Clinical trial NCT03826888: Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders
Official title: Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders: Does it Matter?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anti-Mullerian Hormone Isoforms
Keywords: IVF
AMH isoforms
ovarian reserve test
poor response
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2019-02-01
Enrollment: 72
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infertile female undergoing ovarian stimulation

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: AMH serum levels
timeFrame: 1 day
Secondary outcomes:
measure: Inhibin B and ovarian reserve markers
timeFrame: 1 day
measure: AMH serum and AFC
timeFrame: 1 day
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: IVI Middle East Fertility Clinic
Study officials:
References:
citation: McLennan IS, Pankhurst MW. Anti-Mullerian 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.
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 Mullerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986 Jun 6;45(5):685-98. doi: 10.1016/0092-8674(86)90783-x.
citation: Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Mullerian duct syndrome. Hum Reprod Update. 2005 Jul-Aug;11(4):351-6. doi: 10.1093/humupd/dmi014. Epub 2005 May 5.
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.
citation: Pankhurst MW, Chong YH, McLennan IS. Enzyme-linked immunosorbent assay measurements of antimullerian 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.
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.
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 antimullerian hormone in women approaching menopause using sensitive antimullerian hormone enzyme-linked immunosorbent assays. Menopause. 2014 Dec;21(12):1277-86. doi: 10.1097/GME.0000000000000244.
citation: Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. Changes in serum antimullerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause. 2011 May;18(5):521-4. doi: 10.1097/gme.0b013e3181f8d9e0.
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.
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.
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.
citation: Koshy AK, Gudi A, Shah A, Bhide P, Timms P, Homburg R. Pregnancy prognosis in women with anti-Mullerian hormone below the tenth percentile. Gynecol Endocrinol. 2013 Jul;29(7):662-5. doi: 10.3109/09513590.2013.797395.
citation: Seifer DB, Tal O, Wantman E, Edul P, Baker VL. Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimullerian 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.
citation: 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.