Infertility, Female Clinical Trial
— OPIFOfficial 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
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.
Status | Recruiting |
Enrollment | 140 |
Est. completion date | March 17, 2028 |
Est. primary completion date | March 17, 2025 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years to 42 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Germany | University of Luebeck | Luebeck | Schleswig-Holstein |
Lead Sponsor | Collaborator |
---|---|
University of Luebeck |
Germany,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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* Note: There are 14 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Ovarian response | Number of retrieved COCs per intention-to-treat | 34-36 hours following hCG administration at the end of ovarian stimulation | |
Secondary | Hormone levels | 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) | Follow-up period of three months entailing monthly evaluation | |
Secondary | Follicular response | 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) | On the day of triggering of final oocyte maturation or the day before | |
Secondary | COCs and MII oocytes | Mean number of retrieved COCs per protocol and mean number of metaphase II (MII) oocytes per protocol | Day 0 after follicle puncture | |
Secondary | Number of 2PN oocytes | Mean number per protocol | Day 1 after follicle puncture | |
Secondary | Mean number and quality of embryos | Grade a for cleavage stage embryo, >=3BB for blastocyst | Day 2-5 after follicle puncture | |
Secondary | Biochemical pregnancy rate | Incidence of serum beta-hCG test > 25 mIU/ml per ITT and PP | 12-16 days after oocyte pick-up | |
Secondary | Clinical pregnancy rate | Incidence of gestational sac with heartbeat assessed by TVS per ITT and PP | 4 weeks after embryo transfer | |
Secondary | Ongoing pregnancy rate | Incidence of at least one foetus with heart beat assessed by TVS | 8-10 weeks after embryo transfer | |
Secondary | Miscarriage rate | 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 | early (week 7-12 weeks of gestation); late (between 12 to 22 weeks of gestation) | |
Secondary | Still birth rate | Incidence of the delivery of a dead fetus | after 22 weeks of gestation | |
Secondary | Live birth rate | Incidence of the birth of at least one live newborn after 22 weeks of gestation | at a follow-up time of 30 days after delivery | |
Secondary | Gestational age | Gestational week estimated by calculating days from oocyte retrieval + 14 days | at the day of delivery | |
Secondary | Weight of newborn | Birth weight measured in gram | at the day of delivery | |
Secondary | Length of newborn | Birth length measured in centimeter | at the day of delivery | |
Secondary | Incidence of birth sex | Incidence of female or male newborn | at the day of delivery | |
Secondary | Incidence of multiple birth | Incidence of singleton/multiple newborns | at the day of delivery | |
Secondary | Neonatal health | major and minor congenital anomalies | at a follow-up time of 30 days after delivery | |
Secondary | Post procedure pain | measured by a numerical rating scale from 0 (no pain) to 10 (worst pain) | on the day of follicle puncture | |
Secondary | Fertility Quality of Life Questionnaire | 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". | on the day of follicle puncture and embryo transfer | |
Secondary | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of adverse and serious adverse events with potential relationship to treatment | at a follow-up time after 1, 2 and 5 years |
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