Yishen Huatan Huoxue decoction and quercetin ameliorate decidualization dysfunction in polycystic ovary syndrome: A comprehensive investigation combining clinical trial and experimental studies.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.

Exposure to biologic therapy before and during pregnancy in patients with psoriasis: Systematic review and meta-analysis.

Biologicals have transformed the management of severe disease phenotypes in psoriasis and are often prescribed in women of childbearing age. However, information on safety of biologicals in pregnancy are lacking. We conducted a systematic review and meta-analysis aimed to describe the characteristics and pregnancy outcomes in women with psoriasis exposed to biologics within 3 months before or during pregnancy, and to estimate the pooled prevalence of spontaneous, elective and total abortions, and congenital malformations in their newborns. Bibliographic searches were performed in the PubMed, Embase, Scopus and Web of Science databases up to 14 April 2022. No restrictions on sample size or publication date were applied. Review performance complied with PRISMA guidelines, and two reviewers assessed randomized controlled trials and nonrandomized studies reporting pregnancy outcomes in women exposed to biologics indicated for psoriasis during the pre-gestational and/or gestational period. Studies focusing on rheumatologic or gastroenterological immune-mediated inflammatory diseases were excluded. Regardless of data heterogeneity, a random-effects model was used to pool prevalence estimates. We included 51 observational studies, involving 739 pregnancies exposed to approved biologics for psoriasis. Administration was mostly (70.4%) limited to the first trimester, and the most common drug was ustekinumab (36.0%). The estimated prevalence of miscarriage was 15.3% (95% confidence interval [CI] 12.7-18.0) and elective abortions, 10.8% (95% CI 7.7-14.3). Congenital malformations occurred in about 3.0% (95% CI 1.6-4.8) of live births exposed to biologics during pregnancy. Altogether, exposure to biologics for psoriasis during pregnancy and/or conception does not seem to be associated with an increased risk of miscarriage/abortion or congenital malformations, showing similar rates to the general population. These results suggest that biologic drugs are safe and pose an acceptable risk to the foetuses/neonates.

Chemical profile and miscarriage prevention evaluation of Jiao-Ai Decoction, a classical traditional Chinese formula.

Jiao-Ai Decoction (JAD), a classical traditional Chinese formula composed of seven Chinese herbs, has been widely used in clinical practice for the treatment of abortion for a long time. However, the material basis and pharmacological mechanism remain unclear. An integrative method combining ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) analysis and therapeutic effect evaluation based on the hypothalamus-pituitary-ovarian axis (HPOA) was employed to elaborate these problems. Firstly, the chemical profile of JAD was identified by UPLC-Q-TOF-MS. Secondly, the main target ingredients from JAD were determined by UPLC-T-Q-MS. Finally, the miscarriage prevention of JAD on threatened abortion pregnant rats induced by mifepristone was investigated. Threatened abortion model in rats were replicated, uterine bleeding quantity (UBQ) and histopathological sections were measured, the contents of luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2) and progesterone (P) were determined by ELISA, related genes and protein expression levels were detected by RT-PCR and western blotting. As a result, a total of 101 compounds were identified and 27 ingredients were determined to evaluate the quality of JAD. In the model rats, JAD could effectively regulate the HPOA to achieve miscarriage prevention, and the mechanism might be related to the regulation of gene and protein expression on the HPOA. This work could provide a novel and valuable approach for the quality evaluation of JAD and were expected to provide ideas and methods for the basic research on the scientific application of similar traditional Chinese medicine prescriptions.

Mechanisms of Traditional Chinese Medicine Bushenantai granules in promoting angiogenesis at the maternal-fetal interface of recurrent spontaneous abortion mice.

OBJECTIVE: To assess the effects of Bushenantai (BSAT) granule() on angiogenesis-related factors [E2, P, and vascular endothelial growth factor (VEGF)] at the maternal-fetal interface of recurrent spontaneous abortion (RSA) mice, and to evaluate the role of BSAT in promoting angiogenesis at the maternal-fetal interface by influencing the expression of sex hormones, and VEGF. METHODS: A mouse model with normal pregnancy and another with Clark's classic RSA were established. The RSA mice were randomly assigned to six groups: normal, model, progesterone, high-doseBSAT granule (BSAT-H), medium-dose-BSAT granule (BSAT-M), and low-dose-BSAT granule (BSAT-L) (n = 10 for each group). The embryo loss rate and the histopathological changes in the decidual tissues were measured. Serum levels of estrogen (E2), progesterone (P), and VEGF were detected by enzyme-linked immunosorbent assay. The mRNA and protein expressions of estradiol receptor (ER), progesterone receptor (PR), VEGF, and vascular endothelial growth factor receptor 2 (VEGFR2) in the decidual tissues were identified by immunohistochemistry, Western blotting, and quantitative reverse transcription polymerase chain reaction. RESULTS: The embryo loss rate in all groups that received BSAT treatment was reduced, while the number of blood vessels at decidual tissues was increased. The serum levels of E2, P and VEGF were elevated, and the mRNA and protein expressions of ER, PR, VEGF, and VEGFR2 in the decidual tissues were enhanced. CONCLUSION: BSAT can improve angiogenesis at the maternal-fetal interface and reduce the embryo loss rate, which may be associated with its ability to increase the serum levels of estrogen, progesterone, and VEGF, in addition to up-regulation of mRNA and protein expression of ER, PR, VEGF, and VEGFR2 in the decidual tissue.

Regulative effect of Taohong Siwu decoction on extracellular matrix of endometrium in drug-induced abortion.

OBJECTIVE: To explore the effects of Taohong Siwu decoction (, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion. METHODS: Thirty-six pregnant female rats were administered mifepristone and misoprostol to induce abortion, and amounts of uterine bleeding were recorded. Pathological damage and collagen accumulation were detected by hematoxylin-eosin staining and Masson's trichrome staining in uterus, respectively. Myeloperoxidase was evaluated by immunohistochemistry.The expression levels of fibronectin, laminin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were quantified using western blotting. RESULTS: THSWD could promote endometrial protection in rats following drug-induced abortion. The contents of cellulose and myeloperoxidase were significantly decreased in uterine tissue of THSWD-treated groups. Moreover, THSWD significantly decreased the expression levels of fibronectin, laminin, and TIMP-1. THSWD also significantly increased MMP-9 expression and the MMP-9/TIMP1 ratio. CONCLUSION: THSWD plays a critical role in endometrial protection by reducing extracellular matrix deposition and uterine fibrosis. These effects may have been achieved by increasing MMP-9, reducing TIMP-1, and/or altering the ratio of MMP-9/TIMP-1.

The Efficacy of Traditional Chinese Medicine Shoutai Pill Combined with Western Medicine in the First Trimester of Pregnancy in Women with Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta-Analysis.

BACKGROUND: Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta-analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion. METHODS: The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: A total of 12 studies (916 patients) with URSA were contained in this meta-analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34-0.52; P < 0.01, I 2 = 0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D-dimer level, while higher incidence of live birth. CONCLUSIONS: Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.

Prophylactic Effects of Bee Venom Phospholipase A2 in Lipopolysaccharide-Induced Pregnancy Loss.

Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-α and IFN-γ expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations.

Reproductive toxicity of ZishenYutai pill in rats: Perinatal and postnatal development study.

ZishenYutai pill (ZYP) is one of the most commonly used Chinese patent medicines for threatened miscarriage. Although ZYP is widely used, its toxic effects are rarely assessed. We aimed to investigate whether ZYP had reproductive toxicity during perinatal and postnatal period. Pregnant rats (F0) were continuously exposed to 6, 12 and 24 g/kg body weight/d of ZYP by intragastric administration from gestation day15 to post-natal day21. Vehicle and propylthiouracil (PTU, 15 mg/kg) were used as the negative control and positive control, respectively. The mating was done between the treatment (ZYP or PTU) group and negative control group when the F1 pups were born 63-70 days. Body weight, reproductive ability, physical development and neurodevelopment of F0, F1 and F2 pups were observed. The reproductive capacity of F0 and F1 generation decreased significantly after PTU exposure; however, the body weight and reproductive ability of F0, the physical development, weight, feed consumption and reproductive ability of F1, as well as the physical development and body weight of F2 rats were not significantly changed in the ZYP-treated group compared with the negative control group. ZYP exposure had no perinatal toxicity in 3 generations of rats and may be widely used for miscarriage.

Traditions and plant use during pregnancy, childbirth and postpartum recovery by the Kry ethnic group in Lao PDR.

BACKGROUND: Activities and diet during the postpartum period are culturally dictated in many Southeast Asian cultures, and a period of confinement is observed. Plants play an important role in recovery during the postpartum period in diet and traditional medicine. Little is known of the Kry, a small ethnic group whose language was recently described, concerning its traditions and use of plants during pregnancy, parturition, postpartum recovery and infant healthcare. This research aims to study those traditions and identify medicinal plant use. METHODS: Data were collected in the 3 different Kry villages in Khammouane province, Lao PDR, through group and individual interviews with women by female interviewers. RESULTS: A total of 49 different plant species are used in women's healthcare. Plant use is culturally different from the neighboring Brou and Saek ethnic groups. Menstruation, delivery and postpartum recovery take place in separate, purpose-built, huts and a complex system of spatial restrictions is observed. CONCLUSIONS: Traditions surrounding childbirth are diverse and have been strictly observed, but are undergoing a shift towards those from neighboring ethnic groups, the Brou and Saek. Medicinal plant use to facilitate childbirth, alleviate menstruation problems, assist recovery after miscarriage, mitigate postpartum haemorrhage, aid postpartum recovery, and for use in infant care, is more common than previously reported (49 species instead of 14). The wealth of novel insights into plant use and preparation will help to understand culturally important practices such as traditional delivery, spatial taboos, confinement and dietary restrictions, and their potential in modern healthcare.

[Effect of Chinese drugs for invigorating qi and tonifying shen on expression of CD4+CD25+ regulatory T cells in spleen and maternal-fetal interface of abortion-prone mice].

OBJECTIVE: To study the effect of Chinese drugs for invigorating qi and tonifying Shen (IQTS) on expression of CD4+CD25+ regulatory T cells in spleen and maternal-fetal interface of abortion-prone mice during pregnancy. METHODS: CBA female mice were mated with DBA/2 male mice to establish abortion-prone models, which were randomly divided into 4 groups, the negative control group (fed with normal saline), the positive control group (treated with CsA), the Chinese medicine group (treated with IQTS), and the Chinese and Western medicine group (treated with IQTS+CsA). Mice were sacrificed in batches on the 9th and the 14th day of gestation, their splenic and decidual tissues were taken out to analyse CD4+CD25+ regulatory T-cell expression by flow cytometry. RESULTS: Compared with the negative control group, the expression of splenic CD4+CD25+ regulatory T all significantly increased on the 9th day of gestation (P < 0.01 or P < 0.05). There was no statistical difference in intergroup comparison of the three treatment groups (P > 0.05). Compared with the negative control group, the expression of splenic CD4+CD25+ regulatory T all significantly increased on the 14th day of gestation (P < 0.01 or P < 0.05). Of them, its expression was the highest in the Chinese and Western medicine group, showing significant difference from that in the Chinese medicine group and the positive group (P < 0.01). The difference between the Chinese medicine group and the positive group was insignificant (P > 0.05). On day 9 of gestation, compared with the negative control group, the expressions of CD4+CD25+ regulatory T in maternal-fetal interface increased in the three treated groups, showing no statistical significance (P > 0.05). Its expression was ordered from high to low in sequence as the Chinese and Western medicine group, the positive control group, the Chinese medicine group, and the negative control group. On day 14 its expression was obviously enhanced in the Chinese and Western medicine group, showing statistical difference from that in the negative control group (P < 0.05). But its expression was obviously enhanced in the Chinese medicine group and the positive group, showing insignificant difference from that in the negative group. The same sequence was found in the percentage of CD4+CD25+ T cells in CD4+ T cells. CONCLUSIONS: Chinese drugs for IQTS could up-regulate the expression of CD4+CD25+ regulatory T in spleen of abortion-prone mice in the early and late pregnancy stages. When combined with CsA, it also could up-regulate its expression in maternal-fetal interface in the mid and late pregnancy stages, suggesting that Chinese drugs for IQTS are facilitate to maintain the immune tolerance state in mice during pregnancy.

Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy.

BACKGROUND: Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome. OBJECTIVE: To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement. METHODS: Prospective examination of 104 patients, registered in EURAP from 1999-2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999. RESULTS: 388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results. CONCLUSIONS: This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

Effect of Gutai Decoction on the abortion rate of in vitro fertilization and embryo transfer.

OBJECTIVE: To study the effect of Chinese herbal medicine Gutai Decoction (GTD) on the abortion rate of in vitro fertilization and embryo transfer (IVF-ET). METHODS: Observed were two hundred and forty-seven women having received IVF-ET and with beta-human chorionic gonadotropin (beta-HCG) > 25 IU/L on the 14th day after transferring. All were treated conventionally with progesterone 20 - 80 mg per day after transferring and if necessary the treatment was supplemented with Progynova 2 - 4 mg per day, with the medication withdrawn gradually from the 9th week of pregnancy till stopped completely. Among them 131 cases received GTD medication additionally, for 109 cases of whom the medication started from the 2nd day of transferring (taken as Group A) and for the other 22 cases from the 14th day after transferring (taken as Group B), the other 116 cases with no additional GTD treatment given were taken as the control group, with the medication lasting to the 12th week. The abortion rate in them was observed. RESULTS: The abortion rate in Group A, Group B and the control group was 12.84%, 13.64% and 23.28%, respectively, the difference between the GTD treated groups and the control group was significant (P < 0.05). CONCLUSION: Chinese medicine GTD could reduce abortion rate in women receiving IVF-ET.

Problemas de la gestación en la mujer diabética / Pregnancy problems in diabetes mellitus

La diabetes es la enfermedad metabólica que con mayor frecuencia coincide con la gestación. Además la gestación induce una resistencia insulínica que evidencia a aquellas mujeres con reservas insulínicas limitadas, dando origen a las diabetes gestacionales. Cualquiera de estas dos formas de diabetes se asocia a un peor pronóstico de la gestación, aunque en las diabetes gestacionales la repercusión se centra casi sólo en la macrosomía fetal. La diabetes franca presenta una mayor incidencia de preeclampsia, hidramnios, parto pretérmino; con tasas más elevadas de abortos espontáneos y malformaciones fetales, y con trastornos del crecimiento fetal intrauterino (aceleración, raramente restricción), de la maduración fetal y con hipoxia y muerte intrauterina. Un perfecto control metabólico, previo al inicio de la gestación y mantenido durante la misma, es la mejor profilaxis de estos problemas que también se pueden beneficiar de dietas ricas en antioxidantes, suplementos de ácido fólico, de calcio y la inclusión de antiagregantes plaquetarios (aspirina). Tiene relevancia el diagnóstico precoz de las cromosomopatías fetales (cuya frecuencia parece aumentada en las diabetes gestacionales) y de las malformaciones, mediante ecografías dirigidas a la búsqueda de marcadores en las semanas 12 y 20, y de los trastornos del crecimiento fetal con ecografías a la 28 y 34 semanas. La amenaza de parto pretérmino puede tratarse con Atosiban (Tractocile®), que evita los trastornos metabólicos de los betamiméticos. El control del bienestar fetal mediante cardiotocografía no estresante se inicia, en las diabetes bien controladas, en la semana 34, repitiéndose cada 3 días, mientras que en las diabetes gestacionales bien compensadas no se necesita inciar este control hasta la semana 37. La interpretación de los trazados cardiotocográficos debe de considerar el retraso madurativo del sistema nervioso vegetativo de estos fetos. La finalización de la gestación en las diabetes bien controladas, con feto no macrosómico, conviene planificarlas en la semana 40. Un peor control metabólico, en especial con la presencia de aceleración del crecimiento fetal, aconsejaría la finalización en el momento que el peso fetal se estimara en 4000 g, pero en cualquier caso, si los controles de bienestar fetal son normales y el control metabólico es adecuado y no existen otras complicaciones, convendría esperar hasta la semana 38. La finalización con pesos fetales estimados superiores a 4500 g. se realizaría mediante cesárea. Una conducción de este tipo restaría importancia al retraso madurativo pulmonar (AU)

Metodologia e tratamento do abortamento infectado / Methodology and treatment of infected abortion

Visa este estudo mostrar a metodologia empregada por 143 pacientes que provocaram o abortamento e que foram atendidas na Maternidade da Encruzilhada, Recife, de 1 de janeiro a 30 de junho de 1994. Todas as pacientes com abortamento atendidas no período referido eram submetidas a uma anamnese acurada quando se investigava se o abortamento fora provocado ou espontâneo. Nos casos de abortamento provocado, investigava-se o método utilizado. Nos casos simples sem infecçao, o tratamento de escolha era a curetagem uterina. Na presença de infecçao ou manuseio por sonda ou gotas cáusticas, associava-se um ou mais antibióticos, conforme a gravidade do caso. Os métodos mais utilizados pelas pacientes para provocar o abortamento foram: misoprostol 77 por cento, sonda só ou associada a gotas 17 por cento, chás diversos 11 por cento e injetáveis 5 por cento. Os seguintes métodos terapêuticos foram realizados: curetagem uterina 70 por cento, curetagem uterina e um antibiótico 16 por cento, curetagem uterina e dois antibióticos 7 por cento e curetagem uterina e três antibióticos 7 por cento. Nao houve complicaçoes sérias a registrar e o misoprostol foi o método mais freqüentemente utilizado para provocar o abortamento. Em 70 por cento das vezes, a curetagem uterina foi o tratamento único e em 30 por cento das oportunidades foi acrescido o antibiótico. Enfatiza-se, por fim, a grande importância do planejamento familiar como soluçao definitiva para o problema do abortamento provocado.

[Experimental study on anti-abortional effect of yunkang oral liquid].

Yunkang oral liquid (YK) had an obviously anti-abortional effect on the abortional testing model of both rats and mice, which was induced by acupuncture and oxytocin (P < 0.05, P < 0.01); there is no statistic difference between the effect of progesterone and the effect of YK. The results showed that YK could relax obviously the uteri of both rats and mice in vitro and the uteri of rabbits in vivo. It also could antagonize the effects of oxytocin and acetylcholine on animals uteri in vivo and in vitro (P < 0.01, P < 0.05). The acute toxicologic test showed the maximal tolerance dose of ig. in mice and rats were higher than 240 g/kg and 96 g/kg respectively. The LD50 in mice (ip.) was 61.56 +/- 5.29 g/kg (p = 0.95). Subacute toxicologic test for 8 weeks of continuous drug feeding among rats did not show obvious toxicity. Mutagenicity test also showed negative results. Feeding to pregnant rats with YK did not result in teratogenicity to the offsprings. The growth and development, memory of filial generations were not affected, either. So Yunkang oral liquid, a Chinese compound recipe, has a safe and reliable effect of anti-abortion.