Progresses in Integrated Traditional Chinese and Western Medical Research on Reproductive Immunology

Reproductive immunology is a crossed subject of reproductive biology and immunobiology. Great progresses have been achieved in the subject along with the deep development in life science. Modern reproductive immunology includes immunological regulation of fertility, materno-fetal immuno-regu-lation, and neuro-reproductive endocrino-immune network. With the integrated traditional Chinese and western medicine (ICWM) applied to reproductive immunology it has been greatly enriched in research contents and depth. The present review is to introduce the recent progresses in research of integrated medicine on reproductive immunology.

Intratubal Methotrexate Injection Combined with Chinese Herbal Medicine for Tubal Pregnancy and Following Pregnancy Prognosis

Objective: To compare the effects of treatment of tubal pregnancy (TP)and its following second pregnancy by intratubal methotrexate injection(IMI) alone and combination of IMI with Chinese herbal medicine. Methods: Thirty-five patients suffering from unruptured TP were divided into two groups at random, to the 19 patients in the treated group, the treatment of combined IMI with Ectopic Pregnancy decoction No. 2 (EP2, a traditional Chinese medical decoction) was applied, and to the other 16 patients in the control group, IMI alone was applied for control. Serum concentrations of human chorionic gonadotro-pinβ(β-HCG), size of the gestational sac, existent time of fetal cardiac beat and peritoneal fluid were measured before and after treatment. And hysterosalpingography were performed 6 months after ending the treatment to verify the presence of tubal obstruction and the condition of relapse.Results: The treatment of all the 35 women was successful. The recovery duration of serumβ-HCG, disappearance duration of TP sac and existent time of peritoneal fluid in the treated group were 20.0±7. 8 days, 1.2±0. 7 months and 10. 7±2. 9 days respectively, which were significantly different from those in the control group (24. 4 ±8.1 days, 3.6±1.7 months and 19.1±3. 2 days respectively(P<0. 05, P<0.01 and P<0. 05 respectively), but the existent time of fetal cardiac beat in the two groups (8.8±1. 9 days vs 9.0±1. 3 days) was not significantly different (P>0.05). The post-treatment oviduct obstructive rate in the two groups was 10.5% and 43.8% respectively, that in the treatment group was less significant (P<0.05). The relapse rate of EP in the treatment group was insignificantly different from that in the control group (5.3% vs 18.8%, P>0.05). Conclusion: The two therapies (IMI alone and IMI combined with EP2) could obtain e-qual efficacy in curing TP. Compared with IMI alone, the combined therapy appears to have the effects of accelerating the resorption of gestational sac and peritoneal fluid, improving the patency of fallopian tube and ameliorating the circumstance of pregnancy, which is favorable to improvement of the re-pregnancy rate and reduction of the re-occurrence of ectopic pregnancy as well as to the enhancement of the effect of IMI in killing trophocytes. But there is not enough proof to show the potency of EP2 in killing embryo.

子宫内膜异位症性不孕症患者外周血单核细胞趋化蛋白-1水平的测定

Objective: To test whether serum monocyte chemotactic protein-1 (MCP-1) chemokine levels correlate with endometriosis in infertile women. Study design: A group of women with endometriosis (n = 18, infertile) was compared with patients with uterine leiomyoma (n = 16, fertile), unexplained infertility (n = 5, infertile), and healthy women (n = 16, fertile). MCP-1 expression levels were evaluated by ELISA assay. The data obtained were statistically analyzed using the Mann-Whitney test. P-Values < 0.05 were considered as significant. Results: MCP-1 concentrations (median; range of values) in serum were as follows: women with endometriosis (221; 101-635 pg/ml), women with unexplained infertility (167, 114-234 pg/ml), women with uterine leiomyoma (137; 88-200 pg/ml), and healthy donors (123; 98-194 pg/ml). Significant differences were observed in the women with endometriosis compared with those with uterine leiomyoma (p = 0.02) and healthy donors (p = 0.002). Among the women with endometriosis, the level of significance in MCP-1 level at rAFS stages III-IV was higher than that at rAFS stages I-II compared with healthy donors and women with leiomyoma (p = 0.002 and p = 0.02, respectively). Conclusions: These data show that an increased level of MCP-1 can characterize infertile women with endometriosis. However, further studies are needed to be able to determine whether increased MCP-1 chemokine expression can be related to infertility or is a result of endometriosis progress.

Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune system.In the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological pregnancy.Immune cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy establishment.However,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.

The number and cytotoxicity and the expression of cytotoxicity-related molecules in peripheral natural killer(NK)cells do not predict the repeated implantation failure(RIF)for the in vitro fertilization patients

Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.

A Retrospective Review of 10 Cases of Villoglandular Papillary Adenocarcinoma of the Uterine Cervix Including One with Successful Pregnancy

Objective:Villoglandular papillary adenocarcinoma(VGPA)of the uterine cervix is a subtype of cervical adenocarcinoma.In the present study,we summarized the clinical features of VGPA of the uterine cervix and discussed the potential indications for a conservative treatment.Methods:A retrospective review of clinical characteristics and treatment aspects of 10patients with VGPA at the Obstetrics and Gynecology Hospital of Fudan University was conducted between January 2007 and December 2016.Almost all of the existing 40 English papers on“villoglandular papillary adenocarcinoma[title/abstract]”identified from PubMed were obtained.Clinical data from these papers were analyzed in terms of age,International Federation of Gynecology and Obstetrics(FIGO)stage,recurrence rate,mortality,and conservation treatment aspects.Results:The median age of 10patients with VGPA was 40years.All cases had Stage IB 1 disease.Seven patients underwent human papillomavirus examinations,which revealed 6 positive and 1 negative case(s)of infection.Six patients underwent ThinPrep cytologic tests,which revealed 4patients with atypical glandular cells,1 with a high-grade squamous intraepithelial lesion,and 1 who tested negative for intraepithelial malignancy.None of the patients had lymph node metastases.During the 6-114months of follow-up,no disease recurrence or death occurred.Of note,one patient who received conservative treatment successfully became pregnant.Conclusions:VGPA can be detected at an early FIGO stage with excellent prognosis.For young patients who do not exhibit poor prognosis factors,conservative treatment may be the first treatment choice based on overall assessment of clinical conditions.