Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation

NCT05279560 | Active Not Recruiting

• 1 other identifier: Aktenzeichen 21-348
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to investigate the efficacy, defined as an increase in oocyte numbers upon ovarian stimulation, and safety of a single intra-ovarian PRP injection vs. saline solution (NaCl) injection (Placebo) transvaginally or laparoscopically for follicular activation in patients with child wish and with low ovarian reserve/expected poor ovarian response planning to undergo IVF or ICSI using own eggs. Pain score as numerical rating score and validated quality of life questionnaire will be requested after the procedure. Longterm follow-up of all participants will be performed 1, 2 and 5 years after end of study.

Conditions

Premature Ovarian Insufficiency; Infertility, Female; Sterility, Female; PRP

Keywords

poor ovarian response; low ovarian response; ICSI; IVF; ART; Platelet rich plasma; PRP

Outcome Measures

Primary Outcomes (1)

• Ovarian response

  Number of retrieved COCs per intention-to-treat

  34-36 hours following hCG administration at the end of ovarian stimulation

Secondary Outcomes (20)

• Hormone levels

  Follow-up period of three months entailing monthly evaluation

• Follicular response

  On the day of triggering of final oocyte maturation or the day before

• COCs and MII oocytes

  Day 0 after follicle puncture

• Number of 2PN oocytes

  Day 1 after follicle puncture

• Mean number and quality of embryos

  Day 2-5 after follicle puncture

Study Arms (2)

Autologous intra-ovarian PRP injection

EXPERIMENTAL

Study group, treated with autologous intra-ovarian PRP injection and undergoing a subsequent fresh ET-IVF/ICSI cycle in the third cycle after intervention

Biological: autologous PRP (platelet rich plasma)

intra-ovarian saline solution (NaCL) injection

PLACEBO COMPARATOR

Control group, treated with intra-ovarian NaCl injection and undergoing a subsequent fresh ET-IVF/ICSI cycle in the third cycle after intervention

Other: Saline solution (NaCL) Injection

Interventions

autologous PRP (platelet rich plasma) BIOLOGICAL

The required volume of PRP will be extracted from 60 ml of the patient's peripheral blood. Injecting PRP into the ovaries will be performed likewise to the standard operating procedure of oocyte retrieval. After centrifugation of the whole blood, 5ml PRP will be injected in each ovary intra-medullar and subcortical using a 17-gauge single lumen needle under sedation und under transvaginal ultrasound monitoring.

Autologous intra-ovarian PRP injection

Saline solution (NaCL) Injection OTHER

Injecting NaCL into the ovaries will be performed likewise to the standard operating procedure of oocyte retrieval. NaCL will be injected in each ovary intra-medullar and subcortical using a 17-gauge single lumen needle under sedation und under transvaginal ultrasound monitoring.

intra-ovarian saline solution (NaCL) injection

Eligibility Criteria

• Age: 18 Years - 42 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Serum AMH \< 0.5 ng/ml (at screening visit and in the absence of OC or sex-steroid intake)
• Antral follicular count (AFC) in both ovaries ≤ 5 (at screening visit and in the absence of OC or sex-steroid intake)
• Spontaneous cycle, menstrual cycle length 21-35 days
• Body mass index (BMI) ≥18 kg/m2 and ≤38 kg/m2
• Both ovaries must be visible by transvaginal ultrasound examination
• Both ovaries must be judged accessible by transvaginal puncture
• Indication for IVF or ICSI treatment
• Willingness to participate and provide written consent prior to initiation of any study-related procedures
• The subject and male partner must agree to participate in the infant follow-up if she becomes pregnant
• The subject must be able to communicate well with the investigator and research staff and to comply with the requirements of the study protocol.

You may not qualify if:

• ≥ four cumulus-oocyte-complexes (COCs) retrieved in a previous IVF cycles with a conventional stimulation protocol (within 6 months before enrollment)
• Serum value of FSH ≥25 IU/l (within 12 months measured in the absence of OC or hormone replacement intake)
• Thrombocytopenia defined as \< 100.000 platelets/µl at screening
• Oral contraceptive or sex steroid intake within 1 month prior to enrollment
• Presence of structural or numerical chromosomal abnormality in cytogenetic analysis
• Relevant autoimmune disease
• History of malignancy and systemic chemotherapy or pelvic radiation
• Severe endometriosis (stage III-IV)
• Ovaries located outside the inner pelvis
• Presence of unilateral or bilateral hydrosalpinx
• Relevant endocrine disorders such as hypothalamic-pituitary disorder or thyroid dysfunction (except substituted Hashimoto's thyroiditis or latent hypothyroidism)
• Relevant thrombophilic disorder
• Contraindication for pregnancy
• Contraindication for transvaginal ovarian puncture (such as previous major lower abdominal surgery and known severe pelvic adhesion)
• Uterine malformations or pathologies (such as sub mucosal fibroid(s), endometrial hyperplasia, endometrial fluid accumulation, or endometrial adhesions)

Sponsors & Collaborators

• University of Luebeck: lead

Study Sites (1)

University of Luebeck

Lübeck, Schleswig-Holstein, 23562, Germany

Location

Related Publications (14)

• Gougeon A, Ecochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod. 1994 Mar;50(3):653-63. doi: 10.1095/biolreprod50.3.653.

  PMID: 8167237 BACKGROUND

• Martin JJ, Woods DC, Tilly JL. Implications and Current Limitations of Oogenesis from Female Germline or Oogonial Stem Cells in Adult Mammalian Ovaries. Cells. 2019 Jan 28;8(2):93. doi: 10.3390/cells8020093.

  PMID: 30696098 BACKGROUND

• Maleki-Hajiagha A, Razavi M, Rouholamin S, Rezaeinejad M, Maroufizadeh S, Sepidarkish M. Intrauterine infusion of autologous platelet-rich plasma in women undergoing assisted reproduction: A systematic review and meta-analysis. J Reprod Immunol. 2020 Feb;137:103078. doi: 10.1016/j.jri.2019.103078. Epub 2019 Dec 31.

  PMID: 32006776 BACKGROUND

• 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.

  PMID: 29486615 BACKGROUND

• Danforth DR, Arbogast LK, Ghosh S, Dickerman A, Rofagha R, Friedman CI. Vascular endothelial growth factor stimulates preantral follicle growth in the rat ovary. Biol Reprod. 2003 May;68(5):1736-41. doi: 10.1095/biolreprod.101.000679. Epub 2002 Dec 11.

  PMID: 12606430 BACKGROUND

• Quintana R, Kopcow L, Sueldo C, Marconi G, Rueda NG, Baranao RI. Direct injection of vascular endothelial growth factor into the ovary of mice promotes follicular development. Fertil Steril. 2004 Oct;82 Suppl 3:1101-5. doi: 10.1016/j.fertnstert.2004.03.036.

  PMID: 15474081 BACKGROUND

• Bakacak M, Bostanci MS, Inanc F, Yaylali A, Serin S, Attar R, Yildirim G, Yildirim OK. Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary. Gynecol Obstet Invest. 2016;81(3):225-31. doi: 10.1159/000440617. Epub 2015 Oct 24.

  PMID: 26496072 BACKGROUND

• Ozcan P, Takmaz T, Tok OE, Islek S, Yigit EN, Ficicioglu C. The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage. J Assist Reprod Genet. 2020 Apr;37(4):865-873. doi: 10.1007/s10815-020-01689-7. Epub 2020 Feb 4.

  PMID: 32020412 BACKGROUND

• Atkinson L, Martin F, Sturmey RG. Intraovarian injection of platelet-rich plasma in assisted reproduction: too much too soon? Hum Reprod. 2021 Jun 18;36(7):1737-1750. doi: 10.1093/humrep/deab106.

  PMID: 33963408 BACKGROUND

• Melo P, Navarro C, Jones C, Coward K, Coleman L. The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study. J Assist Reprod Genet. 2020 Apr;37(4):855-863. doi: 10.1007/s10815-020-01710-z. Epub 2020 Feb 7.

  PMID: 32030554 BACKGROUND

• Urman B, Boza A, Balaban B. Platelet-rich plasma another add-on treatment getting out of hand? How can clinicians preserve the best interest of their patients? Hum Reprod. 2019 Nov 1;34(11):2099-2103. doi: 10.1093/humrep/dez190.

  PMID: 31725883 BACKGROUND

• Farimani M, Heshmati S, Poorolajal J, Bahmanzadeh M. A report on three live births in women with poor ovarian response following intra-ovarian injection of platelet-rich plasma (PRP). Mol Biol Rep. 2019 Apr;46(2):1611-1616. doi: 10.1007/s11033-019-04609-w. Epub 2019 Feb 5.

  PMID: 30725347 BACKGROUND

• Sills ES, Wood SH. Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response. Biosci Rep. 2019 Jun 4;39(6):BSR20190805. doi: 10.1042/BSR20190805. Print 2019 Jun 28.

  PMID: 31092698 BACKGROUND

• Hsu CC, Hsu L, Hsu I, Chiu YJ, Dorjee S. Live Birth in Woman With Premature Ovarian Insufficiency Receiving Ovarian Administration of Platelet-Rich Plasma (PRP) in Combination With Gonadotropin: A Case Report. Front Endocrinol (Lausanne). 2020 Feb 19;11:50. doi: 10.3389/fendo.2020.00050. eCollection 2020.

  PMID: 32140135 BACKGROUND

MeSH Terms

Conditions

Primary Ovarian Insufficiency; Infertility, Female

Interventions

Saline Solution; Injections

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Infertility

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Georg Griesing, MD

  University of Luebeck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Gynecological Endocrinology and Reproductive Medicine

Study Record Dates

• First Submitted: January 16, 2022
• First Posted: March 15, 2022
• Study Start: March 17, 2022
• Primary Completion: April 30, 2025
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will not be available before 2027
• Access Criteria: reasonable request

Locations

DE (1)