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Premature ovarian failure (POI) is a loss of normal function before age 40, leading to infertility and hypoestrogenism. About 1% of women younger than 40 years old and 0.1% before 30 are affected. Most patients already had impaired or complete loss of fecundity when diagnosed. Hence, the treatment of POI is particularly tough. Currently, no optimal regimen exists to ameliorate ovarian function.
In women, the non-growing population of follicles that comprise the ovarian reserve is determined at birth and serves as the reservoir for future fertility. This reserve of dormant, primordial follicles and the mechanisms controlling their selective activation which constitute the committing step into folliculogenesis are essential for determining fertility outcomes in women.
While POI is sometimes called premature menopause, it is not identical with menopause. Women with POI may still have occasional irregular periods and may even occasionally achieve a pregnancy. Symptoms of POI include irregular menses or amenorrhea, infertility, hypoestrogenic symptoms and decreased libido. POI may be caused by chromosomal defects such as mosaic Turner's syndrome, exposure to toxins (chemotherapy or radiation), autoimmunity, genetic factors (FMR1) and other unknown factors.
Recently, new promising approaches have emerged for infertility treatment in patients with POI, which are based on arousing the still available primordial follicle pool. It is supposed that these techniques activate dormant primordial follicles using a combination of mechanical signaling and biochemical factors. The hypothesis that mild local ovarian injury, such as ovarian puncture, which is a usual procedure in an IVF center with minimal side effects, might exert a similar favorable effect in women with POI arouses our curiosity.
Different groups have published case series of ovarian procedures, injecting substances in the ovaries (A-PRP) or ovarian biopsies / scratch in infertile patients with low ovarian reserve (LOR) or/and patients with POF. However, those studies were underpowered, including not enough number of cases, with variable inclusion criteria and reporting results with very low scientific evidence. Furthermore, the mechanical effect of injecting the ovary should be taken into consideration during the evaluation of these patients, yet it might improve the ovarian function as well.
There are no previous randomized controlled trials considering a procedure as ovarian puncture, which is easier and accessible at any fertility center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | The cortex of selected ovary will be punctured up to ten times. In the surgical report, the surgeon will state how many punctures have been done. |
| |
| Control | No intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ovarian puncture | Procedure | Egg collection |
| |
| Hormonal blood Test |
| Measure | Description | Time Frame |
|---|---|---|
| Follicle growth above 4 mm | One or more follicles evaluated by transvaginal ultrasound. Defined by number of follicles growing, quantitative variable. | 1 day |
| Anti-Müllerian hormone evaluation after intervention. | Anti-Müllerian hormone evaluation after intervention. | 1 day |
| Follicle-stimulating hormone evaluation after intervention. | Follicle-stimulating hormone evaluation after intervention. | 1 day |
| Luteinizing hormone evaluation after intervention. | Luteinizing hormone evaluation after intervention. | 1 day |
| Estradiol hormone evaluation after intervention. | Estradiol hormone evaluation after intervention. | 1 day |
| Progesterone hormone evaluation after intervention. | Progesterone hormone evaluation after intervention. | 1 day |
| Spontaneous menstruation. | Spontaneous menstruation. | 1 day |
| Arteria ovarica doppler results. | Arteria ovarica doppler results. Resistance index. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of follicles | Number of follicles | 1 day |
| Number of oocytes retrieved | Number of oocytes retrieved | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical pregnancy by blood test | pregnancy (yes or no) defined by a βhCG test of > 15IU | 12 weeks |
| Implantation rate (%) | defined by the number of gestational sacs/number of embryos transferred |
Inclusion Criteria:
Exclusion Criteria:
Adult women with primary or secondary infertility with a diagnosis of POI, willing to perform an IVF treatment
Adult women with primary or secondary infertility with a diagnosis of POI, willing to perform an IVF treatment
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| barbara Lawrenz, PhD | Contact | +97126528000 | 1108 | jonalyn.edades@artfertilityclinics.com |
| Jonalyn Edades | Contact | +97126528000 | 1122 | jonalyn.edades@artfertilityclinics.com |
| Name | Affiliation | Role |
|---|---|---|
| Laura Melado, PhD | ART Fertility Clinics LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ART Fertility Clinics LLC | Recruiting | Abu Dhabi | Abu Dhabi Emirate | 60202 | United Arab Emirates |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31376814 | Result | Ford EA, Beckett EL, Roman SD, McLaughlin EA, Sutherland JM. Advances in human primordial follicle activation and premature ovarian insufficiency. Reproduction. 2020 Jan;159(1):R15-R29. doi: 10.1530/REP-19-0201. | |
| 30541396 | Result | Zhang X, Han T, Yan L, Jiao X, Qin Y, Chen ZJ. Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency. Reprod Sci. 2019 Feb;26(2):207-213. doi: 10.1177/1933719118818906. Epub 2018 Dec 12. |
| Label | URL |
|---|---|
| Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment | View source |
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| ID | Term |
|---|---|
| D007247 | Infertility, Female |
| D016649 | Primary Ovarian Insufficiency |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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Blood sample
| Other |
AMH (ng/ml), FSH (IU/mL), E2(pg/mL), P4(ng/mL), LH (IU/mL) |
|
| Transvaginal ultrasound | Diagnostic Test | Doppler of arteria ovarica. Resistance index |
|
| 1 day |
| Fertilization rate | percentage of 2PN embryos per oocyte injected | 1 day |
| Blastulation rate | percentage of blastocysts per 2PN embryos | 1 day |
| Aneuploidy rate | percentage of aneuploid blastocysts per total blastocyst biopsied | 1 day |
| 4 weeks |
| Clinical pregnancy by ultrasound | defined by the ultrasonographic visualization of one or more gestational sacs, including ectopic pregnancies | 12 weeks |
| 27022685 | Result | Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol. 2016 Jun;28(3):217-22. doi: 10.1097/GCO.0000000000000268. |
| 21479340 | Result | Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011 May;105 Suppl 1:S13-33. doi: 10.1160/THS10-11-0720. Epub 2011 Apr 11. |
| 18480812 | Result | Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. |
| 20351977 | Result | Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1-9. |
| 30134239 | Result | Sfakianoudis K, Simopoulou M, Nitsos N, Rapani A, Pantou A, Vaxevanoglou T, Kokkali G, Koutsilieris M, Pantos K. A Case Series on Platelet-Rich Plasma Revolutionary Management of Poor Responder Patients. Gynecol Obstet Invest. 2019;84(1):99-106. doi: 10.1159/000491697. Epub 2018 Aug 22. |
| 29486615 | Result | 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. |
| 30796792 | Result | Sills ES, Li X, Rickers NS, Wood SH, Palermo GD. Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: First qualitative data. Neuro Endocrinol Lett. 2019 Jan;39(6):427-433. |
| 32195207 | Result | Sills ES, Rickers NS, Svid CS, Rickers JM, Wood SH. Normalized Ploidy Following 20 Consecutive Blastocysts with Chromosomal Error: Healthy 46, XY Pregnancy with IVF after Intraovarian Injection of Autologous Enriched Platelet-derived Growth Factors. Int J Mol Cell Med. 2019 Winter;8(1):84-90. doi: 10.22088/IJMCM.BUMS.8.1.84. Epub 2019 May 15. |
| 27008889 | Result | European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI; Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, Cifkova R, de Muinck Keizer-Schrama S, Hogervorst E, Janse F, Liao L, Vlaisavljevic V, Zillikens C, Vermeulen N. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016 May;31(5):926-37. doi: 10.1093/humrep/dew027. Epub 2016 Mar 22. |
| D000091662 | Genital Diseases |
| D007246 | Infertility |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |