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DuoStim in Cases of PGT: Comparison of Embryo Quantity and Embryonic Quality Using MitoScore

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ClinicalTrials.gov Identifier: NCT03291821
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
IVI Madrid

Brief Summary:

Since preimplantation genetic testing (PGT) is being more frequently requested from patients as women pursue infertility treatments at an advanced age with a poorer prognosis, sometimes physicians are compelled to perform several stimulation cycles to obtain more eggs and, consequently, a greater number of biopsied embryos. Hence, the idea of carrying out this study arises as an attempt to optimize each menstrual cycle to the maximum.

It is believed that the double stimulation (DuoStim) protocol could be an alternative for this group of patients, allowing to obtain a larger number of oocytes in a shorter period, thus, increasing the number of biopsied embryos and possibly decreasing the interval to achieve a successful pregnancy.

The investigators aim to evaluate the potential usefulness of the DuoStim protocol for patients desiring to obtain oocytes as soon as possible. Using PGT, the investigators will compare the rate of euploid embryos per cycle in patients undergoing DuoStim protocol versus patients undergoing two conventional controlled ovarian hyperstimulation in consecutive cycles. Patients will include women with advanced age and poor response.

This is a unicentric, prospective, randomized, non-blind, parallel-group controlled phase IV clinical study. The investigators hypothesize that the rate of euploid embryos per cycle is similar in the DuoStim group compared to the group undergoing two conventional controlled ovarian hyperstimulation in consecutive cycles.

Furthermore the investigators will evaluate if there are differences regarding the number of total oocytes obtained, the number of mature oocytes, the number of biopsied blastocysts and the MitoScore index of the available euploid embryos.


Condition or disease Intervention/treatment Phase
Infertility, Female Drug: human menopausal gonadotropin Drug: GnRH antagonist Drug: GnRH analog Procedure: Trophectoderm biopsy Diagnostic Test: MitoScore Procedure: Intracytoplasmic sperm injection Procedure: Ovarian puncture Diagnostic Test: Preimplantation genetic test Procedure: Embryo transfer Diagnostic Test: Pregnancy test Procedure: Embryo freezing Procedure: Embryo thawing Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Unicentric, prospective, randomized, non-blind, parallel-group controlled phase IV clinical study.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Double Ovarian Stimulation in Cases of Preimplantation Genetic Testing: Comparison of Embryo Quantity and Embryonic Quality Using MitoScore
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
Drug: human menopausal gonadotropin
human menopausal gonadotropin subcutaneously
Other Names:
  • menopur
  • meriofert

Drug: GnRH antagonist
GnRH antagonist subcutaneously
Other Names:
  • orgalutran
  • cetrotide

Drug: GnRH analog
GnRH analog subcutaneously
Other Name: decapeptyl

Procedure: Trophectoderm biopsy
Trophectoderm biopsy is the process of removing few cells from an in vitro fertilization embryo.
Other Names:
  • embryo biopsy
  • blastocyst biopsy

Diagnostic Test: MitoScore
The cells removed from an in vitro fertilization embryo during the trophectoderm biopsy will be used to assess the mitochondrial DNA content as a viability indicator in the euploid embryos.

Procedure: Intracytoplasmic sperm injection
ICSI is an in vitro fertilization procedure in which a single sperm is injected directly into an oocyte.
Other Name: ICSI

Procedure: Ovarian puncture
Egg retrieval is a simple procedure. It is performed in an operating room for safety reasons. It is performed vaginally and involves aspirating the follicular fluid through a thin needle. Embryologists then retrieve from this fluid the eggs that have matured during stimulation. It lasts for 5 to 15 minutes, and a mild sedative is administered to prevent any kind of pain during the procedure.
Other Names:
  • pick up
  • egg retrieval

Diagnostic Test: Preimplantation genetic test
The cells removed from an in vitro fertilization embryo during the trophectoderm biopsy will be tested for chromosomal normalcy before transferring the embryo to the uterus.

Procedure: Embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus

Diagnostic Test: Pregnancy test
A pregnancy test is used to determine whether a woman is pregnant.

Procedure: Embryo freezing
Embryo freezing is a method for cryopreserving embryos.
Other Names:
  • embryo cryopreservation
  • embryo vitrification

Procedure: Embryo thawing
Embryo thawing is the procedure to recover previously frozen embryos prior to an embryo transfer.

Active Comparator: Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
Drug: human menopausal gonadotropin
human menopausal gonadotropin subcutaneously
Other Names:
  • menopur
  • meriofert

Drug: GnRH antagonist
GnRH antagonist subcutaneously
Other Names:
  • orgalutran
  • cetrotide

Drug: GnRH analog
GnRH analog subcutaneously
Other Name: decapeptyl

Procedure: Trophectoderm biopsy
Trophectoderm biopsy is the process of removing few cells from an in vitro fertilization embryo.
Other Names:
  • embryo biopsy
  • blastocyst biopsy

Diagnostic Test: MitoScore
The cells removed from an in vitro fertilization embryo during the trophectoderm biopsy will be used to assess the mitochondrial DNA content as a viability indicator in the euploid embryos.

Procedure: Intracytoplasmic sperm injection
ICSI is an in vitro fertilization procedure in which a single sperm is injected directly into an oocyte.
Other Name: ICSI

Procedure: Ovarian puncture
Egg retrieval is a simple procedure. It is performed in an operating room for safety reasons. It is performed vaginally and involves aspirating the follicular fluid through a thin needle. Embryologists then retrieve from this fluid the eggs that have matured during stimulation. It lasts for 5 to 15 minutes, and a mild sedative is administered to prevent any kind of pain during the procedure.
Other Names:
  • pick up
  • egg retrieval

Diagnostic Test: Preimplantation genetic test
The cells removed from an in vitro fertilization embryo during the trophectoderm biopsy will be tested for chromosomal normalcy before transferring the embryo to the uterus.

Procedure: Embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus

Diagnostic Test: Pregnancy test
A pregnancy test is used to determine whether a woman is pregnant.

Procedure: Embryo freezing
Embryo freezing is a method for cryopreserving embryos.
Other Names:
  • embryo cryopreservation
  • embryo vitrification

Procedure: Embryo thawing
Embryo thawing is the procedure to recover previously frozen embryos prior to an embryo transfer.




Primary Outcome Measures :
  1. Rate of euploid embryos per cycle [ Time Frame: up to 9 months ]
    Rate of chromosomally normal embryos per cycle in the DuoStim group compared to the group undergoing two controlled ovarian hyperstimulation in consecutives cycles.


Secondary Outcome Measures :
  1. Number of oocytes obtained [ Time Frame: up to 9 months ]
    Total number of oocytes obtained in both arms after ovarian puncture

  2. Number of fertilized oocytes [ Time Frame: up to 9 months ]
    Number of fertilized oocytes in both arms after FIV/ICSI procedure

  3. Number of biopsied blastocysts [ Time Frame: up to 9 months ]
    Number of biopsied blastocysts in both arms

  4. MitoScore index of the euploid embryos [ Time Frame: up to 9 months ]
    Analysis of the MitoScore index of the euploid embryos obtained in both arms

  5. Implantation rate [ Time Frame: up to 9 months ]
    Implantation rate of euploid embryos in both arms after single or double embryo transfer

  6. Pregnancy rate [ Time Frame: up to 9 months ]
    Pregnancy rate of euploid embryos in both arms after single or double embryo transfer

  7. Abortion rate [ Time Frame: up to 9 months ]
    Abortion rate presented by each arm after single or double embryo transfer

  8. Time until embryo transfer [ Time Frame: up to 9 months ]
    Period elapsed from the beginning of the ovarian stimulation until the embryo transfer



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent;
  • 35-42 years of age;
  • Patients from the IVI Madrid undergoing controlled ovarian hyperstimulation cycle including PGT analysis for infertility treatment;
  • BMI 18-30 kg/m2;
  • Suspicion of suboptimal or poor response:

AMH < 1.5 ng/mL; AFC < 8; FSH > 10; Poor response in a previous cycle (defined as < 6 oocytes).

Exclusion Criteria:

  • Simultaneous participation in another clinical trial or in any other study that could result in a confounding factor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03291821


Contacts
Contact: Juan A Garcia Velasco, M.D., Ph.D. 911802900 juan.garcia.velasco@ivi.es
Contact: Mónica T Paredes 34 911 802 900 invesmadrid@ivi.es

Locations
Spain
IVI Madrid Recruiting
Madrid, Spain, 28035
Contact: Juan A Garcia Velasco, M.D., Ph.D.    34 9111802900    juan.garcia.velasco@ivi.es   
Contact: Mónica T Paredes    34 911 802 900    invesmadrid@ivi.es   
Principal Investigator: Maria Cerrillo, M.D., Ph.D.         
Sub-Investigator: Maria Cruz         
Sub-Investigator: Fernando Bronet         
Sub-Investigator: Gustavo N Cecchino, M.D.         
Sub-Investigator: Javier MS Romero, M.D.         
Sub-Investigator: Juan A Garcia Velasco, M.D., Ph.D.         
Sponsors and Collaborators
IVI Madrid
Investigators
Principal Investigator: Maria Cerrillo, M.D., Ph.D. IVI Madrid

Publications:

Responsible Party: IVI Madrid
ClinicalTrials.gov Identifier: NCT03291821     History of Changes
Other Study ID Numbers: 1702-MAD-014-MC
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by IVI Madrid:
DuoStim
MitoScore
Preimplantation genetic diagnosis
MII oocyte

Additional relevant MeSH terms:
Infertility
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female
Prolactin Release-Inhibiting Factors
Menotropins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents