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

NCT03291821 | Completed

• 1 other identifier: 1702-MAD-014-MC
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility, Female

Keywords

DuoStim; MitoScore; Preimplantation genetic diagnosis; MII oocyte

Outcome Measures

Primary Outcomes (1)

• Rate of euploid embryos per cycle

  Rate of chromosomally normal embryos per cycle in the DuoStim group compared to the group undergoing two controlled ovarian hyperstimulation in consecutives cycles.

  up to 9 months

Secondary Outcomes (8)

• Number of oocytes obtained

  up to 9 months

• Number of fertilized oocytes

  up to 9 months

• Number of biopsied blastocysts

  up to 9 months

• MitoScore index of the euploid embryos

  up to 9 months

• Implantation rate

  up to 9 months

Study Arms (2)

DuoStim

EXPERIMENTAL

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; 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

Conventional Stimulation

ACTIVE COMPARATOR

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; 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

Interventions

human menopausal gonadotropin DRUG

human menopausal gonadotropin subcutaneously

Also known as: menopur, meriofert

Conventional Stimulation; DuoStim

GnRH antagonist DRUG

GnRH antagonist subcutaneously

Also known as: orgalutran, cetrotide

Conventional Stimulation; DuoStim

GnRH analog DRUG

GnRH analog subcutaneously

Also known as: decapeptyl

Conventional Stimulation; DuoStim

Trophectoderm biopsy PROCEDURE

Trophectoderm biopsy is the process of removing few cells from an in vitro fertilization embryo.

Also known as: embryo biopsy, blastocyst biopsy

Conventional Stimulation; DuoStim

MitoScore DIAGNOSTIC_TEST

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.

Conventional Stimulation; DuoStim

Intracytoplasmic sperm injection PROCEDURE

ICSI is an in vitro fertilization procedure in which a single sperm is injected directly into an oocyte.

Also known as: ICSI

Conventional Stimulation; DuoStim

Ovarian puncture PROCEDURE

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.

Also known as: pick up, egg retrieval

Conventional Stimulation; DuoStim

Preimplantation genetic test DIAGNOSTIC_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.

Conventional Stimulation; DuoStim

Embryo transfer PROCEDURE

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

Conventional Stimulation; DuoStim

Pregnancy test DIAGNOSTIC_TEST

A pregnancy test is used to determine whether a woman is pregnant.

Conventional Stimulation; DuoStim

Embryo freezing PROCEDURE

Embryo freezing is a method for cryopreserving embryos.

Also known as: embryo cryopreservation, embryo vitrification

Conventional Stimulation; DuoStim

Embryo thawing PROCEDURE

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

Conventional Stimulation; DuoStim

Eligibility Criteria

• Age: 35 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent;
• 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).

You may not qualify if:

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

Sponsors & Collaborators

• IVI Madrid: lead

Study Sites (1)

IVI Madrid

Madrid, 28035, Spain

Location

Related Publications (12)

• Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.

  PMID: 12849812 BACKGROUND

• Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013 Dec;100(6):1673-80. doi: 10.1016/j.fertnstert.2013.07.1992. Epub 2013 Aug 26.

  PMID: 23987516 BACKGROUND

• Cakmak H, Rosen MP. Random-start ovarian stimulation in patients with cancer. Curr Opin Obstet Gynecol. 2015 Jun;27(3):215-21. doi: 10.1097/GCO.0000000000000180.

  PMID: 25919235 BACKGROUND

• Sonmezer M, Turkcuoglu I, Coskun U, Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil Steril. 2011 May;95(6):2125.e9-11. doi: 10.1016/j.fertnstert.2011.01.030. Epub 2011 Feb 3.

  PMID: 21292255 BACKGROUND

• von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, Strowitzki T. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009 Oct;92(4):1360-1365. doi: 10.1016/j.fertnstert.2008.08.011. Epub 2008 Oct 18.

  PMID: 18930226 BACKGROUND

• Bedoschi GM, de Albuquerque FO, Ferriani RA, Navarro PA. Ovarian stimulation during the luteal phase for fertility preservation of cancer patients: case reports and review of the literature. J Assist Reprod Genet. 2010 Aug;27(8):491-4. doi: 10.1007/s10815-010-9429-0. Epub 2010 May 9.

  PMID: 20455017 BACKGROUND

• Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.

  PMID: 25444501 BACKGROUND

• Ubaldi FM, Capalbo A, Vaiarelli A, Cimadomo D, Colamaria S, Alviggi C, Trabucco E, Venturella R, Vajta G, Rienzi L. Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation. Fertil Steril. 2016 Jun;105(6):1488-1495.e1. doi: 10.1016/j.fertnstert.2016.03.002. Epub 2016 Mar 25.

  PMID: 27020168 BACKGROUND

• Bentov Y, Esfandiari N, Gokturk A, Burstein E, Fainaru O, Casper RF. An ongoing pregnancy from two waves of follicles developing during a long follicular phase of the same cycle. Fertil Steril. 2010 Jun;94(1):350.e8-11. doi: 10.1016/j.fertnstert.2009.12.033.

  PMID: 20138269 BACKGROUND

• Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.

  PMID: 24161646 BACKGROUND

• Chen H, Wang Y, Lyu Q, Ai A, Fu Y, Tian H, Cai R, Hong Q, Chen Q, Shoham Z, Kuang Y. Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles. Fertil Steril. 2015 May;103(5):1194-1201.e2. doi: 10.1016/j.fertnstert.2015.02.020. Epub 2015 Mar 23.

  PMID: 25813280 BACKGROUND

• Diez-Juan A, Rubio C, Marin C, Martinez S, Al-Asmar N, Riboldi M, Diaz-Gimeno P, Valbuena D, Simon C. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015 Sep;104(3):534-41.e1. doi: 10.1016/j.fertnstert.2015.05.022. Epub 2015 Jun 11.

  PMID: 26051102 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Menotropins; LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; ganirelix; cetrorelix; Gonadotropin-Releasing Hormone; Triptorelin Pamoate; Sperm Injections, Intracytoplasmic; Embryo Transfer; Pregnancy Tests

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biological Products; Complex Mixtures; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins; Fertilization in Vitro; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Obstetrical and Gynecological

Study Officials

• Maria Cerrillo, M.D., Ph.D.

  IVI Madrid

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Unicentric, prospective, randomized, non-blind, parallel-group controlled phase IV clinical study.

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 25, 2017
• Study Start: December 1, 2017
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: December 29, 2020

Record last verified: 2020-12

Locations

ES (1)