Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation (OPIF)
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|ClinicalTrials.gov Identifier: NCT05279560|
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : May 9, 2023
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|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, 2024|
|Estimated Study Completion Date :||March 17, 2027|
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.
- Ovarian response [ Time Frame: 34-36 hours following hCG administration at the end of ovarian stimulation ]Number of retrieved COCs per intention-to-treat
- 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)
- 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)
- 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
- Number of 2PN oocytes [ Time Frame: Day 1 after follicle puncture ]Mean number per protocol
- Mean number and quality of embryos [ Time Frame: Day 2-5 after follicle puncture ]Grade a for cleavage stage embryo, >=3BB for blastocyst
- 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
- Clinical pregnancy rate [ Time Frame: 4 weeks after embryo transfer ]Incidence of gestational sac with heartbeat assessed by TVS per ITT and PP
- Ongoing pregnancy rate [ Time Frame: 8-10 weeks after embryo transfer ]Incidence of at least one foetus with heart beat assessed by TVS
- 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
- Still birth rate [ Time Frame: after 22 weeks of gestation ]Incidence of the delivery of a dead fetus
- 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
- Gestational age [ Time Frame: at the day of delivery ]Gestational week estimated by calculating days from oocyte retrieval + 14 days
- Weight of newborn [ Time Frame: at the day of delivery ]Birth weight measured in gram
- Length of newborn [ Time Frame: at the day of delivery ]Birth length measured in centimeter
- Incidence of birth sex [ Time Frame: at the day of delivery ]Incidence of female or male newborn
- Incidence of multiple birth [ Time Frame: at the day of delivery ]Incidence of singleton/multiple newborns
- Neonatal health [ Time Frame: at a follow-up time of 30 days after delivery ]major and minor congenital anomalies
- 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)
- 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".
- 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
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
|Contact: Georg Griesinger, MD||+49 firstname.lastname@example.org|
|Contact: Tanja Eggersmann, MD||+49 451-500-41950||TanjaKristina.Eggersmann@uksh.de|
|University of Luebeck||Recruiting|
|Luebeck, Schleswig-Holstein, Germany, 23562|
|Contact: Tanja Eggersmann, MD 0451-505778-10 TanjaKristina.Eggersmann@uksh.de|
|Principal Investigator:||Georg Griesing, MD||University of Luebeck|