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
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Ovarian response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •≥ 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
研究组 & 干预措施
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
干预措施: autologous PRP (platelet rich plasma) (Biological)
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
干预措施: Saline solution (NaCL) Injection (Other)
结局指标
主要结局
Ovarian response
时间窗: 34-36 hours following hCG administration at the end of ovarian stimulation
Number of retrieved COCs per intention-to-treat
次要结局
- Biochemical pregnancy rate(12-16 days after oocyte pick-up)
- Ongoing pregnancy rate(8-10 weeks after embryo transfer)
- Weight of newborn(at the day of delivery)
- Incidence of multiple birth(at the day of delivery)
- Still birth rate(after 22 weeks of gestation)
- Live birth rate(at a follow-up time of 30 days after delivery)
- Clinical pregnancy rate(4 weeks after embryo transfer)
- 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)
- Gestational age(at the day of delivery)
- Incidence of birth sex(at the day of delivery)
- Post procedure pain(on the day of follicle puncture)
- Fertility Quality of Life Questionnaire(on the day of follicle puncture and embryo transfer)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](at a follow-up time after 1, 2 and 5 years)
- Length of newborn(at the day of delivery)
- Miscarriage rate(early (week 7-12 weeks of gestation); late (between 12 to 22 weeks of gestation))
- Neonatal health(at a follow-up time of 30 days after delivery)
研究者
Prof. Dr. med. M.Sc. Georg Griesinger
Head of Department of Gynecological Endocrinology and Reproductive Medicine
University of Luebeck