Perinatal follow-up of children born after preimplantation genetic diagnosis between 1995 and 2014.

PURPOSE: We aim to evaluate the safety of PGD. We focus on the congenital malformation rate and additionally report on adverse perinatal outcome. METHODS: We collated data from a large group of singletons and multiples born after PGD between 1995 and 2014. Data on congenital malformation rates in live born children and terminated pregnancies, misdiagnosis rate, birth parameters, perinatal mortality, and hospital admissions were prospectively collected by questionnaires. RESULTS: Four hundred thirty-nine pregnancies in 381 women resulted in 364 live born children. Nine children (2.5%) had major malformations. This percentage is consistent with other PGD cohorts and comparable to the prevalence reported by the European Surveillance of Congenital Anomalies (EUROCAT). We reported one misdiagnosis resulting in a spontaneous abortion of a fetus with an unbalanced chromosome pattern. 20% of the children were born premature (< 37 weeks) and less than 15% had a low birth weight. The incidence of hospital admissions is in line with prematurity and low birth weight rate. One child from a twin, one child from a triplet, and one singleton died at 23, 32, and 37 weeks of gestation respectively. CONCLUSIONS: We found no evidence that PGD treatment increases the risk on congenital malformations or adverse perinatal outcome. TRIAL REGISTRATION NUMBER: NCT 2 149485.

Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors.

Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC are evaluated in an observational cohort study on treatments carried out in two of Western-Europe's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. 70 Couples underwent PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(PGD) in female carriers needs further evaluation.

ESHRE PGT Consortium good practice recommendations for the organisation of PGT.

The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for preimplantation genetic diagnosis, published in 2005 and 2011, are considered outdated and the development of new papers outlining recommendations for good practice in PGT was necessary. The current updated version of the recommendations for good practice is, similar to the 2011 version, split into four documents, one of which covers the organisation of a PGT centre. The other documents focus on the different technical aspects of embryo biopsy, PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). The current document outlines the steps prior to starting a PGT cycle, with details on patient inclusion and exclusion, and counselling and information provision. Also, recommendations are provided on the follow-up of PGT pregnancies and babies. Finally, some further recommendations are made on the practical organisation of an IVF/PGT centre, including basic requirements, transport PGT and quality management. This document, together with the documents on embryo biopsy, PGT-M and PGT-SR/PGT-A, should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis.

OBJECTIVE: To evaluate the growth, health, and motor development of children born after preimplantation genetic diagnosis (PGD). DESIGN: Observational cohort study and comparison of 5-year-old children born after PGD to similar aged children born after IVF/intracytoplasmic sperm injection (ICSI) and children from families with a genetic disorder born after natural conception (NC). SETTING: University hospital. PATIENT(S): One hundred three children were included in the PGD group. The two control groups consisted of 90 children born after IVF/ICSI and 58 children born after NC. INTERVENTION(S): PGD. MAIN OUTCOME MEASURE(S): We measured height, weight, body circumferences, body mass index, and blood pressure and performed a dysmorphological and neurological examination. We also collected data about the children's medical history, health care consultations, and motor milestones. RESULT(S): The mean height, weight, and body mass index were comparable for all groups. Six (5.8%) PGD, four (4.4%) IVF/ICSI, and five (8.6%) NC children had a major congenital abnormality. The incidence of acute and chronic illnesses was similar in all groups. Motor milestones were achieved on time, but the IVF/ICSI group had a slightly younger mean sitting age. None of the children had severe neurological problems. CONCLUSION(S): Five-year-old children born after PGD show normal growth, health, and motor development when compared with children born after IVF/ICSI and NC children from families with a genetic disorder. TRIAL REGISTRATION NUMBER: NCT02149485.

Dynamic cervical length changes: preliminary observations from 30-minute transvaginal ultrasound recordings.

OBJECTIVE: The purpose of this study was to visualize and quantify dynamic changes in the cervix and to study factors influencing cervical length. METHODS: Eighteen women with a gestational age between 23 and 40 weeks were examined by transvaginal ultrasound during a continuous observation period of 30 minutes. RESULTS: All women delivered at >34 weeks of gestation, fourteen at term. The overall mean difference between the shortest and longest cervical length during the 30-minute recordings (cervical length variation) was 10.9 mm (range 1.6-26.7 mm). In the presence of fetal movements directed at the cervix, peristaltic movement of the bowel or contractions, cervical length variation was larger than in the absence of these conditions (mean 12.7 mm, range 5.2-26.7 mm and mean 6.1 mm, range 1.6-9.4 mm, respectively; p = 0.03). CONCLUSIONS: Dynamic changes in cervical length are present at early gestation and long before delivery and can be observed either spontaneously or associated with contractions, fetal movements or peristalsis. These conditions must be considered as pitfalls in cervical length measurement. In critical cases, such as early threatened preterm labor, increases in the frequency and duration of sonographic ultrasound measurements may be helpful to obtain a more reliable estimation of the cervical status.

Methods of sonographic cervical length measurement in pregnancy: a review of the literature.

In this review we give an overview of the methods and pitfalls in cervical length measurements. We compared the different techniques and investigated factors that influence visualization of the cervix. The data in this overview may be used to establish guidelines in clinical practice.