Is the AMH Intrafollicular Level a Predictor of the Ploidy Status of the Blastocyst?

Infertility Clinical Trial

Official title:

Is the AMH Intrafollicular Level a Predictor of the Ploidy Status of the Blastocyst? A Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05837325
• Other study ID #: 2212-ABU-015-LM
• Status: Recruiting
• Start date: May 23, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: ART Fertility Clinics LLC
• Contact: Barbara Lawrenz, PhD
• Phone: 0097126528000
• Email: barbara.lawrenz[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To investigate, whether on the day of egg retrieval, after ovarian stimulation for ICSI (intracytoplasmic sperm injection), there is a correlation between the intrafollicular AMH (Anti-Müllerian hormone) levels and the ploidy status of the blastocyst.

Description:

In clinical practice, AMH is used as a diagnostic and/or prognostic marker in women in association with ovulation induction and in various pathophysiological conditions. This study looks to investigate if the hormonal environment that surrounds an oocyte has an impact on the ploidy status of the blastocyst. Nowadays, using NGS (Next Generation Sequencing) platform for analysis of 23 pairs of chromosomes for Preimplantation Genetic Testing on blastocysts, the ploidy status of the embryo is more adequately assessed. Furthermore, embryo culture to blastocyst will provide further information about embryo quality and possibilities of implantation.

To have complete information between the serum hormones, follicular hormones, embryo development and ploidy will provide to clinicians, embryologist and patients further information on embryo selection and adequate ovarian stimulation protocols.

The database will be exported from the clinical information manager, VRepro, to a table in excel format through a database-based query system. The exported data will be duly codified to protect the clinical and personal information of the participants. Prior to the statistical study, an exploratory data analysis will be carried out to review the quality of the information extracted.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2024
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• At least one follicle from each ovary at day of trigger

• Age from 18 to 40 years old

• Normal menstrual cycle of 25-35 days

• Poor, normal and high response will be included

• First follicle punctured from each ovary will be consider for inclusion: if the COC (Cumulus Oocyte Complex) is present in clear FF (Follicular fluid), the FF will be collected separately for further analysis and the oocyte included in the study

Exclusion Criteria:

• Very hematic follicular fluid

• If the COC is not found in the follicular fluid

• Azoospermia

• Known chromosomal abnormalities

• Severe OAT (Oligoasthenoteratozoospermia)

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

Procedure:
• Oocyte Pick Up - Out of Study
Aspiration of follicles. search for the oocyte(s) All oocytes are grouped in one dish.
• Denudation - Out of Study
All oocytes are denuded together. Maturational stages are recorded.
• ICSI
One oocyte injected at a time.
• Culture
One embryo per culture drop. Individual follow-up of the embryo development.

Genetic:
• Biopsy
One embryo per culture drop.

Procedure:
• Vitrification
One embryo per vitrification straw.
• OPU - Study Group
Measure the size of the follicle and aspirate only one follicle and flush. The needle before moving to the second ovary. Oocyte included in the study will be cultured separately (each ovary separately too).
• Denudation - Study Group
Oocyte included in the study will be denuded separately. Maturational stages are recorded per follicle.

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 (7)

Calzada M, Lopez N, Noguera JA, Mendiola J, Hernandez AI, Corbalan S, Sanchez M, Torres AM. AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome. J Obstet Gynaecol. 2019 Nov;39(8):1130-1136. doi: 10.1080/01443615.2019.1587604. Epub 2019 Jun 17. — View Citation

Capkin SI, Ozyer S, Karayalcin R, Moraloglu O, Ozcan S, Ugur M. Serum and follicular fluid Anti-Mullerian hormone concentrations at the time of follicle puncture and reproductive outcome. J Turk Ger Gynecol Assoc. 2012 Mar 1;13(1):21-6. doi: 10.5152/jtgga.2011.71. eCollection 2012. — View Citation

Devroey P, Aboulghar M, Garcia-Velasco J, Griesinger G, Humaidan P, Kolibianakis E, Ledger W, Tomas C, Fauser BC. Improving the patient's experience of IVF/ICSI: a proposal for an ovarian stimulation protocol with GnRH antagonist co-treatment. Hum Reprod. 2009 Apr;24(4):764-74. doi: 10.1093/humrep/den468. Epub 2009 Jan 19. — 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

Hammoud I, Vialard F, Bergere M, Albert M, Gomes DM, Adler M, Malagrida L, Bailly M, Wainer R, Selva J. Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy. J Assist Reprod Genet. 2012 Oct;29(10):1123-34. doi: 10.1007/s10815-012-9841-8. Epub 2012 Aug 14. — View Citation

Hattori Y, Sato T, Okada H, Saito C, Sugiura-Ogasawara M. Comparison of follicular fluid and serum anti-Mullerian hormone levels as predictors of the outcome of assisted reproductive treatment. Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):252-6. doi: 10.1016/j.ejogrb.2013.03.021. Epub 2013 Apr 25. — View Citation

Melado Vidales L, Fernandez-Nistal A, Martinez Fernandez V, Verdu Merino V, Bruna Catalan I, Bajo Arenas JM. Anti-Mullerian hormone levels to predict oocyte maturity and embryo quality during controlled ovarian hyperstimulation. Minerva Ginecol. 2017 Jun;69(3):225-232. doi: 10.23736/S0026-4784.16.03958-7. Epub 2016 Jun 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oocyte maturity	Calculated as percentage transformation of an oocyte from prophase I to metaphase II	1 day
Primary	Fertilization	Percentage of mature oocytes - metaphase II (MII) that become 2 pronucleii embryos (2PN)	1 day
Primary	Blastulation	Ability of the embryo to form a cavity (=to blastulate) 114-118 hours post ICSI. Number of blastocysts divided by the number of 2PN	1 day
Primary	Blastocyst quality	Four Embryo Quality Scores (EQ1, 2, 3, 4) based on the expansion stage of the blastocyst, the grade of the inner cell mass and the grade of the trophectoderm.	6 days
Primary	Ploidy status	Determined after biopsy of trophectoderm cells, taken from the blastocyst on day 5, 6 or 7 from development	14 days
Primary	Mitochondria status	Measured as mtDNA ratio, the ratio of mitochondrial DNA (mtDNA) read counts to autosomal (chromosome 1-22) DNA read counts	14 days
Secondary	AMH in the follicular fluid.	To evaluate if there is an association between the levels of serum AMH on day 2-3 of the stimulation, AMH day of OPU and the intra-follicular AMH.	1 day
Secondary	FSH in the follicular fluid.	To evaluate if there is an association between serum FSH on day 2-3 of the stimulation, serum FSH day of OPU and the intra-follicular FSH.	1 day
Secondary	LH in the follicular fluid.	To evaluate if there is an association between serum LH on day 2-3 of the stimulation, serum LH day of OPU and the intra-follicular LH.	1 day
Secondary	E2 in the follicular fluid.	To evaluate if there is an association between serum E2 on day 2-3 of the stimulation, serum E2 day of OPU and the intra-follicular E2.	1 day
Secondary	P4 in the follicular fluid.	To evaluate if there is an association between serum P4 on day 2-3 of the stimulation, serum P4 day of OPU and the intra-follicular P4.	1 day
Secondary	Inhibin B in the follicular fluid.	To evaluate if there is an association between serum Inhibin B on day 2-3 of the stimulation, serum Inhibin B day of OPU and the intra-follicular Inhibin B.	1 day
Secondary	AMH in serum day of OPU	To evaluate if there is an association between the levels of serum AMH on day 2-3 of the stimulation, AMH day of OPU and the intra-follicular AMH.	1 day
Secondary	FSH in serum day of OPU	To evaluate if there is an association between serum FSH on day 2-3 of the stimulation, serum FSH day of OPU and the intra-follicular FSH.	1 day
Secondary	LH in serum day of OPU	To evaluate if there is an association between serum LH on day 2-3 of the stimulation, serum LH day of OPU and the intra-follicular LH.	1 day
Secondary	E2 in serum day of OPU	To evaluate if there is an association between serum E2 on day 2-3 of the stimulation, serum E2 day of OPU and the intra-follicular E2.	1 day
Secondary	P4 in serum day of OPU	To evaluate if there is an association between serum P4 on day 2-3 of the stimulation, serum P4 day of OPU and the intra-follicular P4.	1 day
Secondary	Inhibin B in serum day of OPU	To evaluate if there is an association between serum Inhibin B on day 2-3 of the stimulation, serum Inhibin B day of OPU and the intra-follicular Inhibin B.	1 day
Secondary	AMH in serum day of day 2/3 of stimulation.	To evaluate if there is an association between the levels of serum AMH on day 2-3 of the stimulation, AMH day of OPU and the intra-follicular AMH.	1 day
Secondary	FSH in serum day of day 2/3 of stimulation.	To evaluate if there is an association between serum FSH on day 2-3 of the stimulation, serum FSH day of OPU and the intra-follicular FSH.	1 day
Secondary	LH in serum day of day 2/3 of stimulation.	To evaluate if there is an association between serum LH on day 2-3 of the stimulation, serum LH day of OPU and the intra-follicular LH.	1 day
Secondary	E2 in serum day of day 2/3 of stimulation.	To evaluate if there is an association between serum E2 on day 2-3 of the stimulation, serum E2 day of OPU and the intra-follicular E2.	1 day
Secondary	P4 in serum day of day 2/3 of stimulation.	To evaluate if there is an association between serum P4 on day 2-3 of the stimulation, serum P4 day of OPU and the intra-follicular P4.	1 day
Secondary	Inhibin B in serum day of day 2/3 of stimulation.	To evaluate if there is an association between serum Inhibin B on day 2-3 of the stimulation, serum Inhibin B day of OPU and the intra-follicular Inhibin B.	1 day