Predictive Value of AMH in IVF; a Prospective RCT
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      The primary aim of this trial is to compare two groups of women undergoing IVF (IVF=in vitro
      fertilisation ) treatment, to investigate if assessment of AMH (AMH=Anti-Müllerian hormone ),
      in addition to assessment of maternal age, AFC (AFC=antral follicle count ) and BMI (BMI=body
      mass index ) gives a more optimal COH (COH=controlled ovarian stimulation than does
      assessment of only age, AFC and BMI, measured as number of patients obtaining 5-12 oocytes
      during COH.
    

Detailed description: 
      At the first visit to the IVF-clinic a CRF (CRF=Case Report Form) of demographics will be
      filled in regarding age, BMI, parity, presence of PCOS (PCOS=polycystic ovarian syndrome ),
      smoking and duration of infertility and a blood sample for serum-AMH is taken and frozen for
      later analysis. The serum-AMH level is constant during the menstrual period (La Marca et al
      2006) and a blood sample can be taken on any cycle day. The AMH assay used is the Beckman
      Coulter AMH Gene II assay. Classification of the serum AMH values into expected low-,
      normal-, or high ovarian response is based on the data presented a large prospective cohort
      study of patients going through COH (Nelson et al 2009). Since that publication used an older
      assay the reference intervals are calculated and translated as described in a recent
      publication on AMH assays (Nelson et al 2012). Serum-AMH level increases during GnRH (GnRH=
      gonadotropin releasing hormone) agonist downregulation (Jayaprakasan et al 2008), thus the
      blood sample is preferably taken before start of down-regulation. A long GnRH agonist
      treatment protocol is used. Patients are down-regulated with GnRH agonist from luteal phase,
      or first cycle day when anovulatory patient, until estradiol is < 200 pmol/l. After
      down-regulation, an assessment of AFC will be performed by sonography, and the patient will
      be randomized.

      For the patients randomized to the AMH-group calculation of gonadotropin starting dose will
      be made from an algorithm including age, BMI, AFC and serum-AMH. For the patients randomized
      to the non-AMH-group, calculation of gonadotropin starting dose will be made from an
      algorithm including only age, BMI and AFC. The AMH blood sample in this group will be
      analyzed after completion of the study.

      Stimulation is started with a dose of rFSH (rFSH=recombinat follicle stimulating hormone)
      calculated according to the dose algorithms used in the two groups. The name of the
      gonadotropin preparation, the dose and number of treatment days will be recorded. The same
      applies for all drugs used. Monitoring will be performed with mandatory estradiol on the day
      of stimulation start and on stimulation day 6. The dose of gonodotropin can be adjusted on
      day 7. If estradiol is > 1200 pmol/l the dose is reduced with one step according to the dose
      algorithm. If estradiol is < 350 pmol/l the dose is increased with one step according to the
      dose algorithm. Vaginal sonography is performed on stimulation day 9-11 to estimate the
      number and size of follicles. The number of follicles >10 mm at sonography 0-2 days before
      ovulation induction is recorded. Ovulation induction with 6500 IU (IU=international units)
      rHCG (rHCG=recombinant human chorion gonadotropin ) is given when >=2 follicles >=17 mm. 36
      hours after ovulation induction transvaginal oocyte pickup is performed according to standard
      procedure at the clinic using sedation and paracervical administration of local anaesthetics,
      and all follicles > 10 mm are punctured. The oocytes will be fertilized using standard IVF
      procedure. In the case of an unexpected poor semen sample on the day of ovum pick-up
      microinjection will be performed. The fertilization rate is recorded. Embryo transfer is done
      on day 2 or 3 according to routine procedures in the clinic. In the case of no GQE (GQE=good
      quality embryos ) it is allowed to perform double embryo transfer, otherwise single embryo
      transfer is mandatory. Luteal phase support using vaginal route is given from the day of
      embryo transfer and for 14 more days, until pregnancy test (urinary ). In case of impending
      OHSS (OHSS=ovarian hyperstimulation syndrome ), where decision is made to cryopreserve all
      embryos, the outcome of the first transfer of a cryopreserved embryo will be included in the
      study results for secondary endpoints. In case of pregnancy, an early vaginal sonography is
      performed in pregnancy week 7-8. The number of cancelled cycles due to poor response is
      recorded. The number of patients having moderate or severe OHSS, requiring intervention, will
      be recorded until four weeks after ovum pick up.
    

Intervention name(s): AMH-analysis
Intervention type(s): Other
Intervention description(s): At the first visit to the IVF-clinic a blood sample for serum-AMH is taken and frozen for later analysis in the AMH-group. The AMH assay used is the Beckman Coulter AMH Gene II assay. The analysis result will be added to the algorthm deciding what starting gonadotropin dose the patient is having.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Anti mullerian hormone; In vitro fertilization; Optimal treatment; Randomized controlled trial