scholarly journals Intraovarian insertion of autologous platelet growth factors as cell-free concentrate: Fertility recovery and first unassisted conception with term delivery at age over 40

Author(s):  
E. Scott Sills ◽  
Natalie S. Rickers ◽  
Samuel H. Wood

Background: The use of autologous platelet-rich plasma as an ovarian treatment has not been standardized and remains controversial. Case Presentation: A 41½-year old woman with diminished ovarian reserve (serum anti- Müllerian hormone = 0.163 mg/mL) and a history of 10 unsuccessful in vitro fertilization cycles presented for reproductive endocrinology consult. She and her partner declined donor oocyte in vitro fertilization. They were both in good general health and laboratory tests were unremarkable, except for mild thrombocytosis (platelets = 386K; normal range 150-379K) discovered in the female. The patient underwent intraovarian injection of fresh platelet-derived growth factor concentrate administered as an enriched cell-free substrate. Serum anti- Müllerian hormone increased by 115% within 6 wks of treatment. Spontaneous ovulation occurred the month after injection and subsequently the serum human chorionic gonadotropin was noted at 804 mIU/mL. Following an uneventful obstetrical course, a male infant was delivered at term without complication. Conclusion: This is the first description of intraovarian injection of enriched platelet-derived growth factors followed by unassisted pregnancy and live birth. As a refinement of conventional ovarian platelet-rich plasma therapy, this procedure may be particularly valuable for refractory cases where prognosis for pregnancy appears especially bleak. A putative role for thrombocytosis is also viewed in parallel with mechanisms of action as advanced earlier. With continued experience in ovarian application of autologous platelet growth factors, additional research will evaluate laboratory protocol/sample preparation, injection technique, and patient selection. Key words: Ovarian rejuvenation, Platelet-rich plasma, Cytokines, Infertility, IVF.

2018 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Konstantinos Sfakianoudis ◽  
Mara Simopoulou ◽  
Nikolaos Nitsos ◽  
Anna Rapani ◽  
Athanasios Pappas ◽  
...  

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.


Author(s):  
E. Scott Sills ◽  
E. Scott Sills ◽  
J. L. Petersen ◽  
N. S. Rickers ◽  
Samuel H. Wood ◽  
...  

This registered, prospective clinical trial assessed serum anti-Mullerian hormone (AMH) patterns after treatment with activated platelet rich plasma (PRP). Patients with low ovarian reserve and/or at least 1 prior failed in vitro fertilization (IVF) cycle (n=182) received PRP injected into ovarian tissue under ultrasound guidance. Pretreatment AMH, BMI and platelet (PLT) concentration were recorded and serum AMH, follicle stimulating hormone, and estradiol were then measured at 2-week intervals for up to three months. Mean±SD patient age was 45.4±6.1yrs. Improved serum AMH was observed in 51 patients (28%) with median increase of 167% [95%CI 91; 280] after treatment; mean interval to maximum AMH increase was 4 weeks (range 2-10 weeks). Improved post-treatment AMH was not limited to younger patients; when stratified by age (<42 vs. ≥42yrs), significant AMH improvements were seen in both groups after treatment (p=0.03 and 0.009, respectively). Among responders, mean basal PLT count was higher (274K) vs. non-responders (250K); p<0.001. This is the first clinical trial to describe an intraovarian PRP technique for low reserve and finds the treatment safe and associated with significant increases in serum AMH for some patients, usually within four weeks. The substantially different pre-treatment PLT concentrations measured across PRP response groups warrants further investigation. Additional research can characterize ovarian response better, optimize PRP protocols, and collect outcomes data from those who subsequently undergo IVF with autologous oocytes.


Author(s):  
Namrata Choudhary ◽  
Akash More ◽  
Roshankumar Jha ◽  
Ashish P. Anjankar

One of the key factors in implantation and pregnancy is endometrium. Sufficiently great percentage of in vitro fertilization failure is because of the endometrial receptivity therefore, high quality embryo and adequate receptive endometrial growth are important for successful implantation. Platelet rich plasma has beneficial effect in advancement of endometrial thickness for women with thin endometrial thickness. PRP can be used in various medical conditions including  patients with refractory endometrium as a complementary therapy to conventional  treatment. Aim: To determine the effectiveness of intrauterine infusion of autologous platelet-rich plasma in the treatment of thin endometrium of infertile women. Objectives: To identify infertile female patients with inadequate endometrial growth (less than 7 mm) in the past frozen embryo transfer (FET) cycles despite standard treatments. To observe intrauterine infusion of autologous platelet-rich plasma (PRP) in these infertile female patients with thin endometrium. To determine the effectiveness of intrauterine infusion of autologous PRP in the treatment of thin endometrium of infertile women during In vitro fertilization (IVF). Methods: It is a prospective observational study. Present study will be carried out with 30 patients. Women having inappropriate endometrial thickness of less than 7 mm, in past FET cycles will be included. Sonographic machine will be used; to measure endometrial thickness by  an expert Gynecologist, where thickest part of uterus will be measured in longitudinal  axis.  Expected Results: It is expected that intra uterine infusion of PRP will be effective in thickening of endometrial wall in patients with thin endometrium. Once the results are satisfactory it can be helpful for endometrial preparation in reproduction techniques. Conclusion: Present study is purposed to testify PRP as a novel method for advancement of reproductive medicine, it will be helpful to overcome with the issues such as inadequate thickness of endometrium, poor response to conventional therapy and increase clinical pregnancies and live births positively.


2020 ◽  
Vol 47 (2) ◽  
pp. 94-100
Author(s):  
Samuel H. Wood ◽  
E. Scott Sills

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed <i>in vitro</i> fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.


2008 ◽  
Vol 93 (3) ◽  
pp. 901-904 ◽  
Author(s):  
Steven A. Lietman ◽  
James Goldfarb ◽  
Nina Desai ◽  
Michael A. Levine

Abstract Context: Preimplantation genetic diagnosis (PGD) enables the selection of embryos without mutations for implantation and has not been described to our knowledge for mutations in GNAS. Phocomelia in a patient with Albright hereditary osteodystrophy (AHO) has also not been previously described. Objective: The aim of this study was to identify a GNAS mutation in a patient with a severe form of AHO and pseudohypoparathyroidism type 1a with phocomelia and to perform PGD on embryos derived by in vitro fertilization to deliver an unaffected infant. Design: A proband and his family are described clinically, the GNAS gene was sequenced to identify a novel mutation in the proband, and PGD was performed on embryos. Setting: The setting was in a tertiary-care hospital. Patients: The patients were from a single family in which the proband has a severe form of AHO. Interventions: Interventions were PGD and in vitro fertilization. Main Outcome Measures: The main outcome measures were the clinical phenotypes and GNAS gene sequences of the proband, embryos, and family members. Results: After PGD, three genotypically normal embryos were transferred back to the mother. Pregnancy ensued, and a healthy male infant was delivered at 36.5 wk gestation. The GNAS genes in the baby were confirmed as wild-type, and the infant is free of any signs of AHO. Conclusions: We describe herein a proband with AHO and severe skeletal deformities (including phocomelia) related to a novel GNAS mutation and the delivery of a male infant with homozygous normal GNAS genotype after PGD.


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