Miscarriage in patients with chronic endometritis and luteal phase deficiency. Principles of treatment and prevention

2021 ◽  
Vol 20 (1) ◽  
pp. 55-63
Author(s):  
T.A. Pluzhnikova ◽  
◽  
E.A. Mikhnina ◽  
V.A. Kazantsev ◽  
V.F. Bezhenar ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Patient Treatment ◽  
Chronic Endometritis ◽  
Treatment And Prevention ◽  
Tissue Changes ◽  
Principles Of Treatment ◽  
Group 2 ◽  
The Moment

Permanent inflammation of the endometrium against the background of altered vaginal microbiota is accompanied by a violation of cyclic tissue changes. The revealed deficiency of the secretory phase of the cycle was formed independently of the synthesis of progesterone by the corpus luteum and led to impaired embryo implantation and miscarriage. Objective. To evaluate the efficiency of dydrogesterone in miscarriage in patients with chronic endometritis (CE) with luteal phase deficiency. Patients and methods. The study involved 127 women aged 25 to 40 years non-pregnant and during pregnancy with biopsyverified deficiency of the luteal phase of the cycle and CE of varying degrees of activity according to immunohistochemistry data. Women from group 1 (n = 83) continuously received dydrogesterone in a cyclic regimen from the moment of diagnosis until the 21st week of pregnancy; women from group 2 (n = 44) received dydrogesterone for 4 months of CE treatment, then it was discontinued and resumed again from the onset of pregnancy until the 21st week. Conclusion. There was no normalization of the structure of the endometrium after CE treatment with dydrogesterone removal from therapy in women with miscarriage and deficiency of the luteal phase of the cycle. Administration of dydrogesterone in a cyclic regimen with pregravid preparation before pregnancy, regardless of the initial level of progesterone in the blood, by women with miscarriage, CE and luteal phase deficiency contributes to normalization of morphological state of the endometrium in most patients, to significant decrease in the frequency of early miscarriage and duration of in-patient treatment, in contrast to women who canceled dydrogesterone. Key words: dydrogesterone, luteal phase deficiency, recurrent miscarriage, chronic endometritis

scholarly journals Pregnancy rates and luteal phase characteristics of bovine embryo recipients treated with flunixin meglumine

2020 ◽  
Vol 72 (4) ◽  
pp. 1085-1092
Author(s):  
R.C. Cardoso ◽  
V.M. Codognoto ◽  
P.F. Lainetti ◽  
P.H. Yamada ◽  
G. Rizzoto ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Luteal Phase ◽  
Pregnancy Rates ◽  
Control Group ◽  
Bovine Embryo ◽  
Plasma Progesterone ◽  
Flunixin Meglumine ◽  
Group 3 ◽  
Group 2 ◽  
The Moment

ABSTRACT The aim of this study was to evaluate the effects of flunixin meglumine administration on pregnancy rates and luteal phase characteristics in bovine embryo recipients at the moment of embryo transfer. In experiment 1, in vitro produced embryos were transferred to 184 females divided as control and treated group (recipients treated with 1.1mg/kg flunixin meglumine). In experiment 2, 22 females were divided as control group; group 2 (animals submitted to a reproductive tract manipulation similar to an embryo transfer on the 7th day after estrous); and group 3 (females submitted to a manipulation and treatment with 1.1mg/kg flunixin meglumine). In experiment 1 no difference was observed between control and treated groups (40.2% and 44.6%, respectively) for pregnancy rates. In experiment 2 no difference was observed on the length of luteal phase between groups, however, animals in group 2 presented lower plasma progesterone concentrations than the control group and group 3. Therefore, we concluded that although the administration of flunixin meglumine at the moment of embryo transfer inhibited the reduction plasma progesterone concentrations, it was not effective in increasing pregnancy rates of bovine recipients.

scholarly journals Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study

2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Group 2 ◽  
Group 1

Abstract STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) −2.7%, 95% CI [−11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD −4.2%, 95% CI [−13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD −3.2%, 95% CI [−12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [−4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03740568.

1.  Heme Oxygenase‐1 Enzyme Deficiency Affects Uterine Natural Killer Cell Function During Murine Pregnancy 

2017 ◽  
Author(s):  
Tracy Zhang
Keyword(s):  
Natural Killer ◽  
Heme Oxygenase ◽  
Cell Function ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Killer Cell ◽  
Implantation Site ◽  
Heme Oxygenase 1 ◽  
Unk Cells ◽  
Uterine Natural Killer

Recurrent miscarriage is a condition that affects 1% of all women, and rejection of the fetus by the mother's immune system is thought to be one of the underlying causes. The mechanisms of maternal tolerance vital to a successful pregnancy are not well understood; however, uterine natural killer (uNK) cells are implicated as they comprise over 70% of immune cells in the uterus during early pregnancy. Heme oxygenase‐1 (HO‐1) is an enzyme that is known to be immunosuppressive. Moreover, mice missing HO‐1 have extremely high abortion rates. This study is the first to analyze the effects of HO‐1 deficiency specifically on uNK cells. We posit that an absence of HO‐1 affects normal uNK cell‐mediated immunosuppression, and also possibly their ability to modify uterine spiral arteries supplying blood to the fetus. Our study analyzed embryos from mice lacking or deficient in HO‐1 on days 8, 10, and 12 of pregnancy. Both number of uNK cells and degree of vascularization were analyzed using immunohistochemistry staining. We observed a significantly higher number of uNK cells in one area of the embryo implantation site and a significantly lower number of cells in another, suggesting the uNK cells are failing to localize properly. Analysis of vascularization is currently ongoing. Since women with multiple miscarriages have been shown to down‐regulate HO‐1, confirmation that absence of HO‐1 leads to implantation site abnormalities could pave the way for future clinical treatments.  

scholarly journals Thromboelastometric evaluation of horses submitted to experimental thrombosis and jugular thrombectomy

2016 ◽  
Vol 36 (8) ◽  
pp. 677-686 ◽  
Author(s):  
Dietrich Pizzigatti ◽  
Daniele S. Gonçalves ◽  
Thays C. Trentin ◽  
Regina K. Takahira ◽  
Ana L.G. Alves ◽  
...  
Keyword(s):  
Platelet Count ◽  
Surgical Treatment ◽  
Alpha Angle ◽  
Fogarty Catheter ◽  
Significance Level ◽  
Treatment Groups ◽  
Significant Difference ◽  
Group 2 ◽  
The Moment ◽  
Α Angle

Abstract: Jugular thrombosis in horses occurs commonly in iatrogenic situations, secondary to endotoxemic clinical condition and disseminated vascular coagulation, potentially leading to death. Thus, hemostatic evaluation becomes necessary and extremely important for monitoring the risks of systemic hypercoagulability and for the efficiency of allopathic and surgical treatment. This paper describes the hemostatic behavior in experimental jugular thrombosis of ten healthy equines, subsequently submitted to two thrombectomy techniques and receiving heparin sodium as anti-rethrombosis therapy. These animals were evaluated for 20 days by thromboelastometry (TEM), platelet count, hematocrit and fibrinogen, at four moments: pre-induction to phlebitis (D0-MPF); three days after thrombophlebitis induction (D3-MFM); 6 days after, - moment of thrombophlebitis - (D9-MT); and 54 (D16) and 126 (D19) hours after thrombectomies (PTM). Thrombectomy was performed via a Vollmar Ring (group 1, n=5) and Fogarty catheter (group 2, n=5). All the animals received heparin (150 UI/kg, SC) every 12 hours, for ten days after the respective thrombectomies. Through the blood samples were evaluated TEM, activated partial thromboplastin time (aPTT) and prothrombin time (PT), dosing of fibrinogen, hematocrit and platelet count at the abovementioned moments. For comparison between groups and moments the t test was applied at 5% significance level. No significant difference was verified between treatment groups at any of the moments. There were reductions in clotting time (CT) and clot formation time (CFT), with increase in maximum lysis (ML) until the moment D9-MT. Evaluation through INTEM® reagent presented prolongations of CT and CFT with reduction of α angle and ML starting from D16 and D19. Similarly, aPTT presented significant differences between moments pre- (D0, 3 and 9) and post- (D16 and 19) anticoagulant and surgical treatment. The platelet numbers were diminished at moments D16 and D19. In evaluation with EXTEM® reagent, prolongation of CT and CFT occurred only between the moments D0 vs. D3 and vs. D9. O PT did not present significant differences. The results obtained demonstrate that experimental jugular thrombophlebitis leads to local clinical alterations, with impairment of tissue and of the extrinsic coagulation pathway (EXTEM® ), but without evidence of systemic hypercoagulability status, since there was no increase of the alpha angle or maximum clot firmness (MCF). Furthermore, TEM was shown useful and more sensitive than conventional coagulation tests (PT, aPTT and fibrinogen) for the monitoring of anticoagulant therapy, as demonstrated in other works.

scholarly journals POSSIBILITY FOR NON-INVASIVE DIAGNOSIS OF CHRONIC ENDOMETRITIS IN WOMEN AT RISK DURING PREGRAVID PREPARATION

2019 ◽  
Vol 72 (1) ◽  
pp. 64-67
Author(s):  
Olena О. Taranovska ◽  
Volodymyr К. Likhachov ◽  
Ludmyla М. Dobrovolska ◽  
Oleg G. Makarov ◽  
Yanina V. Shymanska
Keyword(s):  
High Risk ◽  
Luteal Phase ◽  
The Other ◽  
Menstrual Blood ◽  
Control Group ◽  
Simple Method ◽  
Chronic Endometritis ◽  
Non Invasive ◽  
Additional Group ◽  
Clinically Significant

Introduction: Detection and treatment of chronic endometritis (CE) is clinically significant, though involves intrauterine intervention to collect endometrium. The aim: To estimate the possibility to use fertility α2-microglobulin (FAMG) as the marker of the high risk for CE. Materials and methods: 70 women with CE who were planning pregnancy were tested for FAMG in menstrual blood. 40 of them received treatment of CE. The other 30 women refused from the proposed treatment. The control group involved 30 women who had neither CE nor luteal phase deficiency (LPD). Additional group (20 women) had LPD without CE. Results: The decrease of FAMG by 2.4 times was noted in women with CE (16.3 ± 3.9 μg/ml against 39.8 ± 8.3 μg/ml in the controls). In LPD the index was 5.6 times lower. After treatment the level of FAMG was increasing. Conclusions: The decrease of the amount of FAMG in menstrual blood is specific for women both with CE and LPD. Detection of abnormally low rates of FAMG in all women with CE enables, with the exception of absolute hypoprogesteronemia and LPD, using it as a simple method of estimation of the functional state of endometrium. Its application can be very useful both for non-invasive diagnosis of CE and subsequent evaluation of treatment of this pathology.

scholarly journals The role of the new coronavirus infection (COVID-19) in the progression and development of cerebrovascular diseases. A competent choice of pathogenic treatment is the key to success in treatment and prevention. An expert’s view from the ‘red zone’

2021 ◽  
Vol 13 (1) ◽  
pp. 57-66
Author(s):  
V. V. Kovalchuk
Keyword(s):  
Emotional Disorders ◽  
Clinical Manifestations ◽  
Cerebrovascular Diseases ◽  
Recent Experience ◽  
Treatment And Prevention ◽  
State Recovery ◽  
Group 2 ◽  
State Examination ◽  
Group 1

COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (p<0.05). According to Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Multidimensional Fatigue Inventory (MFI-20), and Spiegel Sleep Questionnaire (SSQ), the average indicators improved significantly more in Group 1 than in Group 2 (p<0.05). The absence of quality of life impairment and their minimal severity were observed in Group 1 in 77.9%; in Group 2 – in 33.7% (p<0.001). Statistically significant differences between the groups of patients were also observed in relation to emotional state recovery according to the Wakefield Questionnaire and the Spielberger State Trait Anxiety inventory.Conclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.

scholarly journals Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review

2020 ◽  
Vol 37 (12) ◽  
pp. 2897-2911
Author(s):  
Giovanni Buzzaccarini ◽  
Amerigo Vitagliano ◽  
Alessandra Andrisani ◽  
Carla Mariaflavia Santarsiero ◽  
Rossana Cicinelli ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wave Propagation ◽  
Embryo Transfer ◽  
Embryo Implantation ◽  
Histological Finding ◽  
Vessel Density ◽  
Chronic Endometritis ◽  
Flow Reserve ◽  
Transfer Success

Abstract Purpose Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment. Methods The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway. Results CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua. Conclusion This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

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