Cell-based non-invasive prenatal testing for monogenic disorders: confirmation of unaffected fetuses following preimplantation genetic testing.

PURPOSE: Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M). METHOD: PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS. RESULTS: Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1-6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results. CONCLUSION: These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS. TRIAL REGISTRATION NUMBER: N-20180001.

[Transport-in vitro-fertilization/intracytoplasmic sperm injections in Denmark]. / Transport-in vitro-fertilisation/intracytoplasmatisk sperminjektion i Danmark.

INTRODUCTION: This study describes the results obtained with a small IVF/ICSI-transport programme carried out between a private specialist clinic and a public IVF-clinic. MATERIALS AND METHODS: All women treated in the specialist clinic over a three and a half years period were entered. Ovarian stimulation, oocyte aspiration, and the follow-up after fertilisation were carried out in the specialist clinic, whereas fertilisation, culture and embryo transfer were performed in the public IVF clinic 25 km away. The oocytes were transported in an insulated box kept at 37 degrees C. RESULTS: Totally 314 stimulation cycles were performed with 68% IVF, 19% ICSI, and 13% cycles with cryopreserved oocytes (FER). The material comprises 259 oocyte aspirations with a total of 1969 oocytes, 1229 were fertilised. Oocyte and transfer-data are given in Table 2. The pregnancy rate was 29% for IVF and 27.1% for ICSI, but only 12.2% in FER. DISCUSSION: These results are consistent with that of other private and public IVF treatments in Denmark, where differences in population and oocyte handling are comparable (Table 3). As reported from the Netherlands, the UK, and Argentina (Table 4) transportation of oocytes does not seem to damage their potential for fertilisation and implantation.