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‘’The Position Statement on the transfer of mosaic embryos’’ which was constitued by the International Society for Preimlantation Genetic Diagnosis (PGDIS) was published in the August 2019 issue of Reproductive Biomedicine Online.

Can embryos diagnosed as mosaic by Preimplantation Genetic Diagnosis (PGD) be transferred?

October 2019

A statement on the transfer of mosaic embryos was published by a group of founding members and board members of society at 18th International PREIMPLANTATION GENETICS Congress, April 15-18 2019 In Geneva, Switzerland. A guide was constitued to identify the preferred mosaic embryos to be transferred with the results of the mosaic embryo transfer and current literature by the 20-member team (Cram DS, Leigh D, Handyside A, Rechitsky L, Xu K, Harton G, Grifo J, Rubio C, Fragouli E, Kahraman S, Forman E, Katz-Jaffe M, Tempest H, Thornhill A, Strom C, Escudero T, Jie Q, Munne S, Simpson JL, Kuliev A) including Prof. Dr. Semra Kahraman, who is the founding member of PGDIS and the president of International PGT Society between 2013-2015.

Preimplantation genetic diagnosis (PGD) is the evaluation of the chromosome structures of the cells taken from the embryo by biopsy. Thus, it is aimed to increase the chance of pregnancy by transferring healthy embryos and to increase the number of pregnancies that can reach live birth by decreasing the abortion rate.
Mosaicism is defined as the presence of different chromosome sequences in the biopsy sample. Nowadays, the detection of mosaicism in the embryo can be identified very successfully by the next generation sequencing (NGS) method. Mosaic monosomy, mosaic trisomy and even segmental mosaicism including small region changes such as deletion and duplication can be identified with NGS method.
The rate of mosaicism in embryos is reported to be around 5-10% in the light of information reported from different centers around the world. Around 500 healthy births have been reported in the international literature. In these reports, no anomalies were reported in pregnancies occured by mosaic embryo transfer.
The mosaicism of the embryo less than 40% is defined as low rate mosaicism. In other words, they are defined as mosaics but they are actually completely healthy (euploid) embryos.
It may actually lead to the identification of a non-mosaic embryo as a mosaic embryo depending on the method of biopsy from the embryo and the technique of examining the cells taken. Therefore, the non-conformity of the procedures performed in embryology and genetic laboratories may lead to an increase in the mosaic rate.
The guideline aims to inform both couples and IVF specialists about this issue and to share recommendations.

Recommendations for Embryology Laboratory that will perform biopsy from embryo and follow embryo development;--The technique of the biopsy of the embryo is extremely important.If the number of cells obtained from trophoectoderm cells as a result of biopsy is less than 5, correct evaluation may not be performed due to insufficient data and the embryo can be defined as mosaic even though it is healthy. So it is recommended that the number of cells to be obtained be between 5 and 10 cells.

  • Laser shots should be done as short as possible and from trophoectoderm cell connection points when performing biopsy with laser.
  • If the mosaicism rate in the laboratory is determined above the specified values, it is recommended to review the biopsy technique and genetic cell examination technique.
  • In the literature, while below the threshold of 20% mosaicism is considered as euploidy, over 80% is considered as aneuploidy. When mosaicism is detected between 20%-80%, each laboratory should determine the mosaicism rates at its safe limits and give information of the preferred mosaic embryos to be transferred to the couples. The recommendation is to select low-rate mosaic embryos for transfer.

Recommendations for IVF Clinicians;

  •  It should be explained to couples that mosaicism may occur due to technical reasons in laboratories and that the embryo diagnosed as mosaic can actually be a completely healthy embryo.
  •  The patient information and consent forms for aneuploidy testing should be modified to include the possibility of mosaic results and any potential risks in the event of transfer and pregnancy. This needs to be explained to patients by the person recommending PGT-A.
  •  Instead of mosaic embryo transfer,  first of all with a new IVF trial and transfer of a completely healthy embryo should always be suggested. The possibility of finding a completely healthy embryo in the new trial should be realistically discussed according to the couple's own situation, if this possibility is very poor then the option of low-rate mosaic embryo transfer should be discussed with the couple. In spite of these suggestions, the couple may request the transfer of the mosaic embryo as a priority,then transfer of mosaic embryos with low rate mosaicity and without risky chromosomes should be considered.

Prenatal tests are strictly recommended in pregnancies after mosaic embryo transfer. Early amniocentesis after 14 weeks is recommended. For the early weeks of pregnancy, after 10 weeks, non-invasive prenatal testing (NIPT), which evaluates 24 chromosomes  is recommended. Ultrasonography, Doppler ultrasonography and PAPP-A tests can also be used as additional tests.

Recommendations for priority preference for mosaic embryos to be transferred;

  • -- First of all, transfer of low rate (20% -40%) mosaic embryos should be preferred over high rate mosaic embryos.
  • -- The transfer of mosaic chromosomes 14 and 16, which can cause uniparental disomy, has been reported with the least priority since it causes serious intrauterine growth retardation. The transfer of chromosomes (trisomy 16, 18, 21 and 45, X, 47, XXY, 47, XXX) that may cause  postnatal syndrome after birth should not be preferred. 

The development of PGD and gene technologies has led to the successful identification of genetic abnormalities prior to embryo transfer. In IVF pregnancies, there is no increase in chromosomal abnormalities in babies compared to naturally occurring pregnancies. When the data of the transferred mosaic embryos and the pregnancy results are examined, it is very unlikely that there will be a risk with the transfer of low rate mosaic embryos. Therefore, transfer of low-risk mosaic embryos has been an option of choice for couples. Low risk mosaic embryo transfer can be recommended after discussing the risks in detail and explaining the pregnancy follow-up method, such as a non-invasive comprehensive NIPT that discloses all chromosomes or invasive tests such as amniocentesis where mosaicism can be identified.