The effect of endometrial PRP on fertility outcomes in women with implantation failure or thin endometrium

Naziye Gurkan; Tayfun Alper

doi:10.1007/s00404-025-07948-1

. 2025 Feb 13;311(4):1195–1204. doi: 10.1007/s00404-025-07948-1

The effect of endometrial PRP on fertility outcomes in women with implantation failure or thin endometrium

Naziye Gurkan ^1,^✉, Tayfun Alper ¹

PMCID: PMC11985561 PMID: 39939464

Abstract

Objective

To evaluate the effect of intrauterine platelet-rich plasma (PRP) treatment on frozen–thawed embryo transfer (FET) cycles in patients with recurrent implantation failure.

Materials and methods

The study group consisted of 150 patients. The patients were grouped only as those with thin endometria, those with recurrent implantation failure (RIF), and those with both thin endometria and RIF. All participants underwent frozen embryo transfer. The control group consisted of a total of 150 patients who had normal endometrial thickness and did not have a history of RIF and who presented to the clinic due to unexplained infertility. The rates of biochemical pregnancy, clinical pregnancy, miscarriage and live birth were compared among the groups in terms of fertility outcomes.

Results

In 150 patients with a thin endometrium or a history of RIF who underwent PRP, the endometrial thickness was significantly greater than the pre-PRP endometrial thickness, and this value was found to be statistically significant (7.38 mm vs. 7.96 mm, p < 0.001). In the thin endometrium group, there was also a statistically significant difference between the endometrial thickness measured before and after PRP (5.85 mm vs 6.65 mm, p < 0.001). The rate of not achieving pregnancy in the RIF group without PRP was found to be significantly greater than that in the control group (53.1% vs 28.7%, p < 0.05). There was no significant difference in pregnancy rates between the PRP groups. Morever, no statistically significant relationship was found between pregnancy status and whether or not PRP was performed in RIF patients (p value > 0.05). Overall, although there was an increase in clinical pregnancy and live birth rates in the PRP group compared with the control group, this difference did not reach statistical significance.

Conclusion

In patients suffering from a thin endometrium or RIF, although endometrial PRP increases endometrial thickness, it does not significantly improve fertility outcomes.

Keywords: Frozen embryo transfer, Platelet-rich plasma, Recurrent implantation failure, Thin endometrium

What does this study add to the clinical work

In patients suffering from a thin endometrium or RIF, although endometrial PRP increases endometrial thickness, it does not significantly improve fertility outcomes. Although there is no significant increase in fertility outcome, PRP can be used as an alternative treatment method for couples whose IVF attempts have failed.

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Introduction

Platelets contain many proteins, various growth factors (GFs) and cytokines stored in cytoplasmic granules [1, 2]. In cases where there is no response to the classical treatments applied in couples who want a baby, it is necessary to develop new strategies to increase egg quality and the ovarian reserve and to achieve implantation in the endometrium. PRP, or platelet-rich plasma (PRP), is one of these strategies. It has been used in many clinics. However, there are still no standard guidelines for this application. Although the mechanism of PRP treatment in endometrial and ovarian regeneration has not been fully elucidated, the induction of cell proliferation and migration, chemotaxis, cell regeneration, extracellular matrix synthesis, remodeling, angiogenesis and epithelialization are considered to be the main mechanisms. Recurrent implantation failure (RIF) was defined by Polanski et al. [3] as failure to conceive despite consecutive transfer of three good-quality embryos. While embryo-related causes can be easily diagnosed prior to IVF treatment, problems in endometrial receptivity are much more difficult to assess [4]. Anatomical disorders and fibroids [5], endometrial adhesions [6], hydrosalpinx [7], immunological disorders and inflammation [8] in the endometrium are also accepted as causes of RIF. Finally, studies evaluating metabolomics [9] and microRNAs have suggested that metabolic dysfunction may also play a role in RIF cases, and that correction of these pathways may improve implantation rates [10]. Considering these findings, the search for new treatments for infertile women with a history of RIF has advanced, and the application of PRP into the endometrial cavity has become popular in recent years. However, despite its widespread use in medicine, the regenerative action mechanisms of PRP are not based on precise scientific data.

The important role of platelet growth factors in cell proliferation and neoendothelial cell formation for endometrial receptivity cannot be ignored. Suboptimal endometrial thickness in recurrent implantation failure patients is an important problem. On the other hand, the results of studies on the role of endometrial thickness in implantation and live birth are conflicting [11–15]. The aim of this study was to evaluate the effect of intrauterine PRP treatment on frozen–thawed embryo transfer (FET) cycles in patients who were scheduled for IVF with a diagnosis of RIF or a thin endometrium. The primary end point was the change in endometrial thickness after PRP, and the secondary outcomes were clinical pregnancy, live birth and miscarriage rates.

Materials and methods

Patients who applied to the Samsun VM Medical Park Hospital IVF Center between February 2018 and December 2021 with a history of thin endometrium or recurrent implantation failure (at least 2 times) and who decided to receive PRP were included in the study. They were all FET cycles. The medical files of a total of 177 cycles performed in 150 patients were analyzed retrospectively. For the control group, the files of the first 20 patients each month were randomized and examined within a 3-year period, and patients who met the eligibility criteria were included in the study. The demographic characteristics of the patients included in the study were obtained from hospital archive files. Institutional permission was obtained from the Chief Physician of Samsun VM Medical Park Hospital. All of the cycles were FET cycles and informed written consent was obtained from all patients before the procedure. After excluding 27 cycles (cycles in which PRP was performed, but no ET), the pregnancy outcomes of 150 patients with suboptimal endometrial thickness or RIF who underwent PRP + FET were analyzed. Among the 150 patients, 58 had a thin endometrium, and 96 had a history of RIF. The number of patients with both RIF and a thin endometrium was 25 (Table 1). The control group consisted of 150 patients with optimum endometrial thickness but not PRP, in the same age range, who underwent FET. In addition, an RIF control group of 96 people without PRP was created. In this way, we aimed to explore the qualitative and quantitative effects of PRP more clearly.

Table 1.

Comparisons

	Thin end with PRP without RIF (n = 33)	RIF with PRP without thin end (n = 71)	Thin end + RIF with PRP (n = 25)	RIF without PRP (n = 96)	Control (n = 150)	p value
Age						0.007**
< 35 (n = 179)	7 (%21.2)^a	31 (%43.7)^ab	13 (%52)^ab	44 (%45.8)^ab	84 (%56)^b
> = 35 (n = 196)	26 (%78.8)^a	40 (%56.3)^ab	12 (%48)^ab	52 (%54.2)^ab	66 (%44)^b
Embryo						0.03*
Grade 1 (n = 14)	1 (%3)^a	1 (%1.4)^a	1 (%4)^a	8 (%8.3)^a	3 (%2)^a
Grade 2 (n = 21)	1 (%3)^a	5 (%7)^a	3 (%12)^a	2 (%2.1)^a	10 (%6.7)^a
Grade 3 (n = 81)	8 (%24.2)^ab	25 (%35.2)^b	3 (%12)^ab	18 (%18.8)^ab	27 (%18)^a
Grade 4 (n = 137)	13 (%39.4)^a	17 (%21.1)^a	13 (%52)^a	40 (%41.7)^a	54 (%36)^a
Grade 5 (n = 79)	4 (%12.1)^a	15 (%21.1)^a	2 (%8)^a	19 (%19.8)^a	39 (%26)^a
Morula (n = 43)	6 (%18.2)^a	8 (%11.3)^a	3 (%12)^a	9 (%9.4)^a	17 (%11.3)^a
Pregnancy state						0.028*
No pregnancy (n = 149)	13 (%39.4)^ab	30 (%42.3)^ab	12 (%48)^ab	51 (%53.1)^b	43 (%28.7)^a
Biochemical (n = 34)	3 (%9.1)^a	9 (%12.7)^a	3 (%12)^a	6 (%6.3)^a	13 (%8.7)^a
Miscariage (n = 26)	1 (%3)^a	6 (%8.5)^a	3 (%12)^a	6 (%6.3)^a	10 (%6.7)^a
Clinical pregnancy (n = 166)	16 (%48.5)^ab	26 (%36.6)^ab	7 (%28)^ab	33 (%34.4)^b	84 (%56)^a
Live birth						0.002**
No (n = 210)	18 (%54.5)^ab	45 (%64.8)^ab	18 (%72)^ab	63 (%65.6)^b	66 (%44)^a
Yes (n = 164)	15 (%45.5)^ab	25 (%35.2)^ab	7 (%28)^ab	33 (%34.4)^b	84 (%56)^a

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Pearson Chi-square test

*Significant relationship with 95% confidence

**Significant relationship with 99% confidence

Control: no PRP, no RIF, normal endometrium

^a, ^b, ^ab indicates that this groups statistically different from the other groups with p < 0.05

Estrogen replacement was started on the 2nd day of the menstrual period for each patient included in the FET cycle. Oral estrogen was given twice a day for 4 days, three times a day for 4 days, and then four times a day.

On the 10th day of estrogen replacement, patients who underwent FET cycle had ultrasound performed, and endometrial thickness was evaluated. Ultrasonographically, while the uterus was in the longitudinal plane, measurements were taken three times from the area where the endometrium was thickest, and the average was taken (Voluson S6). Patients whose endometrial thickness was less than 7 mm were considered estrogen resistant, and these patients were included in the PRP group. On the other hand, a history of RIF, regardless of endometrial thickness, was also considered an indication for PRP. Autologous PRP infusion was applied on the same day. Fifteen milliliters of peripheral venous blood was drawn from the left arm into a tube containing 2.5 ml of acid citrate A anticoagulant solution and centrifuged at 3000 rpm for 20 min, and the red blood cells were separated. The plasma was centrifuged again at 2000 rpm for 10 min, the supernatant was discarded, and the remaining 0.5 ml of PRP was infused into the uterine cavity with the IUI catheter. The amount of blood to be taken was determined by considering previous studies. Some studies used 10 ml of blood, whereas others used 20 ml. We decided to collect 15 ml of blood from the patients [16, 17].

We did not encounter insufficiency of the PRP solution we prepared in any of the cases. Since we observed that the authors did not have any problems with insufficient blood volume in previous studies, we deemed it appropriate to use the same volume.

In our study, we applied PRP once to all patients. The blood volume we received was sufficient and we used only 0.5 ml of the volume for endometrial cavity.

After the procedure, the patients were rested for 10 min and then mobilized. They continued their estrogen replacement at the same dose and had their endometrial thickness was evaluated 2 days later. In patients with an endometrium of 7 mm or greater, progesterone replacement was started and embryo transfer was performed on the 5th day.

Cycle cancellation was considered in cases where the endometrial thickness was less than 7 mm. In patients with RIF, PRP was applied on the 10th day of estrogen replacement regardless of endometrial thickness. Those with DM, HT or contraindication to estrogen replacement, such as breast disease and a history of thrombosis, were excluded from the study. The initial platelet counts of the patients were taken into account. The routine blood tests of every patient receiving in vitro fertilization treatment included a hemogram. However, since thrombocytopenia was not observed in any patient, this parameter was not specified. Cases with thrombocytopenia were excluded from the study.

We do not have the technical equipment to provide sufficient objective criteria in a laboratory environment to evaluate the quality of the produced PRP. We did not have a device to determine the number of MNCs (mononuclear cells). Therefore, the following subjective criteria were used as the basis.

For this purpose, a special solution with a density between that of MN cells and shaped cell elements was used. (Lymphoprep). Lymphoprep is a density gradient medium for the isolation of mononuclear cells from peripheral blood (polymorphonuclear cells & red blood cells). Thus, we managed to differentiate the MNCs owing to the line-shaped part that became visible. We removed and retained MNC layer at the plasma:LymphoprepTM interface without disturbing erythrocyte/granulocyte pellet. Then we washed MNCs once with medium and prepared them.

Patients were divided into those over 35 years and those under 35 years of age. Double embryo transfer was performed for each patient over 35 years of age, and the embryo data with the better grade of the two transferred embryos are presented. Only patients with day 5 embryo transfers were included in the study. The grades of the transferred embryos according to group are presented in Table 1.

β-hCG > 50 mIU/ml 14 days after embryo transfer was considered a pregnancy, and the presence of a gestational sac on ultrasound performed 35 days after embryo transfer was considered a clinical pregnancy. The pregnancies that continued after the 22nd gestational week were considered live births. Before the 22nd week, spontaneous miscarriages or when babies died in utero were considered miscarriages.

Statistical analysis

All clinical data were recorded according to the groups via the SPSS program. The IBM SPSS 21 package program was used for statistical analysis. While the study data were being evaluated, descriptive statistical methods (mean, standard deviation, median, minimum, and maximum) were used, and the conformity of the quantitative data to a normal distribution was tested with the Kolmogorov–Smirnov test and the Shapiro–Wilk test. The Wilcoxon signed rank test was used to compare two dependent groups of data that did not have a normal distribution. Appropriate Chi-square analyses were used to compare categorical variables. Accordingly, the Pearson Chi-square independence test was applied when the number of levels in at least one of the variables was more than 2. On the other hand, when the number of levels of both categorical variables was 2, Pearson Chi-square tests were used when the minimum expected frequency was greater than 25, and Yates Chi-square tests were used when it was between 5 and 25. The names of the methods used are given below the tables. In addition, the Z test was used for the comparison of the two ratios. Significance was determined at the p < 0.05 level.

Results

Demographic and clinical characteristics

The patients included in the study were between the ages of 23 and 48 years. All patients were infertile and had PRP indication. The study evaluated five different groups: individuals with thin endometrium and PRP treatment without RIF (n = 33), those with RIF and PRP treatment without thin endometrium (n = 71), individuals with both thin endometrium and RIF undergoing PRP treatment (n = 25), patients with RIF without PRP treatment (n = 96), and a control group (n = 150).

Considering the demographic characteristics of the patients, the percentage of patients aged 35 + (78.8%) among patients without RIF and a thin endometrium who underwent PRP was significantly greater than that in the control group (44%) (Table 1), (Fig. 1).

Fig. 1 — Distribution of ages according to RIF, endometrium and PRP status

Embryo characteristics

All participants underwent frozen embryo transfer and all of them on the 5th day.

Double embryo transfer was performed for each patient over 35 years of age, and the embryo data with the better grade of the two transferred embryos are presented. Only patients with embryo transferred on the 5th day were included in the study. The grades of the transferred embryos according to group are presented in Table 1. Gardner system was used for embryo grading. The percentage of patients with RIF who underwent PRP with Grade 3 embryos (35.2%) was significantly greater than that of the control group (18%) (Fig. 2).

Fig. 2 — Distribution of embryo grades according to RIF, endometrium and PRP status

Pregnancy outcomes

Our examination of pregnancy outcomes reveals insights into the impact of PRP treatment on patients with a history of recurrent implantation failure (RIF). In the RIF cohort, the clinical pregnancy rate with PRP (34.3%, 33/96) was comparable to that without PRP (34.4%), with no statistically significant difference observed between the two groups (p > 0.05) (Table 1) (Fig. 3).

Fig. 3 — Distribution of pregnancy states according to RIF, endometrium and PRP status

Compared with the RIF control group without PRP, patients with RIF but without a thin endometrium had increased clinical and live pregnancy rates compared to the RIF control group without PRP. However, these increases did not reach statistical significance (clinical pregnancy: 36% vs 34%, live birth: 35% vs 34%) (p > 0.05) (Fig. 4).

Fig. 4 — Distribution of live births according to RIF, endometrium and PRP status

Ongoing pregnancy rates were significantly associated with age and RIF history (p value = 0.024 < 0.05). Younger patients with a history of RIF demonstrated a higher ongoing pregnancy rate (50%) than older patients (21%).

No statistically significant difference in pregnancy rates was observed when PRP was applied to patients with and without RIF (p > 0.05). A strong correlation was identified between RIF status and the thickness of the endometrium among patients who underwent PRP, with a confidence level of 99.9% (p < 0.001).

When PRP was applied to patients with only thin endometria and those with both thin endometria and a history of RIF, no statistically significant difference in pregnancy rates was identified (p > 0.05). Ongoing pregnancies were comparable in patients without a history of RIF (48%) and those with a history of RIF (34%), with no significant relationship found between these rates (p value = 0.317 > 0.05).

PRP increased the live birth rate, but this increase was not statistically significant. In RIF patients without PRP, the clinical and live pregnancy rates were significantly lower than those in the control group (34% vs 56%) (p = 0.028 < 0.05), underscoring the negative effect of RIF on fetal outcomes.

Analysis of pregnancy test results revealed a positive outcome in 57.3% of patients, with 66.2% of those presenting a positive fetal heart motion (FHM +). The live birth rate was 36.7%. PRP had positive effects on patients with thin endometria and no RIF, with a 60% positive pregnancy test rate and a 45.5% live birth rate.

Since chemical and early pregnancy loss rates were similar in patients with and without PRP, no statistically significant relationship was found between the two groups in terms of miscarriage rates (p > 0.05) (Table 1).

Endometrial thickness

In this study, although the pregnancy results of patients with RIF and without PRP were reported, the pregnancy results of patients with thin endometria without PRP were not reported. The reason for this is very simple. The pregnancy rates of patients with thin endometria are low, as shown in many studies. Therefore, if PRP was not applied to patients with thin endometria, transfer was not applied. Therefore, patients with thin endometria for which PRP was not applied were not included in the study.

In 150 patients with a thin endometrium and/or a history of RIF who underwent PRP, the endometrial thickness at the 48th hour after PRP was significantly greater than the pre-PRP endometrial thickness, and this value was statistically significant (7.38 mm vs. 7.96 mm, p < 0.001).

In patients without RIF but with a thin endometrium, a significant increase in endometrial thickness was observed following PRP treatment. The mean thickness increased from 5.8 ± 0.81 mm before PRP to 6.65 ± 0.91 mm after PRP, with median values increasing from 5.9 mm (range 3.7–6.9 mm) to 6.8 mm (range 5–8.8 mm). This improvement was statistically significant (p < 0.001) (Table 2).

Table 2.

Endometrial thicknesses of patients according to thin endometrium or RIF status before and after PRP

Status	Endometrium	Ort ∓ SS	Median (min–max)	P value
RIF ( – ) and thin end	Before PRP	5.8 ∓ 0.81	5.9 (3.7–6.9)	0.000 < 0.001*
RIF ( – ) and thin end	After PRP	6.65 ∓ 0.91	6.8 (5–8.8)	0.000 < 0.001*
RIF ( +) and normal end	Before PRP	8.52 ∓ 1.57	8 (7–13.5)	0.000 < 0.001*
RIF ( +) and normal end	After PRP	8.9 ∓ 1.55	8.6 (6.9–13)	0.000 < 0.001*
RIF ( +) and thin end	Before PRP	5.94 ∓ 0.77	6 (4–6)	0.000 < 0.001*
RIF ( +) and thin end	After PRP	6.89 ∓ 0.62	6.8 (5.8–8.5)	0.000 < 0.001*

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*Wilcoxon signed rank test

For patients with RIF and a normal endometrium, PRP treatment also resulted in an increase in endometrial thickness. The mean thickness before PRP treatment was 8.52 ± 1.57 mm, which increased to 8.9 ± 1.55 mm after PRP. Similarly, the median values similarly increased from 8 mm (range 7–13.5 mm) to 8.6 mm (range 6.9–13 mm), and this change was statistically significant (p < 0.001) (Table 2).

Finally, in the group of patients with RIF and a thin endometrium, PRP therapy led to a significant improvement in endometrial thickness. The mean thickness was 5.94 ± 0.77 mm before PRP and increased to 6.89 ± 0.62 mm after the treatment. The median values showed a similar trend, increasing from 6 mm (range 4–6 mm) to 6.8 mm (range 5.8–8.5 mm), with a p value < 0.001, indicating a significant increase (Table 2).

No statistically significant correlation was found between age group and pregnancy status in patients with thin endometria (p value = 0.231 > 0.05).

Discussion

A good-quality embryo and a receptive endometrium are needed for successful implantation.

Many studies have shown that PRP infusion increases the endometrium, implantation rates and clinical pregnancy rates in infertile women undergoing ART [16, 18–21]. The results of other studies are contradictory [22, 23]. The endometrial thickness should be at least 7 mm for human embryo implantation [24]. Therefore, a thin endometrium in the ART cycle may lead to cycle abortion and, surprisingly, embryo cryopreservation [16]. PRP has recently been applied to increase endometrial thickness, because of its strong effect on the upregulation of genes associated with endometrial receptivity and proliferation [25]. It has also been reported that PRP treatment before embryo transfer can significantly increase implantation rates [26]. In our study, considering all patients who underwent PRP (regardless of endometrial thickness/RIF/age factor), no statistically significant relationships were found between PRP and pregnancy status, live birth rate or miscarriage rate. In line with this, one randomized clinical trial showed that intrauterine infusion of PRP improved the endometrium, implantation rate and clinical pregnancy rate in patients with thin endometrium, whereas three other studies involving subjects with recurrent implantation failure reported conflicting results regarding clinical pregnancy rates [11, 12].

Tandulwadkar et al. applied intrauterine autologous PRP to 68 women with thin endometria and reported increases in biochemical and clinical pregnancy rates and endometrial thickness [27]. Eftekhar et al. conducted the first randomized controlled trial with 66 eligible participants. A statistically significant increase in endometrial thickness (p = 0.001) and higher implantation rate (p = 0.002) were noted in the PRP group compared with the control group. They also reported a lower cycle cancellation rate and higher pregnancy rate in the PRP group; however, this difference was not statistically significant [28]. After understanding the effectiveness of suboptimal endometrial thickness in the etiopathogenesis of RIF, PRP was proposed for RIF patients with thin endometria.

Although the mechanisms by which PRP increases endometrial receptivity are not yet clear, it is believed that growth factors play a very important role [25]. It has also been reported that recurrent implantation failure is the result of inefficient expression of adhesion molecules that could be improved with PRP [26]. Intrauterine administration of PRP can facilitate implantation via the following mechanisms: (1) upregulation of COX2, the convertor of arachidonic acid to prostaglandins; (2) increased expression of ER and PR, which are involved in the endometrial response to ovarian hormones; (3) upregulation of MMP expression and thus tissue remodeling; and (4) reduction in proinflammatory factors in abnormal conditions such as endometritis. Although the growth factors of PRP have beneficial effects on the endometrium, it has been shown that high concentrations of PRP have also been shown to prevent proliferation and cause negative side effects [25, 29]. The blood volume we received was sufficient and we used only 0.5 ml of the volume for endometrial cavity.

Although many treatment methods have been applied thus far for RIF, the evidence level of most of these methods is not sufficient. Implantation failure is caused by either a poor-quality embryo or an endometrial receptivity problem. In this context, several studies have been conducted on RIF patients and the results have shown the efficacy of PRP therapy in increasing implantation and pregnancy rates [21, 26, 30].

In this study, PRP had the greatest effect on patients with thin endometria without RIF. Since age is the most important factor in infertility, the results are not satisfactory in the older age group.

In our study, administering PRP to patients with RIF but without a thin endometrium increased the clinical and live pregnancy rates compared with those in the RIF control group without PRP. However, these increases did not reach statistical significance (clinical pregnancy: 36% vs 34%, live birth: 35% vs 34%) (p > 0.05).

The putative mechanisms of action regarding the use of PRP in RIF patients are as follows:

fibroblast growth factor-1 (FGF-1) levels are decreased in RIF patients and FGF-1 in PRP may compensate for this deficiency [31]. Many of the growth factors in PRP, such as insulin-like growth factors, growth hormone, PDGF, EGF and TGF-β, can bind to the corresponding receptors in the endometrial tissue, increasing endometrial remodeling and thus endometrial receptivity, thereby increasing implantation [32]. EGF in PRP can regulate the expression of uterine VEGF, which contributes locally to decidual vascularization, placental angiogenesis and endometrial proliferation [33]. Aghajanzadeh et al. analyzed the data of 30 women aged 18–40 years with a history of recurrent implantation failure. Endometrial preparation with 6 mg/day estradiol was started on day 2 or 3 of the menstrual cycle, and the endometrium was evaluated on day 9 or 10 of the cycle [34]. Women with endometrial thickness < 7 mm received same-day intrauterine infusion of autologous PRP and embryo transfer was performed 48–72 h later. There was also no statistically significant difference in the clinical pregnancy rate, chemical pregnancy rate or ongoing pregnancy rate between the control and PRP groups [34]. In a prospective randomized study involving 80 women with RIF, Zargar et al. reported that the use of PRP in women with RIF did not significantly improve outcomes. However, 80 women were administered a mix of fresh and frozen cycles, making the results and interpretation of the study questionable. Ideally, the researchers have suggested the use of either fresh or whole FET cycles rather than a mix of both [35]. In the present study, however, pregnancy outcomes were positively affected by PRP application in patients with a history of RIF, but this effect was not statistically significant only in the FET group. Despite the sufficient number of cases, the lack of investigations of chronic endometritis as a cause of a thin endometrium is a limitation of our study.

Conclusions

The optimal endometrial thickness can be achieved with PRP in patients with thin endometria and recurrent implantation failure.

Limitations of the study

Our laboratory conditions were not very good that can provide more objective criteria in PRP preperation equipment.
The embryo characteristics of all cases are not the same.
Chronic endometritis as a cause of a thin endometrium was not investigated, and endometrial receptivity was only evaluated by ultrasonographic measurement.
Additionally, it is unclear whether the patients had a history of D&C or hysterectomy, which could be the cause of thin endometrium.

Abbreviations

FET: Frozen embryo transfer
PRP: Platelet-rich plasma
RIF: Recurrent implantation failure
end: endometrium

Funding

The authors have not disclosed any funding.

Data availability

Sharing patients' file records is against their personal rights and would be unethical. Because of this, the research data are not shared. The data are not publicly available due to privacy or ethical restrictions. All materials and patient data used in the study are available in hospital records.

Declarations

Conflict of interest

None of the authors have any conflicts of interest related to this publication. On behalf of all the authors, the corresponding author states that there are no conflicts of interest.

Ethical approval

Ethical approval for this research was obtained from Ondokuz Mayıs University, Clinical Research Ethical Committee, on January 17, 2023, with the number 2023000007-1. IRB approval is available for the study. All authors have approval to participate in the study. All authors have approved publication. No special software application or special code was used in the study.

Footnotes

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12.Wolff EF, Vahidi N, Alford C, Richter K, Widra E (2013) Influences on endometrial development during intrauterine insemination: clinical experience of 2,929 patients with unexplained infertility. Fertil Steril 100:194–199. 10.1016/j.fertnstert.2013.03.023. ([PMCfreearticle][PubMed][CrossRef][GoogleScholar]) [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Shakerian B, Turkgeldi E, Yildiz S, Keles I, Ata B (2021) Endometrial thickness is not predictive for live birth after embryo transfer, even without a cutoff. Fertil Steril 116(1):130–137. 10.1016/j.fertnstert.2021.02.041. (Epub 2021 Mar 31) [DOI] [PubMed] [Google Scholar]
14.Lebovitz O, Orvieto R (2014) Treating patients with “thin” endometrium - an ongoing challenge. Gynecol Endocrinol. 30(6):409–414. 10.3109/09513590.2014.906571. (Epub 2014 Apr 2.PMID: 24693854 Review) [DOI] [PubMed] [Google Scholar]
15.Gleicher N, Vidali A (2011) Successful treatment of unresponsive thin endometrium. Fertil Steril. 95(6):2123.e13–7. 10.1016/j.fertnstert.2011.01.143. (Epub 2011 Feb 16PMID: 21324451) [DOI] [PubMed] [Google Scholar]
16.Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X (2015) Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med 8(1):1286–1290 [PMC free article] [PubMed] [Google Scholar]
17.Enatsu Y, Enatsu N, Kishi K, Otsuki J, Iwasaki T (2021) Clinical outcome of intrauterine infusion of platelet-rich plasma in patients with recurrent implantation failure. Reprod Med Biol. 21(1):e12417. 10.1002/rmb2.12417. (eCollection 2022 Jan.PMID: 34938145) [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Mouanness M, Ali-Bynom S, Jackman J, Seckin S, Merhi Z (2021) Use of Intra-uterine injection of platelet-rich plasma (PRP) for endometrial receptivity and thickness: a literature review of the mechanisms of action. Reprod Sci 28(6):1659–1670. 10.1007/s43032-021-00579-2. (Epub 2021 Apr 22 PMID: 33886116) [DOI] [PubMed] [Google Scholar]
19.Okitsu O, Kiyokawa M, Oda T, Miyake K, Sato Y, Fujiwara H (2011) Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 92(1–2):82–87. 10.1016/j.jri.2011.07.001. (Epub 2011 Oct 27 PMID: 22035703) [DOI] [PubMed] [Google Scholar]
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21.Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L (2016) Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: a pilot study. Int J Reprod Biomed. 14(10):625–628 (PMID: 27921085; PMCID: PMC5124324) [PMC free article] [PubMed] [Google Scholar]
22.Cai QF, Wan F, Huang R, Zhang HW (2011) Factors predicting the cumulative outcome oIVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod 26:2532–2540. 10.1093/humrep/der228. ([PubMed][CrossRef][GoogleScholar]) [DOI] [PubMed] [Google Scholar]
23.Remohí J, Ardiles G, García-Velasco JA, Gaitán P, Simón C, Pellicer A (1997) Endometrial thickness and serum estradiol concentrations as predictors of outcome in oocyte donation. Hum Reprod 12:2271–2276. 10.1093/humrep/12.10.2271. ([PubMed][CrossRef][GoogleScholar]) [DOI] [PubMed] [Google Scholar]
24.El-Toukhy T, Coomarasamy A, Khairy M, Sunkara K, Seed P, Khalaf Y, Braude P (2008) The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril 89(4):832–839. 10.1016/j.fertnstert.2007.04.031 [DOI] [PubMed] [Google Scholar]
25.Marini MG, Perrini C, Esposti P, Corradetti B, Bizzaro D, Riccaboni P, Fantinato E, Urbani G, Gelati G, Cremonesi F (2016) Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro. Reprod Biol Endocrinol 14(1):58. 10.1186/s12958-016-0195-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Farimani M, Bahmanzadeh M, Poorolajal J (2016) A new approach using autologous platelet-rich plasma (prp) to treat infertility and to improve population replacement rate. J Res Health Sci. 16(3):172–173 (PMID: 27840348; PMCID: PMC7191021) [PMC free article] [PubMed] [Google Scholar]
27.Tandulwadkar SR, Naralkar MV, Surana AD, Selvakarthick M, Kharat AH (2017) Autologous intrauterine platelet-rich plasma instillation for suboptimal endometrium in frozen embryo transfer cycles: a pilot study. J Hum Reprod Sci. 10(3):208–212. 10.4103/jhrs.JHRS_28_17. (PMID: 29142450; PMCID: PMC5672727) [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Eftekhar M, Neghab N, Naghshineh E, Khani P (2018) Can autologous platelet rich plasma expand endometrial thickness and improve pregnancy rate during frozen–thawed embryo transfer cycle? A randomized clinical trial. Taiwan J Obstet Gynecol 57(6):810–813. 10.1016/j.tjog.2018.10.007. (Erratum.In:TaiwanJObstetGynecol.2021Sep;60(5):973 PMID: 30545532) [DOI] [PubMed] [Google Scholar]
29.LangeConsiglio A, Cazzaniga N, Garlappi R, Spelta C, Pollera C, Perrini C, Cremonesi F (2015) Platelet concentrate in bovine reproduction: effects on in vitro embryo production and after intrauterine administration in repeat breeder cows. Reprod Biol Endocrinol 13(1):65. 10.1186/s12958-015-0064-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Nazari L, Salehpour S, Hosseini MS, Hashemi MP (2020) The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil (Camb) 23(3):209–213. 10.1080/14647273.2019.1569268. (Epub 2019 Feb 4 PMID: 30714427) [DOI] [PubMed] [Google Scholar]
31.Sak ME, Gul T, Evsen MS, Soydinc HE, Sak S, Ozler A, Alabalik U (2013) Fibroblast growth factor-1 expression in the endometrium of patients with repeated implantation failure after in vitro fertilization. Eur Rev Med Pharmacol Sci 17(3):398–402 (PMID: 23426545) [PubMed] [Google Scholar]
32.Anitua E, de la Fuente M, Ferrando M, Quintana F, Larreategui Z, Matorras R, Orive G (2016) Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts. Eur J Obstet Gynecol Reprod Biol 206:125–130. 10.1016/j.ejogrb.2016.09.024 [DOI] [PubMed] [Google Scholar]
33.Furukawa Y, Kawano Y, Fukuda J, Matsumoto H, Narahara H (2009) The production of vascular endothelial growth factor and metalloproteinase via protease-activated receptor in human endometrial stromal cells. Fertil Steril 91(2):535–541. 10.1016/j.fertnstert.2007.11.080 [DOI] [PubMed] [Google Scholar]
34.Aghajanzadeh F, Esmaeilzadeh S, Basirat Z, Mahouti T, Heidari FN, Golsorkhtabaramiri M (2020) Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure. JBRA Assist Reprod 24(1):30–33. 10.5935/1518-0557.20190055. (PMID:31689042;PMCID:PMC6993157) [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Zargar M, Pazhouhanfar R, Najafian M (2021) Parastoo moradi choghakabodi effects of intrauterine autologous platelet-rich plasma infusions on outcomes in women with repetitive in vitro fertilization failures: a prospective randomized study. Clin Exp Obstet Gynecol. 10.31083/j.ceog.2021.01.2131 [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

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[CR9] 9.RoyChoudhury S, Singh A, Gupta NJ, Srivastava S, Joshi MV, Chakravarty B, Chaudhury K (2016) Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level. Hum Reprod 31(6):1265–1274. 10.1093/humrep/dew064. (Epub 2016 Apr 8 PMID: 27060172) [DOI] [PubMed] [Google Scholar]

[CR10] 10.Shi C, Shen H, Fan LJ, Guan J, Zheng XB, Chen X et al (2017) The endometrial MicroRNA signature during the window of implantation changed in patients with repeated implantation failure. Chin Med J. 10.4103/0366-6999.200550 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR11] 11.Cai QF, Wan F, Huang R, Zhang HW (2011) Factors predicting the cumulative outcome of IVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod 26:2532–2540. 10.1093/humrep/der228. ([PubMed][CrossRef][GoogleScholar]) [DOI] [PubMed] [Google Scholar]

[CR12] 12.Wolff EF, Vahidi N, Alford C, Richter K, Widra E (2013) Influences on endometrial development during intrauterine insemination: clinical experience of 2,929 patients with unexplained infertility. Fertil Steril 100:194–199. 10.1016/j.fertnstert.2013.03.023. ([PMCfreearticle][PubMed][CrossRef][GoogleScholar]) [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR13] 13.Shakerian B, Turkgeldi E, Yildiz S, Keles I, Ata B (2021) Endometrial thickness is not predictive for live birth after embryo transfer, even without a cutoff. Fertil Steril 116(1):130–137. 10.1016/j.fertnstert.2021.02.041. (Epub 2021 Mar 31) [DOI] [PubMed] [Google Scholar]

[CR14] 14.Lebovitz O, Orvieto R (2014) Treating patients with “thin” endometrium - an ongoing challenge. Gynecol Endocrinol. 30(6):409–414. 10.3109/09513590.2014.906571. (Epub 2014 Apr 2.PMID: 24693854 Review) [DOI] [PubMed] [Google Scholar]

[CR15] 15.Gleicher N, Vidali A (2011) Successful treatment of unresponsive thin endometrium. Fertil Steril. 95(6):2123.e13–7. 10.1016/j.fertnstert.2011.01.143. (Epub 2011 Feb 16PMID: 21324451) [DOI] [PubMed] [Google Scholar]

[CR16] 16.Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X (2015) Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med 8(1):1286–1290 [PMC free article] [PubMed] [Google Scholar]

[CR17] 17.Enatsu Y, Enatsu N, Kishi K, Otsuki J, Iwasaki T (2021) Clinical outcome of intrauterine infusion of platelet-rich plasma in patients with recurrent implantation failure. Reprod Med Biol. 21(1):e12417. 10.1002/rmb2.12417. (eCollection 2022 Jan.PMID: 34938145) [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR18] 18.Mouanness M, Ali-Bynom S, Jackman J, Seckin S, Merhi Z (2021) Use of Intra-uterine injection of platelet-rich plasma (PRP) for endometrial receptivity and thickness: a literature review of the mechanisms of action. Reprod Sci 28(6):1659–1670. 10.1007/s43032-021-00579-2. (Epub 2021 Apr 22 PMID: 33886116) [DOI] [PubMed] [Google Scholar]

[CR19] 19.Okitsu O, Kiyokawa M, Oda T, Miyake K, Sato Y, Fujiwara H (2011) Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 92(1–2):82–87. 10.1016/j.jri.2011.07.001. (Epub 2011 Oct 27 PMID: 22035703) [DOI] [PubMed] [Google Scholar]

[CR20] 20.Li S, Wang J, Cheng Y, Zhou D, Yin T, Xu W, Yu N, Yang J (2017) Intrauterine administration of hCG-activated autologous human peripheral blood mononuclear cells (PBMC) promotes live birth rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 119:15–22. 10.1016/j.jri.2016.11.006. (Epub 2016 Nov 27 PMID: 27915038) [DOI] [PubMed] [Google Scholar]

[CR21] 21.Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L (2016) Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: a pilot study. Int J Reprod Biomed. 14(10):625–628 (PMID: 27921085; PMCID: PMC5124324) [PMC free article] [PubMed] [Google Scholar]

[CR22] 22.Cai QF, Wan F, Huang R, Zhang HW (2011) Factors predicting the cumulative outcome oIVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod 26:2532–2540. 10.1093/humrep/der228. ([PubMed][CrossRef][GoogleScholar]) [DOI] [PubMed] [Google Scholar]

[CR23] 23.Remohí J, Ardiles G, García-Velasco JA, Gaitán P, Simón C, Pellicer A (1997) Endometrial thickness and serum estradiol concentrations as predictors of outcome in oocyte donation. Hum Reprod 12:2271–2276. 10.1093/humrep/12.10.2271. ([PubMed][CrossRef][GoogleScholar]) [DOI] [PubMed] [Google Scholar]

[CR24] 24.El-Toukhy T, Coomarasamy A, Khairy M, Sunkara K, Seed P, Khalaf Y, Braude P (2008) The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril 89(4):832–839. 10.1016/j.fertnstert.2007.04.031 [DOI] [PubMed] [Google Scholar]

[CR25] 25.Marini MG, Perrini C, Esposti P, Corradetti B, Bizzaro D, Riccaboni P, Fantinato E, Urbani G, Gelati G, Cremonesi F (2016) Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro. Reprod Biol Endocrinol 14(1):58. 10.1186/s12958-016-0195-4 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR26] 26.Farimani M, Bahmanzadeh M, Poorolajal J (2016) A new approach using autologous platelet-rich plasma (prp) to treat infertility and to improve population replacement rate. J Res Health Sci. 16(3):172–173 (PMID: 27840348; PMCID: PMC7191021) [PMC free article] [PubMed] [Google Scholar]

[CR27] 27.Tandulwadkar SR, Naralkar MV, Surana AD, Selvakarthick M, Kharat AH (2017) Autologous intrauterine platelet-rich plasma instillation for suboptimal endometrium in frozen embryo transfer cycles: a pilot study. J Hum Reprod Sci. 10(3):208–212. 10.4103/jhrs.JHRS_28_17. (PMID: 29142450; PMCID: PMC5672727) [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR28] 28.Eftekhar M, Neghab N, Naghshineh E, Khani P (2018) Can autologous platelet rich plasma expand endometrial thickness and improve pregnancy rate during frozen–thawed embryo transfer cycle? A randomized clinical trial. Taiwan J Obstet Gynecol 57(6):810–813. 10.1016/j.tjog.2018.10.007. (Erratum.In:TaiwanJObstetGynecol.2021Sep;60(5):973 PMID: 30545532) [DOI] [PubMed] [Google Scholar]

[CR29] 29.LangeConsiglio A, Cazzaniga N, Garlappi R, Spelta C, Pollera C, Perrini C, Cremonesi F (2015) Platelet concentrate in bovine reproduction: effects on in vitro embryo production and after intrauterine administration in repeat breeder cows. Reprod Biol Endocrinol 13(1):65. 10.1186/s12958-015-0064-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR30] 30.Nazari L, Salehpour S, Hosseini MS, Hashemi MP (2020) The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil (Camb) 23(3):209–213. 10.1080/14647273.2019.1569268. (Epub 2019 Feb 4 PMID: 30714427) [DOI] [PubMed] [Google Scholar]

[CR31] 31.Sak ME, Gul T, Evsen MS, Soydinc HE, Sak S, Ozler A, Alabalik U (2013) Fibroblast growth factor-1 expression in the endometrium of patients with repeated implantation failure after in vitro fertilization. Eur Rev Med Pharmacol Sci 17(3):398–402 (PMID: 23426545) [PubMed] [Google Scholar]

[CR32] 32.Anitua E, de la Fuente M, Ferrando M, Quintana F, Larreategui Z, Matorras R, Orive G (2016) Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts. Eur J Obstet Gynecol Reprod Biol 206:125–130. 10.1016/j.ejogrb.2016.09.024 [DOI] [PubMed] [Google Scholar]

[CR33] 33.Furukawa Y, Kawano Y, Fukuda J, Matsumoto H, Narahara H (2009) The production of vascular endothelial growth factor and metalloproteinase via protease-activated receptor in human endometrial stromal cells. Fertil Steril 91(2):535–541. 10.1016/j.fertnstert.2007.11.080 [DOI] [PubMed] [Google Scholar]

[CR34] 34.Aghajanzadeh F, Esmaeilzadeh S, Basirat Z, Mahouti T, Heidari FN, Golsorkhtabaramiri M (2020) Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure. JBRA Assist Reprod 24(1):30–33. 10.5935/1518-0557.20190055. (PMID:31689042;PMCID:PMC6993157) [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR35] 35.Zargar M, Pazhouhanfar R, Najafian M (2021) Parastoo moradi choghakabodi effects of intrauterine autologous platelet-rich plasma infusions on outcomes in women with repetitive in vitro fertilization failures: a prospective randomized study. Clin Exp Obstet Gynecol. 10.31083/j.ceog.2021.01.2131 [Google Scholar]

PERMALINK

The effect of endometrial PRP on fertility outcomes in women with implantation failure or thin endometrium

Naziye Gurkan

Tayfun Alper

Abstract

Objective

Materials and methods

Results

Conclusion

What does this study add to the clinical work

Introduction

Materials and methods

Table 1.

Statistical analysis

Results

Demographic and clinical characteristics

Fig. 1.

Embryo characteristics

Fig. 2.

Pregnancy outcomes

Fig. 3.

Fig. 4.

Endometrial thickness

Table 2.

Discussion

Conclusions

Limitations of the study

Abbreviations

Funding

Data availability

Declarations

Conflict of interest

Ethical approval

Footnotes

References

Associated Data

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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