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The University Hospital Advanced Age Pregnant (UNIHOPE) Cohort is the major part of the National Key Research and Development Program on Reproductive Health & Major Birth Defects Control and Prevention Project, which is funded by the Ministry of Science and Technology of China. The Project is led by Prof. Zhao Yangyu, from the Department of Gynecology & Obstetrics, Peking University Third Hospital, and the UNIHOPE cohort is led by Prof. Jian-meng Liu, the Co-PI of the Project.
This study seeks to evaluate pregnancy outcomes following hysteroscopic uterine cavity expansion surgery for patients with dysmorphic uterine cavities and poor reproductive histories. Patients already planning to undergo surgery at the recommendation of their physicians will be recruited for participation.
50%-60% of the known causes of recurrent pregnancy loss(RPL) are associated with embryonic aneuploidy, such that preimplantation genetic screening (PGS) on embryos acquired by assisted reproductive treatment should improve the rate of pregnancy and live birth in those patients. In dispute though the clinical application of PGS has been, a series of studies show that the new generation of PGS(PGS 2.0), based on blastocyst biopsy followed by whole genome analysis, has significantly improved the clinical outcome of IVF treatment. At present, there is still a need for the evidence of the use of PGS 2.0 in RPL patients, who may benefit from this emerging technology considering the prevalence of genetic abnormalities and the number of transferable embryos in this population. An earlier single center RCT conducted by our IVF center displayed higher implantation rate, clinical pregnancy rate and ongoing pregnancy rate calculated by per embryo transfer(ET) cycle in IVF/ICSI+PGS group compared with IVF/ICSI group. This multi-center prospective randomized clinical trial is to provide more data to determine whether the clinical outcomes are significantly improved per treatment cycle such that provide evidence for the application of PGS in RPL patients. Besides, risk factors of PGS outcome are to be analyzed from multi-center data to build a model for prediction of the possible outcomes of PGS and direction of the clinical choice.
Recurrent miscarriage is a pregnancy loss before 20 weeks of gestation. The recurrent pregnancy loss usually occurring in the first trimester of gestation and its rate is quite high (15-20% even in full reproductive period) . In 2012, the American Society for Reproductive Medicine Practice Committee issued a statement that defined recurrent pregnancy loss as a disease distinct from infertility defined by two or more failed consecutive pregnancies.
evaluation of the role of ultrasonographic parameters (mean gestational sac diameter, yolk sac diameter, crown rump length, embryonic heart rate and uterine artery Doppler) in predicting early pregnancy failure in patients with recurrent pregnancy loss
Infertility and miscarriage ordinary events in reproductive failure in humans, as are affected one couple in every six couples of reproductive age and abortion is including in approximately 15-20% of all pregnancies. Over the decades since the beginning of Assisted Reproductive Technology (ART) and in vitro fertilization (IVF) pregnancy rate still remains below 30% and Recurrent Implantation Failure in one of the most important limiting factor is the assisted reproductive techniques. Determine the causes of Recurrent Pregnancy Loss (RPL) can raise the success rate of assisted reproductive techniques and hope infertile couples and reduce psychological pressure on them and also reduce costs is very important. According to studies conducted in recent years one of the most important mechanisms of recurrent miscarriage is maternal immune system because the fetus as an allograft toxic (Semi allograft) to the mother. Studies have demonstrated that ratio of Th1 to Th2 cells increase in maternal peripheral blood cells can be directly associated with recurrent pregnancy loss. It also increases the number of Natural killer (NK) cells and Th17 cells and their cytokines in peripheral blood of mother and is also associated with an increased risk of infertility. Several studies have also shown that the fertile persons in compare to infertile have increased amount of Treg cells and inhibitory cytokines associated with it. The studies have shown that if patients are properly selected RPL and placed under appropriate immunotherapy approaches it will be seen a significant increase in fertility. In previous years, followed by the production of intravenous immunoglobulin (IVIg) and determine its effect on immune suppression, IVIg uses for the treatment of various diseases such as thrombocytopenic purpura, Guillain-Barre syndrome, Kawasaki disease and Myasthenia gravis. It is also valuable drug for the treatment of patients with infertility problems have also been used but still remains how well the drug and its mechanism of action are unknown. Probably one of the mechanisms of IVIg is its effect in suppressing the activity of NK cells. Likely IVIg cause to increase Cluster of Differentiation 94 (CD94) molecule as an inhibitor molecule on the NK cells and reduced the cytotoxic activity of NK cells. So because of reduce the cytotoxic activity of NK cells by IVIg in patients with RPL injection increases the likelihood of successful pregnancy. Previous studies have shown that the incidence of genetic abnormalities in children who have received immunosuppressive drugs such as IVIg like normal people and normal society. In this study we used IVIg before IVF to suppress the immune system in patients with immunological causes of RPL and the results will be compared with a control group that did not receive any type of drug.
Recurrent miscarriage (RM) defined by >=3 consecutive losses affects 1% of fertile couples. Most women have recurrent early loss with a failure of development before 10 weeks' gestation. Standard investigations fail to reveal any apparent cause in >50% of couples. No study has demonstrated any benefit of any medication in women with Unexplained RM, in the presence or absence of an inherited thrombophilia. Moreover, the benefit of aspirin and/or heparin has not been proved in women with Antiphospholipide (APL) antibody without other clinical manifestations of Antiphospholipide Syndrome. Hydroxychloroquine (HQ) is a molecule whose properties (anti-thrombotic, vascular-protective, immunomodulatory, improved glucose tolerance, lipid-lowering, anti-infectious) could be usefull against mechanisms of Unexplained RM. There is no data concerning the benefit of HQ in RM in the presence or absence of antiphospholipid antibodies or any inherited thrombophilia. Administration in (Systemic Lupus erythematosus (SLE) women and for Malaria prevention provides extensive safety data during pregnancy. Oral administration makes possible treatment since the preconception period. For all of that and its low cost, hydroxychloroquine should be evaluated in RM whatever the woman thrombophilic status.
Background of the study: The etiology of recurrent miscarriage (RM, defined as three or more consecutive miscarriages without any proven maternal or fetal cause), remains undiagnosed in more than 50% of cases. In these cases it is generally considered that a disturbance in the normal mother-embryo interactions is a causal factor. This disturbance may be based on a dysregulation of embryo invasiveness and/or decidual acceptance (e.g. altered decidualization; endometrial changes in preparation for the acceptance of a putative pregnancy). Moreover, dysfunctional maternal immune regulatory natural killer (NK) cells, implicated in tolerance induction and trophoblast invasion,may also underlie the occurrence of RM. The Selection Failure hypothesis for RM suggests that super-receptive endometrium (possibly due to increased embryo invasiveness and/or decidual acceptance and/or dysregulated immune cell function) may allow 'poor quality' embryos to implant and present as a clinical pregnancy before miscarrying. Fundamental knowledge on mechanisms of embryo implantation, decidual function and maternal immune reactivity in successful pregnancies has accumulated over the past 5 years. This study aims to investigate whether dysregulation of (one of) these mechanisms may underlie RM. Objective of the study: To test The Selection Failure hypothesis by assessing A) the degree of embryo invasiveness and decidual acceptance (the quality of decidualization, endometrium-embryo communication and endometrial stromal cell (ESC) migration) and B) the angiogenic capacity of decidual NK (dNK) cells, in order to elucidate the pattern of the mother-embryo equilibrium in women with RM.
Evaluating the effect of intralipid on the natural killer cells
The present study is divided into two groups ,one is the patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations > 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list. The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism in two groups。