Dados do Trabalho

Title

Autologous Platelet-Rich Plasma for Endometrial Regeneration in Patients undergoing IVF Treatment with Thin Endometrium – a Prospective, Interventional Cohort Study.

Objective

A synchronized crosstalk between a receptive endometrium and a viable embryo is crucial to achieve a successful pregnancy. Endometrial thickness is considered ideal if ≥ 7mm triple-line at late follicular phase. Several strategies to improve refractory endometrium have been applied with lack of proven efficacy resulting in cycle’s cancelation. Autologous Platelet-Rich Plasma (PRP) is widely used for tissue regeneration by several areas of medicine, due to the fact that platelets are rich in numerous growth factors such as VEGF, TGF-b, PDGF, IGF1, EGF, among others, with the potential to promote tissue regeneration, proliferation and neoangiogenesis. The primary objective of this study was to evaluate the efficacy of PRP to improve endometrial thickness, volume and flow in patients with thin endometrium.

Methods

Prospective, interventional cohort study, conducted between August/2019-April/2022, including 78 patients undergoing endometrial preparation for Frozen Embryo Transfer, with a history of endometrial thickness <7mm at late follicular phase and hysteroscopy showing normal cavity anatomy. For endometrial preparation, oral estradiol valerate 8 mg/day were used. The autologous preparation of PRP was performed in a blood bank facility (COLSAN) encompassing 2 intrauterine infusion of 1.0 ml between cycle-days 7-10 and 11-14. The protocol was standardized and samples contained a mean of 2753,58±336,43/mm3 platelets. Endometrial thickness, volume and flow were measured by the same professional using a 3D Doppler velocimetry US before the 1st PRP and 2nd infusion and after 48-72h of 2nd infusion. Embryo transfer was performed considering endometrial parameters and hormone levels. All patients signed the informed consent form and the study was approved in the CEP/CONEP System. Statistical tests were performed accordingly and a p<0.05 was considered significant.

Results

Seventy-eight patients performed 110 cycles of endometrial preparation for PRP infusion. Endometrial thickness mean before 1st PRP infusion was 4,84±1,01mm and after 1st and 2nd infusion 5,59±1,04 and 5,99±1,09mm (p<0,0001). Endometrial volume mean before 1st PRP infusion was 0,70±0,36cc and 0,80±0,34 and 0,87±0,33 after 1st and 2nd infusion (p<0,0001). Endometrial flow was evaluated according to Applebaum classification (vascularity zones 1, 2, 3 and 4). The majority of patients had absent flow pre-PRP infusion (43,9%) and after 1st and 2nd infusions were classified in zone 2 (35,4% and 40,2%, p<0,0001). Sixty-seven patients (85,9%) proceed to 79 embryo transfer (ET) cycles. Endometrial thickness and volume were significant different after 1st and 2nd PRP infusions between patients that underwent ET or not (5,74±0,97 versus 5,18±1,10 and 6,24±0,92 versus 5,34±1,25mm, p=0,01 and 0,002; 0,80±0,34 versus 0,66±0,24 and 0,87±0,33 versus 0,68±0,29cc, p=0,03 and 0,008 respectively). Endometrial flow in the majority of patients without an ET were classified as absent flow after 2nd PRP infusion (45,2%), while the majority of patients with ET were classified in zone 2 (40,2%, p=0,0003). Mean maternal age was 38,9±4,5 years old, with ET 39,2±4,6 and without ET 38,1±4,1 (p=0.36). Positive pregnancy test (PPT) were achieved by 44.3% (35/79) of patients. Clinical pregnancy (CP/total ET) was 27,8%, miscarriage (miscarriage/PPT) 25,7%, biochemical pregnancy (BP/PPT) 11,4% and live birth rate (LB/total ET) 26,6%. Oocyte’s origin (donation or autologous), euploid embryo transfer and laboratory variables were similar between patients with a CP and negative PPT. The most prevalent obstetrical complication was preeclampsia (45,45%), and was similar in autologous and donated oocytes (50% versus 40%, p=0,69).

Conclusion

The use of a standard protocol of PRP with a rich concentration of platelets, was effective in improving endometrial thickness, volume and flow for patients with thin endometrium. The majority of patients (86%) were able to proceed to ET and the live birth rate (26,6%), when compared with the rates reported in the literature of patients with thin endometrium without PRP (19,44%), can be considered successful.

Keywords

Platelet-Rich-Plasma, Thin endometrium