Clinical trial NCT04381299: Will Autologous Platelet Rich Plasma Able To Restore Ovarian Function?
Official title: Is Autologous Platelet Rich Plasma Able To Restore Ovarian Function? A Prospective Randomized Control Trial.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Infertility
IVF
Premature Ovarian Failure
Anti-Mullerian Hormone Deficiency
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult women with primary or secondary infertility with a diagnosis of POI, willing to perform an IVF treatment.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Appearance of new ovarian follicles (number of follicles growing) with evidence of estradiol production.
timeFrame: 12 weeks
Secondary outcomes:
measure: Increase in serum AMH above the baseline level
timeFrame: 12 weeks
measure: Increase in AFC above the baseline level in 12 weeks
timeFrame: 12 weeks
measure: Total number of retrieved oocytes in an IVF cycle.
timeFrame: 1 day
measure: Pregnancy rates
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
affiliation: ART Fertility Clinics LLC
name: Laura Melado, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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: 10.1159/000491697. Epub 2018 Aug 22.
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: 10.1080/09513590.2018.1445219. Epub 2018 Feb 28.
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.
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 Mol Cell Med. 2019 Winter;8(1):84-90. doi: 10.22088/IJMCM.BUMS.8.1.84. Epub 2019 May 15.
citation: 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, Vermeulen N. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016 May;31(5):926-37. doi: 10.1093/humrep/dew027. Epub 2016 Mar 22.