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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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.

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Other: conventional ovarian stimulation
* Other: individualized ovarian stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: women with in vitro fertilization treatment indication Exclusion Criteria: none

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional ovarian stimulation<br>women whose protocol of ovarian stimulation was based on age, ovarian size and previous treatment | Other: conventional ovarian stimulation<br>* 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.<br>|
| Active Comparator: individualized ovarian stimulation<br>women whose protocol of ovarian stimulation was based on anti-mullerian hormone | Other: individualized ovarian stimulation<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
In Vitro Fertilization, ovulation induction, anti-mullerian hormone