GYNECOLOGY

Endometrial thickness: How thin is too thin?

Study question Will subendometrial injection of autologous platelet rich plasma (PRP) enhance the implantation by improving endometrial thickness (ET) and vascularity in frozen embryo transfers (FET)? Summary answer In this study it was observed that subendometrial injection of autologous PRP enhances implantation by improving ET and vascularity. What is known already Reports on evaluating effectiveness of injecting PRP hysteroscopically at the endomyometrial junction are limited. PRP has more effect on angiogenic growth cells as it contains high concentrations of vascular endothelial growth factor, epidermal growth factor, platelet derived growth factor, leukemia inhibiting factor, beta 3 integrin, transforming growth factor and cytokines which are essential for the endometrial proliferation. Previous reports suggest that these factors are inadequately expressed in a deficient endometrium and they are enhanced after PRP. Study design, size, duration From December 2019 to December 2021, 172 women with ET less than or equal to 7mm were included in the study and underwent PRP instillation. Patients with Asherman’s syndrome were excluded from the study. The endometrial vascularity zone as per Applebaum criteria was noted. Informed written consent obtained from all participants.The comparison of ET and vascularity before and after PRP was carried out by paired t test. This study was approved by Institutional ethical committee. Participants/materials, setting, methods 8 ml of autologous PRP was instilled at the junctional zone hysteroscopically from day 6-10 of menstrual cycle. After allowing 8 weeks for the endometrium to regenerate, ET and vascularity were measured and prepared for FET. The statistical significance was tested by comparing ET and vascularity before and after PRP using Paired T-test at 5% level of significance. FET was done for 109 women and the outcome was analysed. Main results and the role of chance Based on paired ‘t’test, it is concluded that there is statistically significant effective difference on ET after PRP at 0.05 significance level and vascularity following PRP at CI (-0.663± 0.11). T statistic = 1.653813 p value = 0.000282 and CI (-0.33±0.092),T statistic=1.653813, p value= 0.000254 respectively. Out of 172 women, ET increased in 130, decreased in 22 and remained the same in 20. Mean ET before and after PRP were 5.9mm and 6.6mm respectively which showed significant difference. Endometrial vascularity improved for 56 women decreased for 9 remained the same for 107. Of 172 women, 109 had underwent FET 44 showed positive BHCG value (40.3%) and 38 showed a clinical pregnancy rate (CPR) corresponding to 34.8%. Two others are awaited for the first scan Other two had blighted ovum, missed abortion respectively. CPR was observed to be 34.09% in the group with increased and 33.3% in the group with decreased and 44.4% in the group with no change in ET. Similarly the CPR was 30% in women with increased and 50% in those with decreased and 36% in the group with no change in vascularity. Limitations, reasons for caution The embryo quality and synchrony could have an effect on the pregnancy rate. It involves invasive procedure at a higher cost. It can cause infections and anaesthesia related complications. Wider implications of the findings we can assume that subendometrial injection of PRP is effective in improving the ET and vascularity and there by improve the pregnancy outcome. More studies are needed to confirm the effect of PRP in improving the endometrial thickness and vascularity and thereby implantation. Trial registration number N/A

Intrauterine administration of platelet-rich-plasma (PRP) has shown potential in improving pregnancy outcomes in assisted reproductive technology (ART). However, the efficacy of PRP in enhancing clinical pregnancy and live birth rates remains a topic of debate. This meta-analysis evaluated the effectiveness of intrauterine PRP administration in improving clinical pregnancy and live birth rates. A systematic search of electronic databases was conducted to identify randomized controlled trials (RCTs) comparing intrauterine PRP administration with control in women undergoing ART. The primary outcomes were clinical pregnancy rates and live birth rates. Data were extracted and pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Nineteen RCTs involving 1,918 participants were included for clinical pregnancy rates, and six RCTs involving 777 participants were included for live birth rates. The pooled OR for clinical pregnancy rates was 2.49 (95% CI: 1.84, 3.35), indicating a significant improvement in the PRP group. For live birth rates, the pooled OR was 3.28 (95% CI: 1.18, 9.09), also favouring the PRP group. Moderate heterogeneity was observed for clinical pregnancy rates (I²=43%), while substantial heterogeneity was observed for live birth rates (I²=77%). Funnel plots showed no significant publication bias for either outcome. Intrauterine PRP administration significantly improves clinical pregnancy and live birth rates in women undergoing ART. The pooled ORs of 2.49 for clinical pregnancy rates and 3.28 for live birth rates support the potential clinical utility of PRP in enhancing ART outcomes.

Study question Does intraovarian injection of autologous platelet-rich plasma (PRP) improve fertility outcomes and livebirths in women with ovarian insufficiency? Summary answer An increase in number of eggs retrieved, embryos created and pregnancy rates (clinical and live birth) were seen in women post PRP injection. What is known already A gradual increase in childbearing age have resulted in age-related fertility decline and high-risk pregnancies in older women. Ovarian aging is a principal limiting factor for success in both spontaneous and assisted reproductive techniques conceptions. Diminished ovarian reserve (DOR) occurs in about 10% of the subfertile population, with no effective treatment to date. The substantial clinical burden and lack of effective treatments underscore the highly unmet need in this group of women. Intraovarian autologous PRP infusion was recently introduced in the context of addressing ovarian insufficiency, with several studies showing an increase in ovarian function and promising ART outcomes. Study design, size, duration A pilot study was conducted in an academic medical centre between 2023 to 2024. Women aged 21 to 40 years old with diminished ovarian reserves and a history of poor ovarian response at prior IVF stimulation cycle despite maximum doses of gonadotrophin were recruited (n = 13). Duration of participation was 6-12 months. Primary outcome measures were improvements in ovarian reserves and response to IVF stimulation. Secondary outcomes measures were clinical pregnancy and live birth rates. Participants/materials, setting, methods Anti-mullerian hormone (AMH) and antral follicle count (AFC) were measured on day 2-3 of the menstrual cycle. Autologous PRP was injected on Day 5 -15 subsequently. A one-step closed system using RegenKit®-THT kit was used for PRP preparation. Blood (8mls) obtained and 2 ml of PRP were injected intravaginally within an hour. Post PRP, day 2-3 AMH and AFC were repeated 2-3 months after, with ovarian stimulation commencing 3-6 months after. Main results and the role of chance Thirteen women underwent PRP injection from July 2023 to April 2024. Mean age was 36.9 years old and body mass index 24.1kg/m2. These women underwent between 1-5 cycles of IVF previously, with three women having no eggs collected. Two patients were pregnant from previous cycles – one had a live birth and one miscarriage. Although mean AMH fell post-PRP (0.34 ± 0.33 ng/ml (0.01-1.04) vs 0.27 ± 0.16 ng/ml (0.01-0.57)), six women (46.2%) had higher AMH post PRP. Mean AFC increased post-PRP (5 to 6 respectively), with an increase seen in 11 women (84.6%). One patient had her cycle cancelled in view of no follicular growth during ovarian stimulation. Mean number of oocytes retrieved increased post-PRP (2.0 ± 1.53 vs 3.27 ± 0.96), with 69.2% (9/13 women) showing an increase. Mean number of embryos created increased from 1.40 ± 0.73 to 2.09 ± 0.79 post PRP, with an improvement seen in 77% of women (10/13). Ten women underwent a fresh embryo transfer, and 2 a frozen embryo transfer. Clinical pregnancy rate was 38.5% (5/13 women), and live birth rate was 15.4% (2/13 women). There are 2 ongoing pregnancies, and 1 first trimester miscarriage. Limitations, reasons for caution Although results from the pilot study were encouraging, a larger sample size would be helpful in supporting our results. There was also no control group in this study, and intercycle variability may have resulted in bias. Wider implications of the findings This pilot study will allow technical expertise to be established, and form the basis for a planned randomised controlled trial adequately powered to derive the clinical efficacy for improving fertility outcomes for a significant proportion of women with ovarian insufficiency seeking fertility treatment. Trial registration number No

Assisted reproductive technologies (ART) in Canada: 2004 results from the Canadian ART Register

Objective This study aimed to comprehensively examine the correlation between success trends in platelet-rich plasma (PRP) therapy and the advancing age of patients undergoing fertility interventions. Methods Female participants were categorized randomly into five age groups undergoing PRP or conventional hormone replacement therapy. Procedures included controlled ovarian stimulation, escalating estrogen dosage, gonadotrophin injections, and embryo transfer post-ovulation trigger. A pivotal PRP intervention was provided to half of the age sub-groups, and endometrial thickness was assessed 24 hours prior to embryo transfer. Statistical analysis employed SPSS 26.0 for Windows Student Version (IBM Inc., Armonk, New York), incorporating descriptive statistics, one-way analysis of variance (ANOVA), Tukey's honestly significant difference (HSD) testto explore age-PRP success relationships (p<0.05). Results The study, involving 60 participants, revealed a balanced patient distribution across age groups, with 20-30 age groups contributing 23.33% each. Baseline characteristics showed no significant differences between PRP and hormone replacement therapy (HRT) groups. Post-intervention, PRP demonstrated consistently higher endometrial thickness (p<0.001) and clinical pregnancy rates (63.33%) compared to HRT (40%). These findings suggest a positive association between PRP therapy and improved outcomes, particularly in younger age cohorts. Conclusion The study challenges traditional perspectives on hormonal influences in fertility, highlighting a potential link between PRP therapy and favorable outcomes among younger age groups. Improved endometrial thickness and clinical pregnancy rates in the PRP group emphasize the need for further exploration of PRP's mechanisms and applications in reproductive medicine.

Intrauterine injection of human chorionic gonadotropin before embryo transfer may improve clinical pregnancy and implantation rates in blastocysts transfers

New Belgian legislation regarding the limitation of transferable embryos in in vitro fertilization cycles does not significantly influence the pregnancy rate but reduces the multiple pregnancy rate in a threefold way in the Leuven University Fertility Center

A comparative evaluation of subendometrial and intrauterine platelet-rich plasma treatment for women with recurrent implantation failure

Recurrent implantation failure (RIF) has a multifactorial etiology. An umbrella review was undertaken to evaluate the multiple proposed interventions. To summarize and assess the strength of evidence of interventions for RIF from published systematic reviews (SR) of randomized clinical trials (RCTs). After prospective registration (PROSPERO CRD42023414255), a systematic search was conducted in the Cochrane Library, Scopus and Medline from inception until March 2024. SRs of RCTs, with or without meta-analyses (MA), were included if they reported clinical pregnancy rates (CPR) or live birth rates (LBR). The methodological quality of the included SRs was appraised independently in duplicate using the AMSTAR 2 tool. For each intervention, the MAs of RCTs with statistically significant improvements were counted as a percentage of the total assessing the strength of evidence using the GRADE system. A total of 47 SRs were included: 32 reviews covered immunomodulatory interventions, 10 (68 RCTs) covered uterine and endometrial interventions, one covered antibiotics, and four (69 RCTs) addressed mixed approaches, including laboratory interventions. AMSTAR 2 appraised 41 (88%) SRs as critically low or low, and 6 (12%) as moderate or high in quality. The SRs often had a level of overlap of RCTs (median 33.3%), inconsistent definitions of RIF, and varied comparisons for the interventions. Considering the significant meta-analytic evidence of high-moderate GRADE strength: Granulocyte colony-stimulating factor (G-CSF) showed improvement in CPR in 9/13 (69.2%) MAs and LBR in 1/7 (14%); intralipid infusion showed improvement in CPR in 4/6 (57.14%) MAs and LBR in 3/4 (75%); peripheral blood mononuclear cells (PBMC) showed improvement in CPR in 4/8 (50%) MAs and LBR 3/5 (60%); platelet-rich plasma (PRP) intervention showed improvement in CPR in 6/10 (60%) MAs and LBR in 1/5 (20%); human chorionic gonadotropins showed improvement in CPR in 3/3 (100%) MAs; growth hormone showed improvement in CPR in 1/1 (100%) MA; low molecular weight heparin showed improvement in CPR in 1/1 (100%) MAs and LBR in 1/2 (50%); hysteroscopy showed improvement in CPR in 1/2 (50%) MAs; and, intentional endometrial injury showed improvement in CPR in 3/4 (75%) MAs and LBR in 2/3 (66.66%). Evidence syntheses of RCTs evaluating interventions for RIF suggest a consistent direction, with high to moderate strength, indicating that immunomodulatory treatments, including G-CSF, PBMC, PRP, intralipid infusion, and intentional endometrial injury are likely to be effective. However, this conclusion should be interpreted with caution due to the generally low methodological quality of the included studies and the clinical heterogeneity observed in most SRs.

Study question How does the intrauterine instillation of autologous platelet rich plasma (PRP) affect the endometrial thickness and live birth rate in frozen embryo transfer cycles? Summary answer Intrauterine instillation of autologous PRP resulted in significant improvement in endometrial thickness. The live birth rates were satisfactory post-PRP instillation. What is known already Autologous Platelet rich plasma (PRP) had resulted in significant improvement in endometrial thickness, when instilled intrauterine in women with thin endometrium in FET cycles. Study design, size, duration A retrospective observational study was performed at a tertiary care university teaching hospital in South India. 35 women who received intrauterine autologous PRP during endometrial preparation for frozen embryo transfer from June 2017 to December 2020, were included. Patients who underwent donor oocyte recipent cycles, those with a history of tubercular endometritis, Asherman syndrome, previous intrauterine manipulations such as manual removal of placenta, and uterine anomalies were excluded. Participants/materials, setting, methods All the women underwent endometrial preparation in artificial cycles by depot GnRH agonist suppression and HRT (Hormone replacement therapy) was initiated by 4–6 mg of estradiol valerate and stepped up as required. Autologous PRP was offered to all women who had endometrial thickness &amp;lt; 7 mm on day 16 of HRT. PRP was prepared by the two-step centrifugation method and administered intrauterine by IUI catheter. The patients underwent repeat evaluation after 5 days post-PRP instillation. Main results and the role of chance Optimal response to PRP was considered as the attainment of an endometrial thickness (ET) ≥ 7mm after 5 days of post-PRP. 25 (71.4%) had an optimal response to PRP. There was a significant improvement in the endometrial thickness(mm) in the study participants following PRP instillation: 6.3 ± 0.6 vs. 7.1 ± 1.2; P = 0.0001.The study participants were divided into two groups based on their response to intrauterine PRP instillation. Those who optimally responded to PRP were categorized as Group A and those who didn’t were categorized as Group B. The study participants of both the groups were comparable by their demographic characteristics such as age, cause of infertility, indications for ART, and the dose of estradiol valerate before PRP. The dose of estradiol valerate (mg) after PRP was significantly higher in Group B compared to Group A: 19.9 ± 4.9 vs. 15.6 ± 3.9; P = 0.014. A total of 26 women underwent embryo transfer and 9 (25.7%) women had cycle cancellation. Of these 22 were from Group A and 4 from Group B. The pregnancy, clinical pregnancy, miscarriage and live birth rates were 36.3%(8/22) and 25% (1/4); 31.8% (7/22) and 25% (1/4); and 31.8% (7/22) and 25% (1/4), respectively. Limitations, reasons for caution As the study was retrospective in nature and the PRP was offered only in patients who had consented, there was a significant bias. Hence the results of the study should be interpreted with caution. Further large prospective RCTs (Randomised controlled trials) are required to confirm our findings. Wider implications of the findings: Autologous PRP may enhance the response to the estrogen preparations. It may produce satisfactory live birth rates and reduce cycle cancellations in a reasonable proportion of patients with thin endometrium in FET cycles. However, these findings should be confirmed by dose finding clinical trials, and studies involving a comparison group. Trial registration number Not applicable

ObjectiveThe aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on the rate of implantation and pregnancy in women with repeated failed implantation during frozen embryo transfer. MethodsThis study was conducted on 50 infertile women candidates (who were referred to the Infertility Treatment Center of Besat Hospital in Sanandaj) with a history of failed implantation for the purpose of frozen embryo transfer. The participants were randomly divided into two groups (n = 25). In the first group (control), the intrauterine infusion of 0.5 ml of Ringer serum was done 48 h before embryo transfer. In the second group (treatment), the intrauterine infusion of 0.5 ml of PRP was performed 48 h before embryo transfer. ResultsIn this study, there was no significant difference between the two groups in the rate of chemical and clinical pregnancy. The rate of chemical pregnancy was 28% in the treatment group and 36% in the control group, while the rate of clinical pregnancy was 28% in the treatment group and 24% in the control group. ConclusionThe intrauterine infusion of PRP before frozen embryo transfer in infertile women with a history of failed implantation will not make any significant effect on the result of pregnancy.

Cetrorelix lowers premature luteinization rate in gonadotropin ovulation induction–intrauterine insemination cycles: a randomized-controlled clinical trial

Study question Does autologous PRP improve endometrial receptivity and IVF outcomes in RIF patients with embryo’s PGT-A? Summary answer Compared to the control group, patients treated with PRP demonstrated significantly higher biochemical and clinical pregnancy rates using PGT-A screened embryos in cases with RIF. What is known already RIF represents an important challenge for assisted reproductive technology (ART) and is frequently correlated with defective endometrial receptivity. PRP has shown potential for improving receptivity by promoting cell regeneration and neovascularization. Early studies using PRP in IVF cycles showed improved pregnancy outcomes, with higher rates of both biochemical and clinical pregnancies. However, there is still a lack of strong data regarding its efficacy in such cases using PGT-A screened embryos. Study design, size, duration In this prospective cohort study, a total of 98 patients were enrolled, divided into 38 patients who underwent endometrial PRP treatment and 60 patients in the control group. All patients performed two prior embryo transfers with implantation failures and embryos tested for PGT-A. The study was conducted between December 2022 and December 2024 at the Reproductive Medicine Center at Villa Mafalda Clinic in Rome. Participants/materials, setting, methods The study(38) and the control(60) groups were matched for age,BMI,endometrial thickness,and aetiology of infertility. Exclusion criteria were:&amp;gt;45 years, endometrial thickness&amp;lt;7 mm, severe male infertility, intrauterine factors, thrombophilia, thyroid dysfunction, autoimmune disorders, and chromosomal abnormalities. 10 ml of peripheral venous blood was prepared and centrifuged at 1500 rpm for 5 min. Independent t-tests were used to compare quantitative differences; chi-square tests were used to compare qualitative variables. A P-value &amp;lt; 0.05 was considered for statistical significance. Main results and the role of chance The study’s primary endpoints were biochemical pregnancy (defined as a beta-hCG level &amp;gt; 50 mIU/ml) and clinical pregnancy (presence of a gestational sac identifiable by ultrasound). The study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. No statistically significant differences were observed between the study groups regarding patient characteristics, including age, BMI, endometrial thickness, and the aetiology of infertility. A significantly higher biochemical pregnancy rate [34/38 (89.5%) vs 6/60(10%), p &amp;lt; 0.0001] and clinical pregnancy rate [14/38(36.8%) vs 4/60(6.7%), p = 0.0007] in PRP group were detected compared to the control. Limitations, reasons for caution This study’s main limitation is its small sample size. Larger randomized controlled trials are necessary to confirm these findings. Wider implications of the findings These results suggest that PRP may be an attractive intervention to enhance IVF pregnancy rates and reduce infertility in patients with RIF with PGT-A. If confirmed in larger trials, PRP could be a new therapeutic option for IVF outcomes in assisted reproductive methods. Trial registration number No

The studies posits that there is not sufficient evidence to support the use of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF). This study aims to investigate the effects of infusion of PRP on patients with unexplained-RIF in fresh and frozen embryo transfer (ET) cycles. A total of 80 participants were included in this study. The participants were randomly assigned to one of two groups with and without PRP infusion. Each of the PRP and control groups were also divided into fresh and frozen ET subgroups. ET outcomes were compared between groups. Clinical pregnancy rate was significantly higher in Frozen ET in PRP group than other subgroups (p < 0.0001). Miscarriage rate were significantly lower in PRP group than control group. Pregnancy complications and preterm labor were significantly higher in PRP group than control group (p < 0.0001). Live birth and healthy baby rate were significantly higher in PRP group than control group (p < 0.0001). The intrauterine infusion of 0.8-1 ml of PRP 48 h before blastocyst ET at fresh and frozen cycles can be an efficient treatment option for u-RIF patients. Also, results indicated that the clinical pregnancy rate was equal to the live birth rate at fresh ET cycles, whereas the live birth rate was lower than the clinical pregnancy rate at frozen ET cycles. Therefore, considering the superiority of fresh cycles over freeze cycles, the infusion of PRP into the uterus of patients with RIF is recommended to be done at fresh ET cycles.Trial registration: NCT, NCT03996837. Registered 25/06/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03996837.