New therapeutic protocol for improvement of endometrial receptivity (PRIMER) for patients with recurrent implantation failure (RIF) - A pilot study

Abstract

Objective: To evaluate whether or not one should use a new Protocol for Endometrial Receptivity Improvement (PRIMER) based on platelet-rich plasma (PRP) and granulocyte colony-stimulation factor (G-CSF) to enhance ongoing pregnancy rates in patients with recurrent implantation failure (RIF). Methods: Women undergoing IVF/ICSI were prospectively divided into two groups: - PRIMER/RIF group (n:33): patients with RIF (defined as ≥2embryo transfers (ETs) and at least 5 morphologically good embryos transferred) in which intrauterine PRP injection and subcutaneous G-CSF-injection were performed. - Control group (n:33): patients in their first IVF/ICSI attempt/cycle (without PRP or G-CSF injection). The PRP was prepared using autologous fresh-whole blood processed to increase platelet-concentration in 2 to 4 fold. All patients undergoing the PRP-treatment received 0.7ml of it through intrauterine-injection 48 hours before the ET. G-CSF (300mg/0.5ml) started simultaneously to PRP and was administered subcutaneously every week. Results: Regarding implantation, clinical pregnancy and miscarriage rates, we found no statistically significant difference (18.2% versus 17.6%, p =0.90; 36.4% versus 30.3%, p =0.61 and 25.0% versus 9.0%, p =0.43, respectively). The use of PRIMER enabled RIF patients (previous ET µ: 4.0±1.5) to reach similar ongoing pregnancy and live birth rates like those patients who had their first IVF/ICSI cycle attempt (27.3% versus 27.3%, p =0.99). Conclusions: Our results showed, for the first time, evidence that this therapeutic protocol (PRIMER) could be used as a feasible treatment based on biological rationale for patients with RIF, considering its promising outcomes, it is a simple procedure and not associated with patient complications.

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

“…Dieamant et al recently proposed a new therapeutic protocol to improve endometrial receptivity in which IU infusion of PRP was associated with the systemic use of G‐CSF. The authors observed similar gestational results (eg, implantation rates [IRs] and pregnancy and abortion rates) between the treated group (history of 4.0 ± 1.5 previous ETs) and an untreated group that was in its first attempt at IVF 33 …”

PRP-Therapy of Endometrium: The Latest Methods in the Field of Assisted Reproductive Technologies

“…Instead, in their work, F. Dieamant, L. D. Vagnini, J. B. Oliveira et al (2019) did not note a significant difference in the frequency of pregnancy between the two groups (study group, whom in the protocols of preparation for ET performed PRP of the endometrium and subcutaneous administration of granulocyte colony-stimulating factor; control group -did not undergo the above procedures) [25].…”

Platelet-Rich Plasma as a Potential New Strategy in the Endometrium Treatment in Assisted Reproductive Technology

“…compared the effect of intrauterine infusion of PRP with systemic administration of granulocyte colony stimulating factor(G-CSF) in a sample size of 123, and they demonstrated that intrauterine infusion of PRP could significantly enhance clinical pregnancy rate in RIF patients in comparison with systemic administration of G-CSF ( 32 ). One study demonstrated the efficacy of the combined use of intrauterine PRP and subcutaneous G-CSF ( 33 ). When compared with control patients in their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle attempt without PRP or G-CSF treatment, no statistically significant difference regarding implantation, clinical pregnancy and miscarriage rates was found between the two groups, suggesting the combined use of intrauterine PRP and subcutaneous G-CSF a potential new strategy for endometrial receptivity improvement ( 33 ).…”

“…One study demonstrated the efficacy of the combined use of intrauterine PRP and subcutaneous G-CSF ( 33 ). When compared with control patients in their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle attempt without PRP or G-CSF treatment, no statistically significant difference regarding implantation, clinical pregnancy and miscarriage rates was found between the two groups, suggesting the combined use of intrauterine PRP and subcutaneous G-CSF a potential new strategy for endometrial receptivity improvement ( 33 ). However, another study holds opposing opinions.…”