Endometrium Immunomodulation to Prevent Recurrent Implantation Failure in Assisted Reproductive Technology.

After more than four decades of assisted reproductive technology (ART) practice worldwide, today more than 60% of women undergoing in vitro fertilization (IVF) treatments fail to become pregnant after the first embryo transfer and nearly 20% of patients are suffering from unexplained recurrent implantation failures (RIFs) and repeated pregnancy loss (RPL). The literature reported different causes of RIF-RPL, mainly multifactorial, endometrial and idiopathic. RIF remains a black box because of the complicated categorization and causes of this physio-pathological dysregulation of implantation and pregnancy process after ovarian stimulation. Many options were suggested as solutions to treat RIF-RPL with controversial results on their usefulness. In this article, we reviewed different possible therapeutic options to improve implantation rates and clinical outcomes. Based on our experience we believe that endometrium immunomodulation after intrauterine insemination of activated autologous peripheral blood mononuclear cells (PBMCs) or platelet-rich plasma (PRP) can be a promising therapeutic solution. On the other hand, peripheral lymphocyte balance typing, specific cytokines and interleukins profiling can be proposed as predictive biomarkers of implantation before embryo transfer.

Decline in semen quality of North African men: a retrospective study of 20,958 sperm analyses of men from different North African countries tested in Tunisia over a period of 6 years (2013-2018).

BACKGROUND: According to numerous studies from around the world, semen quality seems to have declined dramatically in recent times. However, the data available on male fertility status and semen quality in North Africa are limited. AIM: To investigate the status of semen quality in North-African men and to understand its variations. SUBJECTS & METHODS: 20,958 sperm-analyses (Spermogram - Spermocytogram) of North-African men (19-77 years old) consulting for infertility, performed in a private laboratory of medical analyses (Tunis, Tunisia) over a period of 6 years (2013-2018), were investigated. All patients had at least 1 year of unprotected intercourse with their partners before the test. Statistical analyses were performed using SPSS 22.0 software for windows. RESULTS: Libyan men presented a clear decline in all sperm parameters. A continuous decline in sperm morphology quality was shown in Tunisian and Algerian men. Mauritanian men presented a significant increase in sperm vitality with pseudo-stability in the rest of the sperm parameters during the whole study period. CONCLUSION: North-African men presented remarkable decreases in their semen quality over the last decade. This data could confirm possible global common-causes that need to be identified in order to limit their negative impact on sperm quality, and consequently on male-fertility.

Circulating MMP-7 and VEGF as potential predictive biomarkers for recurrent implantation failures.

Recurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen-thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33-614) pg/ml vs 119.92 (27-441) pg/ml; P-value = 0.030] and [82.54 (25.94-210.20) pg/ml vs 30.93 (13.62-193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.