Infertility
Conditions
Keywords
sperm selection, ICSI, Assisted Reproductive Techniques
Brief summary
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
Interventions
DEVICESperm 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.
OTHERAttractant 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
PROCEDUREICSI
An in vitro fertilization procedure in which a single sperm is injected directly into an egg
Sponsors
Universidad Nacional de Córdoba
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fertilization rate | within 24 hs | Fertilization rate= number of fertilized oocyte (oocytes with 2 pronuclei) / Total of injected oocytes in metaphase II |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transferable embryo rate | within 72hs post injection | Transferable embryo rate= Number of embryos in condition to be transferred / Number of oocytes |
| Pregnancy rate | within 30 days post injection | pregnancy rate= Number of positive implantation / Total of patients with transferred embryos |
| Birth rate | Up to 42 weeks after positive implantation | Birth rate= Number or live birth / Total of positive pregnancy |
| Implantation yield | 72 hs post injection | Implantation rate= Number of implanted embryos / Number of transferred embryos |
| Division rate | within 24-72 hs post injection | Division rate= divided embryos / oocytes with 2 pronuclei |
| Fecundation failures in ICSI rate | Within every cycle of ICSI | ICSI cycles with no oocyte fecundated / ICSI cycles |
| Embryo quality | within 48 to 66hs post injection | 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). |
| Abortion rate | within 3 months post injection | number of abortions / number of pregnancies |
| multiple embryo rate | within a month post injection | number of embryos with more than one gestational sac / total of embryos |
| clinic gestational rate | within one month after injection | number of cycles when gestational sac is observed / total of cycles |
| biochemist gestational rate | within 45 days after injection | number of cycles with positive beta human chorionic gonadotropin without gestational sac / total of cycles |
| Cycles without transferred embryos rate | within 2 months after recruitment | number of cycles without transfer / number of cycles with ovaric puncture |
| Degree Fragmentation | within 48hs to 66hs post injection | 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. |
| Blastocyst formation rate | within 3 to 5 days after injection | number of embryos that reach blastocyst stage / number of total embryos |
Countries
Argentina
Contacts
Primary ContactLaura C Giojalas, PhD
Backup ContactMaria J. Figueras, PhD
Outcome results
None listed