Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

<b><i>Objective:</i></b> Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. <b><i>Methods:</i></b> A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT &#x3e;3 mm with septations. Cases of simple increased NT without septations were excluded. <b><i>Results:</i></b> During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). <b><i>Conclusions:</i></b> Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration

Purpose The aim of our study was to evaluate the impact of severe male infertility (SMF) on the chromosomal status of embryos and any possible correlation between chromosomal status and embryo morphokinetics in younger women using data obtained from comprehensive preimplantation genetic tests. Methods The trial was conducted in an ART and Reproductive Genetics Centre between 2011 and 2018. A total of 326 cycles in cases with SMF where the female partner’s age was ≤ 35 years were evaluated. SMF is defined as sperm concentration below 5 mil/ml (million per milliliter) and divided into three subgroups according to sperm concentrations: 1–5 mil/ml, < 1mil/ml and testicular sperm. The control group of 190 cycles had normal sperm parameters. Results Significantly lower chromosomal euploidy rates were found in the testicular sperm group compared with the normal sperm controls when the female age was ≤ 35 years. In SMF, statistically significantly affected chromosomes were 2, 10, 11, 17, 21 and sex chromosomes. The mosaicism and abnormal morphokinetic development rates were higher in the SMF group than in control group, and this difference was significant when testicular sperm was used. Conclusion Lower euploidy rates, higher mosaicism rates and a higher incidence of abnormal morphokinetic development were observed in cases with testicular sperm with female partners ≤ 35 years compared with normal sperm controls. These findings suggest that PGT-A may be advisable in severe male infertility cases. Furthermore, the correlation between morphokinetics and chromosomal status was greatly reduced or absent in these most severe forms of male infertility, thus the need for new morphokinetic models.

Embryos Arising from Apronuclear (0PN) and Unipronuclear (1PN) Have Similar Euploidy Rates with Those from 2PN and Should be Considered for Transfer

Background: Fertilisation assessment is routinely made at 16–18 hours post-ICSI and 18–20 hours post-insemination. However, the absence of pronuclei (PN) during standard fertilisation assessment does not necessarily indicate fertilisation failure. The aim of this study is to assess the chromosomal status of blastocysts derived from 0PN and 1PN zygotes as well as to assess the clinical outcome after transfer of such embryos. Methods: In this study, we use microarray comparative genomic hybridisation (MaCGH) or next generation sequencing (NGS) to analyse the chromosomal status of 271 blastocysts (204 from 2PN, 41 from 0PN, 26 from 1PN) obtained from 42 patients who underwent conventional IVF (cIVF) and ICSI cycles with preimplantation genetic testing for aneuploidy (PGT-A). Results: Euploidy was confirmed in 126 (126/204; 61.8%), 31 (31/41; 75.6%) and 18 (18/26; 69.2%) 2PN-, 0PN- and 1PN-derived blastocysts respectively while the remaining 96 blastocysts displayed various chromosomal abnormalities. A Y-chromosome was observed in 0PN-derived blastocysts (19/41; 46.3%) and 1PN-derived blastocysts (13/26; 50%), indicating that sperm had penetrated the oocyte and not due to parthenogenetic activation. Four euploid 0PN-derived blastocysts were transferred to 4 patients and 3 healthy live births were achieved. Four euploid 1PN-derived blastocysts were transferred to 4 patients and 1 on-going pregnancy was achieved. Conclusion(s): 0PN- and 1PN-derived zygotes can be chromosomally normal and result in healthy live births. Such zygotes should not be discarded but instead be subjected to extended culture with PGT-A to ascertain the chromosomal and ploidy status and be considered for transfer.

Gonadal Cytogenetic Damage from Exposure to Extrinsic Agents

This chapter is a compendium of what is known about the susceptibility, or resistance, of the gonad to agents that might seem candidates for possibly causing damage, and with particular reference to chromosomal status of gametes. A main focus is on cancer treatments. A majority of children and young adults who receive modern cancer treatment survive. Some treatments cause sterility, but in quite a number, fertility is unscathed, or at any rate, subsequently recovers. The chapter also references industrial, environmental, and recreational factors. A notable and substantially reassuring conclusion from these data is the apparent dearth of instances of an extrinsic factor having caused a chromosome abnormality in the sperm or egg of an exposed person.