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

Abstract

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 ...