Chronic endometritis screening in patients who experience euploid embryo implantation failure does not improve IVF outcomes after a subsequent euploid FET

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

Download Full-text

P–345 Reproductive outcome after treatment of chronic endometritis in patients with recurrent implantation failure

Human Reproduction ◽

10.1093/humrep/deab130.344 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Vega. Carrill. d. Albornoz ◽

E Carrill. D. Alborno. Riaza ◽

Á Martíne. Acera ◽

I Lópe. Carrasco ◽

N Monter. Pastor ◽

...

Keyword(s):

Antibiotic Therapy ◽

Case Series ◽

Pregnancy Rates ◽

Diagnostic Methods ◽

Microbiological Analysis ◽

Implantation Failure ◽

Reproductive Outcome ◽

Recurrent Implantation Failure ◽

Chronic Endometritis ◽

Number Of Patients

Abstract Study question Does the treatment of chronic endometritis (CE) improve reproductive outcome in patients with recurrent implantation failure (RIF)? Summary answer Treatment and resolution of CE seem to improve pregnancy rates in patients with implantation failure and CE. What is known already Over the last 10 years, the interest in the study of CE has increased given its important association with reproductive failure. The main cause of CE is an infection of the endometrial cavity caused by common microorganisms. Therefore, the recommended treatment is antibiotic therapy. Numerous studies demonstrate an improvement in reproductive outcome in patients with treated and resolved CE. The objectives of this study are to evaluate the resolution rate of CE after antibiotic treatment in patients with implantation failure diagnosed with CE and to analyse their reproductive outcome after treatment. Study design, size, duration In this prospective case series, all patients with RIF who underwent diagnostic hysteroscopy, IHC analysis with CD138 of an endometrial biopsy and microbiological analysis of an endometrial sample between October 2018 and February 2019 were included. Participants/materials, setting, methods Hysteroscopic findings suggestive of CE were collected and endometrial biopsies were taken for pathological study with CD138 and microbiological assessment. Likewise, treated endometrial samples and the results of hysteroscopy or control biopsies after treatment were collected. The data of embryo transfers post-treatment were also included in our study. Main results and the role of chance 30 patients with implantation failure were included. 15 patients (50%) were diagnosed with CE using any of the aforementioned diagnostic methods. All diagnosed patients were treated with antibiotic therapy: positive microbiological samples (9) were treated according to our antibiogram whereas those samples who were negative but were confirmed to have CE by hysteroscopy or pathological assessment (6) were treated with doxycycline. In all cases, CE resolved after treatment, except only one patient who required a second course of antibiotics to acquire a negative result. Ten patients underwent an embryo transfer after resolution of CE, resulting in 60% of ongoing pregnancies. Limitations, reasons for caution Although our results are encouraging and in accordance with other studies, we are aware that this is an observational non-randomised study with a limited number of patients. Wider implications of the findings: It seems that the treatment of CE, following its diagnosis using the aforementioned methods, can improve pregnancy rates in patients with RIF and CE. Therefore, it is likely recommendable to study CE using these three tests. Trial registration number Not applicable

Download Full-text

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

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-020-01955-8 ◽

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.

Download Full-text

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa007 ◽

2020 ◽

Vol 26 (3) ◽

pp. 154-166 ◽

Cited By ~ 2

Author(s):

Vanessa de Oliveira ◽

Jennifer Schaefer ◽

Basim Abu-Rafea ◽

George A Vilos ◽

Angelos G Vilos ◽

...

Keyword(s):

Embryo Development ◽

Ovarian Stimulation ◽

Embryo Implantation ◽

Pathological State ◽

Implantation Failure ◽

Uterine Receptivity ◽

Spatial Expression ◽

Aqp4 Expression ◽

Abnormal Expression ◽

Aquaporin Gene

Abstract The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

Download Full-text