Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders

Anti-Mullerian Hormone Isoforms Clinical Trial

Official title:

Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders: Does it Matter?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03826888
• Other study ID #: 1807-ABU-055-LM
• Status: Completed
• Start date: February 25, 2019
• Est. completion date: May 30, 2022

Study information

• Verified date: August 2022
• Source: ART Fertility Clinics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study wants to evaluate significant clinical impact of different AMH isoforms in serum can be present or absent in expected poor responder participants. The specific AMH isoforms could therefore be measured in expected poor responder participants in order to obtain a more realistic clinical picture and therefore be able to give proper information to the participants and selection of medication dose for ovarian stimulation.

Description:

The study has a prospective observational multicentric design and the investigators aim to investigate the presence of AMH isoforms and the levels of Inhibin B in serum among a population of participants with low ovarian reserve (AMH blood test below 1.1 ng/ml). Transvaginal scan for AFC and blood drawn from participants will be obtained on day 2-3 of menstrual period. The serum will be divided for AMH analysis using different assays: Elecsys Cobas assay for AMH and AnshLabs AMH isoforms specific assays (picoAMH 24/32 Pro-Mature, 24/37 Midpro-Midpro, 17/15 Mature-Mature and 10/24 Pro-Midpro) and AnshLabs Inhibin B ELISA. Clinically it is not uncommon to see a discrepancy between the AFC count and the levels of AMH; this could be potentially explained by the presence of different AMH isoforms not measured with conventional commercial assays. Also, the evaluation of Inhibin B may be helpful for ovarian reserve assessment. Quantitation of specific Isoforms of AMH by different ELISA methods will investigate a possible relationship(s) between specific isoforms of AMH and poor responders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: May 30, 2022
• Est. primary completion date: December 23, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• pre-treatment AMH recording below 1.1 ng/ml on day 2 or 3 of the menstrual cycle.
• BMI between 18 and 30 kg/m2.

Exclusion Criteria:

• Pregnancy.
• Breastfeeding.
• Intake of oral contraceptive pills or steroids for the last two menstrual cycles.
• Endometriosis.
• Previous surgical intervention, which could have an impact on the ovarian reserve, e.g. ovarian cyst removal, removal of one or both tubes, tubal ligation for sterilisation

Related Conditions & MeSH terms

• Anti-Mullerian Hormone Isoforms

Locations

Country	Name	City	State
United Arab Emirates	IVI Middle East Fertility Clinic	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (14)

Broekmans FJ, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F. The antral follicle count: practical recommendations for better standardization. Fertil Steril. 2010 Aug;94(3):1044-51. doi: 10.1016/j.fertnstert.2009.04.040. Epub 2009 Jul 8. Review. — View Citation

Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP, et al. Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986 Jun 6;45(5):685-98. — View Citation

Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19. — View Citation

Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E. Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod. 2008 Jun;23(6):1359-65. doi: 10.1093/humrep/den108. Epub 2008 Apr 2. — View Citation

Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Müllerian duct syndrome. Hum Reprod Update. 2005 Jul-Aug;11(4):351-6. Epub 2005 May 5. Review. — View Citation

Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A. Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One. 2013 Dec 16;8(12):e81629. doi: 10.1371/journal.pone.0081629. eCollection 2013. — View Citation

Koshy AK, Gudi A, Shah A, Bhide P, Timms P, Homburg R. Pregnancy prognosis in women with anti-Müllerian hormone below the tenth percentile. Gynecol Endocrinol. 2013 Jul;29(7):662-5. doi: 10.3109/09513590.2013.797395. — View Citation

McLennan IS, Pankhurst MW. Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions. J Endocrinol. 2015 Sep;226(3):R45-57. doi: 10.1530/JOE-15-0206. Epub 2015 Jul 10. Review. — View Citation

Pankhurst MW, Chong YH, McLennan IS. Enzyme-linked immunosorbent assay measurements of antimüllerian hormone (AMH) in human blood are a composite of the uncleaved and bioactive cleaved forms of AMH. Fertil Steril. 2014 Mar;101(3):846-50. doi: 10.1016/j.fertnstert.2013.12.009. Epub 2014 Jan 11. — View Citation

Pankhurst MW, Clark CA, Zarek J, Laskin CA, McLennan IS. Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post-Partum: A Longitudinal Study. PLoS One. 2016 Sep 9;11(9):e0162509. doi: 10.1371/journal.pone.0162509. eCollection 2016. — View Citation

Pankhurst MW, McLennan IS. Human blood contains both the uncleaved precursor of anti-Mullerian hormone and a complex of the NH2- and COOH-terminal peptides. Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1241-7. doi: 10.1152/ajpendo.00395.2013. Epub 2013 Sep 17. — View Citation

Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. Changes in serum antimüllerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause. 2011 May;18(5):521-4. doi: 10.1097/gme.0b013e3181f8d9e0. — View Citation

Robertson DM, Kumar A, Kalra B, Shah S, Pruysers E, Vanden Brink H, Chizen D, Visser JA, Themmen AP, Baerwald A. Detection of serum antimüllerian hormone in women approaching menopause using sensitive antimüllerian hormone enzyme-linked immunosorbent assays. Menopause. 2014 Dec;21(12):1277-86. doi: 10.1097/GME.0000000000000244. — View Citation

Seifer DB, Tal O, Wantman E, Edul P, Baker VL. Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimüllerian hormone: a multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013. Fertil Steril. 2016 Feb;105(2):385-93.e3. doi: 10.1016/j.fertnstert.2015.10.004. Epub 2015 Oct 26. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AMH serum levels	Differences in AMH serum levels due to the presence of different AMH isoforms when results are compared with AMH measurement in blood performed with Elecsys Cobas AMH assay.	1 day
Secondary	Inhibin B and ovarian reserve markers	Correlation between Inhibin B and ovarian reserve markers (AMH serum levels and AFC)	1 day
Secondary	AMH serum and AFC	Correlation between AMH serum levels (measured with different ELISA tests) and AFC.	1 day