Is There A Role For Mechanical Stimulation In Ovarian Follicular Activation?

Infertility, Female Clinical Trial

Official title:

Is There A Role For Mechanical Stimulation In Ovarian Follicular Activation? A Randomized Control Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04390308
• Other study ID #: 2004-ABU-005-LM
• Status: Not yet recruiting
• Start date: November 23, 2023
• Est. completion date: July 31, 2024

Study information

• Verified date: November 2023
• Source: ART Fertility Clinics LLC
• Contact: Barbara Lawrenz, PhD
• Phone: +97126528000
• Email: shieryl.digma[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: July 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Signed and dated informed consent
• Women 40 years of age and younger with documented primary ovarian insufficiency (12).
• Normal Karyotype
• BMI </= 35 kg/m2
• Oligo/amenorrhea for at least 4 months
• FSH > 25 IU/mL
• AMH </= 0,1 ng/ml
• No evidence of follicles > 4mm
• Must have two ovaries of approximately equal volume.
• Willingness to undergo further fertility treatment, including IVF if there is evidence of response
• A transvaginal scan including Doppler for arteria ovarica will be performed previously to the surgical procedure.

Exclusion Criteria:

• Premature ovarian failure due to a genetic origin, such as Turner's Syndrome or chromosomal abnormality.
• Oncological diseases (specially, skeletal system and blood).
• Autoimmune diseases, for example, lupus erythematosus, etc.
• Previous treatments including radiotherapy or chemotherapy.
• Other conditions not suitable for surgical procedures and/or anesthesia.
• Anticoagulant or antiaggregant treatment.
• Acute and chronic infectious diseases.
• Active substance abuse or dependence.
• Major Mental health disorder.

Related Conditions & MeSH terms

• Infertility
• Infertility, Female
• IVF
• Menopause, Premature
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Procedure:
• Ovarian puncture
Egg collection

Other:
• Hormonal blood Test
AMH (ng/ml), FSH (IU/mL), E2(pg/mL), P4(ng/mL), LH (IU/mL)

Diagnostic Test:
• Transvaginal ultrasound
Doppler of arteria ovarica. Resistance index

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (11)

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, V — View Citation

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. — View Citation

Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. — View Citation

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. — View Citation

Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1-9. — View Citation

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. — View Citation

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: 10.1 — View Citation

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. — 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: 10.1080/095 — View Citation

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 — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical pregnancy by blood test	pregnancy (yes or no) defined by a ßhCG test of > 15IU	12 weeks
Other	Implantation rate (%)	defined by the number of gestational sacs/number of embryos transferred	4 weeks
Other	Clinical pregnancy by ultrasound	defined by the ultrasonographic visualization of one or more gestational sacs, including ectopic pregnancies	12 weeks
Primary	Follicle growth above 4 mm	One or more follicles evaluated by transvaginal ultrasound. Defined by number of follicles growing, quantitative variable.	1 day
Primary	Anti-Müllerian hormone evaluation after intervention.	Anti-Müllerian hormone evaluation after intervention.	1 day
Primary	Follicle-stimulating hormone evaluation after intervention.	Follicle-stimulating hormone evaluation after intervention.	1 day
Primary	Luteinizing hormone evaluation after intervention.	Luteinizing hormone evaluation after intervention.	1 day
Primary	Estradiol hormone evaluation after intervention.	Estradiol hormone evaluation after intervention.	1 day
Primary	Progesterone hormone evaluation after intervention.	Progesterone hormone evaluation after intervention.	1 day
Primary	Spontaneous menstruation.	Spontaneous menstruation.	1 day
Primary	Arteria ovarica doppler results.	Arteria ovarica doppler results. Resistance index.	1 day
Secondary	Number of follicles	Number of follicles	1 day
Secondary	Number of oocytes retrieved	Number of oocytes retrieved	1 day
Secondary	Fertilization rate	percentage of 2PN embryos per oocyte injected	1 day
Secondary	Blastulation rate	percentage of blastocysts per 2PN embryos	1 day
Secondary	Aneuploidy rate	percentage of aneuploid blastocysts per total blastocyst biopsied	1 day

External Links

•   Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment