The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation (OPIF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05279560
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : May 8, 2024
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. med. M.Sc. Georg Griesinger, University of Luebeck

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.

Condition or disease Intervention/treatment Phase
Premature Ovarian Insufficiency Infertility, Female Sterility, Female PRP Biological: autologous PRP (platelet rich plasma) Other: Saline solution (NaCL) Injection Not Applicable

Detailed Description:

Age-related infertility and premature loss of ovarian reserve has become a major challenge for ART professionals as the the average age at first child wish has dramatically increased over time. Under physiological circumstances, most follicles in the human ovary remain dormant throughout the female life span and eventually become atretic, however, histological samples reveal that the follicular pool in the ovary is completely exhausted only as late as the early 70ies and that the ovary holds oogonial stem cells, which may have the ability to differentiate into functional follicles. The pressing problem for reproductive medicine is therefore the question how to reactivate some of the putative ovarian 'reproductive reserve' in those women with premature follicular depletion or those who wish to become pregnant at advanced age.

Platelet rich plasma (PRP) is a blood-derived product, characterized by high concentrations of growth factors and chemokines. PRP is produced by centrifuging a small quantity of the patient's own blood and extracting the active, platelet-rich fraction. The platelet-rich fraction is applied to the human body typically by injection. PRP is used for therapeutic purposes in different medical areas ranging from orthopedics to plastic surgery, for its putative ability to stimulate and facilitate cell proliferation and thereby tissue differentiation and regeneration.

In the context of reproductive medicine, PRP has been proposed to increase pregnancy rates after uterine flushing in women with recurrent implantation failure or thin endometrium. Intra-ovarian injection of PRP has been proposed to activate dormant ovarian follicles pre IVF-treatment in cases of idiopathic low ovarian reserve, premature ovarian insufficiency or ovarian depletion because of advanced maternal age. To date, there is no randomized placebo-controlled trial available that has evaluated intra-ovarian PRP injection in terms of efficacy and safety for premature ovarian failure, and, more specifically, also not in patients with depleted ovarian reserve/poor ovarian response (POR) who constitute a significant proportion of patients undergoing assisted reproduction.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Efficacy and Safety of Intra-ovarian PRP Injection Within a Prospective, Single-blinded, Placebo-controlled, Randomized, Clinical Superiority Trial in Subjects With Low Ovarian Reserve/Expected Poor Ovarian Response
Actual Study Start Date : March 17, 2022
Estimated Primary Completion Date : March 17, 2025
Estimated Study Completion Date : March 17, 2028

Arm Intervention/treatment
Experimental: Autologous intra-ovarian PRP injection
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)
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.

Placebo Comparator: intra-ovarian saline solution (NaCL) injection
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
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.




Primary Outcome Measures :
  1. Ovarian response [ Time Frame: 34-36 hours following hCG administration at the end of ovarian stimulation ]
    Number of retrieved COCs per intention-to-treat


Secondary Outcome Measures :
  1. Hormone levels [ Time Frame: Follow-up period of three months entailing monthly evaluation ]
    Change from baseline in absolute and relative terms for Anti-Müllerian hormone (AMH), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and antral follicle count (AFC)

  2. Follicular response [ Time Frame: On the day of triggering of final oocyte maturation or the day before ]
    Number of follicles (classified and summarised for every ovary as follows: mean diameter 10.0 - 11.9 mm, 12.0 - 13.9 mm, 14.0 - 15.9 mm, 16.0 - 17.9 mm, 18.0 - 19.9 mm and larger 19.9 mm)

  3. COCs and MII oocytes [ Time Frame: Day 0 after follicle puncture ]
    Mean number of retrieved COCs per protocol and mean number of metaphase II (MII) oocytes per protocol

  4. Number of 2PN oocytes [ Time Frame: Day 1 after follicle puncture ]
    Mean number per protocol

  5. Mean number and quality of embryos [ Time Frame: Day 2-5 after follicle puncture ]
    Grade a for cleavage stage embryo, >=3BB for blastocyst

  6. Biochemical pregnancy rate [ Time Frame: 12-16 days after oocyte pick-up ]
    Incidence of serum beta-hCG test > 25 mIU/ml per ITT and PP

  7. Clinical pregnancy rate [ Time Frame: 4 weeks after embryo transfer ]
    Incidence of gestational sac with heartbeat assessed by TVS per ITT and PP

  8. Ongoing pregnancy rate [ Time Frame: 8-10 weeks after embryo transfer ]
    Incidence of at least one foetus with heart beat assessed by TVS

  9. Miscarriage rate [ Time Frame: early (week 7-12 weeks of gestation); late (between 12 to 22 weeks of gestation) ]
    Defined as spontaneous loss of a clinical pregnancy rate, where embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus or surgically removed

  10. Still birth rate [ Time Frame: after 22 weeks of gestation ]
    Incidence of the delivery of a dead fetus

  11. Live birth rate [ Time Frame: at a follow-up time of 30 days after delivery ]
    Incidence of the birth of at least one live newborn after 22 weeks of gestation

  12. Gestational age [ Time Frame: at the day of delivery ]
    Gestational week estimated by calculating days from oocyte retrieval + 14 days

  13. Weight of newborn [ Time Frame: at the day of delivery ]
    Birth weight measured in gram

  14. Length of newborn [ Time Frame: at the day of delivery ]
    Birth length measured in centimeter

  15. Incidence of birth sex [ Time Frame: at the day of delivery ]
    Incidence of female or male newborn

  16. Incidence of multiple birth [ Time Frame: at the day of delivery ]
    Incidence of singleton/multiple newborns

  17. Neonatal health [ Time Frame: at a follow-up time of 30 days after delivery ]
    major and minor congenital anomalies

  18. Post procedure pain [ Time Frame: on the day of follicle puncture ]
    measured by a numerical rating scale from 0 (no pain) to 10 (worst pain)

  19. Fertility Quality of Life Questionnaire [ Time Frame: on the day of follicle puncture and embryo transfer ]
    FertiQoL International is a validated relational scale to assess the relational domain regarding quality of life in women undergoing infertility treatment. For each question, the patient will check the response that is closest to her current thoughts and feelings. Scale reaches depending on the question from "very dissatisfied" to "very satisfied", "always" to "never" or "an extreme amount" to "not at all".

  20. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: at a follow-up time after 1, 2 and 5 years ]
    Incidence of adverse and serious adverse events with potential relationship to treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • ≥ 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)
  • Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subjects in or to complete the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05279560


Contacts
Layout table for location contacts
Contact: Georg Griesinger, MD +49 451-500-41950 georg.griesinger@uni-luebeck.de
Contact: Tanja Eggersmann, MD +49 451-500-41950 TanjaKristina.Eggersmann@uksh.de

Locations
Layout table for location information
Germany
University of Luebeck Recruiting
Luebeck, Schleswig-Holstein, Germany, 23562
Contact: Tanja Eggersmann, MD    0451-505778-10    TanjaKristina.Eggersmann@uksh.de   
Sponsors and Collaborators
University of Luebeck
Investigators
Layout table for investigator information
Principal Investigator: Georg Griesing, MD University of Luebeck
Publications:

Layout table for additonal information
Responsible Party: Prof. Dr. med. M.Sc. Georg Griesinger, Head of Department of Gynecological Endocrinology and Reproductive Medicine, University of Luebeck
ClinicalTrials.gov Identifier: NCT05279560    
Other Study ID Numbers: Aktenzeichen 21-348
First Posted: March 15, 2022    Key Record Dates
Last Update Posted: May 8, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be shared upon reasonable request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will not be available before 2027
Access Criteria: reasonable request

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Dr. med. M.Sc. Georg Griesinger, University of Luebeck:
poor ovarian response
low ovarian response
ICSI
IVF
ART
Platelet rich plasma
PRP
Additional relevant MeSH terms:
Layout table for MeSH terms
Infertility
Infertility, Female
Menopause, Premature
Primary Ovarian Insufficiency
Genital Diseases
Urogenital Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases