Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve

Activation of Primordial Follicles Clinical Trial

Official title:

Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04608695
• Other study ID #: HU02
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: September 1, 2023

Study information

• Verified date: September 2022
• Source: Hacettepe University
• Contact: Sezcan Mumusoglu, Assoc. Prof.
• Phone: +905326404673
• Email: sezcanmumusoglu[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of women younger than 40 years old and 0.1% before 30 are affected. POI imposes a great challenge on women's reproductive and long-term health, such as infertility, amenorrhea, osteoporosis, and cardiovascular disease. Most patients already had impaired or complete loss of fecundity when diagnosed. Currently, no optimal regimen exists to ameliorate ovarian function. Typically, they end up with egg donation or adoption as an alternative way. Less severe form of POI is diminished ovarian reserve (DOR). Although lack of consensus according to Bologna criteria cut off for DOR was defined as (antral follicle count (AFC) <5-7 follicles or anti-Mullerian hormone (AMH) <0.5-1.1 ng/ml).

Previously it has been showed that 24% of women with POI had resumption of ovarian function and 4% resulted in baby births. These data indicates residual follicles are available in atrophic ovaries and have potential for development and even fertilization. In routine IVF practice 15% percent of patients have poor ovarian response to ovarian stimulation. Patients with DOR with a previous poor ovarian response (cycles cancelled or yielding ≤3 oocytes with a conventional protocol) might have benefit from the strategies increasing follicle activation and number of growing follicles and oocyte retrieved. Therefore, strategies enabling ovarian resumption predictable and follicle activation feasible are promising for POI/DOR treatment. Recently, In vitro Activation (IVA) approach has been proposed and live births have been achieved in patients with POI. Phosphatase and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase activators could activate AKT pathway and activate the dormant follicles. Ovarian fragmentation could lead to ovarian primary follicle growth by interfering with Hippo signaling pathway. Residual follicles in patients with POI could be activated to develop for egg retrieval by combination of mechanical and chemical stimulation.

In 2019, Zhang et al retrospectively analyzed the follicle development and pregnancy outcome in 80 POI patients after laparoscopic ovarian biopsy/scratch without using chemical agents as was the case in IVA. 11 (13.75%) patients presented with ovarian function resumption, three metaphases II oocytes were retrieved in 10 patients and two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. They concluded that the technique of ovarian biopsy/scratch without chemical activation could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI.

In patient with POI/DOR, activation of residual follicles is a promising option and further studies are warranted. Previous studies included laparoscopic surgery which may lead to possible surgical complications. Without using chemical agents and laparoscopic surgery, main object of this study is mechanical follicle activation with trans-vaginal ovarian needle puncture with 17 gauge oocyte pickup needle in IVF patients with DOR.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: September 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 40 Years

Eligibility

Inclusion Criteria:

• Patients with diminished ovarian reserve

• <3 oocytes collected in previous cycle (with anti-mullerian hormone <0.5 ng/mL and/or antral follicle count <5)

• Cycles stimulated with flexible antagonist protocol

• Cycles triggered with recombinant hCG

• Fresh transfer cycles

• Patients with <40 years of age

• BMI <30 kg/m2

Exclusion Criteria:

• Preimplantation genetic testing

• Azospermia

Related Conditions & MeSH terms

• Activation of Primordial Follicles

Intervention

Procedure:
• Ovarian puncture
One side ovary of each patient included in the study, will be punctured 10 times under trans-vaginal ultrasound guidance with 17 gauge ovarian pick up needle, 1 month before the scheduled IVF cycle. Control group will be the other side ovary for each patient. Number of = 14 mm follicle and collected oocytes will be compared.

Locations

Country	Name	City	State
Turkey	Hacettepe UniversityHacettepe University School of Medicine, Department of Ob/Gyn	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Hacettepe University

Country where clinical trial is conducted

Turkey, 

References & Publications (7)

Bachelot A, Nicolas C, Bidet M, Dulon J, Leban M, Golmard JL, Polak M, Touraine P. Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency. Clin Endocrinol (Oxf). 2017 Feb;86(2):223-228. doi: 10.1111/cen.13105. Epub 2016 Jun 14. — View Citation

Chen X, Chen SL, Ye DS, Liu YD, He YX, Tian XL, Xu LJ, Tao T. Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development. Reprod Biomed Online. 2016 Apr;32(4):427-33. doi: 10.1016/j.rbmo.2015.12.011. Epub 2016 Jan 14. — View Citation

De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010 Sep 11;376(9744):911-21. doi: 10.1016/S0140-6736(10)60355-8. Epub 2010 Aug 11. Review. — View Citation

Ferraretti AP, Gianaroli L. The Bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod. 2014 Sep;29(9):1842-5. doi: 10.1093/humrep/deu139. Epub 2014 Jul 9. — 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. Review. — View Citation

Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency - an update on recent advances in understanding and management. F1000Res. 2017 Nov 29;6:2069. doi: 10.12688/f1000research.11948.1. eCollection 2017. Review. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of =14 mm follicle	Number of =14 mm follicle on the trigger day	4 month after intervention as a response to ovarian stimulation
Primary	Antral follicle count	Antral follicle count	4 month after intervention on the second/third day of menstrual cycle
Secondary	Number of collected oocytes	Number of collected oocytes on the oocyte pick-up day	4 month after intervention as a response to ovarian stimulation