Reactivating Ovarian Function through Autologous Platelet-Rich Plasma Intraovarian Infusion: Pilot Data on Premature Ovarian Insufficiency, Perimenopausal, Menopausal, and Poor Responder Women
Abstract
:1. Introduction
2. Materials and Methods
2.1. General Exclusion Criteria
2.2. Participants in the Poor Ovarian Response Pilot Study
2.3. Participants in the Premature Ovarian Insufficiency Pilot Study
2.4. Participants in Perimenopause Pilot Study
2.5. Participants in Menopause Pilot Study
2.6. Standard Examinations Prior to Platelet-Rich Plasma Treatment
2.7. Platelet-Rich Plasma Preparation Method
2.8. Platelet-Rich Plasma Intraovarian Infusion Method
2.9. Follow-Up Monitoring
2.10. Statistics
2.11. Study Approval
3. Results
3.1. Platelet-Rich Plasma Preparation and Infusion
3.2. Results Following Platelet-Rich Plasma Intraovarian Infusion in Women Presenting with Poor Ovarian Response
3.3. Results Following Platelet-Rich Plasma Intraovarian Infusion in Women Presenting with Premature Ovarian Insufficiency
3.4. Results Following Platelet-Rich Plasma Intraovarian Infusion Regarding Women in Perimenopause
3.5. Results Following Platelet-Rich Plasma Intraovarian Infusion Regarding Women in Menopause
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pilot Study | Screening for Eligibility | Standard Examination Prior to PRP Treatment | PRP Intraovarian Infusion | Follow-Up Monitoring |
---|---|---|---|---|
POR (n = 30) | Bologna Criteria | - Assessment of AFC, serum FSH, LH, AMH and E2 - HSG and semen analysis | Performed at least 2 months following the last ICSI-ET cycle | - AFC, serum FSH, LH, AMH and E2 assessment for three consecutive months following PRP treatment - In the third month following PRP participants were subjected to an ICSI-ET cycle |
POI (n = 30) | - Age <40 years - Amenorrhea for at least four months, and elevated FSH >25 IU/L | -Assessment of AFC, serum FSH, LH, AMH and E2 -HSG and semen analysis | Performed immediately following standard investigation or at least six months following HR discontinuation | - AFC, serum FSH, LH, AMH and E2 assessment for three consecutive months following PRP treatment. - Participants were invited to conceive naturally |
Perimenopause (n = 30) | -Age ≥40 years -Menstrual cycle irregularities | |||
Menopause (n = 30) | - Age 45–55 years - Amenorrhea for at least 12 months without HR supplementation, and FSH >30 IU/L |
Parameters | Poor Ovarian Response Group (n = 30) | |||
General Participants’ Characteristics | ||||
Patient age (years) | 38.40 ± 2.01 | |||
Partner age (years) | 40.9 ± 2.52 | |||
Years of infertility | 5.83 ± 1.02 | |||
Body Mass Index (kg/m2) | 23.12 ± 2.52 | |||
Ovarian Reserve Markers | Prior ICSI Cycle | 1st Menstrual Cycle | 2nd Menstrual Cycle | Post ICSI Cycle |
FSH (IU/mL) | 10.71 ± 1.62 | 9.05 ± 1.76 a(**) | 8.87 ± 1.68 a(**) | 8.95 ± 1.40 a(**) |
LH (IU/mL) | 9.02 ± 0.80 | 7.10 ± 1.03 a(**) | 6.50 ± 0.98 a(**) | 6.08 ± 0.92 a(**) |
AMH (ng/mL) | 0.66 ± 0.20 | 0.85 ± 0.26 a(*) | 1.17 ± 0.28 a(**),b(**) | 1.14 ± 0.26 a(**),b(**) |
AFC | 2.63 ± 0.93 | 3.80 ± 1.06 a(*) | 5.33 ± 1.32 a(**),b(**) | 5.20 ± 1.35 a(**),b(**) |
ICSI Cycle’s Performance | Prior ICSI Cycle | 1st Menstrual Cycle | 2nd Menstrual Cycle | Post ICSI Cycle |
Dur. of stimulation (Days) | 10.57 ± 0.90 | NA | NA | 9.40 ± 1.10 a(**) |
Gonadotropin Dose (IU) | 4234.30 ± 261.58 | NA | NA | 4316.70 ± 217.93 |
E2 (pg/mL) (hCG Trigger) | 710.33 ± 226.36 | NA | NA | 1522.90 ± 472.02 a(**) |
Retrieved Oocytes | 1.20 ± 0.76 | NA | NA | 3.37 ± 1.54 a(**) |
MII Oocytes Obtained | 1.00 ± 0.79 | NA | NA | 2.97 ± 1.38 a(**) |
2PN Embryos Obtained | 0.73 ± 0.52 | NA | NA | 2.43 ± 1.38 a(**) |
Cleavage Stage Embryos | 0.60 ± 0.56 | NA | NA | 1.93 ± 1.26 (**) |
Total Number of Cleavage Stage Embryos | 18 | NA | NA | 58 |
Good quality (Grade 1 & 2) | 8/18 (44.4%) | NA | NA | 28/58 (48.2%) |
Cancellation Rate | 19/30 (63.3%) | NA | NA | 9/30 (30%) a(*) |
General Participants’ Characteristics | PRP Success (n = 18) | PRP Failure (n = 12) | p Value | |||||||||
Participant age (years) | 35.11 ± 1.57 | 35.92 ± 1.93 | NS | |||||||||
Partner age (years) | 37.94 ± 1.21 | 37.88 ± 1.70 | NS | |||||||||
Duration of amenorrhea (months) | 10.06 ± 2.62 | 10.17 ± 4.76 | NS | |||||||||
Time to menstrual cycle recovery (days) | 42.06 ± 6.43 | NA | NA | |||||||||
Outcome Measures Following PRP | Prior to Treatment | Follow-Up Month 1 | Follow-Up Month 2 | Follow-Up Month 3 | ||||||||
PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | |
Menstrual cycle duration (days) | NA | NA | NA | 34.22 ± 4.10 | NA | NA | 34.06 ± 4.33 | NA | NA | 33.44 ± 3.57 | NA | NA |
Menstruation duration (days) | NA | NA | NA | 4.22 ± 1.31 | NA | NA | 4.56 ± 1.20 | NA | NA | 4.89 ± 1.18 | NA | NA |
FSH (IU/mL) | 40.61 ± 6.05 | 63.65 ± 6.41 | <0.001 | 35.87 ± 4.77 | 54.07 ± 8.98 | <0.001 | 27.18 ± 5.82 | 52.47 ± 8.09 | <0.001 | 20.67 ± 3.58 | 59.40 ± 9.47 | <0.001 |
LH (IU/mL) | 25.14 ± 3.10 | 24.33 ± 3.04 | NS | 21.91 ± 2.00 | 22.23 ± 2.38 | NS | 20.11 ± 1.45 | 17.51 ± 2.53 | NS | 19.31 ± 1.93 | 23.50 ± 4.37 | 0.001 |
AMH (ng/mL) | 0.18 ± 0.04 | 0.15 ± 0.04 | NS | 0.53 ± 0.10 | 0.21 ± 0.06 | <0.001 | 0.65 ± 0.08 | 0.27 ± 0.09 | <0.001 | 0.75 ± 0.06 | 0.30 ± 0.05 | <0.001 |
E2 (pg/mL) | 17.13 ± 2.22 | 17.38 ± 2.61 | NS | 26.75 ± 4.56 | 23.43 ± 2.86 | NS | 38.92 ± 9.46 | 25.14 ± 1.99 | <0.001 | 48.08 ± 6.28 | 20.86 ± 7.11 | <0.001 |
AFC | 0 | 0 | NS | 1.56 ± 0.51 | 0 | <0.001 | 2.06 ± 0.73 | 0 | <0.001 | 2.33 ± 0.49 | 0 | <0.001 |
Spontaneous Pregnancies Recorded Following PRP | PRP Success | PRP Failure | p Value | |||||||||
Number of Pregnancies achieved | 3 | 0 | NS | |||||||||
Number of Live Births | 3 | 0 | NS |
General Participants’ Characteristics | PRP Success (n = 24) | PRP Failure (n = 5) | p Value | |||||||||
Participant age (years) | 43.25 ± 1.42 | 44 ± 2.55 | NS | |||||||||
Partner age (years) | 44.92 ± 3.23 | 49 ± 2.00 | <0.001 | |||||||||
Menstrual cycle irregularities (months) | 16 ± 2.43 | 17 ± 2.35 | NS | |||||||||
Outcome Measures Following PRP | Prior to Treatment | Follow-Up Month 1 | Follow-Up Month 2 | Follow-Up Month 3 | ||||||||
PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | |
Differences in menstrual cycle duration between two consecutive cycle (days) | 10.08 ± 2.10 | 12.00 ± 1.58 | NS | NA | NA | NA | 0.79 ± 0.66 | 12.40 ± 3.91 | <0.001 | 1.29 ± 1.27 | 10.20 ± 2.68 | <0.001 |
Menstrual cycle duration (days) | 41.13 ± 1.85 | 47 ± 10.42 | NS | 37.08 ± 5.32 | 40.80 ± 8.61 | NS | 36.88 ± 5.62 | 36.80 ± 9.36 | NS | 36.75 ± 4.93 | 38.60 ± 4.88 | NS |
Menstruation duration (days) | 3.17 ± 1.17 | 3.60 ± 1.52 | NS | 3.92 ± 1.72 | 4.40 ± 1.52 | NS | 5.33 ± 1.69 | 4.60 ± 1.95 | NS | 4.92 ± 1.38 | 5.00 ± 1.41 | NS |
FSH (IU/mL) | 18.51 ± 2.62 | 18.32 ± 1.78 | NS | 17.03 ± 3.57 | 17.82 ± 1.41 | NS | 15.10 ± 3.65 | 18.24 ± 1.89 | NS | 15.28 ± 4.03 | 18.14 ± 1.82 | NS |
LH (IU/mL) | 16.28 ± 2.64 | 16.62 ± 1.97 | NS | 14.72 ± 3.43 | 15.90 ± 1.84 | NS | 13.20 ± 3.53 | 16.22 ± 1.80 | NS | 13.18 ± 3.52 | 16.30 ± 1.36 | NS |
AMH (ng/mL) | 0.96 ± 0.28 | 0.86 ± 0.36 | NS | 1.42 ± 0.16 | 0.80 ± 0.37 | <0.001 | 1.41 ± 0.17 | 0.82 ± 0.38 | <0.001 | 1.41 ± 0.23 | 0.66 ± 0.36 | <0.001 |
E2 (pg/mL) | 29.67 ± 3.82 | 27.80 ± 6.87 | NS | 39.50 ± 2.06 | 28.70 ± 5.97 | <0.001 | 39.29 ± 5.82 | 31.34 ± 7.14 | 0.026 | 40.83 ± 4.30 | 30.24 ± 9.86 | <0.001 |
AFC | 1.54 ± 0.51 | 1.00 ± 0.71 | NS | 2.79 ± 0.78 | 1.20 ± 0.45 | <0.001 | 3.38 ± 0.92 | 1.40 ± 0.89 | <0.001 | 4.25 ± 0.68 | 1.20 ± 1.10 | <0.001 |
Spontaneous Pregnancies Recorded Following PRP | PRP Success | PRP Failure | p Value | |||||||||
Number of Pregnancies achieved | 4 | 0 | NS | |||||||||
Number of Live Births | 3 | 0 | NS |
General Participants’ Characteristics | PRP Success (n = 13) | PRP Failure (n = 12) | p Value | |||||||||
Participant age (years) | 48.85 ± 1.57 | <0.05 | ||||||||||
Partner age (years) | 49.15 ± 3.91 | NS | ||||||||||
Duration of amenorrhea (months) | 15.69 ± 1.75 | NS | ||||||||||
Time to menstrual cycle recovery (days) | 40.92 ± 7.57 | NA | ||||||||||
Outcome Measures Following PRP | Prior to Treatment | Follow-Up Month 1 | Follow-Up Month 2 | Follow-Up Month 3 | ||||||||
PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | PRP Success | PRP Failure | p Value | |
Menstrual cycle duration (days) | NA | NA | NA | 35.62 ± 3.62 | NA | NA | 34.38 ± 4.52 | NA | NA | 32.77 ± 4.19 | NA | NA |
Menstruation duration (days) | NA | NA | NA | 4.69 ± 0.95 | NA | NA | 4.69 ± 1.18 | NA | NA | 5.31 ± 1.65 | NA | NA |
FSH (IU/mL) | 80.27 ± 5.03 | 81.15 ± 6.19 | NS | 43.63 ± 6.10 | 68.54 ± 7.26 | <0.001 | 38.42 ± 2.50 | 65.40 ± 6.50 | <0.001 | 30.55 ± 2.50 | 66.98 ± 8.12 | <0.001 |
LH (IU/mL) | 30.82 ± 3.78 | 30.18 ± 5.04 | NS | 22.62 ± 3.79 | 25.41 ± 4.23 | NS | 18.80 ± 3.80 | 24.65 ± 3.10 | 0.001 | 17.04 ± 3.08 | 26.60 ± 2.84 | <0.001 |
AMH (ng/mL) | 0.13 ± 0.03 | 0.11 ± 0.05 | NS | 0.32 ± 0.08 | 0.18 ± 0.08 | <0.001 | 0.40 ± 0.13 | 0.24 ± 0.06 | <0.001 | 0.61 ± 0.19 | 0.19 ± 0.04 | <0.001 |
E2 (pg/mL) | 14.01 ± 2.59 | 13.26 ± 2.30 | NS | 22.19 ± 5.63 | 16.31 ± 2.10 | 0.002 | 32.95 ± 2.73 | 15.29 ± 1.78 | <0.001 | 41.53 ± 8.61 | 13.63 ± 2.30 | <0.001 |
AFC | 0 | 0 | NS | 1.31 ± 0.48 | 0 | <0.001 | 1.77 ± 0.60 | 0 | <0.001 | 2.38 ± 0.65 | 0 | <0.001 |
Spontaneous Pregnancies Recorded Following PRP | PRP Success | PRP Failure | p Value | |||||||||
Number of Pregnancies achieved | 1 | 0 | NS | |||||||||
Number of Live Births | 1 | 0 | NS |
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Sfakianoudis, K.; Simopoulou, M.; Grigoriadis, S.; Pantou, A.; Tsioulou, P.; Maziotis, E.; Rapani, A.; Giannelou, P.; Nitsos, N.; Kokkali, G.; et al. Reactivating Ovarian Function through Autologous Platelet-Rich Plasma Intraovarian Infusion: Pilot Data on Premature Ovarian Insufficiency, Perimenopausal, Menopausal, and Poor Responder Women. J. Clin. Med. 2020, 9, 1809. https://doi.org/10.3390/jcm9061809
Sfakianoudis K, Simopoulou M, Grigoriadis S, Pantou A, Tsioulou P, Maziotis E, Rapani A, Giannelou P, Nitsos N, Kokkali G, et al. Reactivating Ovarian Function through Autologous Platelet-Rich Plasma Intraovarian Infusion: Pilot Data on Premature Ovarian Insufficiency, Perimenopausal, Menopausal, and Poor Responder Women. Journal of Clinical Medicine. 2020; 9(6):1809. https://doi.org/10.3390/jcm9061809
Chicago/Turabian StyleSfakianoudis, Konstantinos, Mara Simopoulou, Sokratis Grigoriadis, Agni Pantou, Petroula Tsioulou, Evangelos Maziotis, Anna Rapani, Polina Giannelou, Nikolaos Nitsos, Georgia Kokkali, and et al. 2020. "Reactivating Ovarian Function through Autologous Platelet-Rich Plasma Intraovarian Infusion: Pilot Data on Premature Ovarian Insufficiency, Perimenopausal, Menopausal, and Poor Responder Women" Journal of Clinical Medicine 9, no. 6: 1809. https://doi.org/10.3390/jcm9061809