A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment
Pantos, K., Simopoulou, M., Pantou, A., Rapani, A., Tsioulou, P., Nitsos, N., Syrkos, S., Pappas, A., Koutsilieris, M., & Sfakianoudis, K. (2019). A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment. Cell transplantation, 28(9-10), 1333-1340. https://doi.org/10.1177/0963689719859539
Pantos K, Simopoulou M, Pantou A, Rapani A, Tsioulou P, Nitsos N, et al. A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment. Cell Transplant. 2019;28(9-10):1333-1340. doi:10.1177/0963689719859539
Pantos, Konstantinos, et al. "A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment." Cell transplantation, vol. 28, no. 9-10, 2019, pp. 1333-1340.
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Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece
Department of Physiology, Medical School, National and Kapodistrian University of Athens, Greece04gnjpq42
Centre for Human Reproduction, Genesis Athens Clinic, Greece
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Abstract
Since the introduction of autologous platelet-rich plasma (PRP) in medical practice, various studies have documented that implementing PRP can enhance healing and the anti-aging process, employing angiogenesis regeneration due to the multiple growth factors and cytokines involved. Numerous reports have shown promising results with the use of PRP in ovarian treatment, regarding ovarian regeneration and reactivation of folliculogenesis. This case series reports on two women with premature ovarian failure (POF) aged 40 and 27 years, respectively, and one menopausal woman aged 46 years. All patients presented with lack of menstrual cycle for over a year. The women reported previous failed in vitro fertilization (IVF) attempts, and, after rejecting the option of oocyte donation, they opted for the approach of autologous ovarian PRP treatment. Following PRP treatment, the three patients were invited to conceive naturally. The primary outcome was the restoration of menstruation following autologous ovarian PRP treatment, as well as an improvement in hormonal profile, a decrease in follicle-stimulating hormone (FSH) levels, and a concurrent increase in anti-Müllerian hormone (AMH) levels. Further to that, our patients achieved pregnancy through natural conception within 2-6 months following PRP treatment, resulting in currently ongoing complication-free clinical pregnancies - a first report in the literature for menopausal and POF patients. Implementation of PRP should be further investigated through randomized controlled trials (RCTs), as it may hold the key to successful treatment for a certain cohort of patients exploring reproductive treatment options following menopause.
Sfakianoudis K et al., 2020·Journal of clinical medicine·Free full text on PubMed Central
Intraovarian platelet-rich plasma (PRP) infusion was recently introduced in the context of addressing ovarian insufficiency. Reporting on its effectiveness prior to adopting in clinical routine practice is imperative. This study aims to provide pilot data regarding PRP application for ovarian rejuvenation. Four pilot studies were conducted on poor ovarian response (POR), premature ovarian insufficiency (POI), perimenopause, and menopause, respectively. Each pilot study reports on thirty patients, 120 participants were recruited in total. All participants provided written informed consent prior to treatment. Primary outcome measures for the POR pilot study were levels of anti-müllerian hormone (AMH), antral follicle count (AFC) and oocyte yield. For the POI, perimenopausal and menopausal pilot studies primary outcome measures were restoration of menstrual cycle, and Follicle Stimulating Hormone (FSH) levels. A significant improvement on the hormonal profile and the ovarian reserve status was noted, along with improved intracytoplasmic sperm injection (ICSI) cycle performance concerning POR participants. Menstruation recovery was observed in 18 out of 30 POI patients, along with a statistically significant improvement on levels of AMH, FSH, and AFC. Similarly, 13 out of 30 menopausal women positively responded to PRP treatment. Finally, menstruation regularity, improved hormonal levels and AFC were reported for 24 out of 30 perimenopausal women. To conclude, PRP infusion appears to convey promising results in addressing ovarian insufficiency.
Sfakianoudis K et al., 2019·Gynecologic and obstetric investigation
Poor responders are described as those In Vitro Fertilization (IVF) patients who are failing to respond to controlled ovarian stimulation protocols. Extensive research has focused on crafting the optimal treatment. However, it appears that each approach fails to be established as effective or guaranteed towards successful management. Platelet-Rich Plasma (PRP) is a novel, highly promising approach that has been successfully applied for an array of medical issues. In this case series, we present 3 poor responder patients with the common denominator of: failed IVF attempts, poor oocyte yield, and poor embryo quality. The option of oocyte donation was rejected. All patients were treated with autologous PRP ovarian infusion following written consent. Within a 3-month interval, follicle-stimulating hormone decreased by 67.33%, while Anti-Müllerian hormone increased by 75.18%. These impressive results on the biochemical infertility markers alone are classified as a complete biological paradox, coupled by improved embryo quality. Results report a natural conception at 24 weeks, an uncomplicated healthy pregnancy at 17 weeks and a successful live birth. To our knowledge, this is the first time such an approach and results are reported, where PRP treatment on poor responders lead to overcoming their challenging reproductive barrier.
Sfakianoudis K et al., 2019·In vivo (Athens, Greece)·Free full text on PubMed Central
[BACKGROUND/AIM] Patients diagnosed with chronic endometritis (CE) may fail to respond to standard antibiotic treatment. The driver behind the approach reported here was the imperative need for alternative therapeutic solutions. [CASE REPORT] This case report presents a woman with CE and premature ovarian insufficiency having experienced repeated implantation failures following donated embryo transfers. The patient was diagnosed with CE through hysteroscopy, microbiological analysis and scanning electron microscopy. Following the suggested antibiotic treatment, she underwent a new embryo transfer, but with subsequent pregnancy loss. Following a second antibiotic scheme, all diagnostic procedures certified the persistence of CE. The patient underwent autologous, intrauterine platelet-rich plasma treatment and a subsequent embryo transfer. The diagnostic procedures indicated no signs of CE, while the embryo transfer resulted in a twin pregnancy and birth. [CONCLUSION] Platelet-rich plasma may be employed as a first-line CE treatment, especially for patients who fail to respond to conventional antibiotic schemes.
Sfakianoudis K et al., 2018·J Clin Med·Free full text on PubMed Central
This report presents the case of a woman aged 40 who has experienced premature menopause from the age of 35. Having rejected oocyte donation, she opted for intraovarian injection of autologous platelet-rich plasma with the aim to rejuvenate the ovarian tissue and enable the employment of her own gametes through in-vitro fertilization. Six weeks following the autologous platelet-rich plasma treatment, a significant reduction in the patient's follicle-stimulating hormone (FSH) levels were noted. A natural in-vitro fertilization cycle led to a biochemical pregnancy, resulting in a spontaneous abortion at the 5th week of pregnancy. This is the first report of a successful autologous platelet-rich plasma application leading to pregnancy in menopause. This report uniquely contributes to the medical knowledge and challenges current practice in the context of infertility. The efficiency and safety of this treatment with regard to the reproductive system merits further investigation.
Petryk N et al., 2020·Reproductive sciences (Thousand Oaks, Calif.)
Due to the fact that modern American and European women postpone childbirth until later in life, they are more likely to face the problem of ovarian insufficiency by the time they are ready to have children. So, the ability to restore the ovarian function safely is crucially important. Our study involved 38 women 31-45 years of age with low ovarian reserves and at least two unsuccessful attempts to receive their oocytes through IVF. The blood from the patients was collected into two BD vacutainers for PRP preparation. The platelet concentration in the PRP was 1 × 106 μl. PRP injections into the ovaries were performed by a gynecologist with a special 25G needle, 20 cm in length, as an ultrasound-guided procedure or a laparoscopic-assisted approach. After PRP treatment, women were tested with several criteria for 12 months. We saw a significant improvement in hormone levels; six healthy babies were born, ten pregnancies were achieved, and four out of the ten were from natural conception. The PRP injections into the ovaries are safe, productive, and a natural treatment that may help women with premature ovarian insufficiency to give birth to their own child. The difference and novelty with our method of ovarian rejuvenation is in obtaining a higher platelet concentration (about 1 × 106 μl), which allows us to achieve long-lasting results, within 12 months, after a single procedure. Additionally, for the first time, we proposed and successfully performed a laparoscopically assisted technique for administering PRP into the ovary.
Fraidakis M et al., 2023·Cureus·Free full text on PubMed Central
Ovarian rejuvenation is an innovative procedure intended to restore ovarian fertility and development during the climacteric and has been used to enhance fertility in women with premature ovarian insufficiency (POI). This retrospective study was conducted to determine the effects of an intraovarian platelet-rich plasma (PRP) injection on ovarian stimulation outcomes in women referred to an in vitro fertilisation centre. Methods- Population: This was a retrospective observational study, and the inclusion criteria included women of reproductive age with at least one ovary with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure. During the patient's first consultation, a detailed reproductive history was recorded, a pelvic scan for ovarian size was conducted, and hormonal analysis for follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH) was conducted. In the study, 469 women with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure had hormonal levels recorded up to four months after treatment, and these were included in the study. The volume of peripheral blood required to prepare 6-8 mL of PRP for administration was 40-60 mL. The initial concentration of platelets in the peripheral blood sample was about 25000/µL, whereas the prepared PRP had a concentration of 900.000/µL. A volume of approximately 2-4 mL per ovary, depending on the ovarian volume, was used for the intraovarian injection. PRP intervention had significant effects on FSH concentration at the α = 0.05 level. Statistically significant increases in normal values of FSH and E2were observed for months three and four after the PRP intervention for all age groups. The results of our observational study revealed that a PRP intraovarian injection is associated with improved ovarian tissue and function. Future randomised clinical trials are needed to shed light on the use of PRP in ovarian rejuvenation before offering it routinely in clinical practice.
Pacu I et al., 2021·Exp Ther Med·Free full text on PubMed Central
Couple infertility is a pathology with an absolute number of cases growing markedly over the last decade in connection mainly with the increased age of couples wishing to conceive. Platelet-rich plasma (PRP) is an alternative treatment used for several years for experimental purposes. Yet, this method is not yet defined as a standard therapeutic option in the infertility protocol for poor responders in assisted human reproduction procedures. Thus, the present study is a retrospective study conducted between February 2019 and February 2020 to evaluate the effect of ovarian PRP injection in patients with a poor ovarian response (POR) to ovarian stimulation. Women (n=20; age 31-44 years) diagnosed with POR based on the European Society of Human Reproduction and Embryology criteria underwent ovarian injection with autologous PRP injection. Markers of ovarian reserve before, during the following two menstrual cycles, and at six months after treatment were followed as well as stimulation and fertilisation parameters before and post-treatment. PRP treatment resulted in increased antral follicle count and serum anti-Mullerian hormone, while levels of serum follicle-stimulating hormone and luteinising hormone were decreased. These changes were more pronounced during the 2nd menstrual cycle following treatment. By six months following the injection, their values return to pre-treatment levels and any small differences were not considered statistically significant. The average dose of gonadotropin used and duration remained statistically unchanged, but a significant increase in estradiol achieved by the day of the human chorionic gonadotropin trigger day was achieved. The cancellation rate decreased following PRP treatment while the number of collected oocytes, number of oocytes in metaphase II rose. The number of embryos (of A and B quality) resulting also increased but fell short of the significance level set (α=0.073). Following the PRP injection, two singleton pregnancies were achieved, resulting in live births at term without complications during pregnancy. Another pregnancy was achieved spontaneously 45 months following the PRP and a failed assisted human reproduction procedure. Although the group included a small number of women, the results indicate the potential benefits of an ovarian autologous PRP injection in women with POR. Positive results appear to be short-term for 2-6 months after the procedure.
Sills ES et al., 2018·Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
Platelets modulate clinically relevant yet incompletely understood tissue regeneration processes, and platelet rich plasma (PRP) has been previously used with some success in various non-reproductive medical contexts. Here, we extended PRP application to ovarian tissue with a view to document impact on ovarian reserve among women attending for infertility treatment. PRP was freshly isolated from patients (n= 4) with diminished ovarian reserve as determined by at least one prior IVF cycle canceled for poor follicular recruitment response or estimated by serum AMH and/or FSH, no menses for ≥1 year. Immediately following substrate isolation and activation with calcium gluconate, approximately 5 mL of autologous PRP was injected into each ovary under direct transvaginal sonogram guidance. For each study subject, AMH, FSH, and serum estradiol data were recorded at two-week intervals post-PRP and compared to baseline (pre-PRP) values. In this pilot group, mean (±SD) patient age was 42 ± 4 years with infertility duration reported as 60 ± 25 months. Following this protocol of intraovarian PRP administration, increases in serum AMH (p = .17), decreases in FSH (p < .01), or both, were observed in all cases, sufficient to permit retrieval of 5.3 ± 1.3 MII oocytes. IVF occurred 78 ± 22 (range = 59-110) days after activated PRP injection, and results appeared independent of patient age, infertility duration, baseline platelet concentration or pretreatment antral follicle count. Each patient had at least one blastocyst suitable for cryopreservation. While autologous PRP has been successfully applied therapeutically to various tissues to accelerate healing and wound repair, this is the first description of direct injection of activated PRP into the human ovary of poor prognosis IVF patients. Evidence of improved ovarian function was noted in all who received intraovarian PRP, possibly as early as two months after treatment. Additional research is needed to clarify (and enhance) which PRP components are responsible for altered ovarian function, and to identify predictive characteristics for patients most likely to benefit from this intervention.
Konstantinos Pantos, Mara Simopoulou, Anna Rapani, Petroula Tsioulou, Athanasios Pappas, Michael Koutsilieris, Konstantinos Sfakianoudis, Nikolaos Nitsos, Agni Pantou, Stephen Syrkos
K Pantos, M Simopoulou, A Rapani, P Tsioulou, A Pappas, Mike Koutsilieris, M Koutsilieris, K Sfakianoudis, N Nitsos, A Pantou, Steve Syrkos, S Syrkos
PMID 31271054 31271054 DOI 10.1177/0963689719859539 10.1177/0963689719859539 Pantos et al. 2019, Pantos 2019
Cite this article
Pantos, K., Simopoulou, M., Pantou, A., Rapani, A., Tsioulou, P., Nitsos, N., Syrkos, S., Pappas, A., Koutsilieris, M., & Sfakianoudis, K. (2019). A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment. Cell transplantation, 28(9-10), 1333-1340. https://doi.org/10.1177/0963689719859539
Pantos K, Simopoulou M, Pantou A, Rapani A, Tsioulou P, Nitsos N, et al. A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment. Cell Transplant. 2019;28(9-10):1333-1340. doi:10.1177/0963689719859539
Pantos, Konstantinos, et al. "A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment." Cell transplantation, vol. 28, no. 9-10, 2019, pp. 1333-1340.
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