GENETICS: COUNSELLING AND LABORATORY

What is SecureSelect?

SecureSelect is an embryo selection technique based on non-invasive chromosome screening, which consists of analysing an aliquot of the culture medium in which the embryos have been developing. In this culture medium, genetic material is found that has its origin in the cells of the embryo. The study of this material provides us with information on the chromosomal status of the embryo with a hight concordance around 82% with respect to the trophectoderm biopsy, thus allowing us to select those embryos with more possibilities of being chromosomally normal without the need for embryo biopsy.

How is it carried out?

Embryo selection is based on the analysis of the DNA present in the culture medium. To achieve this, the embryo is left in culture until day three of development, it is washed and transferred to another clean culture medium where it will develop until expanded blastocyst stage. This is the moment when the embryo is vitrified, and the culture medium is collected for analysis by massive or next generation sequencing in the Genetics Unit.

Once the results have been obtained, priority will be given to the transfer of the embryos most likely to be euploid (without chromosomal alterations).

What benefits do we obtain?

Thanks to this advanced embryo selection based on the chromosomal status and morphology of the embryo, couples will increase the chances of success of an IVF cycle compared to conventional embryo selection. This entire procedure is performed without subjecting the embryo to any aggressive manipulation that could alter it in any way.

SecureSelect allows the genetic status of the embryo to be known with 82% certainty.

This package is designed to ensure the maximum guarantee of pregnancy that today’s technology allows.

Couples who select this product will undergo a complete study of both partners and the embryo. Once pregnancy has been achieved, the health of the future baby will be ensured by carrying out a state-of-the-art non-invasive prenatal test.

The first stage of the genetic study focuses on both members of the couple, both of whom are tested:

• Karyotype. Thanks to this test we can rule out any chromosomal anomaly, both structural and numerical. This test consists of obtaining a culture of lymphocytes taken from a blood sample and then studying the number and structure of the chromosomes. It is indicated, among other cases, in sub-fertile patients, when there are repeated miscarriages and when chromosomal abnormalities are detected in offspring.
• Panel of the most frequent and serious recessive and X-linked diseases in our environment. With this test we will check that the members of the couple do not share pathogenic variants in the same genes, thus reducing to a minimum the probabilities of having offspring affected by any of the diseases included in the panel. This result is expressed in a genetic matching report.
• FISH spermatozoa in the male. This test allows us to know if the patient generates altered sperm (meiosis). It involves the study of sperm chromosomes using fluorescent DNA probes and fluorescence microscopy (Fluorescence In Situ Hybridization) in order to analyse numerical chromosomal abnormalities. The study allows us to check for alterations in meiosis (spermatogenesis). Chromosomes 13, 18, 21, X and Y are routinely studied.

  Indicated for:

  • severe oligozoospermia and/or teratozoospermia
  • patients with sex chromosome abnormalities
  • translocation carriers
  • patients who have undergone chemo-/radiotherapy
  • recurrent miscarriages of unknown cause
• Endometrial receptivity test. Before performing the IVF cycle, this test is performed to establish the optimal time to perform the transfer. The result will indicate the best day to perform the transfer to the mother’s uterus.
• PGT-A. Once we know the previous test results for the patients, an IVF will be performed to generate embryos. These embryos will be biopsied and genetically studied to select those with a normal number of chromosomes (euploid). With this, we increase the probability of pregnancy per transfer, avoiding transferring embryos whose implantation potential is almost null.
• Non-invasive Prenatal Testing (NIPT). Once pregnancy has been achieved, the NIPT test is performed at 10 weeks of gestation. With this test, we can rule out that the foetus has any chromosomal alterations greater than 5Mb.

This package is designed for women who have suffered more than one gestational loss to determine if the loss is due to a chromosomal cause and to initiate a new cycle by ruling out immunological (KIR), chromosomal (PGT-A) and endometrial receptivity causes.

• Karyotype. Thanks to this test we can rule out any chromosomal anomaly, both structural and numerical.
• Karyotyping of abortive remains (or QF-PCR). Chromosomal abnormalities are the most frequent cause of early gestational losses. The probability of miscarriage due to chromosomal abnormalities increases with the age of the woman, ranging from 15-20% in women under 35 years of age to more than 50% in women over 40 years of age. The karyotype of samples from aborted remains will allow us to determine if the foetus was a carrier of any chromosomal abnormality.
• KIR + HLA-C genotype. The intrauterine immunological factor is showing increasing importance in implantation problems. It has been shown that patients with an AA genotype on the KIR natural killer cell surface receptor have a rejection of embryos with a C2C2 genotype on the HLA-C gene, leading to an increase in repeated implantation failures and a decrease in live birth rates when two embryos are transferred versus single embryo transfers.
• PGT-A. Once we know the previous test results for the patients, an IVF will be performed to generate embryos. These embryos will be biopsied and genetically studied to select those with a normal number of chromosomes (euploid). With this, we increase the probability of pregnancy per transfer, avoiding transferring embryos whose implantation potential is almost null.
• Endometrial receptivity test. Before performing the IVF cycle, this test is performed to establish the optimal time to perform the transfer. The result will indicate the best day to perform the transfer to the mother’s uterus.

With this package we will try to rule out the most common causes of male infertility in order to increase success rates in IVF procedures.

• Karyotype. Thanks to this test we can rule out any chromosomal anomaly, both structural and numerical. This test consists of obtaining a culture of lymphocytes taken from a blood sample and then studying the number and structure of the chromosomes. It is indicated, among other cases, in sub-fertile patients, when there are repeated miscarriages and when chromosomal abnormalities are detected in offspring.
• FISH spermatozoa in the male. This test allows us to know if the patient generates altered sperm (meiosis). It involves the study of sperm chromosomes using fluorescent DNA probes and fluorescence microscopy (Fluorescence In Situ Hybridization) in order to analyse numerical chromosomal abnormalities. The study allows us to check for alterations in meiosis (spermatogenesis). Chromosomes 13, 18, 21, X and Y are routinely studied.

  Indicated for:

  • severe oligozoospermia and/or teratozoospermia
  • patients with sex chromosome abnormalities
  • translocation carriers
  • patients who have undergone chemo-/radiotherapy
  • recurrent miscarriages of unknown cause
• Microdeletions of the Y-chromosome. Microdeletions of the Y-chromosome represent an important cause of male infertility, between 10-15%. Their study could explain infertility in a certain number of patients with secretory azoospermia and severe oligozoospermia. The region involved in these conditions has been classically named AZF (azoospermia factor), which in turn has been divided into AZFa, AZFb and AZFc.
• CFTR genes (if no basic panel).
  Up to 10% of males with obstructive azoospermia have bilateral agenesis of the vas deferens. In many of these cases (up to 70%) the underlying alteration is a pathogenic variant in the CFTR gene. With this study, targeting the 50 most common pathogenic variants in the CFTR gene, we can rule out the genetic cause with a high probability.

• Karyotype. Thanks to this test we can rule out any chromosomal anomaly, both structural and numerical. This test consists of obtaining a culture of lymphocytes taken from a blood sample and then studying the number and structure of the chromosomes. It is indicated, among other cases, in sub-fertile patients, when there are repeated miscarriages and when chromosomal abnormalities are detected in offspring.
• Panel of the most frequent and serious recessive and X-linked diseases in our environment. With this test we will check that the members of the couple do not share pathogenic variants in the same genes, thus reducing to a minimum the probabilities of having offspring affected by any of the diseases included in the panel. This result is expressed in a genetic matching report.
• PGT-A. Once we know the previous test results for the patients, an IVF will be performed to generate embryos. These embryos will be biopsied and genetically studied to select those with a normal number of chromosomes (euploid). With this, we increase the probability of pregnancy per transfer, avoiding transferring embryos whose implantation potential is almost null.
• Endometrial receptivity test. Before performing the IVF cycle, this test is performed to establish the optimal time to perform the transfer. The result will indicate the best day to perform the transfer to the mother’s uterus.
• Non-invasive Prenatal Testing (NIPT). Once pregnancy has been achieved, the NIPT test is performed at 10 weeks of gestation. With this test, we can rule out that the foetus has any chromosomal alterations greater than 5Mb.

• SEF Vistahermosa Panel: Spanish Fertility Society + 22 X-linked diseases

  The genes included are those recommended by the Spanish Fertility Society (SEF) as the minimum study that should be performed to gamete donors. Seven genes are studied (Appendix I). This provides us with a guarantee of reduced risk of hereditary diseases, with the advantage of being a test that is easy to handle clinically and complies with the recommendations of the SEF. At the request of the Reproduction Unit, the study in female donors will include an additional 22 genes located on the X chromosome.

• Basic Vistahermosa Panel: 38 genes

  This test studies the genes that cause the most severe recessive diseases with the highest known carrier frequency and childhood onset.
  A total of 38 genes are studied. In the case of genes related to recessive diseases, all of them have a carrier prevalence greater than 1/100 (Annex II). In addition, 23 genes located on the X chromosome, which follow X-linked inheritance, are included. This panel increases the security offered by the SEF panel. In the case of males, the study of the 23 X-linked genes is excluded due to the type of inheritance.

• Extended Vistahermosa Panel: 552 genes

  Both the SEF and other groups recommend considering extended studies. This study is focused on couples who want to have offspring with the “maximum genetic information” or to carry out genetic matching in the case of using gamete donors. This approach allows to optimise the gamete donation programme, in addition to increasing safety.

  In this case, the test analyses 552 genes related to recessive and X-linked diseases (Annex III), with an emphasis on early onset severe recessive diseases caused by pathogenic mutations in coding regions of DNA and exon-intron junction sites. The genes included are either pre-implantation actionable, which means it would allow couples at reproductive risk to perform PGT-M on embryos, or prenatal and/or neonatal actionable, which would allow couples to know before birth the genetic status of the future baby.

  This test uses exome technology, which makes it compatible with any recessive and X-linked disease panel on the market. In addition, it allows us to adapt the genetic study to the needs of each Reproduction Unit.

  Given the large amount of information studied, it must be taken into account that in 70-80% of the individuals who undergo this extended study, at least 1 or 2 variants will be found, so the study should be performed to both female and male gametes (matching).

• Impact of Genetics in Reproductive Medicine

  In particular, Clinical Genetics has experienced great advances in the field of Reproductive Medicine in recent years. Currently, the prevalence of infertility is around 14%, which means that approximately 1 in 7 couples of reproductive age have difficulties in having children. Among the causes of infertility, it is estimated that around 30% of cases are due to known genetic pathologies. For this reason, genetic studies are increasingly necessary as part of the routine evaluation of infertile patients.

  However, Clinical Genetics is not only useful in cases of infertile patients, but also allows couples without reproductive problems, but at risk of transmitting a certain genetic disease to their offspring, to avoid this transmission by means of pre-implantation genetic testing.

• How can reproductive genetic counselling help you?

  Genetic counselling is a process that consists of providing the patient with information about a specific genetic disease and assisting in decision-making. During this procedure, the geneticist collects information about the patient’s personal and family medical history in order to assess the case in a personalised way. It is essential that genetic counselling is carried out pre- and post-test.

  In the field of reproductive medicine, after the individual assessment of the case, the geneticist informs the couple about different aspects of a specific genetic disease, such as the genetic tests required for diagnosis, the risk of transmission of the disease to offspring, the possibilities of avoiding transmission or the risk of recurrence.

• Which patients are candidates for reproductive genetic counselling?

  In general, reproductive genetic counselling is considered to be appropriate:

  • Couples with reproductive problems and repeated failures in assisted reproduction treatments.
  • Couples with repeated miscarriages.
  • Advanced maternal age.
  • A parent who is a carrier or at risk of being a carrier of a genetic disease (e.g., cystic fibrosis, hemophilia, chromosomal alteration, etc.).
  • History of previous child or family history of genetic disease.
  • Persons belonging to certain ethnic or geographical groups with a higher predisposition to certain diseases.
  • Consanguineous couples.
  • Pregnant women with ultrasound abnormalities or altered first trimester screening for chromosomopathies.