AMH and Dosing Regimens for Initial IVF Stimulation Protocols
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): 300IU Gonal-F; 150IU Menopur; 225IU Gonal-F; 75IU Menopur; 150IU Gonal-F; 75IU Gonal-F
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): <1.5 AMH group; <1.5 AMH group; 1.6-2.5 AMH group; 1.6-2.5 AMH group 2.6-6.9 AMH group >7.0 AMH group; 2.6-6.9 AMH group; >7.0 AMH group
Other intervention name(s): follitropin; menotropin
Intervention MeSH terms: Menotropins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antimullerian Hormone; In vitro fertilization; Medications; Dosing