Autophagy Regulated by Chinese Medicine Monomers in Embryo Implantation： A Review / 中国实验方剂学杂志

Embryo implantation is one of the most critical steps in the reproductive process. The failure of embryo implantation to continue development is one of the important reasons leading to infertility. The success of embryo implantation depends on the high receptivity of endometrium and the embryo with implantation ability. Autophagy is a process in which cytoplasm， organelles， and inclusions are absorbed by double-membrane vesicles and transported to lysosomes for degradation and recycling， which is a way to maintain the homeostasis. A large amount of evidence have shown that autophagy plays an important role in all aspects of embryo implantation. Based on this， this paper explored the relationship between autophagy and endometrial receptivity and embryo implantation ability. According to the latest research progress， this paper combed 5 mechanisms （promotion of decidualization of endometrial stromal cells， promotion of apoptosis， regulation of hormone levels， coordination of inflammation， and promotion of ovulation） of 14 kinds of Chinese medicine monomers， including emodin， catalpol， paeoniflorin， resveratrol， folic acid， zearalenone， curcumin， wogonin， quercetin， chrysin， berberine， apigenin， phisetine， and kaempferol， in regulating different links of autophagy intervention in embryo implantation. This paper is expected to provide references and ideas for future Chinese medicine monomers to improve the success rate of embryo implantation.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

Deciduosis in a cesarean scar

ABSTRACT Deciduosis is the presence of ectopic decidual tissue outside the uterus, pelvic, or abdominal organs usually associated with pregnancy. Cutaneous deciduosis is a highly uncommon manifestation of deciduosis and most commonly is misdiagnosed as a primary malignancy or a metastatic deposit. Typically, it is detected incidentally during operative procedures. It has been rarely documented within a surgical scar; with the incidence of surgically proven deciduosis being approximately 1.6%, and is often difficult to diagnose due to its rarity. Here, we present a case of deciduosis of cesarean scar in a 34-year-old pregnant female.

Effects of the relationship between adenomyotic lesions and embryo implantation site on pregnancy outcomes in pregnant patients with adenomyosis / 中华妇产科杂志

Objective:To investigate the relationship between embryo implantation site and adenomyotic lesions in pregnant patients with adenomyosis and its effects on pregnancy outcomes.Methods:Between January 2018 and December 2020, the clinical data of 95 pregnant patients with adenomyosis who were hospitalized in the Women′s Hospital, School of Medicine, Zhejiang University, which could identify the implantation site of embryo or placenta (≥11 weeks of pregnancy) through the nuchal translucency test under ultrasonography were analyzed retrospectively. According to the relationship between embryo implantation site and adenomyotic lesions, 95 patients were divided into two groups:short-distance group ( n=59, the embryo or placenta implantation was very close to or over the adenomyotic lesion), and long-distance group ( n=36, the implantation site of embryo or placenta was far away from the lesion, or the implantation site and the adenomyotic lesion were on different sides of the uterus). Next, taking 28 weeks of pregnancy as cut-off value, 95 patients were divided into <28 weeks of pregnancy group (pregnancy was terminated because of adverse pregnancy outcome before 28 weeks) and ≥28 weeks of pregnancy group (pregnancy lasted to 28 weeks and later), the differences of pregnancy outcomes between the two groups in different gestation times were analyzed. Results:(1) The age of 95 pregnant patients with adenomyosis was (34.8±3.5) years. There were no significant differences with regard to age, uterine size before pregnancy, the proportions of primipara, assisted reproductive technology conception, endometriosis, history of estrogen and progesterone treatment, diffuse adenomyotic lesions between the short-distance group and the long-distance group (all P>0.05). (2) Among the 95 patients, 12 patients (13%, 12/95) had adverse pregnancy outcomes before 28 weeks of pregnancy (i.e. pregnancy <28 weeks), including 11 cases (19%, 11/59) in the short-distance group and 1 case (3%, 1/36) in the long-distance group, there was significant difference between the two groups ( χ2=5.100, P=0.027). Among the 11 patients with adverse pregnancy outcomes at <28 weeks of gestation in the short-distance group, 1 case had threatened rupture of uterus before delivery of twin pregnancy at 26 weeks of gestation, 5 cases had intra uterine fetal death in the second trimester of pregnancy, 4 cases had late inevitable abortion, and 1 case had live birth of singleton at 26 weeks of gestation. In the long-distance group, one patient with adverse pregnancy outcome less than 28 weeks of pregnancy was late inevitable abortion. (3) Of the 95 patients, 83 cases were pregnant for ≥28 weeks (48 cases in the short-distance group and 35 cases in the long-distance group), and their final pregnancy outcome was all live birth. Compared with the long-distance group, the incidence of placental abnormalities (60% vs 14%), fetal distress (27% vs 6%), preterm delivery (67% vs 23%) and intrapartum bleeding [median 350 ml (range: 100-1 500 ml) vs 300 ml (range: 100-800 ml)] in the short-distance group were significantly higher (all P<0.05). While the gestational weeks in the short-distance group [median 37 weeks (range: 30-41 weeks) vs 38 weeks (range: 28-41 weeks)] and neonatal birth weight [median 2 790 g (range: 1 170-4 040 g) vs 3 010 g (range: 980-4 320 g)] decreased significantly (all P<0.05), compared with those in the long-distance group. Conclusion:Patients with pregnancy complicated with adenomyosis are prone to adverse pregnancy outcomes if the embryo implantation is located on or very close to adenomyotic lesions, so close monitoring and early intervention should be carried out to improve pregnancy outcomes.

Effectiveness of noninvasive embryo chromosome screening in preimplantation genetic testing at different ages / 中国医师杂志

Objective:To study the effectiveness of noninvasive embryo chromosome screening (NICS) based on blastocyst culture medium and cystic fluid in preimplantation genetic detection (PGT) of embryos in different age groups.Methods:A retrospective analysis of 62 couples who underwent PGT assisted pregnancy in Shenzhen Hospital of Peking University from January 2019 to June 2021. A total of 310 blastocysts were biopsied. At the same time, D3-6 blastocyst culture medium and blastocyst cavity fluid were collected for NICS. According to the age of the patients, they were divided into three groups: <35 years old group, 35≤age<40 years old group and ≥40 years old group. The results of NICS were compared with those of embryonic trophoblast (TE) biopsy in each group, and the consistency, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Then the consistency, sensitivity, specificity, positive predictive value and negative predictive value of NICS and TE among the three age groups were statistically analyzed.Results:There was no statistically significant difference in the consistency rate of NICS and TE among the three age groups ( P>0.05), but there was an upward trend in the elderly group (35≤age<40 years and ≥40 years). There was no statistically significant difference in specificity, sensitivity and PPV among the three age groups ( P>0.05). There was significant difference in NPV between the ≥40 years group and the other two groups ( P<0.05). Conclusions:There was no statistical difference in the effectiveness of NICS among different age groups, However, there was an increasing trend in people ≥35 years of age.

Research Progress of Non-coding RNA and Endometrial Receptivity / 中国医学科学院学报

Endometrial receptivity has become the main cause of fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.

Conceptos básicos en inmunología de la reproducción: revisión narrativa de la bibliografía / Basic concepts in reproductive immunology: a narrative review of the literature

Resumen: ANTECEDENTES: La inmunología de la reproducción no es un área nueva: siempre ha estado relacionada con el aborto recurrente y con la falla repetida en la implantación, sobre todo en el contexto de una fertilización in vitro. Recientemente emergieron nuevos conceptos importantes que los ginecoobstetras deben considerar. OBJETIVO: Interrelacionar los conceptos básicos de inmunología, embriología y reproducción asistida para comprender mejor lo que la primera puede resolver y lo que no. METODOLOGÍA: Estudio retrospectivo efectuado con base en la búsqueda electrónica, llevada a cabo en febrero de 2020 en las bases de datos: PubMed y Google Scholar con los siguientes términos (MeSH): abortion, spontaneous/immunology; embryo implantation/immunology; HLA-c antigens/immunology; immune tolerance/immunology; immunity, maternally-acquired/immunology; uterus/immunology; killer cells, natural/immunology; placentation/immunology; receptors, kir/immunology; antigen presentation/genetics; antigen presentation/immunology; maternal-fetal exchange/genetics; maternal-fetal exchange/immunology. RESULTADOS: Se reunieron 289 artículos y se eliminaron 248 por no cumplir con los criterios de inclusión; solo se analizaron 41. Los artículos identificados sirvieron de base para actualizar la situación de la inmunología en el contexto de la medicina de la reproducción. Durante el proceso se revisaron otros artículos que sirvieran de soporte bibliográfico a los conceptos descritos en esta revisión. CONCLUSIONES: Debido al destacado interés en el estudio de la genética de los embriones, la medicina de la reproducción se enfocó más en ella y dejó de lado a la inmunología. Sin embargo, como la genética sigue sin poder explicar de manera adecuada las fallas en la implantación, la inmunología de la reproducción vuelve a cobrar impulso.

Abstract: BACKGROUND: Reproductive immunology is not a new area in reproductive medicine, it has always been related to recurrent miscarriage and repeated implantation failure, especially in the context of IVF. Recently, new concepts have emerged that are important for OBGYN specialists to keep in mind. OBJECTIVE: Interrelating the basic concepts of immunology, embryology and assisted reproduction to better understand what the former can and cannot solve. METHODOLOGY: Retrospective study based on the electronic search, carried out in February 2020, in the databases: PubMed and Google Scholar with the following terms (MeSH) The following MeSH terms were used: Abortion, Spontaneous/immunology; Embryo Implantation/immunology; HLA-C Antigens/immunology; Immune Tolerance/immunology; Immunity, Maternally-Acquired/immunology; Uterus/immunology; Killer Cells, Natural/immunology; Placentation/immunology; Receptors, KIR/immunology; Antigen Presentation/genetics; Antigen Presentation/immunology; Maternal-Fetal Exchange/genetics; Maternal-Fetal Exchange/immunology. RESULTS: 289 articles were collected, and 248 articles were deleted because they did not meet the inclusion criteria; only 41 were analyzed. The articles identified served as a basis for updating the status of immunology in the context of reproductive medicine. During the process, other articles were reviewed to serve as bibliographic support for the concepts described in this review. CONCLUSIONS: Due to the outstanding interest in the study of embryo genetics, reproductive medicine focused more on it and left immunology aside. However, since genetics still cannot adequately explain implantation failures, reproductive immunology is gaining momentum again.

Implantación embrionaria. Algunos aspectos moleculares en la receptividad endometrial. Revisión Bibliográfica / Embryonic implantation. Some molecular aspects in endometrial receptivity. Bibliographic review

RESUMEN La implantación embrionaria es un proceso que tiene lugar durante un breve periodo de tiempo donde el tejido endometrial alcanza un estado receptivo y donde se expresan moléculas que son necesarias para el proceso de implantación y posterior invasión del blastocisto. Este periodo se conoce como ventana de implantación y tiene lugar alrededor del día 20-21 del ciclo menstrual. El endometrio receptivo ha sido ampliamente estudiado desde el punto de vista histológico y molecular, y se conocen gran número de marcadores que forman parte de la firma molecular del endometrio receptivo, lo cual ha servido para desarrollar herramientas moleculares genómicas para el diagnóstico de la receptividad endometrial con utilidad clínica. Sin embargo, hasta ahora no se ha tenido en cuenta que la capacidad receptiva del endometrio tiene un componente inmunológico importante que facilita la entrada del tejido embrionario en el tejido materno. El objetivo de esta revisión es destacar ciertos grupos de biomarcadores identificados con un papel fundamental en el mecanismo de implantación.

ABSTRACT Embryo implantation is a process that takes place during a short period of time where the endometrial tissue reaches a receptive state and where molecules are expressed that are necessary for the implantation process and subsequent invasion of the blastocyst. This period is known as the window of implantation and takes place around day 20-21 of the menstrual cycle. The receptive endometrium has been widely studied from the histological and molecular point of view, and a large number of markers are known that are part of the molecular signature of the receptive endometrium, which has served to develop molecular genomic tools for the diagnosis of endometrial receptivity. with clinical utility. However, until now it has not been taken into account that the receptive capacity of the endometrium has an important immunological component that facilitates the entry of embryonic tissue into the maternal tissue. The objective of this review is to highlight certain groups of biomarkers identified with a fundamental role in the implementation mechanism.

The intervention effect of N-carbamoyl glutamic acid on embryo implantation disorder induced by carbon disulfide and its possible molecular mechanism / 中华劳动卫生职业病杂志

Objective@#To explore the preventive effect and possible molecular mechanism of dietary supplementation of N-carbamylglutamate (NCG) in the implantation of carbon disulfide (CS2) into embryo implantation disorders.@*Methods@#embryo implantation disorder model was established by single intraperitoneal exposure to CS2 on the 3rd, 4th, and 5th days after pregnancy. Endometrial tissues were collected for 24h after exposure to CS2 for western-blot and immunohistochemical staining.@*Results@#The number of embryo implantation was increased in NCG+CS2 group, compared with CS2 alone group. Day 4 of pregnancy when CS2-exposed after 24 h, the expression of pAKT protein in NCG+CS2 group was significantly increased (P<0.05), the expression level of pAMPK protein in NCG+CS2 group was significantly decreased, compared with CS2 alone group, respectively. Immunohistochemical results showed that pAKT, pAMPK, AKT and AMPK proteins were expressed in luminal epithelial cells, glandular epithelial cells and stromal cells of endometrium; Day 4 of pregnancy when CS2-exposed after 24 h, deep staining of ATK and pAKT protein in NCG+CS2 group, the AMPK and pAMPK protein staining became lighter.@*Conclusion@#Dietary supplementation of NCG can interfere with the embryo loss induced by CS2 by altering the total amount of AKT/AMPK molecules.

Relationship between fallopian tube abnormality and repeated failure of IVF / 中国实用妇科与产科杂志

Repeated IVF failure has been a pain pointin the assisted reproductive process.The fallopian tubehas long been considered as a conduit for transporta-tion,ignoring its important role in embryo implantation.The main reasons for the repeated failure of IVF areembryonic factors,endometrial receptivity and otherfactors.The article mainly focuses on the effects ofvarious types of fallopian tube lesions on the abovethree factors,and analyzes the relationship betweenvarious oviduct chronic inflammatory lesions and IVFfailure.IVFfallopian tube obstructionendome-

Embryo implantation dysfunction via the decreased uterine dendritic cells's non-immune function after exposed to carbon disulfide / 中华劳动卫生职业病杂志

Objective@#To study the effect of CS2 on dendritic cells (DCs) in the uterus and the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor(fms-like tyrosine kinase-1, Flt-1), and to explore the toxic mechanism of CS2-induced embryo implantation dysfunction.@*Methods@#The Kunming mice were randomly divided into control group,gestational day 4(GD4) exposure group and GD5 exposure group. The endpoints of each group(GD5, GD6, GD7) was set up according to their respective exposure time points. The mice in the exposure group were given intraperitoneal injection of CS2 at an injection dose of 631.4 mg/kg and the control group was given olive oil. The effect of CS2 on DCs in the uterus of pregnant mice was observed by flow cytometry. The levels of VEGF and Flt-1 were measured by Real-time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA).@*Results@#In the GD4 and GD5 exposure groups, the number of DCs in the uterus of pregnant mice decreased at all endpoints and the GD5 endpoint in the GD4 exposure group decreased by 21%(P=0.039), when compared with the control group. In the GD4 exposure group, the levels of VEGF mRNA and protein in the uterus of the pregnant mice were 79% and 30% lower than those in the control group, respectively (P=0.03、P=0.017); the levels of Flt-1 mRNA and protein at the endpoints of GD6 and GD7 in the uterus decreased by 54%, 36%, 60% and 56%, respectively, when compared with the control group(P=0.017、P=0.012、P=0.004、P=0.007). In the GD5 exposure group, the levels of VEGF mRNA and protein in the uterus of pregnant mice at the endpoint of GD7 decreased by 62% and 36%, when compared with the control group (P=0.005、P=0.035); the levels of Flt-1 mRNA and protein in the uterus at the endpoint of GD7 decreased by 60% and 44%, respectively, when compared with the control group (P=0.004、P=0.009).@*Conclusion@#CS2 reduced the number of DCs in the uterus of pregnant mice, and affected the non-immune function of DCs, which affected uterine angiogenesis, this may be one of the mechanisms of CS2-induced embryo implantation dysfunction.

Expression and regulation of mixed lineage kinase domain-like protein in uterus during early pregnancy and decidua in mice / 第二军医大学学报

Objective To investigate the expression of mixed lineage kinase domain-like protein (MLKL) in uterus during early pregnancy and decidua in mice. Methods Different mouse models including early pregnancy model, artificially induced decidualization model and hormone and/or progesterone treatment of uterine model were constructed; human endometrial stromal cells were cultured in vitro and were induced for decidualization by treating with estradiol-17β, medroxyprogesterone acetate and dibutyryl cyclic adenosine monophosphate. The expression of MLKL mRNA and protein in the uterus of early pregnancy, decidual uterus, and hormone-treated uterus in mice were analyzed by real-time fluorescent quantitative PCR, in situ hybridization and Western blotting. The expression of MLKL mRNA in human decidual cells induced in vitro was detected by real-time fluorescent quantitative PCR. Results (1) In the uterus during early pregnancy in mice, the expression of MLKL mRNA and protein in uterine epithelium on the 1st to 4th day of pregnancy (day 1 was day of vaginal sperm) was low and irregular. It was expressed in the uterine epithelium and surrounding decidual cells on the 5th day of pregnacy, and was mainly expressed in the decidua from the 6th to 8th day of pregnancy. After the implantation, the expression of MLKL mRNA and protein was day-by-day increased and reached the highest on the 7th day of pregnancy, with a slight decrease on the 8th day. (2) In the uterus of mice with artificially induced decidualization, MLKL mRNA was expressed in the entire decidual region with high level; while there was no significant expression in the uterus of the control mice. The expression of MLKL protein was consistent with the expression of MLKL mRNA. The expression of MLKL mRNA in human decidual cells induced in vitro was significantly higher than that in the control group (P0.05). (3) The expression of MLKL mRNA and protein in progesterone-treated uterus was significantly increased compared with the control group (P0.05). Conclusion MLKL regulated by steroid hormone progesterone is involved in embryo implantation and decidualization of mammals.

Effects of Yun Kang oral liquid on rats model of embryo implantation disorder / 中国应用生理学杂志

OBJECTIVE@#Through the establishment of abortion model caused by embryo implantation difficulties, exploring the role of Yun Kang oral liquid in protecting embryos.@*METHODS@#The pregnant rats were divided into 6 groups:normal control group (NC), model group (MG), dydrogesterone group (DT), and three dose groups of low, medium and high levels of Yun Kang oral liquid (YK-L, YK-M, YK-H), 11 in each group.From the first day of pregnancy, daily intragastric administration, the dose of DT group was 3.02 mg/kg, and the doses of Yun Kang oral liquid were 4, 6, and 9 ml/kg, respectively.The rats in NC and MG were treated with an equal volume of purified water for 10 days.On the third day of pregnancy, except for the NC group, the other groups were injected with mifepristone subcutaneously at the back of the neck at a dose of 5 mg/kg to cause an embryo implantation barrier model.On the 10th day of pregnancy, blood was collected from the abdominal aorta in each group.Serum follicle stimulating hormone (FSH), interferon-γ (IFN-γ) and interleukin (IL-4) were measured by enzyme-linked immunosorbent assay.The number of embryo implantation was observed in the uterus, and the pathological changes of the uterus were observed by HE staining.@*RESULTS@#Compared with the NC group, the number of embryo implantation and the serum levels of FSH and IL-4 in the MG group were decreased significantly (< 0.05, 0.01), and pathological changes such as uterine glandular epithelial hyperplasia and inflammatory cell infiltration in the glandular cavity were observed.Compared with MG group, the number of embryo implantation and serum FSH and IL-4 levels of rats in YK-M and YK-H groups were increased significantly (<0.05, 0.01).The pathological changes such as uterine glandular epithelial hyperplasia and inflammatory cell infiltration in the gland were also improved.There was no significant difference in serum IFN-γ levels between the groups.@*CONCLUSIONS@#Yun Kang oral liquid may improve the endometrial pathological changes and increase the number of embryo implantation by increasing the levels of serum sex hormone FSH and immune cytokine IL-4 in embryo implantation impediment rats.

Efecto en los resultados reproductivos con la "magnetic-actived cell sorting (MACS)" para la eliminación de espermatozoides positivos a anexina V en parejas con infertilidad inexplicable / Effect on reproductive outcomes by using "magnetic-actived cell sorting (MACS)" for the elimination of sperm-positive annexin-V in couples with unexplained infertility

Resumen Objetivo: Determinar si la eliminación de espermatozoides positivos a marcadores tempranos de apoptosis en parejas con infertilidad inexplicable incrementa la tasa de nacidos vivos. Materiales y métodos: Ensayo piloto, con asignación al azar, controlado y triple ciego; y un estudio paralelo de dos grupos. Se incluyeron parejas con diagnóstico de infertilidad inexplicable que se asignaron en una proporción 1:1 al grupo A (método de capacitación espermática swim-up) o grupo B (método de capacitación espermática swim-up complementado con separación magnética de células activadas; magnetic-actived cell sorting; MACS). Posteriormente, a todas las muestras se les efectuó una inyección intracitoplasmática de espermatozoides, como técnica de fertilización. Por último, todos los embriones obtenidos se analizaron hasta la etapa de blastocisto y todas las transferencias se llevaron a cabo en la misma etapa. Resultados: Se incluyeron 40 parejas y no se encontraron diferencias en la tasa de fertilización. Con la aplicación de MACS se obtiene mayor porcentaje de embriones de buena calidad en día 3 (90.3 vs 99.5%; p = 0.03) y en día 5 (77.3 vs 90.1%; p = < 0.0001) disminuyó el porcentaje de embriones arrestados (16.3 vs 7.9%; p = 0.01). Por último, las tasas de implantación (42.1 vs 57.1%), embarazo clínico (60 vs 80%) y nacidos vivos (55 vs 80%) aumentaron, sin diferencias estadísticamente significativas. Conclusiones: La separación magnética de células activadas (MACS) en parejas con infertilidad inexplicable mejora el desarrollo embrionario. A pesar de no existir una diferencia significativa se observa una tendencia al incremento de embarazos clínicos y nacidos vivos.

Abstract Objective: To determine if the live births delivery rate with the eliminating sperm positive to early apoptotic events is higher in couples with unexplained infertility. Materials and methods: A pilot randomized controlled trialA pilot and triple-blinded; using a parallel study of two groups. We included a total of 40 couples with unexplained infertility assigned in a 1:1 proportion either to the group A (sperm training method swim-up) or to the group B (swim-up sperm training method supplemented with the use of "magnetic-actived cell sorting (MACS)"). Subsequently, all samples were submitted to intracytoplasmic sperm injection as a fertilization technique. Finally, all embryos obtained were analyzed until the blastocyst stage, and all the transfers were performed in the same stage. Results: There are no differences in the fertilization rate; however, with the use of "magnetic-actived cell sorting" there is a higher percentage of good quality embryos on day 3 (90.3% vs 99.5%, p = 0.03) and day 5 (77.3% vs 90.1%, p = <0.0001). In addition, a decrease in the percentage of arrested embryos was demonstrated (16.3% vs 7.9%, p = 0.01). Finally, implantation (42.1% vs 57.1%), clinical pregnancy (60% vs 80%) and live birth rates (55% vs 80%) increased; however, no statistically significant differences were reported. Conclusions: The use of "magnetic-actived cell sorting" in couples with unexplained infertility improves embryonic development. Although there is no significant difference, a trend is observed in relation to the increase in the number of clinical pregnancies and live births.

Live birth after transfer of vitrified-warmed embryo derived from vitrified-warmed oocyte and frozen-thawed sperm following failed ICSI: case report / Embarazo a partir de un embrión vitrificado derivado de oocitos vitrificados y espermios descongelados: reporte de un caso

Since the first successful pregnancy from a frozen human oocyte was reported, remarkable technological progress has been made in the area of cryopreservation of human oocytes. We report a successful delivery of two healthy babies after transfer of vitrified-warmed embryos derived from intracytoplasmic sperm injection (ICSI) with vitrified-warmed oocytes and frozen-thawed sperm. A female patient and her husband with severe oligoasthenspermia are reported. At the day of oocyte collection, very few inactive sperms were found in her husband semen. Multiple site open testicular biopsy was performed on her husband, but no sperm was retrieved. The patient did not become pregnant after transferring two embryos coming from half of oocytes and inactive sperms. The patient got pregnant and delivered two healthy babies after receiving a transfer of vitrified-warmed embryos from vitrified-warmed oocytes and frozen-thawed sperm.

La criopreservación de oocitos humanos ha progresado mucho desde que el primer embarazo exitoso desde un oocito congelado fue informado. Nosotros informamos el parto de dos bebés sanos después de transferir embriones vitrificados y recalentados y espermios descongelados. Se trata de una mujer y su marido con una oligoastenoespermia severa. En el día de la recolección de oocitos, se encontraron muy pocos espermios inactivos en el semen del marido. Se tomaron biopsias testiculares pero se encontraron muy pocos espermios inactivos. La mujer logró quedar embarazada y dio luz a dos bebés sanos después de recibir una trasferencia de embriones vitrificados y recalentados, y de espermios descongelados.

Thawing cycle sequential embryo transfer in patients with repeated implantation failure / 天津医药

Objective To compare the outcome of in vitro fertilization (IVF) between sequential embryo transfer and simple blastocyst transplantation in patients with previous multiple IVF failures. Methods A total of 170 patients with repeated implantation failure were divided into sequential transfer group (n=71) and blastocyst transfer only group (n=99). A retrospective matched case-control analysis was made for the medical files of 71 patients who underwent sequential transfer of D3 embryos and blastocysts. The control group included 99 matched women who underwent embryo transfer on D5/6 only. All of the patients in two groups used the same protocols of emdometrium preparation (natural cycle or hormone-replacement cycle) and ultrasound-guided transplantation. The embryo implantation rate and clinical pregnancy rate were compared and analyzed between two groups. Results Sequential transfer of embryos resulted in a clinical pregnancy rate of 60.6%compared with that of 31.3%following D5/6 embryo transfer, and the implantation rate was 34.8%and 23.8%respectively (P<0.05). Although the total number of transfered embryos were higher in sequential transfer group than that of blastula transfer only group, the number of D5/6 embryo transfered in sequential transfer group were less than blastula transfer only group (P<0.05). And the number of high quality blastula transfered showed no statistical significant difference between two groups. There were 20 cases of twin and 5 cases of triplet pregnancy in sequential transfer group, which were 5 cases and 1 case in blastula transfer only group respectively. While, there was no case of muliple pregnancy beyond triplet in both groups Conclusion Sequential transfer of embryos can be used for women with repeated IVF cycles. The program avoids the possibility of eliminating the transplant, and which is effective in patients with more transplant embryos.

Impacts on thepregnancy outcome in the mice of controlled ovarian hyperstimulation treated with acupuncture at different time points / 中国针灸

<p><b>OBJECTIVE</b>To explore the optimal time of acupuncture intervention in the assisted reproduction.</p><p><b>METHODS</b>One hundred and twenty female mice and 60 male mice were collected. 20 female mice were selected in the natural period group and the rest 100 female mice were prepared as the model of controlled ovarian hyperstimulation (COH). The model mice were randomized into a COH group, a down-regulation group, a gonadotropins (Gn) start group, an injection of human chorionic gonadotropin (HCG) group and an embryo culture group, 20 mice in each one. The donor mice and receptor mice were subdivided in each group, 10 mice in each subgroup. One week before the experiment, vas deferens ligature was done in 30 male mice and the other 30 male mice did not receive ligature. In the down-regulation group, the Gn start group, the HCG injection group and the embryo culture group, electroacupuncture (EA) was applied to "Guanyuan" (CV 4), "Zhongji" (CV 3) and "Sanyinjiao" (SP 6) at the time points accordingly. EA stimulation was in the condition of continuous wave, 2 Hz and 1 mA. No inter-vention was given in the natural period group and the COH group. On the day of HCG injection, the donor mice and the non-ligatured male mice were put in the same cage of each group. The fertilized ovum was collected with the date of fertilization marked and was fostered in the incubator. At the ratio of 1:1, the receptor mice and ligatured mice were put in the same cage in each group. The vaginal plug was examined in the next morning. The pseudopregnancy was marked with the date of plug observed. In the 68th hour of embryo culture, the embryo of the donor was shifted to the receptor on the same day when the plug was observed. The clinical pregnancy rate and embryo imbed site number were observed. RT-PCR assay was adopted to determine the expression of insulin-like growth factor-1 (IGF-1) mRNA in endometrium.</p><p><b>RESULTS</b>In the COH group, the pregnancy rate, average imbed site number and endometrial IGF-1 mRNA expression were all significantly lower than those in the natural period group (all<0.01). After EA treatment, in the Gn group, the HCG injection group and the embryo culture group, the pregnancy rates were higher significantly than those in the COH group (<0.05,<0.01). In the HCG injection group, the average imbed site number and IGF-1 mRNA expression were increased apparently as compared with those in the COH group (both<0.01), better than those in the Gn group and the embryo culture group (all<0.01).</p><p><b>CONCLUSIONS</b>In the treatment with acupuncture combined with IVF-ET for infertility, the intervention of acupuncture on the day of HCG injection is the optimal time point. It increases the secretion of endometrial IGF-1 so as to improve the clinical pregnancy rate, the mean imbed site number and the embryo implantation.</p>

Effect of Yiqixue Buganshen Recipe on Endometrial Integrinβ3 Expression and Pinopode Formation in Mice with Embryo Implantation Dysfunction / 广州中医药大学学报

Objective To observe the effect of Yiqixue Buganshen Recipes(YBR), the compound recipes of Chinese herbal medicine with the actions of replenishing Qi and blood and tonifying liver and kidney, on the endometrial integrin β3 of the mice with embryo implantation dysfunction, and to explore the molecular mechanism of YBR in improving embryo implantation. Methods Ninety mice were divided normal group, model group, and YBR group, 30 mice in each group. YBR group was given Jinghou Zengzhi granules 8mg/kg for promoting post-menstruation proliferation and Cuhuangti granules 8mg/kg for promoting the formation of corpora luteum. At 8∶00 am of pregnant day 4 (Pd4), subcutaneous injection of mifepristone was used for inducing embryo implantation dysfunction in the model group and YBR group. Twenty mice from each group were executed 12 hours after subcutaneous injection of mifepristone, and the uterus was isolated for the detection of mice endometrial integrin β3 mRNA and protein expression with real-time RT-PCR and Western blotting method respectively. Ten mice from each group at Pd4 were executed, and the uterus was isolated and then fixed in 2.5% glutaraldehyde solution for the detection of the formation of pinopode in mice endometrium under scanning electron microscope. Results The detection by real-time PCR and Western blotting method revealed that integrinβ3 mRNA and protein expression levels of the model group were significantly lower than those of the normal group (P<0.05), and YBR group had higher integrin β3 mRNA and protein expression levels than the model group(P<0.05). The formation of pinopodes in the model group was less than the normal group and YBR group, but the number of formed pinopodes in YBR group was similar to that in the normal group. Conclusion YBR can up-regulate the expression of integrin β3 in the endometrium of mice with embryo implantation dysfunction, and have positive regulatory effect on the formation of pinopodes on Pd4.

Research progress of the measures to improve the receptivity of endometrium / 中国医师进修杂志

The embryo quality and endometrial receptivity is the two important factors that affects human implantation. Many patients with infertility caused by the disorder of endometrial receptivity fails in embryo implantation. Improving the receptivity of endometrium to improve clinical pregnancy rate has become a hot issue of research in recent years. In this paper, the current use of drugs and surgery on the measures to improve the receptivity of endometrium was summarized, in order to provide references for improving the success rate of assisted reproductive technology.

Effect of blastocyst quality on the strategy of single blastocyst transfer in frozen-thawed cycles / 中华妇产科杂志

Objective To investigate the effect of blastocyst quality on the strategy of single blastocyst transfer in frozen-thawed cycles. Methods A retrospective analysis was performed in Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region on clinical data of single frozen-thawed blastocyst transfer cycles from January 2008 to December 2013. All cycles were divided into four groups (AA, AB/BA, BB, BC/CB) according to the blastocyst score, then the clinical outcomes were compared between groups. And on this basis, the clinical outcomes were further explored when the group of outcomes with single blastocyst transfer wasn′t ideal, which would diverted to transfer two blastocyst. Results In single frozen blastocyst transfer cycles, the clinical pregnancy rate of each group with the blastocyst scored AA, AB/BA, BB, BC/CB were 61.4%(470/765), 51.2%(330/645), 40.5%(407/1 005), 22.9%(60/262), live births rate in each group were 52.2%(399/765), 41.2%(266/645), 30.4%(306/1 005), 13.7%(36/262), and the abortion rate were 13.6%(64/470), 16.7%(55/330), 21.4%(87/407), 35.0%(21/60), separately. This showed that the clinical pregnancy rate and live births rate decreased significantly with the decline of blastocyst quality (P40%) and live births rate (>30%) could be obtained, however, the clinical pregnancy rate of 22.9% and live births rate of 13.7%could only be acquired when blastocyst scored BC/CB only transferred one embryo, which significant lower than those of each group scored ≥BB grade (P0.05). Conclusions Of single blastocyst transfer in frozen-thawed cycles, the clinical pregnancy rate and liver births rate showed significant upward trend, but the abortion rate showed significant downward trend, with the decline of blastocyst quality. When the blastocyst scored ≥BB grade, the single blastocyst transfer could be considered to be performed.