The ERA Endometrial receptivity analysis should be performed during a HRT cycle or natural cycle. The receptivity diagnosis is valid just for the type of cycle during which the test is performed, therefore, the embryo transfer must be carried out in the same kind of cycle with which the receptive result is obtained.
The biopsy of the uterine fundus is performed following a standard procedure with a Pipelle catheter or similar. About 70 milligrams of tissue are enough. For illustration purposes, this equates to a cube with sides measuring 7 millimetres. Once the endometrial biopsy is taken, the tissue must be inserted into the ERA cryotube. Under no circumstances should the tissue volume exceed 1/3 of the total volume of the cryotube so as to ensure successful preservation.
Natural cycle
If it is determined in urine or serum, the LH surge is considered as LH+0. The endometrial biopsy is taken at LH+7 (approx. 168 hours). If the ovulation is determined by ultrasound, the day of ovulation is taken as Ov+0. The endometrial biopsy is taken six days later at Ov+6 (approx. 144 hours).
Hormone Replacement Therapy cycle
Upon starting the HRT cycle, the endometrial biopsy is taken after five full days of progesterone exposure (approx. 120 hours). The day in which progesterone treatment begins is considered as P+0 and the biopsy is taken at P+5.
In this type of cycle it is important to check that the progesterone level in blood is <1ng/ml before starting the progesterone intake.
The time of ovulation in natural cycles can be measured using LH urine test strips, by direct measurement of LH in blood serum, or by monitoring follicle rupture by ultrasound.
An endometrial biopsy is taken during a natural cycle or a HRT cycle to perform the ERA test.
Result: “Receptive”
If the patient has frozen eggs or embryos, or has fresh eggs or embryos from a donor, these may be transferred in the same type (natural or HRT) and day of cycle in which the ERA test was performed and a receptive result was obtained.
If the patient does NOT have frozen eggs or embryos and wants to use their own eggs, a cycle of ovarian stimulation for egg or embryo cryopreservation will be performed. Embryo transfer will be performed in a subsequent cycle of the same type (natural or HRT) and on the same day in which a receptive ERA test result was obtained.
Result: Result: “Non-Receptive” with a recommendation of a new window of implantation
If the result of the first ERA test is non-receptive and the expression profile analysis suggests that the window of implantation may be displaced, it is necessary to validate the new window with a second ERA test.
Where there is a displaced window of implantation that has been validated with a second ERA, the thawing of eggs or embryos and their transfer must be scheduled to coincide with the specific day for which the woman’s receptive result has been obtained.
Embryo biopsy is the removal of one or just a few cells from the embryo (depending on the stage of development). If the embryo is handled correctly by a skillful embryologist, the embryo develops normally after embryo biopsy. Published studies demonstrate that there is no increased rate of birth defects in IVF babies that are born after biopsy compared to IVF babies that are born without embryo biopsy.
Igenomix can perform PGS testing on embryos that are biopsied at either day 3 or day 5. A 3-day-old embryo has approximately 8 cells, and so only a single cell is removed for a biopsy done at day 3. A 5-day-old embryo has a few hundred cells, and so several cells can be safely removed during the biopsy. There are several good reasons to do either a day-3 or a day-5 biopsy. The number of cells that can be safely removed, rates of mosaicism, expertise of the embryologist, and embryo quality are all important factors in deciding when to do embryo biopsy. Patients should discuss with their IVF doctor the best time to do the biopsy. (Mir et al., 2016).
No genetic test can detect all potential genetic abnormalities. PGS testing for aneuploidy can only assess numerical changes in chromosome number and other imbalances in genetic material including deletions and duplications. PGS will identify any missing or extra chromosomes, deletions, duplications, and unbalanced rearrangements that are larger than our detection limit of 6 Mb. PGS for aneuploidy screening cannot rule out single gene disorders, balanced structural abnormalities, uniparental disomy, and genetic imbalances including deletions and duplications smaller than our detection limit of 6 Mb. PGS can detect some types of polyploidy but cannot detect polyploidy in which the sex chromosomes are found as a multiple of normal (triploidy 69,XXX and tetraploidy 92,XXXX or 92,XXYY).
When an embryo is identified as normal after PGS testing, the likelihood of a pregnancy is higher than 60% in women younger than 40 years. In women over 40 years, there is a higher percentage of cycles in which all embryos are abnormal, but when normal embryos are found, the likelihood of pregnancy is about 50%.
The likelihood that embryos will be chromosomally normal decreases as women get older. According to data generated at Igenomix, the average percentages of normal embryos are:
| Maternal Age (years) | %Normal Embryos |
|---|---|
| 30-34 | 60% |
| 35-39 | 40% |
| 40+ | 20% |
These estimates are based off of a large data set from many combined PGS cases and may not apply to small numbers of embryos from a single PGS case. Igenomix cannot guarantee that there will be normal embryos for any PGS test.
Although PGS for aneuploidy screening is highly accurate, there is still a chance of misdiagnosis. PGS cannot detect mosaicism in the embryo because only a single cell or just a few cells are analyzed. Prenatal testing is recommended to confirm the results of PGS testing and may detect other abnormalities not tested for by PGS. Pregnant mothers should discuss options for prenatal testing with their obstetrician. Non invasive prenatal testing could be also an alternative.
In most cases, documentation of the mutation responsible for the disorder is necessary. In some cases, a clinical report with a clear family history can be sufficient.
Aneuploidy is a numerical chromosome abnormality. Igenomix recommends that PGS for aneuploidy screening be performed in conjunction with PGD testing. Both tests can be done on the same embryo biopsy, so there is no additional risk to the embryo to do PGS testing. PGS for aneuploidy screens for abnormalities in chromosome numbers that could cause miscarriage or could result in the birth of a baby with birth defects and mental retardation. Down syndrome is an example of a genetic disorder that is caused by a numeric chromosome abnormality. The risk of having embryos with aneuploidy increases with maternal age. The goal of PGS testing is to identify embryos that are the most likely to develop to term and to be born healthy.
After the probe has been developed, the IVF cycle and testing of embryos can be completed at the convenience of the patient and the clinic. The probe can be kept long term. Patients needing to delay IVF for longer than 6 months after the probe has been developed should make special arrangements with Igenomix.
No, there is no set-up time necessary for subsequent PGD cycles. This is because the same probe that was made for the couple can be used again for any future testing. If a probe has been made for previous PGD testing with Igenomix, we can proceed directly with embryo testing for future PGD cycles.
At a chromosomal level, NACE detects anomalies in the number of chromosomes, not in their structure. It only detects anomalies for a limited number of chromosomes related with problems in gestations after the second trimester of pregnancy.
If the transfusion was with complete blood you should wait a minimum of six weeks after the transfusion for the NACE test blood extraction.
If you were transfused only with red cells, these do not contain a nucleus or DNA.
In trauma interventions where a lot of blood is transfused the presence of donated leukocytes has been detected up to a year and a half later.
Yes, the test can be done in both cases.
Yes, the NACE test can be done in case of twin gestations, bearing in mind that in these cases we cannot provide information on the fetal sexes, or about any alterations in sexual chromosomes; the test only informs about the presence or the absence of a Y chromosome.
If the sack has disappeared, the NACE test can be indicated. However, it should be noted that DNA originating from the reabsorbed sack could remain in the maternal blood; this could result in a false positive regarding the chromosome number in the viable fetus.
If the sack remains (although it hasn’t developed) the NACE test should not be indicated.
The probability that the sack has disappeared is very high although there is still an elevated risk that the test could produce a false positive if the other fetus had disappeared not long before performing the test, given that quite a lot of DNA from the other fetus will still be present.
Currently there isn’t any empirical data that can confirm the percentage risk or lowest levels of sensitivity of the test in these cases – it is a possible scenario because the DNA analyzed comes from the placenta.
An amniocentesis or chorionic villus biopsy should be carried out. Occasionally, in cases of arrested pregnancy conventional curettage is performed. The chromosomal analysis performed depends on the alteration found and may be:
Conventional karyotype: which will serve to confirm/discard complete or partial aneuploidies in any chromosome as well as results suggestive of mosaicism.
Quantitative fluorescent polymerase chain reaction (QF-PCR): to discard/confirm aneuploidies of chromosomes 13, 18, 21, or sexual chromosomes.
Fluorescent in situ hybridization (FISH) and/or short tandem repeat (STR) analysis: to discard/confirm aneuploidies of chromosomes 9 or 16.
FISH and/or microarray-based comparative genomic hybridization (array CGH): to discard/confirm some microdeletions.
A new maternal blood sample should be taken in a Streck tube and the Igenomix laboratories will determine the fetal sex (free of charge).
Yes, in fact it is estimated that each person carries between 3 and 5 recessive genetic mutations. Being a carrier is not the same as getting the disease. Everyone has two copies of each gene. In individuals carrying, one of the copies is working correctly, and the other copy has the mutation.
The carriers are asymptomatic, so that they are not aware of this condition until a test carrier of genetic mutations are performed.
Most carriers have no family history, so it is not valid to determine whether or not the person is a carrier of mutations that can be transferred to their offspring by just family history.
The prevalence of carriers for some of these diseases is quite common in the population. In fact, one in 25 people are carriers of Cystic Fibrosis, and one in 50 for Spinal Muscular Atrophy.
The American College of Medical Genetics (ACMG) and American Congress of Obstetricians and Gynecologists (ACOG) recommend genetic testing for carriers regardless of pregnancy occurring naturally or through assisted reproduction techniques. If both partners test positive in a Carrier Genetic Test with the same gene mutation, the recommendation is to consult a specialist about options for conceiving a healthy child.
Each test uses its own technology, and provides the screening for a number of mutations and diseases that do not match for all tests available in the market. Moreover, not all are clinically validated; the CGT at IGENOMIX is, thus ensuring only validated results are accepted and compared with the CGT Igenomix.
There is a risk that a person is a carrier despite a negative CGT analysis. There is currently no test able to detect all existing mutations, so there remains a residual risk that the person who has done the test is a carrier of other less frequent mutations.
If you are a carrier, your immediate family will have greater risk of being carriers, so we recommend that CGT is done if they are planning to have children.
When two people carry a mutation in the same gene they have a 50% chance that their children will be carriers of a genetic mutation, 25% will be non-carriers and 25% will be born sick.
Moreover, when there is a parent that is a carrier of a genetic mutation and the other is not, the probability that their child will inherit the mutation of the carrier parent is 50%, the chance of not inheriting, 50%.
Test results are available in 20 business days. In cases where the beginning of treatment is very close, always take the CGT of the two partners simultaneously so that the results are obtained at the same time and the process is not delayed.
If a chromosomal abnormality was detected in a previous pregnancy, a customized SAT can be requested and additional FISH probes can be included in the test to target the implicated chromosomes.
A previous period of 2-3 days of sexual abstinence is recommended before colleting the sample.
There is not a minimal concentration to request a sperm test, the only requirement is the presence of any sperm, even in a concentration below 1 million sperm/mL and also in samples from the epididymis or testes. Seldom there are not enough sperm to perform the test, and additional samples can be requested.
It is possible to test sperm from carriers of translocations using DNA probes implicated in the chromosome rearrangement.
A fresh POC sample is collected from the D&C procedure. The sample is placed in the POC container provided (with saline in the cup), labeled, and placed in the Igenomix kit. The sample can be stored in a cool location (4ºC) for up to 2 days and may be transported at room temperature.
Yes, POC testing can be done if a twin pregnancy has been lost. In this case, samples from each of the fetuses would need to be collected and placed in separate tubes.
Igenomix can perform MitoScore testing on embryos that are biopsied at either day 3 or day 5. A 3-day-old embryo has approximately 8 cells, and so only a single cell is removed for a biopsy done at day 3. A 5-day-old embryo has a few hundred cells, and so several cells can be safely removed during the biopsy. There are several good reasons to do either a day 3 or a day 5 biopsy. The number of cells that can be safely removed, rates of mosaicism, expertise of the embryologist, and embryo quality are all important factors in deciding when to do embryo biopsy. Patients should discuss with their IVF doctor about the best time to do biopsy.
No, MitoScore only gives a value of relative mitochondrial DNA that is indicative of reduced energetic reserve in early embryos.
High mtDNA copy number in euploid embryos is indicative of lower embryo viability and implantation. Using the normalized mtDNA content, Mitoscore (Ms), day-3 embryos with MsA had an implantation rate IR of 59% n=51; those with MsB had an IR of 44%; and those with MsC had an IR of 25% n=52.. Day-5 with MsA had an IR of 81%; MsB had an IR of 56% and those with MsD had an IR of 18% n=17.
High MitoScore value indicates a lower implantation potential; however, it does not mean none of them will be able to implant. Our recommendation is to transfer the embryo or embryos with lower MitoScore and better morphological grade.
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