Key messages
• We do not know if platelet-rich plasma (PRP) injection in the womb is better than no treatment or dummy treatment in terms of live birth (or ongoing pregnancy), miscarriage, clinical pregnancy, multiple pregnancy, or ectopic pregnancy. PRP injection in the womb may increase the risk of preterm birth. We have insufficient information about other potential unwanted effects of PRP.
• We have insufficient information about the use of PRP injection in the ovaries.
• Since we are not confident in the results, we need more high-quality research to investigate whether the use of PRP is beneficial and safe in women trying to become pregnant via assisted reproduction.
What is platelet-rich plasma and how might it help women become pregnant?
Platelet-rich plasma (PRP) is made up of plasma (the liquid portion of the blood) and a high concentration of platelets (the cells that cause blood clots). It is produced from the whole blood of the person being treated. PRP contains growth factors that stimulate human tissue repair, especially in tissues that heal slowly. Some experts believe PRP may help the ovaries react better to ovarian stimulation (hormone treatment given to increase the number of eggs released), and may help the endometrium (lining of the womb) react better to the implantation of embryos. In this way, PRP could help women undergoing assisted reproduction to become pregnant.
What did we want to find out?
We wanted to know if PRP was better than no treatment, placebo (dummy treatment), or other treatments for improving:
• the likelihood of live birth or ongoing pregnancy (fetal heartbeat after 12 weeks of pregnancy); and
• the likelihood of clinical pregnancy (fetal heartbeat at seven weeks of pregnancy).
We also wanted to know if PRP affected the risk of:
• miscarriage;
• pain, infection, or allergic reactions;
• multiple pregnancy (twins, triplets, etc.);
• ectopic pregnancy (when the embryo implants outside the womb);
• fetal growth restriction;
• preterm birth (before 37 weeks of pregnancy); and
• fetal abnormality.
What did we do?
We searched for studies that compared PRP with no treatment, placebo, or other treatments in infertile women undergoing assisted reproduction. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes. We were mainly interested in the results of well-designed studies, so we analyzed them separately.
What did we find?
We found 12 studies involving 1069 women. Nine studies compared PRP injection in the womb with no treatment or placebo. Two studies compared PRP injection in the womb with granulocyte colony-stimulating factor (G-CSF) injection in the womb. One study compared PRP injection in the ovaries with no treatment.
Key results
Platelet-rich plasma injection in the womb versus no treatment
There was only one well-designed study in this comparison. It provided insufficient evidence to show if PRP is better than no treatment in terms of rates of live birth, miscarriage, clinical pregnancy, or ectopic pregnancy. The study suggests that if the likelihood of live birth following no treatment is 17.4%, then the likelihood following PRP injection would be 7% to 40%; and if the risk of miscarriage following no intervention is 4%, then the risk following PRP injection would be 1% to 24%.
Based on the analysis of all studies, we do not know if PRP injection in the womb is better than no treatment or placebo in terms of live birth (or ongoing pregnancy), miscarriage, clinical pregnancy, multiple pregnancy, or ectopic pregnancy. PRP injection in the womb may increase the risk of preterm birth.
No studies reported other unwanted effects of treatment.
Platelet-rich plasma injection in the womb versus granulocyte colony-stimulating factor injection in the womb
Neither study in this comparison was well designed. Based on the results of these studies, we do not know if PRP injection in the womb is better than G-CSF injection in the womb in terms of live birth (or ongoing pregnancy), miscarriage, and clinical pregnancy. Neither study reported unwanted events other than miscarriage.
Platelet-rich plasma injection in the ovaries versus no treatment
The study that evaluated this comparison was not well designed. We are uncertain about the effect of ovarian PRP on ongoing pregnancy and clinical pregnancy. The trial did not report live birth or any unwanted events.
What are the limitations of the evidence?
We are not confident in the evidence because:
• some studies focused on a specific population, and the question we wanted to answer was broader;
• some studies were small;
• most studies were not well designed; and
• the results of different trials were sometimes inconsistent.
Readers should interpret our results with caution. More studies are needed to confirm the findings.
How up to date is this evidence?
The evidence is current to January 2023.
We are uncertain about the effect of intrauterine or intraovarian administration of PRP on outcomes of assisted reproduction technology in infertile women. The pooled results should be interpreted with caution. Only one of the 12 included studies was judged at low risk of bias. Other limitations of the included trials were failure to report live birth, poor reporting of methods, lack of prospective protocol registration, low precision due to the small number of enrolled participants, indirectness due to the specific subpopulations and settings studied, and insufficient or absent safety data.
Autologous platelet-rich plasma (PRP) consists of plasma and a concentrate of platelets extracted from fresh whole blood of the person being treated. Research has suggested that intrauterine or intraovarian infusion/injection of PRP before embryo transfer may improve endometrial receptivity and response to ovarian stimulation in women undergoing assisted reproduction. We compared these interventions to standard treatment, placebo, or other interventions (mechanical or pharmacological).
To assess the effectiveness and safety of intrauterine and intraovarian infusion/injection of platelet-rich plasma in infertile women undergoing assisted reproductive technology cycles.
We searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, and the Epistemonikos database in January 2023. We also searched the reference lists of relevant articles and contacted the trial authors and experts in the field for any additional trials.
We included randomized controlled trials (RCTs) that evaluated the application of PRP in the uterine cavity, ovaries, or both versus no intervention, placebo, or any other intervention (either mechanical or pharmacological) in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles.
We followed standard methodological procedures recommended by Cochrane, including use of the updated risk of bias tool (RoB 2). The primary outcomes were live birth (or ongoing pregnancy) and miscarriage. The secondary outcomes were clinical pregnancy, complications of the procedure, multiple pregnancy, ectopic pregnancy, fetal growth restriction, preterm delivery, and fetal abnormality. We estimated the average effect of the interventions by fitting a Der Simonian-Laird's random-effects meta-analysis model. We reported pooled odds ratios (ORs) with 95% confidence intervals (CIs). We restricted the primary analyses to trials at low risk of bias for the outcomes and performed sensitivity analyses that included all studies.
We included 12 parallel-group RCTs that recruited a total of 1069 women. We identified three different comparison groups. Using GRADE, we assessed the certainty of evidence as very low for almost all outcomes.
Intrauterine injection/infusion of platelet-rich plasma versus no intervention or placebo
Nine studies evaluated intrauterine PRP versus no intervention or placebo. Eight included women with at least two or three previous implantation failures. Only one was assessed at low risk of bias for each outcome. This study provided very low-certainty evidence about the effect of intrauterine PRP injection versus no intervention on live birth (OR 1.10, 95% CI 0.38 to 3.14; 94 women) and miscarriage (OR 0.96, 95% CI 0.13 to 7.09; 94 women). If the likelihood of live birth following no intervention is assumed to be 17%, then the likelihood following intrauterine PRP would be 7% to 40%; and if the risk of miscarriage following no intervention is 4%, then the risk following intrauterine PRP would be 1% to 24%.
When we analyzed all studies (regardless of risk of bias), we found very low-certainty evidence about the effect of intrauterine PRP compared with placebo or no intervention on live birth or ongoing pregnancy (OR 2.38, 95% CI 1.16 to 4.86; I² = 54%; 6 studies, 564 women) and miscarriage (OR 1.54, 95% CI 0.59 to 4.01; I² = 0%; 5 studies, 504 women).
The study at low risk of bias provided very low-certainty evidence about the effect of intrauterine PRP compared with no intervention on clinical pregnancy (OR 1.55, 95% CI 0.64 to 3.76; 94 women) and ectopic pregnancy (OR 2.94, 95% CI 0.12 to 73.95; 94 women).
The synthesis of all studies provided very low-certainty evidence about the effect of intrauterine PRP compared with placebo or no intervention on clinical pregnancy (OR 2.22, 95% CI 1.50 to 3.27; I² = 24%; 9 studies, 824 women), multiple pregnancy (OR 2.68, 95% CI 0.81 to 8.88; I² = 0%; 2 studies, 240 women), and ectopic pregnancy (OR 2.94, 95% CI 0.12 to 73.95; 1 study, 94 women; very low-certainty evidence). Intrauterine infusion of PRP may increase the risk of preterm delivery compared with no intervention (OR 8.02, 95% CI 1.72 to 37.33; 1 study, 120 women; low-certainty evidence).
No studies reported pain, infection, allergic reaction, fetal growth restriction, or fetal abnormality.
Intrauterine infusion of platelet-rich plasma versus intrauterine infusion of granulocyte colony-stimulating factor
Two RCTs evaluated intrauterine PRP versus intrauterine granulocyte colony-stimulating factor (G-CSF); both included women with thin endometrium, and neither was judged at low risk of bias for any outcome. We are uncertain about the effect of intrauterine PRP compared with intrauterine G-CSF on live birth (OR 0.88, 95% CI 0.43 to 1.81; 1 study, 132 women; very low-certainty evidence), miscarriage (OR 1.94, 95% CI 0.63 to 5.96; 1 study, 132 women; very low-certainty evidence), and clinical pregnancy (OR 1.24, 95% CI 0.66 to 2.35; 2 studies, 172 women; very low-certainty evidence). Neither study reported adverse outcomes other than miscarriage.
Intraovarian injection of platelet-rich plasma versus no intervention
One RCT evaluated PRP injection into both ovaries versus no intervention; it was judged at high risk of bias for the two outcomes it reported. We are uncertain about the effect of intraovarian PRP injection compared with no intervention on ongoing pregnancy (OR 1.09, 95% CI 0.33 to 3.63; 73 women; very low-certainty evidence) and clinical pregnancy (OR 0.90, 95% CI 0.31 to 2.60; 73 women; very low-certainty evidence). The study examined no safety outcomes.