Clinical trial NCT04797377: Autologous Intraovarian Platelet Rich Plasma Treatment in Women With Poor Ovarian Response
Official title: Effects of Autologous Intraovarian Platelet Rich Plasma in Women With Poor Ovarian Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Poor Ovarian Reserve
Keywords: Platelet-Rich Plasma
Poor Ovarian Reserve
Oocyte Quality
Embryo Quality
Lead sponsor: Nadezhda Women's Health Hospital
Sponsor class: OTHER
First posted: 2021-03-15
Enrollment: 66
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: After the women are recruited for the study, Antral follicle count (AFC), serum anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) levels will be determined at baseline and will be repeated beginning with the first menstrual cycle after treatment. Approximately 22 ml of blood sample will be collected under sterile conditions, and PRP will be prepared. The same day, within 1 hour of sample preparation, PRP injection will be performed transvaginally under ultrasound guidance and under sedation anesthesia into both ovaries. Ovarian reserve (AFC, FSH, AMH), and ICSI outcome parameters (number of MII oocytes, fertilization rate, oocyte and embryo quality) will be followed up to three months after the intervention.
Primary purpose: TREATMENT

Brief summary: Reproductive age women diagnosed with poor ovarian response (POR) based on Bologna criteria with a history of at least two prior failed ICSI cycle will be recruited for the study. Antral follicle count (AFC), serum anti-mullerian hormone (AMH), and early follicular phase serum follicle stimulating hormone (FSH) levels will determined at baseline. Autologous blood obtained from peripheral vein will be used to prepare PRP following standard protocols and will be injected to both ovaries. Ovarian reserve parameters and ICSI outcomes will be determined.

Detailed description: Reproductive age women diagnosed with POR based on Bologna criteria with a history of at least two prior failed intracytoplasmic sperm injection (ICSI) cycle will recruited for the study. Antral follicle count (AFC), serum anti-mullerian hormone (AMH), and early follicular phase serum follicle stimulating hormone (FSH) levels will be determined at baseline. Autologous blood obtained from peripheral vein will be used to prepare PRP following standard protocols. PRP injection will be performed under sedation anesthesia, using a 11.8 inch (30 cm) single lumen 21G needles under transvaginal ultrasound guidance. On the 2 to 4th days of the first three menstrual cycles following the procedure, AFC, AMH, and FSH levels will be re-assessed. Patients with at least one antral follicle will be started on ovarian stimulation for ICSI, followed by embryo transfer. Biomarkers of ovarian reserve (AFC, FSH, AMH), and ICSI outcome parameters (number of metaphase II (MII) oocytes, blastocyst embryos, fertilization rate, oocyte and embryo quality) will be followed.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with POR based on Bologna criteria and with a history of at least two prior failed ICSI cycles
* A previous assisted reproductive technology cycle with less than 3 oocytes (conventional stimulation protocol) and AFC \< 7
* The same ovarian stimulation protocol before and after the PRP treatment

Exclusion Criteria:

* Age over 46 years,
* Body mass index (BMI) ≥ 30 kg/m2,
* Presence of pregnancy
* Uncontrolled endocrine disorders (polycystic ovary syndrome and others)
* Parental genetic and chromosomal disorders,
* Immunological disorders
* Cancer diagnostics

Primary outcomes:
measure: Oocyte number
timeFrame: 3 months
measure: Oocyte quality
timeFrame: 3 months
measure: Embryo number
timeFrame: 3 months
measure: Embryo quality
timeFrame: 3 months
measure: Fertilization rate
timeFrame: 3 months
Secondary outcomes:
measure: Antral follicle count (AFC)
timeFrame: 3 months
measure: Serum anti-mullerian hormone (AMH)
timeFrame: 3 months
measure: Serum follicle stimulating hormone (FSH)
timeFrame: 3 months
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Nadezhda Women's Health Hospital
Study officials:
References:
citation: Drakopoulos P, Bardhi E, Boudry L, Vaiarelli A, Makrigiannakis A, Esteves SC, Tournaye H, Blockeel C. Update on the management of poor ovarian response in IVF: the shift from Bologna criteria to the Poseidon concept. Ther Adv Reprod Health. 2020 Jul 31;14:2633494120941480. doi: 10.1177/2633494120941480. eCollection 2020 Jan-Dec.
citation: Zhang Y, Zhang C, Shu J, Guo J, Chang HM, Leung PCK, Sheng JZ, Huang H. Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis. Hum Reprod Update. 2020 Feb 28;26(2):247-263. doi: 10.1093/humupd/dmz046.
citation: Panda SR, Sachan S, Hota S. A Systematic Review Evaluating the Efficacy of Intra-Ovarian Infusion of Autologous Platelet-Rich Plasma in Patients With Poor Ovarian Reserve or Ovarian Insufficiency. Cureus. 2020 Dec 12;12(12):e12037. doi: 10.7759/cureus.12037.
citation: Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020 Oct 21;21(20):7794. doi: 10.3390/ijms21207794.
citation: Sills ES, Wood SH. Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response. Biosci Rep. 2019 Jun 4;39(6):BSR20190805. doi: 10.1042/BSR20190805. Print 2019 Jun 28.
citation: Bos-Mikich A, de Oliveira R, Frantz N. Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet. 2018 May;35(5):753-756. doi: 10.1007/s10815-018-1159-8. Epub 2018 Mar 21.
citation: Alves R, Grimalt R. A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord. 2018 Jan;4(1):18-24. doi: 10.1159/000477353. Epub 2017 Jul 6.