Subendometrial autologous platelet rich plasma injection in patients with unresponsive thin endometrium undergoing frozen-thawed embryo transfer

A receptive endometrium, a viable embryo, and cross-talk between the endometrium and the embryo are essential factors for successful embryo implantation. Endometrial thickness is associated with the outcome of frozen-thawed embryo transfer (FET) cycles, and a thin endometrium refractory to available treatment modalities remains a challenge in contemporary reproductive medicine. Platelet-rich plasma (PRP) is rich in growth factors and cytokines and has been used as an agent that induces tissue regeneration. The aim of the current study was to characterize the effects of PRP on endometrial thickness and IVF outcomes in patients with a history of unresponsive thin endometrium undergoing FET. Reproductive age women (n=176; age range 24-45) with a history of suboptimal endometrial proliferation (≤7 mm) after hormone replacement therapy for FET were offered to participate in the study. Women who gave informed consent for subendometrial PRP injection formed Group 1 (n=78); those who did not accept the PRP injection formed the control group (Group 2; n=98). Autologous PRP was prepared from peripheral blood by centrifugation, and was injected transvaginally under ultrasound guidance into the subendometrial region using a 35 cm 17 G single lumen needle within 10 days of the cessation of the menstruation. On the 2-4th days of the second menstrual cycle after the PRP procedure, hormone replacement therapy with gonadotropin releasing hormone agonist down regulation was started. Women who were found to have adequate endometrial thickness (≥7 mm) were started progesterone treatment for ET. Pregnancy (positive serum hCG) and sustained implantation (>8 weeks) outcomes were followed. A total of 176 women (mean age 36.6 ± 5.5) with a diagnosis of unresponsive thin endometrium were included in the study. PRP and control groups were not different in mean age (37.1 +/- 5.6 vs 36.5 +/-5.3; p =0.47) or BMI (26.7 +/- 5.9 vs 26.3 +/- 5.2; p =0.58). PRP treatment resulted in higher endometrial thickness compared to the control group (7.6 ± 1.6 mm vs 5.9 ± 1.3 mm; p=0.02). In the PRP group, 3 women (3.2%) conceived spontaneously and 75 (96.8%) attempted FET; in the control group there were no spontaneous pregnancies. In the PRP group, 24/75 women (32.0% of total) could not undergo ET due to persistent unresponsive thin endometrium or fluid in the endometrial cavity, compared to 77/98 (78.5% of total) in controls (p=0.001). Pregnancy and sustained implantation rates were 28% (21/75) and 18.7% (14/75) of total for the PRP group, compared to 7% (7/98) and 2% (2/98) in controls (p= 0.001 and p =0.001, respectively). In women with a history of suboptimal endometrial development, subendometrial PRP injection resulted in improved endometrial thickness and a cumulative (spontaneous and following FET) sustained implantation rate of 15%.