Mono-menotropins Versus rFSH Protocol on Embryo Quality
Condition: Infertility; Fertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      This study is for couples pursuing in vitro fertilization (IVF) with preimplantation genetic
      screening (PGS) of embryos to achieve pregnancy. The objective of this clinical trial is to
      study the effect of mono-menotropins for COS versus recombinant follicle stimulating hormone
      (rFSH) on cleavage-stage and blastocyst embryo quality after IVF. Embryo quality parameters
      include conventional embryo grade, early embryo viability assessment (Eeva) time-lapse
      parameters, and chromosomal aneuploidy rates after PGS.

      This pilot study is expected to significantly contribute to optimization of treatment
      regimens and stimulation protocols to optimize embryo quality.
    

Detailed description: 
      This proposed study is a single-center, prospective, randomized experimental design.

      One-hundred women between the ages of 21 to 38 (inclusive) pursuing IVF treatment for
      infertility and preimplantation genetic screening (PGS).

      Pre-medication All study patients will take oral contraception pills (OCP) starting between
      day 2-4 of the menstrual cycle before controlled ovarian stimulation (COS) is started for
      IVF, and they are continued for 21 days. Cycle preparation using an oral contraceptive pill
      is thought to be important in improving follicular homogeneity.

      Randomization Randomization of patients into the Stimulation Group 1 (Mono-Menotropin
      Protocol) or Stimulation Group 2 (rFSH) will occur at OCP start using a computerized
      randomization program.

      Ovarian Stimulation Stimulation Group 1: Mono-Menotropin Protocol Fifty patients will undergo
      the standard of care COS for IVF using Menopur (Ferring, Parsippany, New Jersey (NJ) USA)
      only. Patients will receive 300 IU of Menopur injected subcutaneously daily for the first
      five days of stimulation. Thereafter, Menopur may be adjusted (to optimize ovarian response
      by patient's physician) in 75 IU increments up to a total of 450 IU Menopur daily up to and
      including day of hCG trigger.

      Stimulation Group 2: rFSH Protocol Fifty patients will undergo the standard of care
      controlled ovarian stimulation (COS) for IVF using Gonal-f (EMD Serono, USA) protocol.
      Patients will receive 300 IU of Gonal-f administered subcutaneously daily for the first five
      days of stimulation. Thereafter, Gonal-f may be adjusted (to optimize ovarian response by the
      patient's physician) in 75 IU increments up to a total of 450 IU daily up to and including
      day of hCG trigger.

      Menopur and Gonal-f are widely used in controlled ovarian stimulation cycles for the
      development of multiple follicles in assisted reproductive technology (ART) programs.

      Luteinizing Hormone (LH)-surge Suppression Gonadotropin Releasing Hormone (GnRH) antagonist
      will be used to suppress endogenous pituitary LH for the prevention of premature LH surges.
      Patients will receive 0.25 mg/day of Ganirelix Acetate or Cetroelix Acetate when follicle
      size reaches 12 mm and will continue up to and including day of hCG trigger.

      HCG Trigger Human chorionic gonadotropin (hCG) will be used intramuscularly (IM) in both
      stimulation groups to induce oocyte maturation 36 hours prior to the oocyte retrieval
      procedure

      Cycle Monitoring Cycles will be monitored with follicular ultrasound measurements and serum
      estradiol concentrations throughout ovarian stimulation. HCG will be given IM when at least
      three follicles reach a diameter of ≥17 mm. Egg retrieval will be conducted by transvaginal
      ultrasound 36 h after hCG administration.

      Insemination All mature oocytes will have intracytoplasmic sperm injection (ICSI) or standard
      insemination to achieve fertilization.

      Embryo Development Two-pronuclei (2pn) embryos will be placed in the Eeva dish after
      fertilization check at 16-18 hours post ICSI. To maintain a continuous and uninterrupted
      imaging process from day 1 through day 3, no media changes or dish removal from the incubator
      will be permitted. On day 3, imaging will be stopped just before routine embryo grading will
      be performed according to Society for Assisted Reproductive Technology (SART) standards. Cell
      number and quality score based on symmetry of cells and percent fragmentation will be
      recorded. Embryos will be tracked individually. Software will automatically measures cell
      division timings and provide quantitative information regarding embryo development. Embryo
      grading day 5 will be performed according to standard operating procedure. Blastocysts will
      be biopsied on day 5 or 6. Biopsies will be sent to a genetics laboratory (Reprogenetics, New
      Jersey) for aCGH euploidy testing. Biopsied blastocysts will be vitrified for future frozen
      embryo transfer (FET) cycle/s, in which euploid blastocyst/s with the correct number of
      chromosomes will be thawed and transferred back to the uterus in an attempt to achieve
      pregnancy.

      Abnormal embryos (aneuploidy embryos with the incorrect number of chromosomes) may be donated
      to research or discarded.
    

Intervention name(s): menotropin; Recominant Follicle Stimulating Hormone (rFSH)
Intervention type(s): Drug; Drug
Intervention description(s): Menopur is used for controlled ovarian stimulation (COH); Gonal-f is used for controlled ovarian stimulation (COH)
Other intervention name(s): Menopur; Gonal-f
Intervention MeSH terms: Menotropins; Hormones; Follicle Stimulating Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: infertility; in vitro fertilization; fertility; preimplantation genetic screening; embryo; PGS; Eeva; IVF