Impact of prednisone in patients with repeated embryo implantation failures: Beneficial or deleterious?

Lédée, Nathalie; Prat-Ellenberg, Laura; Petitbarat, Marie; Chevrier, L.; Simon, Cynthia; Irani, Elie El; Vitoux, Dominique; Bensussan, Armand; Chaouat, G.

doi:10.1016/j.jri.2018.03.003

Cited by 37 publications

(18 citation statements)

References 30 publications

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“…Due to their potent immune regulatory capacity, glucocorticoids appear as a potential therapeutic option in women suffering from with repeated idiopathic embryo implantation failure. Corticoid therapy is becoming an important medication for patients with history of repeated implantation failures (RIF) after IVF/ICSI and at least a proportion of the patients respond to such intervention (110). Indeed, emerging data accumulated in small group of patients with increased numbers of NK cells in the endometrium suggests potential beneficial effects of corticosteroid therapy (111) as intrauterine perfusion of dexamethasone reduced NK cell frequencies and resulted in successful pregnancy (112).…”

Section: Progesterone Infertility and Early Pregnancy Lossmentioning

confidence: 99%

Steroids, Pregnancy and Fetal Development

2020

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Maternal glucocorticoids critically rise during pregnancy reaching up to a 20-fold increase of mid-pregnancy concentrations. Concurrently, another steroid hormone, progesterone, increases. Progesterone, which shows structural similarities to glucocorticoids, can bind the intracellular glucocorticoid receptor, although with lower affinity. Progesterone is essential for the establishment and continuation of pregnancy and it is generally acknowledged to promote maternal immune tolerance to fetal alloantigens through a wealth of immunomodulatory mechanisms. Despite the potent immunomodulatory capacity of glucocorticoids, little is known about their role during pregnancy. Here we aim to compare general aspects of glucocorticoids and progesterone during pregnancy, including shared common steroidogenic pathways, plasma transporters, regulatory pathways, expression of receptors, and mechanisms of action in immune cells. It was recently acknowledged that progesterone receptors are not ubiquitously expressed on immune cells and that pivotal features of progesterone induced-maternal immune adaptations to pregnancy are mediated via the glucocorticoid receptor, including e.g., T regulatory cells expansion. We hypothesize that a tight equilibrium between progesterone and glucocorticoids is critically required and recapitulate evidence supporting that their disequilibrium underlie pregnancy complications. Such a disequilibrium can occur, e.g., after maternal stress perception, which triggers the release of glucocorticoids and impair progesterone secretion, resulting in intrauterine inflammation. These endocrine misbalance might be interconnected, as increase in glucocorticoid synthesis, e.g., upon stress, may occur in detriment of progesterone steroidogenesis, by depleting the common precursor pregnenolone. Abundant literature supports that progesterone deficiency underlies pregnancy complications in which immune tolerance is challenged. In these settings, it is largely yet undefined if and how glucocorticoids are affected. However, although progesterone immunomodulation during pregnancy appear to be chiefly mediated glucocorticoid receptors, excess glucocorticoids cannot compensate by progesterone deficiency, indicating that additional und still undercover mechanisms are at play.

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Section: Progesterone Infertility and Early Pregnancy Lossmentioning

confidence: 99%

Steroids, Pregnancy and Fetal Development

2020

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“…Adjunction of immunotherapy was proposed in over activated and mixed profiles either to decrease Th-1 cytokines or to control the recruitment and/or activation of uNK cells. As a first-line treatment, corticosteroid adjunction was recommended (33). In routine practice, we still lack precise indications for its use based on objective testing (34-37).…”

Section: Immunotherapymentioning

confidence: 99%

Endometrial Immune Profiling: A Method to Design Personalized Care in Assisted Reproductive Medicine

et al. 2020

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“…Our hypothesis is that re-balancing the initial dialog between the embryo and the endometrium may rescue some viable pregnancies. In patients with a local low activation, the stimulation of the maturation, mobilization, expression of uNK through uterine scratching, hCG luteal supplementation and exposition to seminal plasma aim to improve the mechanisms of angiogenesis and immunotropism ( 33 , 34 , 51 , 52 , 55 , 57 ). In this case, the mechanism leading to the miscarriage would be a local deficiency of angiogenesis and immunotrophism.…”

Section: Discussionmentioning

confidence: 99%

“…As the first-line treatment, glucocorticoids (GC) supplementation was recommended ( 34 ). Patients received 20 mg of prednisolone and vitamin E (an antioxidant, 1 g daily) from day 3 of ovarian stimulation until the pregnancy test.…”

Section: Methodsmentioning

confidence: 99%

The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss

et al. 2021

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IntroductionThe endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.MethodsThis is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.ResultsUterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).ConclusionOur study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

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Impact of prednisone in patients with repeated embryo implantation failures: Beneficial or deleterious?

Cited by 37 publications

References 30 publications

Steroids, Pregnancy and Fetal Development

Steroids, Pregnancy and Fetal Development

Endometrial Immune Profiling: A Method to Design Personalized Care in Assisted Reproductive Medicine

The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss

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