Ovarian ResponseNCT04168892
Anti-Müllerian Hormone (AMH) Measured With Fully Automated Assay Versus AFC in the Prediction of Ovarian Response
An observational study of Ovarian Response, run by Andros Day Surgery Clinic at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Ovarian Response
- What is being tested?
- 150 IU of HMG in patients with age ≤ 35 years and 225 IU of HMG in patients with age > 35 years
- Type of treatment
- Injection or infusion
- How many people
- 160 participants
- Where
- 1 siteItaly
- Study dates
- 20 Sep 2019to 31 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Adult
Study population: This trial will involve couples attending their first IVF/ICSI cycle.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
ANDROS Day Surgery Clinic, Reproductive Medicine Unit
Palermo, 90144
About this study
Official title: Prospective, Observational, Multivariate Study to Evaluate the Best Predictor of Ovarian Response, Between AMH Measured With Fully Automated Assay and AFC
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.
Read the detailed 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.
- Conditions
- Ovarian Response
- Being tested
- 150 IU of HMG in patients with age ≤ 35 years, 225 IU of HMG in patients with age > 35 years
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
150 IU of HMG in patients with age ≤ 35 yearsDrug
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 yearsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Female age ≤ 35 years: 150 IU of HMG | For controlling the effect of the starting dose on the number of retrieved oocytes, the patients will be divided in two groups based on their age. For the patients with an age ≤ 35 years, COS will be carried out by daily injections of 150 IU of Human Menopausal Gonadotropins (HMG) and will be started on the 3rd day of the cycle. The starting dose will be maintained for the first 5 days and followed by individual dose-adjustments according to the patient's follicular response. The pituitary suppression will be obtained by the administration of the Gonadotropin-releasing Hormone (GnRH) antagonist ganirelix (0.25 mg per day), starting from the 6th day of the ovarian stimulation until the day of the induction of the final oocyte maturation. Highly purified urinary human Chorionic Gonadotropin (hCG) 10.000 IU will be used to induce final oocyte maturation. In case of OHSS risk, the final oocyte maturation will be obtained by using a GnRH agonist (buserelin acetate), 0.5 mg subcutaneously. Receives: Drug: 150 IU of HMG in patients with age ≤ 35 years | |
| Female age >35 years: 225 IU of HMG | In order to control the effect of the starting dose on the number of retrieved oocytes, the patients will be divided in two groups based on their age. For the patients with an age >35 years, the controlled ovarian stimulation will be carried out by daily injections of 225 IU of HMG and will be started on the 3rd day of the cycle. The starting dose will be maintained for the first 5 days and followed by individual dose-adjustments according to the patient's follicular response. The pituitary suppression will be obtained by the administration of the GnRH antagonist ganirelix (0.25 mg per day), starting from the 6th day of the ovarian stimulation until the day of the induction of the final oocyte maturation. Highly purified urinary hCG 10.000 IU will be used to induce final oocyte maturation. In case of OHSS risk, the final oocyte maturation will be obtained by using a GnRH agonist (buserelin acetate), 0.5 mg subcutaneously. Receives: Drug: 225 IU of HMG in patients with age > 35 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of oocytes retrieved
The number of oocytes collected after oocyte retrieval
Measured: 13-15 days starting from the first day of the cycle
Secondary outcomes (1)
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.
Measured: 28-32 days after the oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2019
- Study start20 Sep 2019
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Ovarian ResponseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andros Day Surgery Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04168892
- Sponsor's protocol ID
- 01/MR/19
- Status last verified
- Jan 2023
- First submitted
- 16 Nov 2019
- Last updated
- 1 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31272468Pearson 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.
PubMed 26879773Allegra 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.
PubMed 28189417van 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.
PubMed 29121350Andersen 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.
PubMed 21954280
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Observational, Multivariate Study to Evaluate the Best Predictor of Ovarian Response, Between AMH Measured With Fully Automated Assay and AFC
- ClinicalTrials.gov ID
- NCT04168892
- Acronym / sponsor ID
- 01/MR/19
- Conditions
- Ovarian Response
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Andros Day Surgery ClinicUniversity, hospital or other
- Study start
- 20 Sep 2019 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 19 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Female age ≤ 35 years: 150 IU of HMG | – | Drug: 150 IU of HMG in patients with age ≤ 35 yearsFor controlling the effect of the starting dose on the number of retrieved oocytes, the patients will be divided in two groups based on their age. For the patients with an age ≤ 35 years, COS will be carried out by daily injections of 150 IU of Human Menopausal Gonadotropins (HMG) and will be started on the 3rd day of the cycle. The starting dose will be maintained for the first 5 days and followed by individual dose-adjustments according to the patient's follicular response. The pituitary suppression will be obtained by the administration of the Gonadotropin-releasing Hormone (GnRH) antagonist ganirelix (0.25 mg per day), starting from the 6th day of the ovarian stimulation until the day of the induction of the final oocyte maturation. Highly purified urinary human Chorionic Gonadotropin (hCG) 10.000 IU will be used to induce final oocyte maturation. In case of OHSS risk, the final oocyte maturation will be obtained by using a GnRH agonist (buserelin acetate), 0.5 mg subcutaneously. |
| Female age >35 years: 225 IU of HMG | – | Drug: 225 IU of HMG in patients with age > 35 yearsIn order to control the effect of the starting dose on the number of retrieved oocytes, the patients will be divided in two groups based on their age. For the patients with an age >35 years, the controlled ovarian stimulation will be carried out by daily injections of 225 IU of HMG and will be started on the 3rd day of the cycle. The starting dose will be maintained for the first 5 days and followed by individual dose-adjustments according to the patient's follicular response. The pituitary suppression will be obtained by the administration of the GnRH antagonist ganirelix (0.25 mg per day), starting from the 6th day of the ovarian stimulation until the day of the induction of the final oocyte maturation. Highly purified urinary hCG 10.000 IU will be used to induce final oocyte maturation. In case of OHSS risk, the final oocyte maturation will be obtained by using a GnRH agonist (buserelin acetate), 0.5 mg subcutaneously. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Age groups
- Adult
- Study population
- This trial will involve couples attending their first IVF/ICSI cycle.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 150 IU of HMG in patients with age ≤ 35 yearsThe 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. | Drug | Female age ≤ 35 years: 150 IU of HMG |
| 225 IU of HMG in patients with age > 35 yearsThe 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. | Drug | Female age >35 years: 225 IU of HMG |
Primary outcome
Number of oocytes retrieved
Time frame: 13-15 days starting from the first day of the cycle
The number of oocytes collected after oocyte retrieval
1 secondary outcome
Cumulative clinical pregnancy rate per patient
Time frame: 28-32 days after the oocyte retrieval
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
- Background: PubMed 31272468Zhang 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.
- Background: PubMed 26879773Pearson 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.
- Background: PubMed 28189417Allegra 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.
- Background: PubMed 29121350van 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.
- Background: PubMed 21954280Andersen 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.
- Individual participant dataSharing planned: No
Related trials for Ovarian Response
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
RecruitingObservational study
Proteomic and Biological Characterisation of Plasma for the Study of Changes Following Ovarian Reactivation Treatment
Poor Ovarian Response, Ovarian Reactivation
Active, not recruitingPhase 4
Metabolic Responses of Metformin and Genetic Polymorphisms of SLC22A1 Gene in PCOS
Polycystic Ovary Syndrome, Metformin
RecruitingPhase 1
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Associated With Systemic Chemotherapy in Women With Advanced Ovarian Cancer
Metastatic Ovarian Carcinoma, Peritoneal Carcinomatosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ovarian Response, run by Andros Day Surgery Clinic at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of oocytes retrieved (time frame: 13-15 days starting from the first day of the cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04168892, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.