinants in the different ethnic groups, thus enabling more rapid and specific confirmation of alpha-thalassemia in affected pregnancies where antenatal diagnosis is necessary.     

缺氧缺血性脑病的性别差异性研究进展

新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)是指围产期窒息缺氧导致的脑缺氧缺血性损害,可遗留不同程度的神经系统后遗症。动物研究表明,缺氧缺血性损伤后,炎性反应、氧化应激和细胞死亡途径等关键病理生理过程中存在明显的性别差异,雌性动物对亚低温、促红细胞生成素、脑源性营养因子和别嘌呤醇等治疗效果也明显优于雄性。临床研究发现男性HIE患儿病情更重、预后更差。基于性别的治疗干预很有可能在围产期脑损伤中提供更好的神经保护。本文总结了目前HIE性别差异性的相关证据,以期为临床治疗提供新思路。     

Trends in preterm birth in singleton deliveries in a Hong Kong population

Objective

To examine trends in preterm birth and its relationship with perinatal mortality in Hong Kong.

Methods

In a retrospective cohort study, data were reviewed from singletons delivered between 1995 and 2011 at a university teaching hospital. Trends in preterm birth (between 24 and 36 weeks of pregnancy), perinatal mortality, and subtypes of preterm birth (spontaneous, iatrogenic, and following preterm premature rupture of membranes [PPROM]) were examined via linear regression.

Results

There were 103 364 singleton deliveries, of which 6722 (6.5%) occurred preterm, including 1835 (1.8%) early preterm births (24–33 weeks) and 4887 (4.7%) late preterm births (34–36 weeks). Frequency of preterm birth remained fairly consistent over the study period, but that of spontaneous preterm birth decreased by 25% (β = –0.83; P < 0.001), from 4.5% to 3.8%. Frequency of preterm birth following PPROM increased by 135% (β = 0.82; P < 0.001), from 0.7% to 1.7%. The perinatal mortality rate decreased from 56.7 to 37.0 deaths per 1000 deliveries before 37 weeks (β = –0.16; P = 0.54). Early preterm birth contributed to 16.0% of all deaths.

Conclusion

Although the overall rate of preterm birth in Hong Kong has remained constant, the frequencies of its subtypes have changed. Overall perinatal mortality is gradually decreasing, but early preterm birth remains a major contributor.