Combination of CO2 laser and Platlet Rich Plasma: A Safe Treatment as a Possible New Frontier for Poor Ovarian Responders
Keywords:
Platlet Rich Plasma, Decreased Ovarian Reserve, CO2 Laser, Poor ResponderAbstract
The ovarian reserve defines the number of antral follicles in the woman's ovaries. Female gametes from the twentieth week of intrauterine life undergo a process of inexorable progressive exhaustion and the follicles present at the birth continue to reduce in number, due to a degenerative phenomena that determine its loss. The decrease in ovarian reserve is associated with a reduced fertility and this matter represents the major challenge in reproductive medicine. The interventions that support the regeneration of gonads represent the new frontier. This study intends to propose a method to induce a regeneration of ovarian response in ovarian tissue of patients with poor response and to optimise the recruitment of pre-existing dormant follicles to improve the ovarian stimulation in vitro fertilization cycle. We enrolled patients of childbearing age with poor ovarian reserve diagnosed with AFC <5-7 follicles and /or altered hormonal levels (FSH> 12 mIU / ml; AMH <0.5-1,1 ng / ml) and / or with at least one IVF cycle that has given failed oocytes recovery. The main scientific and technical innovation of the study is the combination of treatment with CO2 laser (microdissection on both ovaries performed by laparoscopy) and injection of platlet rich plasma on ovarian subcortical tissue under direct vision. DUOSTIM (double stimulation) to start in a month was planned for all enrolled patients. The aim is to demonstrate that the experimental treatment has a safety profile, with no risk for patients health. No patients manifested any adverse reactions and complications. Data on the effect on the fertility restoration are not yet avilable because patients follow up has not yet ended, thus we will publish them in the near future.
References
Committee Opinion No. 589. American College of Obstetricians and Gynecologists. Fertil Steril. 2014 Mar;101(3):633–4.
Seli E. Ovarian Aging. Semin Reprod Med. 2015 Nov 13;33(06):375–6. https://doi.org/10.1055/s-0035-1567817
Stoop H, Honecker F, Cools M, ET AL. Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Hum Reprod. 2005 Jun 1;20(6):1466–76. https://doi.org/10.1093/humrep/deh800
Ferraretti AP, La Marca A, Fauser BCJM, ET AL. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul1; 26(7):1616–24. https://doi.org/10.1093/humrep/der092
La Marca A, Grisendi V, Giulini S ET AL. Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a
validation study. J Assist Reprod Genet. 2015 Jun 1;32(6):931–7. https://doi.org/10.1007/s10815-015-0476-4
Hosni W, Bastu E. Ovarian stem cells and aging. Climacteric. 2012 Apr 28;15(2):125–32. https://doi.org/10.3109/13697137.2011.636848
Ramaswamy Reddy S, Reddy R, Babu Nc, ET AL. Stem-cell therapy and platelet-rich plasma in regenerative medicines: A review on pros and cons of the technologies. J Oral Maxillofac Pathol. 2018;22(3):367. https://doi.org/10.4103/jomfp.jomfp_93_18
Bukovsky A. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases. Reprod Biol Endocrinol. 2015 Dec 25;13(1):10. https://doi.org/10.1186/s12958-015-0001-8
Hajipour H, Farzadi L, Latifi Z, ET AL. An update on platelet-rich plasma (PRP) therapy
in endometrium and ovary related infertilities: clinical and molecular aspects. Syst Biol Reprod Med. 2021 May 4;67(3):177–88. https://doi.org/10.1080/19396368.2020.1862357
Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1–9.
Arunkalaivanan A, Kaur H, Onuma O. Laser therapy as a treatment modality for genitourinary syndrome of menopause: a
critical appraisal of evidence. Int Urogynecol J. 2017 May 2;28(5):681–5. https://doi.org/10.1007/s00192-017-3282-y
Perino A, Calligaro A, Forlani F, ET AL. Vulvovaginal atrophy: A new treatment modality using thermo-ablative fractional CO2 laser.
Maturitas. 2015 Mar;80(3):296–301. https://doi.org/10.1016/j.maturitas.2014.12.006
Salvatore S, Leone Roberti Maggiore U, Athanasiou S, ET AL. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue. Menopause. 2015 Aug;22(8):845–9. https://doi.org/10.1097/gme.0000000000000401
Salvatore S, França K, Lotti T, ET AL. Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO2 Laser Treatment. Open Access Maced J Med Sci. 2018 Jan 19;6(1):6–14. https://doi.org/10.3889/oamjms.2018.058
Keckstein G, Rossmanith W, Spatzier K, ET AL. The effect of laparoscopic treatment of polycystic ovarian disease by CO2-laser or
Nd:YAG laser. Surg Endosc. 1990;4(2):103–7. https://doi.org/10.1007/bf00591271
Farquhar C, Vandekerckhove P, Lilford R. Laparoscopic “drilling” by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. In: Cochrane
Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2001. https://doi.org/10.1002/14651858.cd001122
Hendriks ML, Konig T, Korsen T, ET AL. Short-term changes in hormonal profiles after laparoscopic ovarian laser evaporation compared with diagnostic laparoscopy for
PCOS. Hum Reprod. 2014 Nov 1;29(11):2544–52. https://doi.org/10.1093/humrep/deu237
Busnelli A, Papaleo E, Del Prato D, ET AL. A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria. Hum
Reprod. 2015 Feb 1;30(2):315–22. https://doi.org/10.1093/humrep/deu319
Bozdag G, Polat M, Yarali I, ET AL. Live birth rates in various subgroups of poor ovarian responders fulfilling the Bologna criteria. Reprod Biomed Online. 2017 Jun;34(6):639–
https://doi.org/10.1016/j.rbmo.2017.03.009
Alviggi C, Andersen CY, Buehler K, ET AL. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016 Jun;105(6):1452–3. https://doi.org/10.1016/j.fertnstert.2016.02.005
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 28;39(6). https://doi.org/10.1042/bsr20190805
Sfakianoudis K, Simopoulou M, Nitsos N, ET AL. Autologous Platelet-Rich Plasma Treatment Enables Pregnancy for a Woman in Premature Menopause. J Clin Med. 2018
Dec 20;8(1):1. https://doi.org/10.3390/jcm8010001
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 2;34(9):756–60. https://doi.org/10.1080/09513590.2018.1445219
Chang Y, Li J, Wei L, ET AL. Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium.
Medicine (Baltimore). 2019 Jan;98(3):e14062. https://doi.org/10.1097/md.0000000000014062
Kim K, Choi JS, Choi E, ET AL. Effects of community-based health worker interventions to improve chronic disease management and care among vulnerable populations: A
systematic review. Am J Public Health. 2016;106(4):e3–28. https://doi.org/10.2105/ajph.2015.302987
Hosseini L, Shirazi A, Naderi MM, ET AL. Platelet-rich plasma promotes the development of isolated human primordial and primary follicles to the preantral stage.
Reprod Biomed Online. 2017 Oct;35(4):343–50. https://doi.org/10.1016/j.rbmo.2017.04.007
Farimani M, Nazari A, Mohammadi S, ET AL. Evaluation of intra-ovarian platelet-rich plasma administration on oocytes-dependent variables in patients with poor ovarian response: A retrospective study according to the POSEIDON criteria. Reprod Biol Endocrinol. 2021 Dec 8;19(1):137. https://doi.org/10.1186/s12958-021-00826-w
Cakiroglu Y, Saltik A, Yuceturk A, ET AL. Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency. Aging (Albany NY). 2020 Jun 5;12(11):10211–22. https://doi.org/10.18632/aging.103403
Sills ES, Sills ES, Petersen JL, ET AL. Regenerative Effect of Intraovarian Injection of Activated Autologous Platelet Rich Plasma: Serum Anti-Mullerian Hormone Levels Measured Among Poor-Prognosis In Vitro Fertilization Patients. Int J Regen Med. 2020 Mar 18;1–5. https://doi.org/10.31487/j.rgm.2020.01.02
