Repeated implantation failure: a new potential treatment option

Makrigiannakis, Antonis; Benkhalifa, Moncef; Vrekoussis, Thomas; Mahjub, S.; Kalantaridou, Sophia Ν.; Gürgan, Timur

doi:10.1111/eci.12417

Cited by 34 publications

(21 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…After the implantation, the embryo suppresses this response and prevents the rejection [40]. The deregulation of expression pattern of CRH was associated with unfavorable reproductive outcomes as well as chronic endometrium-derived inflammatory disorders, such as endometriosis and adenomyosis [41]. Positive outcome was found after the intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) [41] especially when pretreated with corticotropin-releasing hormone that acts by regulating apoptosis of activated T-lymphocytes at the implantation site [42].…”

Section: Endometriummentioning

confidence: 99%

“…The deregulation of expression pattern of CRH was associated with unfavorable reproductive outcomes as well as chronic endometrium-derived inflammatory disorders, such as endometriosis and adenomyosis [41]. Positive outcome was found after the intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) [41] especially when pretreated with corticotropin-releasing hormone that acts by regulating apoptosis of activated T-lymphocytes at the implantation site [42]. The results of eight studies showed that intrauterine administration of activated autologous peripheral blood mononuclear cells prior to embryo transfer improves the reproductive outcomes in women with repeated implantation failure [43].…”

Section: Endometriummentioning

confidence: 99%

See 1 more Smart Citation

Implantation and the Fetal Health

Ljubić¹,

Abazović²,

Ljubić³

et al. 2020

Induced Abortion and Spontaneous Early Pregnancy Loss - Focus on Management

View full text Add to dashboard Cite

Implantation is one of the crucial periods in human reproduction. Increasing body of evidence suggests that the improper (dysfunctional) implantation and the formation of the placenta can endanger life and health of both the fetus and the mother, during prenatal life and decades after delivery. The idea of the inverted pyramid of prenatal care has emerged in the recent years, as the early detection and prevention of health disorders of the fetus are specially focusing on the first trimester. By applying this principle, disorders in the perinatal period could be prevented or treated with better outcome. The changes that lead to the deficient implantation should be sought in the preimplantation period, in relation between the embryo and the endometrium. It is possible that the time is approaching when the disorders of the pregnancy caused by dysfunctional implantation would be the indication for the application of a natural IVF (without ovarian stimulation) with the use of new biotechnological achievements. For better results of the perinatal medicine, it is necessary to apply earlier (in the preconception and preimplantation periods) the therapy based on the subcellular and genetic level by applying the latest biotechnological procedures.

show abstract

Section: Endometriummentioning

confidence: 99%

Section: Endometriummentioning

confidence: 99%

Implantation and the Fetal Health

Ljubić¹,

Abazović²,

Ljubić³

et al. 2020

Induced Abortion and Spontaneous Early Pregnancy Loss - Focus on Management

View full text Add to dashboard Cite

show abstract

“…With the aim of provoking an immune reaction, several efforts have been made by transferring autologous peripheral blood mononuclear cells (PBMCs) in the uterine cavity prior to embryo transfer. PBMCs have been transferred either unstimulated or stimulated by priming the PBMCs with immunomodulatory agents [47,48]. In this context, HCG was the first agent to be used for PBMCs’ activation [48].…”

Section: The Clinical Impact Of Intrauterine Administration Of Hcgmentioning

confidence: 99%

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

Makrigiannakis

Vrekoussis

Zoumakis

et al. 2017

IJMS

Self Cite

View full text Add to dashboard Cite

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes.

show abstract

“…Though in vitro fertilization (IVF) success is generally limited to 30% depending on Indeed, with special interest on immunology of reproduction, Yoshioka et al [23] 20 was the first team which could to realize immunotherapy for patients with repeated IVF 21 failures based on intrauterine administration of peripheral blood mononuclear cells 22 (PBMC). Then, several studies developed this novel approach with some modifications 23 on PBMC preparation protocol, including fresh or frozen cycles, embryo day 3 or 24 blastocyst transfer, patients with at least 2, 3 or 4 RIF in order to improve significantly 25 clinical outcomes and decrease the miscarriage rates [22,24,25]. 26 Furthermore, PBMC immunotherapy could to be efficient for some RPL cases and 27 avoiding miscarriages [22,26,27] despite lack of clear definition toward RIF and 28 RPL [28].…”

Section: Introductionmentioning

confidence: 99%

“…108 Yoshioka et al were the pioneers in this approach application while the research teams' 109 followers could to involve some technical modifications in PBMC preparation 110 protocol [23]. Some could to prove the efficiency of hCG supplementation on PBMC 111 culture for 72h [22,24] or trying to minimize latter to 24h [26,27,34] while others were 112 more focused on the efficiency of CRH [25]. All these technical adaptations were 113 occurred in order to enhance at maximum the function of PBMC and their cytokines 114 secretions to activate thereafter the maternal immune system into endometrium after an 115 intrauterine administration and be ready for embryo implantation.…”

mentioning

confidence: 99%

Luteal progesterone level correlated with immunotherapy success of patients with repeated implantation failures

Sefrioui

Madkour

Bouamoud

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Immunotherapy using PBMC administration demonstrated relatively its effectiveness to treat RIF patients but it still unclear to explain some miscarriages. Luteal progesterone level (LPL) issued from corpus luteum after embryo implantation stage could be informative basis data to personalize immunotherapy for RIF patients predicting clinical outcomes. This randomized controlled study included 70 patients undergoing ICSI program presenting at least 3 RIF: 39 for Control of untreated patients and 31 for PBMC-test concerning treated patients with immunotherapy. For PBMC-test group, Peripheral Blood Mononuclear Cells (PBMCs) were isolated from patients on ovulation induction day and cultured three days to be administered to intrauterine cavity of patients two days before fresh embryo transfer. LPL was analyzed at day 15 after embryo transfer and clinical outcomes were calculated including implantation, clinical pregnancy and miscarriage rates. Clinical outcomes were doubly improved after immunotherapy including implantation and clinical pregnancy rates comparing Control versus PBMC-test (10% and 21% vs 24% and 45%). In the other hand, this strategy showed an increase over double in LPL (4ng/ml for Control vs 9ng/ml for PBMC-test) while the latter was correlated to clinical pregnancy. Bypassing the effectiveness of this immunotherapy approach for RIF patients, it is directly correlated to LPL proving the interactive reaction between immune profile of the treated patients and progesterone synthesis by corpus luteum. 2 embryo implantation, the major part of implantation establishment is bypassing embryo 3 quality and its genetic integrity highlighting the communication between embryo and the 4 mother. This cross talk is essentially orchestrated by hormonal and immune dialogues 5 November 17, 2018 1/10 in order to assure embryo invasion in the maternal endometrium without rejecting the 6 fetal allograft. Furthermore, it is already known that progesterone (P4) is one of the 7 most important implantation/pregnancy success keys for its effects on the endometrium 8 and early pregnancy survival while its removal results in miscarriage [1-3]. 9P4 is a hormonal key to modulate the maternal immune system by reducing natural 10 killer (NK)-cell activity [4], inhibiting cytotoxic T-cell activity [5], increasing HLA-G 11 production in trophoblast cells [6], increasing suppressor-cell levels [7] and as special 12 mechanism, it is able to induce lymphocyte-blocking proteins production such as 13 progesterone-induced blocking factor (PIBF) [8][9][10][11]. Generally, its anti-inflammatory 14 effect reported by several studies showing that it is essential to modify the cytokine 15 response from pro-inflammatory profile presented by Th1 during embryo implantation 16 to anti-inflammatory profile presented by Th2 for pregnancy maintain [12-16, 18, 19]. 17 Thus, Th1/Th2 unbalance could explain implantation failures in some patients with 18 RIF, RPL or recurrent miscarriages (RM) [20-22]. 19 129(r=0.28) (Table 2). However, 4 ng/ml of LPL was ...

show abstract

Repeated implantation failure: a new potential treatment option

Abstract: The current findings support a possible role for the intrauterine administration of autologous CRH-treated PBMC in treating women with RIF. Further randomized controlled trials are needed to investigate the efficacy of this intervention.

Cited by 34 publications

References 40 publications

Implantation and the Fetal Health

Implantation and the Fetal Health

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

Luteal progesterone level correlated with immunotherapy success of patients with repeated implantation failures

Contact Info

Product

Resources

About