Sperm Selection for Infertility Treatment (SSA) (SSA)

Application of the Sperm Selection Assay in Assisted in Reproductive Technology

Infertility is considered a disease by the World Health Organization and it is increasing worldwide affecting more than 70 million couples. About 50% of the cases are due to male inability to fertilize the oocyte. In the last 40 years, several techniques, known as Assisted Reproduction Technology (ART) have been developed to treat infertility, but the efficiency is still relatively low (around 30%) whereas the remaining 70% attempts again several times, an expensive and emotionally moving treatment. Over 4million of infertility treatments are practiced around the world per year and a 50% increment is expected over the next 6years. Even though ART allows the birth of babies that would be impossible under natural circumstances, it is still necessary to improve the procedures in order to increase treatment efficiency. The success of ART depends, to some extent, on sperm quality. Indeed, the relevance of spermatozoa quality is notorious even beyond fertilization, extending to embryo development and implantation. In this context, it has been developed a new technology that allows the selection of those spermatozoa at their best functional state (Sperm Selection Assay, SSA; Patent approved for USA and Europe, pending for Japan and Argentina). This method is based on the attraction of spermatozoa ready to fertilize the egg, towards a physiological attractant molecule. The SSA may be applied to improve diagnosis and infertility treatment. The investigators hypothesis states that the use of the SSA will improve the number of good-quality embryos which are the ones to be transferred by intracytoplasmic sperm injection (ICSI), providing a healthy embryo development. The protocol involves three experimental groups where the SSA will be used or not, before performing the ICSI: 1)SSA containing the sperm attractant molecule, 2)SSA without the attractant molecule, and 3)without SSA. The patient inclusion criteria involve female factors associated to tubal obstruction and/or endometriosis and male factors associated to sperm disability. Several outcome parameters will be determined, the percentage of fertilization, embryo quality, rate of pregnancy and rate of birth. The study will be carried out in the Universitarian Institute of Reproductive Medicine (IUMER) which has been recently established in a public hospital depending on the National University of Córdoba, offering free high complexity infertility treatment to patients without health insurance or economic support

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Procedure: ICSI; Device: Sperm Selection Assay; Other: Attractant Substance

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, 1414
      • Recruiting
      • Halitus Instituto Médico
      • Contact: Rodolfo A Pasqualini; Phone Number: +54 11 5273 2000; Email: agustin.pasqualini@halitus.com
      • Contact: Ines Carretero; Phone Number: +54 11 5273 2000; Email: ines.carretero@halitus.com
      • Principal Investigator: Rodolfo A Pasqualini
  • Córdoba
    • Cordoba, Córdoba, Argentina, X5010AWC
      • Recruiting
      • Instituto Universitario de Medicina Reproductiva (IUMER)
      • Contact: Ana M Babini, MD; Phone Number: 0054 - 351 - 4331050; Email: anababini@gmail.com
      • Contact: Maria J. Figueras, PhD; Phone Number: 0054 - 9351 - 2209799; Email: mjfigueras@gmail.com
      • Principal Investigator: Laura C. Giojalas, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis for primary and secondary infertility
• Healthy females or females with tubal obstruction (uni or bilateral) and/or endometriosis.
• Clinical diagnosis for unexplained infertility.
• Females between 18 and 40 years old.
• Healthy males between 18 and 50 years old.
• Males with oligozoospermia, teratozoospermia, asthenozoospermia or asthenoteratozoospermia.

Exclusion Criteria:

• Low complexity assisted reproductive techniques
• In vitro fertilization treatment
• Other medical diagnosis of female infertility besides the inclusion criteria
• Males with oligoasthenoteratozoospermia and oligoasthenozoospermia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: ICSI Control; Intracytoplasmic sperm injection (ICSI), an in vitro fertilization procedure in which a single sperm is injected directly into an egg, with no intervention of the Sperm Selection Assay	Procedure: ICSI; An in vitro fertilization procedure in which a single sperm is injected directly into an egg; Other Names: Intracytoplasmatic Sperm Injection
PLACEBO_COMPARATOR: ICSI + SSA placebo; Intracytoplasmic sperm injection (ICSI), an in vitro fertilization procedure in which a single sperm is injected directly into an egg, with intervention of the Sperm Selection Assay with control solution (culture medium)	Procedure: ICSI; An in vitro fertilization procedure in which a single sperm is injected directly into an egg; Other Names: Intracytoplasmatic Sperm Injection; Device: Sperm Selection Assay; Sperm Selection Assay (SSA) that allow the investigators to select functional spermatozoa, which are capacitated, with intact DNA, reduced oxidative stress and with good viability and motility, on the basis of sperm chemotaxis towards a physiological attractant molecule.; Other Names: SSA
EXPERIMENTAL: ICSI + SSA Attractant substance; Intracytoplasmic sperm injection (ICSI), an in vitro fertilization procedure in which a single sperm is injected directly into an egg, with intervention of the Sperm Selection Assay with attractant solution (attractant diluted in culture medium at 10 pM)	Procedure: ICSI; An in vitro fertilization procedure in which a single sperm is injected directly into an egg; Other Names: Intracytoplasmatic Sperm Injection; Device: Sperm Selection Assay; Sperm Selection Assay (SSA) that allow the investigators to select functional spermatozoa, which are capacitated, with intact DNA, reduced oxidative stress and with good viability and motility, on the basis of sperm chemotaxis towards a physiological attractant molecule.; Other Names: SSA; Other: Attractant Substance; Capacitated spermatozoa may be oriented by following an increasing concentration gradient of an attractant molecule, a phenomenon called sperm chemotaxis. This is a guidance mechanism observed in vitro, which may transport and retain spermatozoa at the fertilization site. Though several molecules have been suggested to attract human spermatozoa, in the context of gamete interaction prior to fertilization, progesterone has biological importance for several reasons. After ovulation, this hormone is secreted by the cumulus cells that surround the oocyte, diffusing to form a molecular gradient toward the periphery of the cumulus and beyond. Notably, a gradient of very low concentrations (picomolar) of progesterone is sufficient to chemically attract capacitated human spermatozoa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fertilization rate	Fertilization rate= number of fertilized oocyte (oocytes with 2 pronuclei) / Total of injected oocytes in metaphase II	within 24 hs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Embryo quality	Grade I: Embryos with blastomeres of same size without fragmentation (degree 1) with clear and homogeneous cytoplasm, II: Embryos with blastomeres of the same size and less than 30% of fragmentation (degree 2 or 3), III: Embryos with blastomeres of different size and 0% of fragmentation (degree 1), IV: Embryos with blastomeres of the same or different sizes with 30 to 50% of fragmentation (degree 4), V: Embryos with more than 50% of fragmentation (degree 5).	within 48 to 66hs post injection
Transferable embryo rate	Transferable embryo rate= Number of embryos in condition to be transferred / Number of oocytes	within 72hs post injection
Pregnancy rate	pregnancy rate= Number of positive implantation / Total of patients with transferred embryos	within 30 days post injection
Birth rate	Birth rate= Number or live birth / Total of positive pregnancy	Up to 42 weeks after positive implantation
Implantation yield	Implantation rate= Number of implanted embryos / Number of transferred embryos	72 hs post injection
Division rate	Division rate= divided embryos / oocytes with 2 pronuclei	within 24-72 hs post injection
Fecundation failures in ICSI rate	ICSI cycles with no oocyte fecundated / ICSI cycles	Within every cycle of ICSI
Blastocyst formation rate	number of embryos that reach blastocyst stage / number of total embryos	within 3 to 5 days after injection
Abortion rate	number of abortions / number of pregnancies	within 3 months post injection
multiple embryo rate	number of embryos with more than one gestational sac / total of embryos	within a month post injection
clinic gestational rate	number of cycles when gestational sac is observed / total of cycles	within one month after injection
biochemist gestational rate	number of cycles with positive beta human chorionic gonadotropin without gestational sac / total of cycles	within 45 days after injection
Cycles without transferred embryos rate	number of cycles without transfer / number of cycles with ovaric puncture	within 2 months after recruitment
Degree Fragmentation	the embryos will be classified according with the size and distribution of cytoplasmic fragments in 5 categories. 1- Without fragments, 2- Up to 10% of fragmentation, 3- Up to 30% of fragmentation, 4- Between 30 to 50% of fragmentation and 5- More than 50% of fragmentation.	within 48hs to 66hs post injection

Collaborators and Investigators

• Sponsor: Universidad Nacional de Córdoba
• Investigators: Principal Investigator: Laura C. Giojalas, PhD, National University of Cordoba

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: August 1, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (ESTIMATE): August 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Assisted Reproductive Techniques; ICSI; sperm selection
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: IUMER-1; PIDC2014-0016 (OTHER_GRANT: ANPCyT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO