PRP, PBMCs beat G-CSF, hCG for implantation failure in meta-analysis

A new meta-analysis comparing PRP, PBMCs, G-CSF, and hCG for recurrent implantation failure found that only PRP and PBMCs improved clinical pregnancy rates compared to placebo, but none of the treatments significantly improved live birth rates.

Recurrent implantation failure (RIF) generally refers to failure to achieve a clinical pregnancy after transferring several good quality embryos across multiple IVF cycles. Some researchers define RIF based on euploid embryo transfer failure, while others include broader criteria involving embryo morphology alone.

The causes of RIF are complex and can involve the immune system, the endometrium or the embryo, but several intrauterine infusion therapies may help to improve implantation, such as:

• Platelet-rich plasma (PRP)
• Peripheral blood mononuclear cells (PBMCs)
• Granulocyte colony stimulating factor (G-CSF)
• Human chorionic gonadotropin (hCG)

These treatments are administered to the uterus before embryo transfer and aim to improve the endometrial environment to promote implantation, but it’s not clear which of these intrauterine infusions is the most effective, and if they work at all compared to placebo!

This post is a summary of a study by Jiang et al. (2025), who compared the effectiveness of these intrauterine infusions head-to-head by combining the results of 25 randomized controlled trials (RCTs) in a network meta-analysis.

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Study details

• This network meta-analysis combined the results of 25 RCTs, mostly taking place in Asia and Europe. A “network” meta-analysis was used, which lets you combine studies that have different treatment protocols that aren’t directly compared. Check the glossary for “meta-analysis” for more info.
• The studies included 3035 women under age 40 with RIF (defined as no clinical pregnancy after at least 2 IVF cycles with ≥4 good cleavage embryos or ≥2 good blastocysts).
• Some studies involved fresh transfers, some involved frozen, and some involved both.
• The primary outcomes were the clinical pregnancy rate, live birth rate and miscarriage rate (pregnancy loss before 12 weeks)

Here’s a breakdown of the number of studies that examined each type of intrauterine infusion:

• PRP: 10 studies
• PBMCs: 5 studies
• G-CSF: 8 studies
• hCG: 4 studies
• Placebo (saline or Ringer’s solution intrauterine infusion): 12 studies
• Blank (no intrauterine infusion): Used as a control in all 25 studies

One important note: Comparisons with the placebo group are more meaningful than those with the blank group, because the placebo still involves an intrauterine infusion. The act of placing fluid into the uterus, even if it’s just saline, may have effects on the endometrium, so it’s a better control than doing nothing at all.

Clinical pregnancy rate: PRP and PBMCs showed the highest improvement

Now let’s check out the results! First, I’ll explain the results for clinical pregnancy rates from the network meta-analysis and also report the SUCRA scores (a higher SUCRA % indicates that the treatment is better, see the glossary for more info).

All four intrauterine infusions (PRP, PBMCs, G-CSF, hCG), and even the placebo, showed statistically significant improvements in clinical pregnancy rates compared to the blank group (no intrauterine infusion).

• Blank vs PRP: odds ratio [95% CI]: 0.33 [0.25–0.43] — this means that the odds of clinical pregnancy in the blank group were 0.33 times that of the PRP group—that’s a 67% lower chance of pregnancy when no infusion was given.
• Blank vs PBMCs: odds ratio [95% CI]: 0.35 [0.25–0.49] — 65% lower with no infusion.
• Blank vs G-CSF: odds ratio [95% CI]: 0.38 [0.26–0.54] — 62% lower with no infusion.
• Blank vs hCG: odds ratio [95% CI]: 0.42 [0.29–0.60] — 58% lower with no infusion.
• Blank vs placebo: odds ratio [95% CI]: 0.61 [0.43–0.88] — 39% lower with no infusion.

Notice how even the placebo group, which received a saline intrauterine infusion, showed a statistically significant improvement compared to the blank group (odds ratio [95% CI]: 0.61 [0.43–0.88]), suggesting that the act of infusion itself may have a beneficial effect on implantation, potentially through the mechanical stimulation or minor injury caused by the infusion.

When they compared the treatments to placebo, only PRP and PBMCs were significant:

• Placebo vs PRP: odds ratio [95% CI]: 0.53 (0.35, 0.82) — statistically significant
• Placebo vs PBMCs: odds ratio [95% CI]: 0.57 (0.37, 0.89) — statistically significant
• Placebo vs G-CSF: odds ratio [95% CI]: 0.94 (0.61, 1.45) — not statistically significant
• Placebo vs HCG: odds ratio [95% CI]: 0.68 (0.45, 1.03) — not statistically significant

This shows that PRP and PBMCs can improve clinical pregnancy rate compared to placebo, and it also shows that placebo is a much better comparator than the blank!! The placebo itself has an effect on clinical pregnancy rate.

There were no statistically significant differences when the treatments were compared to each other (ie. PRP vs PBMCs).

As for the SUCRA scores: PRP ranked highest for CPR by SUCRA score (84.5%), followed by PBMCs (76.5%), G-CSF (65.7%), and HCG (52.5%).

No significant difference in rates for live birth, miscarriage compared to placebo

In contrast to clinical pregnancy rates, only PRP and PBMCs significantly improved live birth rate when compared to the blank:

• Blank vs PRP: OR 0.27 [0.13–0.58] — statistically significant
• Blank vs PBMCs: OR 0.36 [0.15–0.89] — statistically significant
• Other comparisons — not statistically significant

However, when compared to the placebo, none of the treatments were statistically significant for live birth rate. There were also no differences when treatments were compared to each other.

For the SUCRA rankings for live birth rate: PRP was the highest (81.4%), followed by PBMCs (64.6%), and G-CSF (58%).

As for miscarriage rates, there were no statistically significant differences between any of the groups.

Conclusions

This study showed that all infusions improved pregnancy outcomes, but PRP was the most effective for RIF patients when compared to the blank (no infusion) treatment. This was followed closely by PBMCs, then G-CSF and hCG.

How might these be helping?

• PRP contains a cocktail of growth factors (PDGF, VEGF, TGF, EGF) that may support endometrial repair, vascularization, and receptivity.
• PBMCs may help shift the uterine immune environment from pro-inflammatory (Th1) to implantation-friendly (Th2), and support endometrial differentiation when cultured with HCG.

Importantly, when the blank group (no infusion) was compared to the placebo group (saline infusion), there was still a difference. This suggests that the act of doing the infusion itself, regardless of what’s being infused, can improve pregnancy outcomes, possibly by gently stimulating the uterus.

But when treatments were compared to placebo, only PRP and PBMCs showed a benefit for clinical pregnancy rate, and not for live birth.

The authors note that results with placebo infusions have been mixed — some studies show benefits, others don’t — highlighting how complex this is and the need for more research to understand how these infusions might work. Still, it’s clear that future studies should use placebo as the control, not just a no-treatment group.

Limitations of the meta-analysis include variability in how RIF was defined, and inconsistency across studies in terms of dosing, timing, and how each infusion was administered.

At this time, none of these intrauterine infusion treatments are recommended by ESHRE, underscoring the need for more high-quality studies. You can check out their recommendations in my post Evidence-based recommendations from ESHRE for 27 IVF add-ons.

Reference

Jiang L, Wen L, Lv X, Tang N, Yuan Y. Comparative efficacy of intrauterine infusion treatments for recurrent implantation failure: a network meta‐analysis of randomized controlled trials. J Assist Reprod Genet. 2025;42:1177–1190. doi: 10.1007/s10815-025-03436-2

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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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