AMH and Dosing Regimens for Initial IVF Stimulation Protocols

April 10, 2018 updated by: Reproductive Specialists of New York
This is a research study on a hormone in women called anti-mullerian hormone (AMH) an indicator of the amount of egg reserve in the ovaries. The research involves a blood draw to determine the AMH level. This knowledge will help the investigators decide a dosage of gonadotropins, the hormones used to stimulate the production of more than one egg for use in an in vitro fertilization (IVF) cycle. The amount of gonadotropin given has to be tailored to each individual participant. The investigators can use information about the participant and the hormone levels to determine this dosage and the chances of becoming pregnant as a result of IVF treatment. The reason the investigators are doing this research is to find out if basing the gonadotropin dosage solely on the participant's AMH level will give the investigators a better result than the previous method based on age and other hormone levels.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background / Rationale Anti-Müllerian Hormone (AMH) has been established as a valuable biomarker of ovarian reserve. It is a glycoprotein produced by granulosa cells of the ovary; it regulates the development of the primary follicle while inhibiting further recruitment of other surrounding follicles. Day 3 FSH and basal antral follicle count have traditionally been used to assess ovarian reserve and while they remain excellent predictors of poor ovarian response, they have not been shown to predict IVF success rates. Given the association between AMH and ovarian reserve, it has been proposed that AMH level can be used to predict ovarian response to gonadotropin stimulation and also, IVF success rates. An inverse relationship between AMH and total gonadotropin dosage has previously been demonstrated. As such, the concept of tailoring stimulation protocols to the patient's potential for oocyte production based on AMH level has gained favor. Individualization allows the practitioner to use the minimum dosage of medication required for maximum response, while limiting the risk of ovarian hyperstimulation syndrome. The question becomes how to determine the dosage of medication required for each AMH level and what effect will this have on clinical outcomes?

Hypothesis 1) Knowledge of AMH level used to determine medication dosage at the start of the stimulation cycle will result in a higher oocyte yield at the time of retrieval, higher clinical pregnancy rate, and higher live birth rate.

2) Knowledge of AMH level used to determine initial medication dosage at the start of the stimulation cycle will result in a fewer number of dosage changes mid-cycle.

3) Knowledge of AMH level prior to the start of a stimulation cycle will result in the use of a different initial stimulation dose compared to cycles in which the AMH is unknown.

4) Knowledge of AMH level used to determine medication dosage prior to the start of the stimulation cycle will result in a lower rate of ovarian hyperstimulation syndrome (OHSS). (Defined as >=20 oocytes/follicles) 5) Knowledge of AMH level used to determine medication dosage prior to the start of the stimulation cycle will result in a lower rate of cancelled cycles.

Methods and Procedures. The AMH level for all patients will be assessed at the initial fertility evaluation for each patient.

Patients will undergo controlled ovarian hyperstimulation (COH) with a GnRH antagonist protocol. They will begin COH on day 3 of their menstrual cycle or they may need to begin with approximately one week of oral contraceptives. After one week, the patients will stop taking oral contraceptives if their ovaries appear quiescent on transvaginal ultrasound and their serum E2 levels are low. These patients will then begin COH three days later. Gonadotropin dosage will be determined at the start of the cycle by AMH level.

Dosages will be adjusted, beginning on the third day of gonadotropins, based on clinical response, determined by serum hormone levels and transvaginal ultrasound of the ovaries throughout the cycle. The patient will begin taking the GnRH antagonist, Ganirelix or Cetrotide, when the lead follicle measures ≥14mm on transvaginal ultrasound. Patients will be triggered with Lupron, hCG, or both when the lead follicle measures ≥20mm on transvaginal ultrasound. All medications are administered via subcutaneous injections.

Transvaginal ultrasound-guided oocyte retrieval will be performed 36 hours after the trigger medication(s) is administered. Cycles with a poor ovarian response, defined as <3 follicles and/or a peak estradiol level <600 pg/mL, will be canceled.

Patients will undergo culture day 5 embryo transfer; number of embryos transferred will be according to ASRM guidelines. If the patient exhibits symptoms of OHSS, she will discontinue luteal phase support and will not have an embryo transfer, and all good quality blastocyst mbryos will be cryopreserved. All patients eligible for embryo transfer will continue the luteal phase support protocol until the serum hCG pregnancy test 14 days post-retrieval. If the serum hCG is <5 mIU/mL, luteal phase support will be discontinued. If the serum hCG is ≥5 mIU/mL, Estrace will continue to be taken until 8 weeks gestation and Endometrin or intramuscular progesterone in oil will continue to be used until 10 weeks gestation. At this point, patient is released to the care of the obstetrician. The patient or the obstetrician will be contacted for pregnancy outcome data.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • first cycle of IVF with transfer of fresh embryo

Exclusion Criteria:

  • use of non-autologous oocytes; prior diagnosis of premature ovarian failure or diminished ovarian reserve; BMI>= 40; cryopreservation cycles; smokers; use of PGS/PGD; use of surgically retrieved sperm or patients with severe male factor; and oocyte- or embryo-banking cycles

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AMH<1.5, 300IU Gonal-F + 150 IU Menopur
dosage at 300IU Gonal-F + 150IU Menopur
Drug: 300IU Gonal-F
<1.5 AMH group
Other Names:
  • follitropin
Drug: 150IU Menopur
<1.5 AMH group
Other Names:
  • menotropin
Experimental: AMH 1.6-2.5, 225IU Gonal-F+75IU Menopur
dosage of 225IU Gonal-F + 75IU Menopur
Drug: 225IU Gonal-F
1.6-2.5 AMH group
Drug: 75IU Menopur
1.6-2.5 AMH group 2.6-6.9 AMH group >7.0 AMH group
Experimental: AMH 2.6-6.9, 150IU Gonal-F+75IU Menopur
start dosage of 150IU Gonal-F and 75IU Menopur
Drug: 75IU Menopur
1.6-2.5 AMH group 2.6-6.9 AMH group >7.0 AMH group
Drug: 150IU Gonal-F
2.6-6.9 AMH group
Experimental: AMH >=7.0, 75IU Gonal-F+75U Menopur
start dosage of 75IU Gonal-F and 75U Menopur
Drug: 75IU Menopur
1.6-2.5 AMH group 2.6-6.9 AMH group >7.0 AMH group
Drug: 75IU Gonal-F
>7.0 AMH group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
clinical pregnancy rate
Time Frame: two years
Clinical pregnancy rate is defined as the number of pregnancies with the presence of an intrauterine gestational sac seen on transvaginal ultrasound by six weeks gestation divided by the number of completed embryo transfers.
two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oocyte yield
Time Frame: two years
number of follicles produced
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Reproductive Specialists of New York

Investigators

  • Principal Investigator: Linda Sung, MD, Reproductive Specialists of New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 22, 2015

Primary Completion (Actual)

December 31, 2017

Study Completion (Actual)

December 31, 2017

Study Registration Dates

First Submitted

March 1, 2017

First Submitted That Met QC Criteria

March 27, 2017

First Posted (Actual)

March 31, 2017

Study Record Updates

Last Update Posted (Actual)

April 12, 2018

Last Update Submitted That Met QC Criteria

April 10, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 597102-3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infertility

Clinical Trials on 300IU Gonal-F

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belarus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe