Trigger Time in Advanced Maternal Age Patients With Low AMH

The investigators want to verify if advanced maternal age patients with a low Anti-Müllerian hormone (AMH) level may benefit from an early trigger time (compared to a late trigger).

During assisted reproduction, patients are stimulated in order to achieve a multifollicular development. The final step in this stimulation process is "the trigger" that will induce the final maturation of the oocytes. This timing is historically put once at least one follicle of 16-17 mm is obtained.

When looking at poor ovarian responder (POR) patients (characterized by a low AMH), the investigators observe shorter menstrual cycles and thus it is thought that the oocyte selected for ovulation, will also mature faster. This observation may indicate that POR patients potentially do not benefit from a trigger performed once a leading follicle of 17 mm is present, but rather from an earlier trigger.

The main objective is to analyse if an early trigger (leading follicle of 14 mm) results in the same maturation rate in POR patient as compared to a late trigger (17 mm). As the embryos will be cultured in a time lapse imaging system, annotations on the developmental kinetics can be made and the differences in fertilization rate and embryo development can be analysed as secondary outcome parameter. On top of this, patients will undergo a genetic testing of their embryos and this genetic analysis , together with the mtDNA copy number will also be compared between patients with early or late trigger. Euploid blastocysts will be transferred in subsequent frozen embryo transfer (FET) cycles and give an indication on the clinical outcome between IVF and ICSI.

Eligibility Criteria:
Inclusion Criteria:

* • POR defined according to the Bologna criteria:

  * AMA: ≥40 years and AMH \<1.1 ng/ml
  * Previous poor ovarian response with maximum 3 cumulus oocyte complexes retrieved after conventional stimulation
  * Antral follicle count \< 5-7

    * Cycling patients
    * Fresh ejaculates
    * ICSI
    * BMI 19-32 kg/m2
    * Ovarian stimulation protocol: Antagonist HMG 450 IU to ensure all receptors are covered and to ensure maximum recruitment. Dose adjustments can be made after 5 days of stimulation
    * Type of trigger for final oocyte maturation: dual trigger: 10.000 IU hCG i.m. and 0.3 mg Deca
    * Couples requesting preimplantation genetic testing (for aneuploidies) of their embryos
    * Follicular measurements should be performed at IVI RMA Fertility, Abu Dhabi, UAE: a single operator will perform the ultrasound for the final measurement before trigger. Recruitment can be done by all physicians
    * Only patients with an oral contraceptive pill (OCP) pretreatment to synchronize follicular development:
  * 2 weeks OCP followed by
  * a wash out of 5 days (without OCP) followed by

    * o start stimulation
    * Basal hormone profile (FSH, LH, E2, P4) measured between day 1-3 at IVIRMA Fertility, Abu Dhabi, UAE
  * FSH \<15 IU
  * E2 \<50 pg/ml
  * P \<1ng/ml

    * Only the Arab population
    * Oocyte retrieval: 36 hours after trigger
    * PGT-A

Exclusion Criteria:

* If follicular measurement before randomization shows a leading follicle ≥ 13mm
* IVF
* History of:

  * Endometriosis AFS\>2
  * Chemotherapy/radiotherapy
  * Ovarian surgery (iatrogenic)
  * Cyst puncture in the last three months
* Sonographic finding of:

  * Hydrosalpinx
  * Ovarian cyst
* Testicular samples and frozen ejaculates
* If patients are pre-screened at the start of stimulation but no follicular development is observed, patients will not be randomized
* Asynchronized follicular development at the moment of randomization: if the leading follicle is \>3 mm lager than the smaller follicles.
* All other hormonal pretreatments (except OCP) and all patients without hormonal pretreatment