Clinical trial NCT05279560: Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Premature Ovarian Insufficiency
Infertility, Female
Sterility, Female
PRP
Keywords: poor ovarian response
low ovarian response
ICSI
IVF
ART
Platelet rich plasma
PRP
Lead sponsor: University of Luebeck
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 114
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Ovarian response
timeFrame: 34-36 hours following hCG administration at the end of ovarian stimulation
Secondary outcomes:
measure: Hormone levels
timeFrame: Follow-up period of three months entailing monthly evaluation
measure: Follicular response
timeFrame: On the day of triggering of final oocyte maturation or the day before
measure: COCs and MII oocytes
timeFrame: Day 0 after follicle puncture
measure: Number of 2PN oocytes
timeFrame: Day 1 after follicle puncture
measure: Mean number and quality of embryos
timeFrame: Day 2-5 after follicle puncture
measure: Biochemical pregnancy rate
timeFrame: 12-16 days after oocyte pick-up
measure: Clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer
measure: Ongoing pregnancy rate
timeFrame: 8-10 weeks after embryo transfer
measure: Miscarriage rate
timeFrame: early (week 7-12 weeks of gestation); late (between 12 to 22 weeks of gestation)
measure: Still birth rate
timeFrame: after 22 weeks of gestation
measure: Live birth rate
timeFrame: at a follow-up time of 30 days after delivery
measure: Gestational age
timeFrame: at the day of delivery
measure: Weight of newborn
timeFrame: at the day of delivery
measure: Length of newborn
timeFrame: at the day of delivery
measure: Incidence of birth sex
timeFrame: at the day of delivery
measure: Incidence of multiple birth
timeFrame: at the day of delivery
measure: Neonatal health
timeFrame: at a follow-up time of 30 days after delivery
measure: Post procedure pain
timeFrame: on the day of follicle puncture
measure: Fertility Quality of Life Questionnaire
timeFrame: on the day of follicle puncture and embryo transfer
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: at a follow-up time after 1, 2 and 5 years
Other outcomes:
Locations:
city: Luebeck
country: Germany
facility: University of Luebeck
state: Schleswig-Holstein
Study officials:
affiliation: University of Luebeck
name: Georg Griesing, MD
role: PRINCIPAL_INVESTIGATOR
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