Anti-Müllerian Hormone (AMH) Measured With Fully Automated Assay Versus AFC in the Prediction of Ovarian Response

Ovarian Response Clinical Trial

Official title:

Prospective, Observational, Multivariate Study to Evaluate the Best Predictor of Ovarian Response, Between AMH Measured With Fully Automated Assay and AFC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04168892
• Other study ID #: 01/MR/19
• Status: Completed
• Start date: September 20, 2019
• Est. completion date: January 31, 2023

Study information

• Verified date: January 2023
• Source: Andros Day Surgery Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The primary objective of this prospective, observational, multivariate study will be to compare the reliability of automated AMH (measured with Access AMH assay, Beckman-Coulter Diagnostics, USA) with that of antral follicle count (AFC) evaluated ultrasonographically always by the same operator and with the same ultrasound scanner, in terms of the number of oocytes recovered from oocyte sampling in couples subjected to in vitro fertilization.

Description:

Individual variability in ovarian response to a starting dose of gonadotropins is a well-known aspect during controlled ovarian stimulation (COS) and many efforts have been made for obtaining the personalization of the treatment, identifying different biomarkers that may predict the ovarian response such as age, basal Follicle Stimulating Hormone (FSH), AMH and antral follicle count (AFC). The number of oocytes retrieved is the main expression of ovarian response and it remains a relevant prognostic marker in women undergoing In Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) cycles. Consistent evidence shows that an optimal - rather than a maximal - oocyte yield is the preferred achievement after COS when fresh embryo transfer is scheduled. In fact, live birth rates steadily increase when an optimal number of oocytes is collected, whereas low response and hyper-response are associated with lower implantation rates, increased obstetrical risks and, at least when considering hyper response, increased risk of ovarian hyperstimulation syndrome (OHSS) in the fresh cycle. Among the different biomarkers, AMH and AFC seem to have the best performance in predicting ovarian response to exogenous FSH.

Nevertheless, until now, there is often discordance between the AMH level and AFC in clinical practice. In cases of discordance, which indicator should be chosen to individualize the starting dose of gonadotropins? Until now, no direct comparison of the new automated immunoassay of AMH with AFC has been carried out considering the number of retrieved oocytes as primary endpoint.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: January 31, 2023
• Est. primary completion date: January 31, 2023
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

BMI between 18 and 30 kg/m2, basal serum day 3 FSH = 15 IU/l, normal regular menstrual cycles, ranging from 25 to 33 days in length, normal thyroid-stimulating hormone (TSH) and prolactin levels, normal uterine cavity as assessed by hysteroscopy or sonohysterography or three-dimensional ultrasound and presence of both ovaries.

Exclusion Criteria:

irregular menstrual cycles, severe endometriosis, defined as stage III-IV of the American Society for Reproductive Medicine (ASRM) revised classification, previous ovarian surgery, presence of ovarian cysts, polycystic ovary syndrome, use of hormonal contraception in the previous 3 months and use of gonadotrophins in the previous 3 months, any known metabolic or endocrinological disease

Related Conditions & MeSH terms

• Ovarian Response

Intervention

Drug:
• 150 IU of HMG in patients with age = 35 years
The use of a different starting dose, based on the female age, derives from the necessity to control the effect of a variable starting dose on the primary outcome.
• 225 IU of HMG in patients with age > 35 years
The use of a different starting dose, based on the female age, derives from the necessity to control the effect of a variable starting dose on the primary outcome.

Locations

Country	Name	City	State
Italy	ANDROS Day Surgery Clinic, Reproductive Medicine Unit	Palermo

Sponsors (1)

Lead Sponsor	Collaborator
Andros Day Surgery Clinic

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Allegra A, Marino A, Volpes A, Coffaro F, Scaglione P, Gullo S, La Marca A. A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles. Reprod Biomed Online. 2017 Apr;34(4):429-438. doi: 10.1016/j.rbmo.2017.01.012. Epub 2017 Jan 23. — View Citation

Andersen AN, Witjes H, Gordon K, Mannaerts B; Xpect investigators. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod. 2011 Dec;26(12):3413-23. doi: 10.1093/humrep/der318. Epub 2011 Sep 27. — View Citation

Pearson K, Long M, Prasad J, Wu YY, Bonifacio M. Assessment of the Access AMH assay as an automated, high-performance replacement for the AMH Generation II manual ELISA. Reprod Biol Endocrinol. 2016 Feb 16;14:8. doi: 10.1186/s12958-016-0143-3. — View Citation

van Tilborg TC, Oudshoorn SC, Eijkemans MJC, Mochtar MH, van Golde RJT, Hoek A, Kuchenbecker WKH, Fleischer K, de Bruin JP, Groen H, van Wely M, Lambalk CB, Laven JSE, Mol BWJ, Broekmans FJM, Torrance HL; OPTIMIST study group. Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis. Hum Reprod. 2017 Dec 1;32(12):2485-2495. doi: 10.1093/humrep/dex321. — View Citation

Zhang Y, Xu Y, Xue Q, Shang J, Yang X, Shan X, Kuai Y, Wang S, Zeng C. Discordance between antral follicle counts and anti-Mullerian hormone levels in women undergoing in vitro fertilization. Reprod Biol Endocrinol. 2019 Jul 4;17(1):51. doi: 10.1186/s12958-019-0497-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of oocytes retrieved	The number of oocytes collected after oocyte retrieval	13-15 days starting from the first day of the cycle
Secondary	Cumulative clinical pregnancy rate per patient	The number of clinical pregnancies (gestational sacs with a fetal heartbeat detected at ultrasound 28-32 days after oocyte retrieval) obtained by fresh and frozen embryo transfers per each patient.	28-32 days after the oocyte retrieval