Individualization of Ovarian Stimulation Using AMH Maximizes the Benefits and Minimizes Complications and Risks

Individualization of Controlled Ovarian Stimulation Using Anti-mullerian Hormone as a Biomarker of Ovarian Response Maximizes the Beneficial Effects of Treatment and Minimizes Complications and Risks.

The purpose oh the study is to determine the usefulness of anti-Mullerian hormone (AMH) to identify women at risk of excessive and poor response in controlled ovarian stimulation (COS) for in vitro fertilization (IVF), and the clinical impact of applying individualized COS strategies in these subsets of patients.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Other: conventional ovarian stimulation; Other: individualized ovarian stimulation

Detailed Description

A group of 130 women undergoing conventional COS after pituitary down-regulation for IVF will be studied to determine the best cut-off points of AMH, using receiver operating characteristic (ROC) analysis, to discriminate excessive (≥20 oocytes retrieved) and poor response (≤4 oocytes retrieved). The inclusion criteria is any patient with indication of IVF treatment. Subsequently, a different group of 120 women (with the same criteria) will be assessed using AMH before starting COS, and treatment strategy will be individualized according to AMH results (iCOS). Mild stimulation using daily doses (112.5 to 150 IU) of recombinant follicle stimulation hormone (rec-hFSH) or rec-hFSH combined with recombinant luteinizing hormone (LH) supplementation (375 IU total daily dose) will be given to patients identified as at risk of excessive and poor response, respectively. It will evaluated: number of oocytes, clinical pregnancy rates (defined as fetal heartbeat on ultrasound performed 4 weeks after the transfer of embryos) and occurrence of Ovarian hyperstimulation syndrome). Outcomes will be compared between the groups who received conventional and iCOS using chi-square and Fisher exact tests.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil, 13075-460
      • Androfert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• women with in vitro fertilization treatment indication

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: conventional ovarian stimulation; women whose protocol of ovarian stimulation was based on age, ovarian size and previous treatment	Other: conventional ovarian stimulation; a protocol of ovarian stimulation with recombinant FSH with dose according to age, ovarian size and previous treatment. In patients alder than 35, recombinant LH was added to ovarian stimulation.
Active Comparator: individualized ovarian stimulation; women whose protocol of ovarian stimulation was based on anti-mullerian hormone	Other: individualized ovarian stimulation; After defining cut-off points of anti-mullerian hormone, using a ROC analysis, to discriminate excessive (≥20 oocytes retrieved) and poor response (≤4 oocytes retrieved), a individualized protocol was defined.Mild stimulation using daily doses (112.5 to 150 IU) of recombinant FSH or recombinant FSH combined with recombinant LH supplementation (375 IU total daily dose) were given to patients identified as at risk of excessive and poor response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of oocytes retrieved	number of oocyte retrieved classified as: poor response: ≤4 oocytes normal response: 5 - 19 oocytes excessive response: ≥20 oocytes	1 day (on the day of oocyte retrieval)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy rate	presence of fetal heartbeat on transvaginal ultrasound	4 weeks after embryo transfer
occurrence of ovarian hyperstimulation syndrome	presence of hyperstimulation syndrome during follow up after oocyte retrieval	4 weeks after embryo transfer
cancellation	cancellation of the cycle because of no ovarian response (no follicles >14 mm during ovarian stimulation)	on the 8th day of ovarian stimulation

Collaborators and Investigators

• Sponsor: ANDROFERT - Clinica de Andrologia e Reproducao Humana
• Investigators: Principal Investigator: Rogerio BF Leao, MD, ANDROFERT - Clinica de Andrologia e Reproducao Humana; Study Director: Sandro C Esteves, PhD, ANDROFERT - Clinica de Andrologia e Reproducao Humana; Study Chair: Fabiana Y Nakano, ANDROFERT - Clinica de Andrologia e Reproducao Humana

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 26, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: In Vitro Fertilization; anti-mullerian hormone; ovulation induction
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: ANDRO-03-12