The effective implementation of whole-exome sequencing- and whole-genome sequencing-based diagnostics in the management of children affected with genetic diseases and the rapid decrease in the cost of next-generation sequencing (NGS) enables the expansion of this method to newborn genetic screening programs. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter is aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents. However, the idea of NGS-based screening in healthy children raises issues of medical and ethical integrity as well as technical questions, including interpretation of the observed variants. Pilot studies have shown that both parents and medical professionals have moved forward and are enthused about these new possibilities. However, either the number of participants or the number of genes studied in previous investigations thus far has been limited to a few hundred, restricting the scope of potential findings. Our current study (NCT05325749) includes 7,000 apparently healthy infants born at our center between February 2021 and May 2023, who were screened for pathogenic variants in 2,350 genes. Clinically significant variants associated with early-onset diseases that can be treated, prevented, or where symptoms can be alleviated with timely introduced symptomatic therapy, were observed in 0.9% of phenotypically normal infants, 2.1% of the screened newborns were found to carry variants associated with reduced penetrance or monogenic diseases of adult-onset and/or variable expressivity, and 0.3% had chromosomal abnormalities. Here, we report our results and address questions regarding the interpretation of variants in newborns who were presumed to be healthy.

To date the world community is actively working to optimize the approaches to determining chromosomal abnormalities in embryos. The study was aimed to assess the possibility of using noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) through analysis of cell-free DNA in spent culture medium (SCM). We conducted niPGT-A of aneuploid embryos by analysis of cell-free DNA in SCM. All blastocysts were considered to be aneuploid based on the results of previous preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy. The study involved 11 embryos from seven couples. All the embryos were warmed and individually cultured in the 10 µL drops for 9 h. All SCM was collected and analyzed by niPGT-A. The results obtained were tested for concordance with previous PGT-A data. A total of 12 SCM samples were assessed: 11 samples, in which the embryos were cultured, and one control sample. Chaotic niPGT-A results not allowing the karyotype diagnosis were obtained in one case (9.1%) out of 11. Full concordance of the PGT-A and niPGT-A results was revealed in seven cases out of 10 (70%), while clinical concordance was found in nine cases out of 10 (90%). In one case (10%), the blastocyst was considered to have euploid karyotype based on the niPGT-A data. It has been concluded that niPGT-A can be a promising method of preimplantation embryonal chromosomal status diagnosis that requires no biopsy.

V nastoyashchee vremya v mire idet aktivnaya rabota po optimizacii primeneniya podhodov k opredeleniyu hromosomnoj patologii embrionov. Cel'yu issledovaniya bylo ocenit' vozmozhnost' ispol'zovaniya neinvazivnogo preimplantacionnogo geneticheskogo testirovaniya na aneuploidii (niPGT-A) putem analiza vnekletochnoj DNK v otrabotannoj kul'tural'noj srede (OKS). Provedeno niPGT-A aneuploidnyh embrionov putem analiza vnekletochnoj DNK v OKS. Vse blastocisty byli aneuploidnymi po rezul'tatam predshestvuyushchego preimplantacionnogo geneticheskogo testirovaniya na aneuploidii (PGT-A) s biopsiej trofektodermy (TFE). V issledovanie bylo vklyucheno 11 embrionov ot semi supruzheskih par. Vse embriony razmorazhivali i kul'tivirovali v kaplyah po 10 mkl v techenie 9 ch. Ves' ob"em OKS sobirali i analizirovali putem niPGT-A. Poluchennye rezul'taty sravnivali na sootvetstvie s predshestvuyushchimi dannymi po PGT-A. Summarno vypolnili analiz 12 obrazcov OKS: 11 obrazcov, v kotoryh byli kul'tivirovany embriony, i odin kontrol'nyj obrazec. V odnom sluchae (9,1%) iz 11 byli polucheny haotichnye rezul'taty po dannym niPGT-A, ne pozvolyayushchie provesti diagnostiku sostoyaniya kariotipa. Polnoe sootvetstvie rezul'tatov PGT-A i niPGT-A polucheno v semi sluchayah iz 10 (70%), klinicheskoe sootvetstvie rezul'tatov — v devyati sluchayah iz 10 (90%). V odnom sluchae (10%) po dannym niPGT-A kariotip blastocisty byl diagnostirovan kak euploidnyj. Vyvod: niPGT-A mozhet byt' perspektivnym, ne trebuyushchim biopsii, metodom diagnostiki hromosomnogo statusa preimplantacionnyh embrionov.

Abstract The effective implementation of WES and WGS-based diagnostics in the management of children afflicted with genetic diseases and the rapid decrease in the cost of NGS makes the idea of newborn genetic screening very appealing. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter being aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents. However, the idea of NGS-based screening in healthy children raises issues of medical and ethical integrity as well as technical questions including interpretation of the revealed variants. A few pilot studies have shown that both parents and medical professionals have moved forward and are enthused about these new possibilities. However, the number of participants in studies so far has been limited to a few hundreds, which greatly restricts the scope of potential findings. Our current study includes over 7,000 infants born at our center between February 2021 and May 2023. Clinically significant variants that cause treatable or preventable disorders were observed in 0.9% of inconspicuous infants, 2.1% of the screened newborns being found to carry variants associated with monogenic diseases with incomplete penetrance or late onset and 0.3% having chromosomal abnormalities. Here we report our results and address questions regarding interpretation of variants in newborns who were presumed to be healthy.

Проведение преимплантационного генетического тестирования на определение анеуплоидий (ПГТ-А) при экстракорпоральном оплодотворении (ЭКО) является одним из методов первичной профилактики некоторых наследственных заболеваний. Следовательно, процедура ПГТ-А может способствовать повышению востребованности программ вспомогательных репродуктивных технологий (ВРТ) и быть экономически оправданной. ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить значение и возможности применения ПГТ-А у супружеских пар разных возрастных групп при лечении бесплодия методом ВРТ. МАТЕРИАЛ И МЕТОДЫ За период 2016—2021 гг. проанализировано 1 108 протоколов ЭКО, включающих интрацитоплазматические инъекции сперматозоида в ооцит (ЭКО/ИКСИ) и процедуры ПГТ-А эмбрионов супружеских пар трех возрастных групп: 22—30, 31—36 и 37—46 лет. РЕЗУЛЬТАТЫ Самыми частыми причинами проведения ПГТ-А в программах ВРТ были старший, 37 лет и более, репродуктивный возраст женщин (48%), нарушения сперматогенеза (35%), множественные неудачные попытки ЭКО в анамнезе (20%), а также наличие экстрагенитального эндометриоза у женщин старшего репродуктивного возраста (15%). За период наблюдения количество выполненных комплексов процедур ЭКО/ИКСИ с проведением ПГТ-А увеличилось в 2,1 раза. Эффективность программы ЭКО/ИКСИ с проведением ПГТ-А эмбриона была сопоставима в разных возрастных группах супружеских пар и находилась в пределах 39—41%. ЗАКЛЮЧЕНИЕ Проведение преимплантационного генетического тестирования эмбриона на определение анеуплоидий является экономически оправданной процедурой в определенных клинических ситуациях, повышая тем самым востребованность программ ВРТ. Сопоставимая эффективность выполненных протоколов, включающих ЭКО/ИКСИ и ПГТ-А эмбриона, в различных возрастных группах супружеских пар может быть связана с особенностями критериев включения пациентов в данное исследование, а также свидетельствовать о важной, определяющей, роли качества эмбриона в исходах таких программ.

Расширение возможностей вспомогательных репродуктивных технологий, в частности проведение биопсии клеток трофобласта на 5-е и 6-е сутки культивирования и последующее преимплантационное генетическое тестирование, в настоящее время значительно актуализировало вопросы реализации репродуктивной функции у пациентов с носительством моногенных заболеваний, к которым принадлежит и муковисцидоз. Муковисцидоз является одним из наиболее часто встречающихся моногенных заболеваний в российской популяции. В связи с этим гинекологам и репродуктологам важно понимать правильный алгоритм ведения таких пациентов в рамках программ лечения бесплодия и с целью рождения здоровых детей. В статье описан клинический случай рождения двух здоровых детей у супружеской пары с гетерозиготным носительством генетического варианта F508del в гене CFTR. Рожденные дети физически здоровы, развиваются соответственно возрасту.