Uterine immune profiling for increasing live birth rate: A one-to-one matched cohort study
Nathalie LédéeLaura Prat-EllenbergL. ChevrierR. BaletCynthia SimonClarisse LenobleElie El IraniDominique BouretNino Guy CassutoDominique VitouxKatia VezmarArmand BensussanG. ChaouatMarie Petitbarat
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Placentation
Live birth
Unexplained infertility
Objective To detect the expression of matrixmetalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 protein(TIMP-1) in cycling endometrium of patients with unexplained infertility,normal endometrium and normal early pregnant deciduas and explore the relationship between the expression of MMP-9 and TIMP-1 in unexplained infertility and normal pregancy.Methods Immunohistochememstry(S-P technique) and pathologic image semi-quantification were used to detect the expression of MMP-9 and TIMP-1 in endometrium of 30 unexplained infertility patients and 20 normal early pregnant deciduas and 20 normal endometrium.Results The expression of MMP-9 and TIMP-1 in normal early pregnant deciduas was the highest,showing significant difference as compared with other two groups(P0.05) The expression of MMP-9 and TIMP-1 was also high in normal endometrium as compared with other two groups(P0.05).But the expression of MMP-9 and TIMP-1 in endometrium of patients with unexplained infertility was significantly reduced as compared with other two groups(P0.05).Conclusion In unexplained infertility women,the low expression of MMP-9 and TIM P-1 protein in the implantation window phase may cause the failure of implantation and results in the infertility.
Unexplained infertility
Matrix metalloproteinase 9
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Background: Unexplained infertility is a rising problem and endometrial manipulation could be one of the solutions for enhancing the pregnancy rate and live birth rate in such circumstances.Aims: To evaluate the influence of local endometrial physical manipulation with specializd method for endometrial and tubal hydration (Elgazzar and Alalfy technique) on ICSI outcome and in increasing chemical, clinical, and live birth rate in ICSI after previous recurrent ICSI failure in patients with unexplained infertility.Results: When comparing group 1 (hydrotubation group) and group 2 (the control group with no intervention) with regards to the biochemical, clinical, and live birth rate, the hydrotubation group revealed higher rates and a better ICSI outcome.Conclusion: Hydrotubation is useful in increasing biochemical, clinical, and live birth rates after recurrent failed ICSI trials with a specialized method for hydration of endometrium and tubes (Elgazzar and Alalfy technique).
Live birth
Unexplained infertility
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Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility?Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success.We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome.This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles.AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate.After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%).This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI.Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI.Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work.n/a.
Live birth
Unexplained infertility
Letrozole
Intrauterine insemination
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Immunostaining
Unexplained infertility
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To study the expression of HOXA10 gene in the endometrium of normal fertile women and patients with unexplained infertility during different phases of menstrual cycle.Endometrium samples were obtained by curettage in 52 normal fertile women and 38 patients with unexplained infertility during different phases of menstrual cycle, HOXA10 mRNA expression were detected by in situ hybridization and reverse polymerase chain reaction (RT-PCR).(1) HOXA10 mRNA were detected in the glandular and stromal cells of endometrium of fertile women during the menstrual cycle. By in situ hybridization (positive unite, PU), HOXA10 mRNA levels were significantly higher in the mid-secretory phase [glandular cells (G) 5.69 +/- 0.57, stromal cells (S) 7.48 +/- 0.67] and late-secretory phase(G 5.99 +/- 0.40, S 7.98 +/- 1.08) than those in late proliferative phase (G 3.35 +/- 0.20, S 3.20 +/- 0.37) and early secretory phase (G 3.07 +/- 0.26, S 3.18 +/- 0.27)(P < 0.01). HOXA10 mRNA levels of endometrial stromal cells of mid and late secretory were higher than those of glandular cells (P < 0.01). By RT-PCR, HOXA10 mRNA levels were significantly higher in the mid secretory phase (57.0 +/- 3.4)% and late secretory phase (56.2 +/- 2.9)% than those in early proliferative phase (31.8 +/- 2.6)%, late proliferative phase (32.2 +/- 2.3)% and early secretory phase (32.5 +/- 1.6)% (P < 0.01). (2) Patients with unexplained infertility did not have an increase of endometrial HOXA10 mRNA level in mid and late secretory phase, as compared with the controls (P < 0.01).(1) High expression of HOXA10 gene during mid and late secretory phase indicated that HOXA10 gene may involve in implantation. (2) Aberrant HOXA10 expression of patients with unexplained infertility suggests that altered development of endometrium at the molecular level may contribute to the aetiology of infertility. (3) HOXA10 gene may play a role in decidua lization of endometrium during early pregnancy.
Unexplained infertility
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Live birth
Unexplained infertility
Intrauterine insemination
Assisted Reproductive Technology
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Objective To study the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 protein(TIMP-1) in cycling endometrium with unexplained infertility and normal endometrium,and to explore the relationship between the expression of MMP-9,TIMP-1 in unexplained infertility and normal pregnancy.Methods Immunohistochemistry(S-P technique) was used to detect the expression of MMP-9 and TIMP-1 in endometrium of selected cases consisting of 30 unexplained infertility and 20 normal endometrium.Results The expression of MMP-9 and TIMP-1 in normal endometrium could be observed in glandular epithelium and stromal cells during different phase.They expressed low in proliferative phase,but obviously higher in secretory phase,which showed significant difference in statistics(P0.05).But in unexplained infertility their weak expression was noted during proliferative phase and secretory phase.Between the expression levels of infertility and normal endometrium,the difference was significant(P0.05).Conclusion The weak expression of MMP-9 and TIMP-1 will reduce the potential of endometrial acceptation and embryo implantation,and accordingly may bring about infertility.
Unexplained infertility
Matrix metalloproteinase 9
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In the 12 subsep uteri the endometrium covering the septum was studied using light microscopy, electronic scanning microscopy and electronic transmission microscopy for the purpose of determining if it should be considered a reason for inadequate implantation and therefore justify an anomalous evolution of pregnancy. The results show that compared with a normal endometrium there is only a slight difference with the basal state. This alteration could however negatively influence the stages of development following implantation and particularly the structure of the maternal-fetal relationships which preclude placentation.
Placentation
Basal (medicine)
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Abstract STUDY QUESTIONS In couples with unexplained infertility and a poor prognosis of natural conception, are four cycles of IUI with ovarian stimulation (IUI-OS) non-inferior to one completed cycle of IVF for the outcome of cumulative live birth? Are four cycles of IUI-OS associated with a lower cost per live birth compared to one completed cycle of IVF? Will four cycles of IUI-OS followed by one complete cycle of IVF result in as many live births at lower cost per live birth, than two complete cycles of IVF? Will four cycles of IUI-OS followed by two complete cycles of IVF result in more live births at lower cost per live birth, than two complete cycles of IVF alone? WHAT IS KNOWN ALREADY IUI is widely used in the USA, the UK and Europe as a low cost, less invasive alternative to IVF for couples with unexplained infertility. Although three to six cycles of IUI were comparable to IVF in the three major studies carried out to date, gonadotrophin ovarian stimulation was used in the majority of cases, and this also resulted in a high multiple pregnancy rate in some studies. Ovarian stimulation with clomiphene citrate is known to have lower multiple pregnancy rates. STUDY DESIGN, SIZE, DURATION The FIIX study is a multicentre, open label, parallel, pragmatic non-inferiority randomized controlled trial of 580 couples with unexplained infertility comparing four cycles of IUI-OS with clomiphene citrate and one completed cycle of IVF. Variable block randomization stratified by age and clinic with electronic allocation will be used. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples with poor prognosis for natural conception and who are eligible for publicly funded fertility treatment in six fertility clinics in New Zealand. STUDY FUNDING/COMPETING INTEREST(S) Auckland Medical Research Fund (3718892/1119003), A+ Trust, Auckland District Health Board (A + 8479), Maurice and Phyllis Paykel Trust (3718514). No competing interests. TRIAL REGISTRATION NUMBER ACTRN12619001003167. TRIAL REGISTRATION DATE 15 July 2019 DATE OF FIRST PATIENT’S ENROLMENT 02/08/2019
Live birth
Unexplained infertility
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Objective:To study on the expression of phosphorylated Akt and its significance in the endometrium of the women with unexplained infertility during the period ofimplantation window Methods:18 samples of the endometrium in midterm of the luteum from the women with primary and unexplained infertility were collected as test group,and 30 samples of the endometrium in midterm of the luteum from the patients with secondary infertility and two fallopian tube obstructed were also collected as control group.SP immunohistochemistry assay was used to determine the tissue location of pAKt and LIF and their semi-quantitative expression of the endometrium in the two groups.Results:LIF expression were located in endometrial glandular epithelial cells and luminal epithelial cells of the two group,the expression of pAKt markedly located in stromal cells and cytoplasm showed strong expression in the patients′endometrium of the two groups.Endometrial LIF and pAKt protein semi-quantitative expression in the two groups(SP immunohistochemistry assay)revealed as followed:compared with the patients with two fallopian tube obstructed,LIF and pAKt protein expression were both significantly decreased in the unexplained infertile women(P0.05),the expressions of LIF and pAKt protein in the pregnant patients after IVF/ICSI in the two groups were both significantly higher than those of the non-pregnant patients(P0.01).Conclusion:Decreasing of endometrium receptivity is one of the infertile causes of women with unexplained infertility,decreased expression of pAKt in the endometrium duringimplantation windowmay be one of the causes of infertile women′s decreased endometrium receptivity.
Unexplained infertility
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