Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos

Previous studies assessing the relationship between embryo development, maternal age and chromosome abnormalities were either small or analysed mostly embryos not suitable for replacement. The present study includes >6000 embryos, including many suitable for replacement. Embryos with the best morphology and development were 44% euploid in patients younger than 35, decreasing to 21% in patients 41 and older. The worst morphology group had only 30% normal embryos from patients younger than 35, and 12% in embryos from patients 41 and older. Thus morphological analysis was able to improve the population of normal embryos only from 30 to 44% in the best of cases. Regarding specific abnormalities, 20% of embryos were aneuploid, 32% aneuploid plus other abnormalities, and the rest had post-meiotic abnormalities. Of those, only aneuploidy increased with maternal age. There were no big differences in the frequency of chromosome abnormalities depending on patient indication, within a similar age group. In summary, previous trends detected in suboptimal embryos were also confirmed in the best embryos for replacement. Although dysmorphism and advanced maternal age are both related to chromosome abnormalities, these parameters can yield at most <50% euploid embryos, and other techniques such as preimplantation diagnosis are required to ensure that only euploid embryos are replaced.     

More than the oocyte source,egg donors as patients: a national picture of United States egg donors

PurposeTo characterize national oocyte donation practice patterns from the perspective of individual donors rather than of recipients.MethodsRetrospective cohort including all donor oocyte retrievals and transfers reported to SARTCORS in 2016 and 2017 in the USA. Primary outcomes include characteristics of oocyte donors and of donor oocyte cycles. Secondary outcomes include overall pregnancy rates, elective single embryo transfer (eSET) rates, and perinatal outcomes among donor oocyte recipient transfers.ResultsDuring the study period, 49,193 donor oocyte retrievals were performed, of which the largest proportion were in the Western US. For all reported retrievals, there were 17,099 unique donors, each of whom underwent an average of 2.4 retrievals (range 1–22). Average donor age was 26.3 years (range 18–48). On average, 24.6 oocytes (SD 12.4) were retrieved each cycle, ranging from 0 to 102. Among 37,657 donor oocyte recipient transfers, 20,159 (53.5%) involved eSET, and 17,725 (47.1%) resulted in live birth. Miscarriage rates were 17.5%, and good perinatal outcome (GPO), defined as full-term normal birthweight delivery, was more likely among singleton (75.7%) than multiple (23.8%) pregnancies.ConclusionThe average number of retrievals that donors underwent and oocyte yield mirrored national guidelines; however outliers, exist that may unnecessarily increase donor risk. Additionally, among resultant donor transfers, 46.5% transferred more than one embryo despite national recommendations for eSET. The significantly higher likelihood of GPO among singleton pregnancies points to the need to further increase donor recipient eSET rates.     

High incidence of chromosomal abnormalities in oocyte donors

Oocyte donors are chosen among phenotypically normal and fertile women who are not expected to carry any chromosomal abnormality. A high incidence of balanced structural chromosomal rearrangements has been found within oocyte donors. This result raises the question of a possible bias in their recruitment with respect to their familial background and/or personal reproductive history.     

Chromosome abnormalities in 1255 cleavage-stage human embryos

The relationship was examined between chromosome abnormalities in cleavage stage human embryos and maternal age, embryo morphology and development rate. Embryos that were classified as suboptimal for transfer from patients undergoing IVF treatment were disaggregated, and all or most of their cells were fixed for analysis by fluorescence in-situ hybridization. Chromosomes X, Y, 13, 18 and 21, and in some instances 16 were examined. A total of 731 non-viable embryos was analysed. An increase in chromosome abnormalities with decreasing embryo competence and increasing maternal age was shown. Compared with an earlier study, the major difference was that polyploidy (P<00.01) and aneuploidy were previously more common. After pooling results, it was found that aneuploidy increased with maternal age, from 3.1% in embryos from 20-34 years old patients to 17% in patients 40 years or older. Also, aneuploidy occurred more frequently in embryos with good morphology and development rate than in embryos developing poorly. In contrast, dysmorphic and slowly developing or arrested embryos had significantly more polyploidy and mosaicism than normally developing embryos. Clear associations between maternal age and aneuploidy, and between cleavage anomalies and mosaicism have been established in non-viable embryos. Arrested embryos were mostly polyploid. Moreover, polyploidy was found more frequently in embryos analysed on day 4, suggesting that developmentally compromised embryos became arrested in extended culture. A slightly higher aneuploidy rate in the earlier study may be attributed to differences in hormonal stimulation, which also resulted in different numbers of oocytes recruited and matured.     

Prenatal diagnosis of chromosome abnormalities.

It is possible to define a group of prospective parents who are at risk of producing offspring with disability due to chromosomal abnormalities. Such individuals should have evaluation of the 15 or 16 week fetus by karyotype of amniotic fluid cells. The techniques and problems of such diagnostic procedures are discussed.     

In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage: an analysis of chromosome abnormalities in human preimplantation embryos

Objective: To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage (RM) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases.

Design: Prospective controlled study.

Setting: University laboratory of reproductive genetics and a tertiary referral center for infertility.

Patient(s): Nine women with a mean (±SD) of 3.9 ± 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis, and a control group of young (n = 10) and older (n = 6) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases.

Intervention(s): In vitro fertilization, embryo culture for 72 hours, blastomere biopsy, and analysis of chromosomes 13, 16, 18, 21, 22, X, and Y with the use of fluorescent in situ hybridization. Transfer of chromosomally normal embryos into the uterus.

Main Outcome Measure(s): Numeric chromosomal abnormalities in human embryos.

Result(s): Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients. There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls. Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group, especially those affecting chromosome 13.

Conclusion(s): There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM. The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure.     

性分化异常患者的细胞遗传学病因分析

目的：性分化异常的细胞遗传学病因。方法：每例性分化异常患者取外周血淋巴细胞常规制备染色体。Ｇ带、Ｃ带,高分辨显带及银染技术分析核型。结果：１１１例性分化异常患者中检出染色体异常４５例,数量异常１４例,结构异常３１例,包括缺失、倒位、易位、环状染色体、额外小染色体等。结论：染色体异常是性分化异常的重要原因,分析患者的核型,对于诊断及治疗均有一定意义。     

Chromosomal abnormalities in embryos derived from testicular sperm extraction

OBJECTIVE: To compare the rate of chromosome abnormalities in embryos obtained from karyotypically normal patients with nonobstructive azoospermia undergoing testicular sperm extraction (TESE) to those from patients undergoing intracytoplasmic sperm injection (ICSI) with ejaculated sperm. DESIGN: Retrospective analysis. SETTING: IVF centers. PATIENT(S): Male partners had either nonobstructive zoospermia or oligospermia. INTERVENTION(S) : Preimplantation genetic diagnosis. Chromosome enumeration was performed by fluorescence in situ hybridization (FISH). Embryos classified as abnormal were reanalyzed to study mosaicism. MAIN OUTCOME MEASURE(S): Chromosome abnormalities in embryos. RESULT(S): Embryos from ICSI cycles with ejaculated sperm (group 1) were 41.8% normal, 26.2% aneuploid, and 26.5% mosaic. In contrast, the embryos from ICSI cycles with TESE for nonobstructive azoospermia (group 2) were 22% normal, 17% aneuploid, and 53% mosaic. The difference in mosaicism rate between the two groups of embryos was highly significant. CONCLUSION(S): The present study results indicate a high incidence of mosaicism in embryos derived from TESE in men with a severe deficit in spermatogenesis. Sperm derived from TESE for nonobstructive azoospermia may have a higher rate of compromised or immature centrosome structures leading to mosaicism in the embryo.     

Sonographic findings in fetuses with common chromosome abnormalities

This article has detailed the common prenatal sonographic findings that have been detected in fetuses with Down syndrome, trisomy 13, trisomy 18, Turner syndrome, and triploidy. It should be noted that not all fetuses with these five chromosomal abnormalities will have sonographically detectable malformations and that some may not be easily recognizable even at birth. It is crucial that the approach to the patient with a sonographically detected fetal malformation be thorough, systematic, and expeditious. The first step is to attempt to accurately define the abnormality. Next, syndromes with which this malformation are associated should be researched and a differential diagnosis constructed. Based on this differential, accompanying findings with which this abnormality is often associated should be looked for sonographically. A detailed history including pedigree information, possible teratogen exposure, consanguinity, and ancestry is imperative. In some cases a Mendelian disorder may be identified by obtaining a thorough prenatal genetic history. In virtually all cases of prenatally detected fetal malformations, chromosome analysis is indicated. Amniocentesis is the most common means of fetal chromosome analysis, but usually takes at least 2 weeks for results. In cases where the gestation is approaching the legal limit for elective termination, rapid karyotyping by percutaneous umbilical cord sampling should be considered and referral to a center familiar with this procedure is suggested. Chromosome analysis from fetal blood takes approximately 3 days to accomplish. Alternatively, rapid karyotyping by transabdominal chorionic villus biopsy may also be accomplished and has been performed as late as 37 weeks gestation. This procedure may be especially advantageous in cases where oligohydramnios is present. If a chromosomal abnormality is identified, genetic counseling should be arranged to discuss prognosis, cause, recurrence risks and to help the parents through this difficult time. If applicable, the option of pregnancy termination should be offered. Not all parents faced with a chromosomally abnormal fetus will wish to terminate their pregnancy and others may be too late in gestation to consider this option. In these cases, discussions with other families raising similarly affected children, social workers, clergy, psychiatrists, and geneticists may be helpful to the parents. Late pregnancy prenatal cytogenetic diagnosis may be beneficial both to the parents in helping prepare them psychologically and emotionally for an adverse outcome and in guiding obstetric management.(ABSTRACT TRUNCATED AT 400 WORDS)     

Detection of chromosomal abnormalities in human preimplantation embryos using FISH

Purpose: Multicolour FISH has been used for the preimplantation diagnosis of sex for X-linked disorders and to examine the chromosome constitution of early human embryos. Materials and Methods: Single blastomeres and whole embryos were spread using HCl and Tween 20. Multicolour FISH was performed using directly-labelled human DNA probes for chromosomes X, Y, and I in a two hour FISH procedure. Results: Four groups of chromosome arrangements have been found in human preimplantation embryos (i) normal, all nuclei uniformly diploid, (ii) diploid mosaics, majority of the nuclei diploid, with a small number of nuclei aneuploid (iii) chromosomally abnormal, all nuclei uniformly chromosomally abnormal, e.g. XO, XXY, XXX and (iv) chaotic, all nuclei showing different chromosome complements. Conclusions: For the preimplantation diagnosis of sex, an XX nucleus has always been representative of a female embryo. However, for the diagnosis of dominant disorders or chromosome abnormalities, two cells should be analysed to reduce the chance of misdiagnosis which may arise from chromosomal mosaicism. Implantation and further embryo development may be possible from mosaic or chromosomally abnormal embryos, but those showing chaotic chromosome arrangements would be unlikely to implant.Presented at the 5th Annual Meeting of the International Working Group on Preimplantation Genetics, Hamburg, Germany, June 28, 1995.     

Incidence of fetal chromosome abnormalities in 2264 low-risk women

Among a population of 6305 pregnant women, aged 25 to 34 years and estimated to be at no increased risk of genetic disease in the fetus, 4606 women participated in a randomized controlled trial of genetic amniocentesis between 1980 and 1984. In the study group having amniocentesis (2264 women), 23 fetal chromosome abnormalities (1.0 per cent) were found: eight autosomal aneuploidies, seven sex chromosome aneuploidies, seven balanced structural rearrangements and one case of a marker chromosome. The structural rearrangements and the marker chromosome were all shown to be inherited. The study group seemed representative for the whole population of younger women at low genetic risk. Therefore, a 1.0 per cent total rate of fetal chromosome abnormalities, consisting of one-third autosomal aneuploidies, one-third sex chromosome aneuploidies and one-third structural rearrangements, may be expected in the second trimester in younger low-risk women. In the same period of time, 562 women in the same age group were offered amniocentesis because of an estimated increased risk of fetal genetic disease. The total rate of fetal chromosome abnormality in this 'high-risk' group was 0.9 per cent and thus no different from the rate in the low-risk group.     

Carrier of numerical chromosome abnormalities in infertile married couples

OBJECTIVES: Genetic anomalies are one of many conditions causing infertility. DESIGN: The aim of the study was to define the frequency of numerical chromosome aberrations in infertile married couples. MATERIALS AND METHODS: Metaphasal chromosomes were analysed by G-T-G stration in 650 patients, i.e. 325 married couples. Chromosomes for testing had been obtained from peripheral blood lymphocytes. RESULTS: Of all women and men, numerical chromosome anomalies were found in 14 married couples (4.1%). The aberrations were connected with female factors in 8 couples (2.3%), and with male factors in 6 (1.8%). CONCLUSIONS: Results of the study indicate that diagnostic procedure for infertility should preferably include cytogenetic examinations as well.     

Parental decisions following the prenatal diagnosis of sex chromosome abnormalities

OBJECTIVE: To report parental decisions regarding pregnancy termination following the prenatal diagnosis of a sex chromosome abnormality (SCA) in the fetus. METHODS: Retrospective collection of data from records of 61 families receiving genetic counseling after prenatal diagnosis of a sex chromosome abnormality in the fetus in the Division of Medical Genetics, University Hospital of Geneva during the time period 1980-2001. RESULTS: Among 61 couples with a prenatal diagnosis of a sex chromosome abnormality (SCA), 44 couples (72.1%) decided to terminate pregnancy. Pregnancy termination rates were 100, 73.9, 70, 50 and 42.9% for Turner syndrome, Klinefelter syndrome, 47,XXX females, 47,XYY males, and mosaic cases, respectively. In all 11 cases with a fetal abnormality seen on ultrasound, pregnancy was terminated. Termination rates were higher among couples with a higher mean number of previous children. Maternal age and year of test did not influence parental decisions. CONCLUSIONS: Parental decision to terminate a pregnancy for a fetus with a SCA varied by type of sex chromosome abnormality, by presence of fetal ultrasound anomalies, and by the mean number of previous children.     

Clinical implications of atypical chromosome abnormalities diagnosed prenatally

OBJECTIVE: To determine the frequency of atypical aneuploidy resulting from prenatal testing and assess the implications of these diagnoses on prenatal decision making. METHODS: We reviewed all amniotic fluid and chorionic villus samples obtained between January 1994 and September 1997 and grouped the abnormal cases into typical or atypical subcategories. This distinction was based upon whether the diagnosis provided a straightforward range of prognoses or an ambiguous clinical implication. Results were stratified by sample source to determine whether atypical aneuploidy was more commonly seen in cultures of chorionic villi or amniocytes. We also evaluated the influence of ultrasound findings on prenatal decision making in atypical aneuploid cases. RESULTS: Of 2960 samples, 134 were abnormal (4.4%), with 27 of 134 abnormalities (20%) representing atypical aneuploidies. The percentages of chorionic villus and amniocentesis cases complicated by atypical aneuploidy (22% and 78%, respectively) were consistent with the distribution of procedures in the entire study. Ultrasound abnormalities did not invariably prompt a decision to terminate pregnancy (only two terminations of six fetuses with congenital malformation), whereas atypical karyotypes led to termination even in the presence of normal-appearing fetal anatomy (five terminations of 21 without malformations; P = .63). CONCLUSION: The frequency of atypical aneuploidy resulting from prenatal diagnosis was approximately 1.0%, and these cases represented 20% of all abnormal karyotypes observed. The ambiguity conferred by atypical aneuploidy can influence a family's decision making, even in the presence of normal ultrasound findings.