Meta-analysis combines results of 12 intrauterine, intraovarian PRP studies

A 2024 Cochrane review (meta-analysis) combined the results of 12 randomized controlled trials (RCTs) on the use of PRP during IVF, finding an increased chance of live birth, clinical pregnancy and preterm delivery. However, the quality of this evidence was very low and the “results should be interpreted with caution.”

Platelet rich plasma (PRP) is a fluid processed from blood that is rich in growth factors and platelets that may have regenerative properties. It’s been used for different applications for IVF to potentially improve outcomes, including intrauterine and intraovarian PRP.

Intrauterine PRP involves the administration of PRP to the uterus before embryo transfer, while intraovarian PRP involves the administration of PRP to the ovaries before ovarian stimulation. It’s not clear how it works, but the growth factors in PRP might stimulate tissue growth and blood vessel development (angiogenesis) to improve implantation or egg quality/numbers.

Here we’ll look at a recent Cochrane review (meta-analysis) that combined the results of 12 randomized controlled trials (RCTs), representing 1,069 women who had performed PRP to improve reproductive outcomes. They wanted to assess the effectiveness and safety of PRP.

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Study details

This section covers key details of how the study was performed, including patient characteristics, how they were treated, and other methods used. For those who aren’t interested in these details, and just want to see the results, you can go ahead and skip this part.

This meta-analysis included 12 RCTs with 1,069 women, which consisted of:

• Intrauterine PRP vs no PRP (9 studies, 824 women)
• Intrauterine PRP vs G-CSF (2 studies, 172 women) — not covered here.
• Intraovarian PRP vs no PRP (1 study, 73 women)

Between the studies, there were differences in how PRP was prepared (different volumes of blood collected, amount of anticoagulant used, centrifugation process), the amount of PRP administered (inconsistencies in concentrations of PRP, volume administered, number of injections), the type of control used (no treatment, Ringer’s serum, insertion of an empty catheter) and some differences in the timing ( although most administered the PRP 48 hours before embryo transfer).

The primary outcome was effectiveness (by live birth rate/ongoing pregnancy past 12 weeks) and safety (by miscarriage before 20 weeks). Only studies with a low risk of bias were included in the primary outcome.

Possible increase in live birth rates, preterm delivery with intrauterine PRP

This meta-analysis combined the results of 12 RCTs to determine the impact of PRP on pregnancy outcomes. Of the 12 RCTs, 9 were focused on intrauterine PRP.

The primary outcome of this meta-analysis, or it’s main focus, was live birth/ongoing pregnancy and miscarriage rate but only in studies that had a low risk of bias. This is to ensure that only studies with the most reliable results were included. Of the 9 studies involving intrauterine PRP, only 1 study had a low risk of bias. This study found:

• No difference in live birth/ongoing pregnancy rates (18.8% vs 17.4%; odds ratio [95% CI]: 1.10 [0.38-3.14]; 94 patients).
• No differences in miscarriage or pregnancy rates.
• The quality of evidence reported for this particular study was rated as very low quality, which was related to the lack of generalizability (they only included women with a history of 3 failed transfers) and small sample size.
• Based on these results, the authors conclude that they are “uncertain about the effect” of intrauterine PRP vs no intrauterine PRP.

The other 8 studies were at a high risk for bias, mostly due to missing outcome data and selective reporting (ie. certain data may have been omitted). Combining the results of these studies, they found:

• Increase in live birth rates (29.3% vs 14.2%, odds ratio [95% CI]: 2.38 [1.16-4.86]; 564 patients; 6 studies; I2= 54%). This means that patients with intrauterine PRP had a 2.38-times higher odds of live birth compared to those without intrauterine PRP.
• Increase in clinical pregnancy rate (34.6% vs 19.5%; odds ratio [95% CI]: 2.22 [1.50-3.27]; 824 patients; 9 studies; I2= 24%). This means that patients with intrauterine PRP had a 2.22-times higher odds of clinical pregnancy compared to those without intrauterine PRP.
• No difference in miscarriage rates (odds ratio [95% CI]: 1.54 [0.59-4.01]; 504 patients; 5 studies; I2= 0%).
• The quality of evidence was rated as very low for these outcomes, mainly due to high risk of bias, lack of generalizability (most involved patients with a history of 2-3 implantation failures), heterogeneity and small sample size for the studies.
• Based on these results, the authors conclude that they are “uncertain about the effect” of intrauterine PRP vs no intrauterine PRP/placebo.

Some studies also reported adverse pregnancy outcomes:

• No difference in multiple pregnancies (2 studies).
• No difference in ectopic pregnancies (1 study).
• Increase in preterm delivery (21.2% vs 3.33%, odds ratio [95% CI]: 8.02 [1.72-37.33]; 1 study; 120 patients). This means that patients with intrauterine PRP had a 8.02-times higher odds of preterm birth compared to those without intrauterine PRP. The quality of evidence for this outcome was rated as low, mainly due to high risk of bias and lack of generalizability (they only included women with a history of 3 failed transfers).
• Based on these results, the authors conclude that intrauterine PRP “may increase the risk of preterm delivery considerably.”

Possibly no change in outcomes with intraovarian PRP

This meta-analysis combined the results of 12 RCTs to determine the impact of PRP on pregnancy outcomes. Of the 12 RCTs, only 1 involved intrauterine PRP. This study found:

• No difference in ongoing pregnancy rates (18.4% vs 17.1%; odds ratio [95% CI]: 1.09 [0.33-3.63]; 75 patients).
• No difference in the clinical pregnancy rate.
• The quality of evidence reported for this particular study was rated as very low quality, which was related to the lack of generalizability (they only included women with a poor ovarian response under 38) and small sample size.
• Based on these results, the authors conclude that they are “uncertain about the effect” of intraovarian PRP in women with poor ovarian response vs no intraovarian PRP.

Conclusions

Combining the results of all the studies investigating intrauterine PRP showed a 2.38-times higher odds of live birth/ongoing pregnancy and 2.22-times higher odds of clinical pregnancy rates, with no change in miscarriage rates. There was an 8.02-times higher odds of preterm delivery, but no difference in multiple pregnancies or ectopic pregnancies.

When they only included the 1 study at a low risk of bias, they found no differences in live birth/ongoing pregnancy, clinical pregnancy and miscarriage rates.

For intraovarian PRP, they found no differences in ongoing pregnancy or clinical pregnancy rates (only 1 study).

The quality of evidence was low to very low for these studies, and the authors warn that the “results should be interpreted with caution.” In general, they were “uncertain about the effect” of intrauterine and intraovarian PRP during IVF.

The authors note that these results agree with other meta-analyses (referenced below), finding that intrauterine PRP may improve live birth and pregnancy rates, although more high quality studies are needed.

The authors highlight the need for better designed RCTs with lower risk of bias that are conducted among the general public (and not just those with a history of implantation failure). They also call for more standardization in PRP preparation and administration methods.

Related studies

To learn more about this topic, you can check out a number of studies referenced in this study below (3 links):

Reference

Vaidakis D, Papapanou M, Siristatidis CS. Autologous platelet-rich plasma for assisted reproduction. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD013875. doi: 10.1002/14651858.CD013875.pub2. PMID: 38682756; PMCID: PMC11057220.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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