Will Autologous Platelet Rich Plasma Able To Restore Ovarian Function?

Infertility Clinical Trial

Official title:

Is Autologous Platelet Rich Plasma Able To Restore Ovarian Function? A Prospective Randomized Control Trial.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04381299
• Other study ID #: 2004-ABU-003-LM
• Status: Active, not recruiting
• Start date: April 25, 2021
• Est. completion date: July 31, 2024

Study information

• Verified date: July 2023
• Source: ART Fertility Clinics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A-PRP (Autologous Platelet Rich Plasma) is becoming widely used in a variety of medical procedures seeking tissue remodeling and/or healing as an intervention. To date, applications in orthopedics, wound healing, dermatology and plastic surgery have gained general acceptance, primarily as the role of platelets and their activation in tissue repair and recovery has become better understood at a cellular and molecular level. This study will involve adult women with a diagnosis of Premature ovarian insufficiency (POI) willing to perform an IVF/ICSI treatment.

Description:

POI is a loss of normal function before age 40, leading to infertility and hypergonadotropic hypoestrogenism. Currently, no optimal regimen exists to ameliorate ovarian function. The options to conceive genetically related offspring, are limited. Typically, affected patients end up with egg donation or adoption as an alternative .

A-PRP is plasma with a concentration of platelets above the blood baseline. A-PRP is developed from autologous blood. Within A-PRP, the concentration of platelets delivers an increased number of growth factors. PRP is becoming widely used in a variety of medical procedures seeking tissue remodeling and/or healing as an intervention. To date, applications in orthopedics, wound healing, dermatology and plastic surgery have gained general acceptance, primarily as the role of platelets and their activation in tissue repair and recovery has become better understood at a cellular and molecular level. This knowledge base provides a foundation for the present study because of the ready availability of FDA-approved kits for autologous PRP preparations and the recognition that the aging ovary acquires tissue pathologies in the form of wound healing and fibrosis as a result of repeat ovulations over the reproductive lifespan of women. Since PRP is an autologous blood product and is widely used via injection into various organs and tissues, safety concerns are minimal.

This study will involve adult women with a diagnosis of Premature ovarian insufficiency (POI) willing to perform an IVF/ICSI treatment. A-PRP will be prepared using Eclipse PRP Kit which is approved by US FDA for preparation of PRP. Consenting participants will receive injections of autologous Platelet Rich Plasma (A-PRP) in one randomly selected ovary under ultrasound guidance performed under IV sedation. As it is suggested that only mechanical stimulation by biopsy/scratch could be a potentially effective method for follicle activation, the other ovary will be injected with the same amount of Saline Solution (SS) as control, to replicate the same mechanical effect. Randomization will determine whether the right or left ovary will be treated. Follow up of the participants will be performed with transvaginal ultrasound and hormonal tests including AMH, FSH, LH, estradiol and progesterone, every 10 days for the next 3 months after the injection. If ovarian activity is detected, the participant will undergo an IVF treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: July 31, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Signed and dated informed consent

• Women 40 years of age and younger with documented primary ovarian insufficiency (12).

• Normal Karyotype

• BMI </= 35 kg/m2

• Oligo/amenorrhea for at least 4 months

• FSH > 25 IU/mL

• AMH </= 0,1 ng/ml

• No evidence of follicles > 4mm

• Must have two ovaries of approximately equal volume.

• Willingness to undergo further fertility treatment, including IVF if there is evidence of response

• A transvaginal scan including Doppler for arteria ovarica will be performed previously to the surgical procedure.

Exclusion Criteria:

• Premature ovarian failure due to a genetic origin, such as Turner's Syndrome or chromosomal abnormality.

• Oncological diseases (specially, skeletal system and blood).

• Autoimmune diseases, for example, lupus erythematosus, etc.

• Previous treatments including radiotherapy or chemotherapy.

• Other conditions not suitable for surgical procedures and/or anesthesia.

• Anticoagulant or antiaggregant treatment.

• Acute and chronic infectious diseases.

• Active substance abuse or dependence.

• Major Mental health disorder.

Related Conditions & MeSH terms

• Anti-Mullerian Hormone Deficiency
• Infertility
• IVF
• Menopause, Premature
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Other:
• autologous platelet rich plasma
The cortex of selected ovary will be injected with 1 mL of autologous platelet rich plasma. Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done.
• saline solution
The cortex of contralateral ovary will be injected with 1 mL of saline solution (SS). Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done.

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (11)

European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI; Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, Cifkova R, de Muinck Keizer-Schrama S, Hogervorst E, Janse F, Liao L, Vlaisavljevic V, Zillikens C, V — View Citation

Ford EA, Beckett EL, Roman SD, McLaughlin EA, Sutherland JM. Advances in human primordial follicle activation and premature ovarian insufficiency. Reproduction. 2020 Jan;159(1):R15-R29. doi: 10.1530/REP-19-0201. — View Citation

Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. — View Citation

Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol. 2016 Jun;28(3):217-22. doi: 10.1097/GCO.0000000000000268. — View Citation

Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1-9. — View Citation

Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011 May;105 Suppl 1:S13-33. doi: 10.1160/THS10-11-0720. Epub 2011 Apr 11. — View Citation

Sfakianoudis K, Simopoulou M, Nitsos N, Rapani A, Pantou A, Vaxevanoglou T, Kokkali G, Koutsilieris M, Pantos K. A Case Series on Platelet-Rich Plasma Revolutionary Management of Poor Responder Patients. Gynecol Obstet Invest. 2019;84(1):99-106. doi: 10.1 — View Citation

Sills ES, Li X, Rickers NS, Wood SH, Palermo GD. Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: First qualitative data. Neuro Endocrinol Lett. 2019 Jan;39(6):427-433. — View Citation

Sills ES, Rickers NS, Li X, Palermo GD. First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma. Gynecol Endocrinol. 2018 Sep;34(9):756-760. doi: 10.1080/095 — View Citation

Sills ES, Rickers NS, Svid CS, Rickers JM, Wood SH. Normalized Ploidy Following 20 Consecutive Blastocysts with Chromosomal Error: Healthy 46, XY Pregnancy with IVF after Intraovarian Injection of Autologous Enriched Platelet-derived Growth Factors. Int J — View Citation

Zhang X, Han T, Yan L, Jiao X, Qin Y, Chen ZJ. Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency. Reprod Sci. 2019 Feb;26(2):207-213. doi: 10.1177/1933719118818906. Epub 2018 Dec 12. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Appearance of new ovarian follicles (number of follicles growing) with evidence of estradiol production.	Evaluate the difference of number of follicles growing, means values will be calculated at the two points time (baseline and 12 weeks).; Means differences will be verified using the t test analysis (after confirming the normal distribution of the data by means of Kolmogorov-Smirnoff tests. If normal distribution is not confirmed a non-parametric anova test will be used. This rule will be applied to all analysis	12 weeks
Secondary	Increase in serum AMH above the baseline level	Evaluate the difference of AMH levels between time, means values will be calculated at the two points time (baseline and 12 weeks). Means differences will be verified using the t test analysis.	12 weeks
Secondary	Increase in AFC above the baseline level in 12 weeks	Evaluate the difference of AFC levels between groups, means values will be calculated at the two points time (baseline and 12 weeks). Means differences will be verified using the t test analysis	12 weeks
Secondary	Total number of retrieved oocytes in an IVF cycle.	Number of retrieved oocytes will be calculated in the IVF cycle: total and per groups (per ovary)	1 day
Secondary	Pregnancy rates	Pregnancy rates: Biochemical pregnancy rate: Percentage of bHCG above 15 IU/ml per embryo transfer performed.; Clinical pregnancy rate: percentage of pregnancies with fetal heart rate positive per embryo transfer performed. Miscarriage rate: percentage of miscarriages per embryo transfer	40 weeks

External Links

•   Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment