Abstract
Objective: To assess the efficiency of the endometrial immune profiling as a method to design personalized care to enhance the pregnancy rate in a large heterogeneous infertile population. We hypothesized that some reproductive failures could be induced by a uterine immune dysregulation which could be identified and corrected with a targeted plan.Design: Prospective cohort study.Setting: Multicentric study.Intervention(s) and Main outcome measure(s): One thousand and seven hundred thirty-eight infertile patients had an immune profiling on a timed endometrial biopsy between 2012 and 2018. This test documented the absence or the presence of an endometrial immune dysregulation and identified its type. In case of dysregulation, a targeted personalized plan was suggested to the treating clinician aiming to supply the anomaly. One year after the test, the clinician was contacted to provide the outcome of the subsequent embryo transfer with the applied suggested plan.Result(s): After testing, 16.5% of the patients showed no endometrial immune dysregulation, 28% had a local immune under-activation, 45% had a local immune over-activation, and 10.5% had a mixed endometrial immune profile. In patients with a history of repeated implantation failures (RIF) or recurrent miscarriages (RM), the pregnancy rate was significantly higher if an endometrial dysregulation was found and the personalized plan applied, compared to the patients with an apparent balanced immune profile (respectively 37.7 and 56% vs. 26.9 and 24%, p < 0.001). In contrast, in good prognosis IVF (in vitro fertilization) subgroup and patients using donor eggs, this difference was not significant between dysregulated and balanced subgroups, but higher pregnancy rates were observed in absence of dysregulation. For patients with immune over-activation, pregnancy rates were significantly higher for patients who had a test of sensitivity, regarding the type of immunotherapy introduced, when compared to the ones who did not (51 vs. 39.9%, p = 0.012).Conclusion(s): Local endometrial immunity appears to be a new and important parameter able to influence the prognosis of pregnancy. Targeted medical care in case of local immune dysregulation resulted in significantly higher pregnancy rates in RIF and RM patients.
Highlights
Three demographic surveys published in the new millennium put the infertility figures in the many millions [1,2,3]
Mathematical models suggest that 15% of patients enrolled in in vitro fertilization (IVF) cycles will have an history of repeated implantation failures and 1% of initiated pregnancies end up in recurrent miscarriages [6]
Developed in France for patients with a history of repeated implantation failures (RIF) [25, 26], we describe here the clinical results observed in 1,738 infertile patients and document its efficacy in clinical settings other than those previously studied as good prognosis infertile patients, patients with recurrent miscarriages or oocyte recipients
Summary
Three demographic surveys published in the new millennium put the infertility figures in the many millions (ranging from 48.5 to 186 M) [1,2,3]. Infertility is estimated to affect between 8 and 12% of reproductive-aged couples worldwide [4], with 9% currently cited as the probable global average [1]. In 2010, of an estimated 11 million infertile Europeans (prevalence: 9%), half seek medical assistance and 22% receive fertility treatments. A half million assisted reproductive therapy (ART) cycles are performed annually in Europe [5] and expected to rise within the decade as the prevalence of infertility climbs The main brake for the success of assisted reproductive treatments remains the still low implantation rate of transferred embryos described by R. Most pregnancy losses occur before or during embryo implantation [8]
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