Introduction: Many couples have experienced long-term inability to conceive, repeated miscarriages and other experiences before reaching the stage of IVF. Indeed, couples who need to rely on assisted reproductive methods to give birth to healthy offspring must be lacking in fertility compared to ordinary people, especially those elderly mothers with reduced ovarian function, just want to get a suitable one.” It is already extremely difficult to plant the seeds”. When the number of “seeds” is extremely scarce, should we continue to select through three generations of IVF technology, or should we give priority to ensuring that there are “seeds” that can be planted? This retrospective study came to the conclusion of a research team from Turkey.
Normally, humans have 46 chromosomes, including 22 pairs of autosomes and one pair of sex chromosomes. However, in some cases, the number of chromosomes will be abnormal, resulting in a certain number of chromosomes no longer the normal 2, but 1 more or 1 less, that is, aneuploidy . Embryos with aneuploidy often experience fetal arrest or miscarriage during development, and in a few cases, they may develop into live births. For example, the well-known Down syndrome is chromosome 21 trisomy. Others include Edward’s syndrome (trisomy 18), Patau’s syndrome (trisomy 13), Klinefelter syndrome (XXY syndrome), Turner’s syndrome (monopoly X syndrome) , XXX syndrome, etc.
In general, aneuploidy is sporadic and sporadic. Aneuploidy is the result of nondisjunction or loss of chromosomes during the maturation of germ cells or the early development of a fertilized egg. A wide range of external factors such as smoking, drinking, drugs, ionizing radiation, etc. may increase the rate of aneuploidy, but there are two important direct factors: (1) The woman’s ovarian function, usually and age (2) One or both spouses have chromosomal structural abnormalities, such as translocations. That’s why doctors recommend such couples to seek help with PGT-A technology in third-generation IVF.
PGT-A, the full name is preimplantation genetic testing for aneuploidies, that is, preimplantation chromosomal aneuploidy detection. The general process of PGT-A is to obtain the sperm and eggs of the couple and then perform artificial insemination, and then culture the fertilized eggs in vitro to the blastocyst stage. At this time, the blastocyst has developed two structures: trophectoderm and inner cell mass. Since the outer trophoblast will later develop into structures such as placenta, in order to minimize the impact on fetal development, embryologists will cut 5- 10 cells (i.e. biopsies) are genetically sequenced, and then combined with the sequencing results and morphological scores, the most suitable embryos are selected from a certain number of blastocysts for subsequent transfer. Over the years, with the continuous upgrading of gene sequencing methods, the detection range of aneuploidy has become more comprehensive. The morphological scoring of blastocysts often uses the Gardner scoring method, which is mainly based on the expansion of the cyst cavity, the hatching of the inner cell mass, the number of trophoblast cells and the inner cell mass. The result given by this scoring rule.
However, the reality often presents the dilemma that only one embryo is available until the biopsy is sequenced. If a biopsy is performed, even if the risk of embryo damage is small, it can cause anxiety in the patient, or forfeit the patient’s only chance of pregnancy because of poor sequencing results, especially for those advanced patients with low ovarian reserve, every Embryos are hard-won; if this embryo is transferred blindly, it will increase the risk of miscarriage or aneuploidy, and when the uterus is cured and the pregnancy is terminated, it is very likely to cause physical damage to the uterus and endometrium, greatly reducing the risk of success rate of subsequent retransplantation. To this end, a scientific and objective assessment of whether PGT-A is truly beneficial for patients with only one blastocyst available is required.
A research team from Istanbul Memorial Hospital and Biruni University in Turkey reviewed data from 2,064 embryo transfer cycles and found that PGT-A significantly increased clinical outcomes in a single-available blastocyst setting Pregnancy and live birth rates, and reduce total pregnancy loss, while cancelling the transfer of aneuploid embryos can prevent those ineffective or potentially risky transfers. On September 20, 2022, the results of the study were published in the Journal of AssistedReproduction and Genetics under the title “What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles” (Figure 1)[ 1].
Figure 1 Research results (Source: [1])
A total of 1126 PGT-A cycles and 938 non-PGT-A cycles were included in this study, with women aged 20 to 45 years. Of the 1126 PGT-A cycles, 225 (20%) yielded a transferable, chromosomally normal embryo, of which 126 (56%) underwent Modified natural cycle frozen embryo transfer transfer, MNC-FET), 99 embryos (44%) underwent artificial frozen embryo transfer (ERT-FET). In the non-PGT-A group, 845 patients received fresh embryo transfer and 93 patients received frozen embryo transfer.
Statistics of demographics, causes of infertility, and assisted reproductive cycle characteristics of the two groups of patients showed that the number of patients diagnosed with unexplained infertility in the PGT-A group was significantly lower, and the number of patients diagnosed with unexplained infertility was significantly lower in the PGT-A group. The number of patients with reduced ovarian reserve (DOR) has increased significantly. Mean age, recurrence of women in PGT-A groupThe history of Recurrent spontaneous abortion (RSA) and Repeated implantation failure (RIF) was significantly higher. These are the reasons why they are recommended for PGT-A.
Table 1Comparison of pregnancy outcomes between PGT-A and non-PGT-A patients (only one blastocyst was available)
Data source: [1]|Table: BioQuest editorial team
Comparing the pregnancy results of the two groups, it was found that the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher in the PGT-A group, and the total miscarriage rate was lower than that in the non-PGT-A group. But not significantly. The live birth rate in the PGT-A group was significantly higher than that in the non-PGT-A group.
Univariate and multivariate analysis of generalized linear mixed models found that female age and PGT-A variables were significant variables for clinical pregnancy and live birth rates: The clinical pregnancy rate was 5.548 times higher, 4.497 times higher in cases aged 35-38, 3.907 times higher in PGT-A cases; the live birth rate was 5.850 times higher in cases under 35 years old, 35- The live birth rate was 5.181 times higher in 38-year-old cases and 3.448 times higher in PGT-A cases. For total pregnancy loss, female age and non-PGT-A variables were significant variables: total pregnancy loss was 2.712-fold higher in 41-43-year-old cases and 1.943-fold higher in non-PGT-A cases. It can be shown that In the case of only one blastocyst available, PGT-A can also significantly increase the clinical pregnancy rate and live birth rate, and reduce the total pregnancy loss, regardless of age. Cancellation of aneuploid embryo transfers can prevent ineffective and risky transfers.
Past studies have also pointed to the benefits of PGT-A in avoiding time wasted by ineffective transplants, and in reducing the emotional burden of miscarriages and persistent aneuploidy pregnancies . In the matter of giving birth, patients with infertility will always face more hardships. How to choose the lesser of two evils is a challenge that doctors have to face. PGT-A is in this situation, to help patients reduce possible harm. How to survive the psychological level and treat fertility with a more rational attitude, rather than rushing to blind trial and error, is also a problem that doctors and patients need to think about together.
Writing|Feng Lixiao
Typesetting|Feng Lixiao
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