Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial.

Study Question: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis?

Summary Answer: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years.

What Is Known Already: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial.

Is genetic fatherhood within reach for all azoospermic Klinefelter men?

Background: Multidisciplinary management of Klinefelter cases is now considered good clinical practice in order to ensure optimal quality of life. Reproductive performance of Klinefelter men is an important issue however literature in this domain is limited and prone to bias.

Study Design: This was a retrospective longitudinal cohort study performed at a tertiary referral University Centre for Reproductive Medicine and Genetics.

Gonadotropin Releasing Hormone Agonists or Antagonists for Preimplantation Genetic Diagnosis (PGD)? A Prospective Randomised Trial.

Background: The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children.

Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations.

Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 individual human cells, including fibroblasts, amniocytes and embryonic stem cells (hESCs), using single-cell array-based comparative genomic hybridization (aCGH).

Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles.

Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997-2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers.

Pregnancy outcome in carriers of Robertsonian translocations.

Robertsonian translocation carriers are at increased risk for infertility, spontaneous abortions, or chromosomally unbalanced offspring. Reproductive counseling of these carriers is challenging. We performed a retrospective analysis of all prenatal diagnoses from Robertsonian translocation carriers during the time period January 1, 1992 through December 31, 2007.

Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results.

Background: Several randomized controlled trials have not shown a benefit from preimplantation genetic screening (PGS) biopsy of cleavage-stage embryos and assessment of up to 10 chromosomes for aneuploidy. Therefore, a proof-of-principle study was planned to determine the reliability of alternative form of PGS, i.e.

No relationship between the type of pituitary suppression for IVF and chromosomal abnormality rates of blastomeres: an observational study.

Objective: To investigate whether the incidence of chromosomally abnormal blastomeres is related to the type of pituitary suppression used in ovarian stimulation.

Design: Retrospective study.

Setting: Tertiary referral center.

Prognostic factors for delivery in patients undergoing repeated preimplantation genetic aneuploidy screening.

We performed a retrospective analysis of patients who had a first failed preimplantation genetic aneuploidy screening (PGS) cycle. At least one euploid embryo was found in 64% of the patients who had no euploid embryos available on their first PGS cycle. A previous failed treatment because of lack of euploid embryos does not contraindicate a further assisted reproductive cycle.

What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate.

Preimplantation genetic screening is being scrutinized, as recent randomized clinical trials failed to observe the expected significant increase in live birth rates following fluorescence in situ hybridization (FISH)-based screening. Although these randomized clinical trials are criticized on their design, skills or premature stop, it is generally believed that well-designed and well-executed randomized clinical trials would resolve the debate about the potential benefit of preimplantation genetic screening. Since FISH can analyze only a limited number of chromosomal loci, some of the embryos transferred might be diagnosed as 'normal' but in fact be aneuploid for one or more chromosomes not tested.

A proposal for reproductive counselling in carriers of Robertsonian translocations: 10 years of experience with preimplantation genetic diagnosis.

Background: Carriers of Robertsonian translocations are at increased risk for infertility, repeated miscarriage and aneuploid offspring. In the present study, 10 years of experience with preimplantation genetic diagnosis (PGD) for Robertsonian translocations is reviewed and these data are used to improve the reproductive counselling in the carriers.

Methods: A retrospective analysis was performed of all requests and cycles for PGD for Robertsonian translocations at our centre between January 1997 and December 2006.

Prospectively randomized controlled trial of PGS in IVF/ICSI patients with poor implantation.

This randomized, controlled trial verifies whether patients with recurrent failed implantation benefit from preimplantation genetic diagnosis for aneuploidy, as compared with conventional assisted reproduction treatment procedures. Two hundred patients with recurrent failed implantation were randomized into two groups. A total of 139 patients underwent ovarian stimulation, and preimplantation genetic screening was performed in 72 patients.

Two-year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening.

Background: Embryo biopsy is an essential but invasive procedure to perform preimplantation genetic diagnosis (PGD) or preimplantation genetic screening (PGS). The major objective of this study was to determine whether embryo biopsy might cause post-natal growth restriction.

Methods: We compared growth data and physical findings at birth and 2 years for singletons born either after PGD/PGS (n = 70), ICSI (n = 70) or natural conception (NC) (n = 70).

Recurrent chromosomal abnormalities in human embryonic stem cells.

Cultured human embryonic stem (hES) cells have a known predisposition to aneuploidy of chromosomes 12, 17 and X. We studied 17 hES cell lines by array-based comparative genomic hybridization (aCGH) and found that the cells accumulate other recurrent chromosomal abnormalities, including amplification at 20q11.21 and a derivative chromosome 18.

First successful bone marrow transplantation for X-linked chronic granulomatous disease by using preimplantation female gender typing and HLA matching.

Allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen (HLA)-identical donor is currently the only proven curative treatment for chronic granulomatous disease. Hematopoietic stem cell transplantation with alternative donors is associated with higher morbidity and mortality. Therefore, we performed in vitro fertilization and preimplantation HLA matching combined with female sexing for hematopoietic stem cell transplantation in chronic granulomatous disease.

Diagnostic efficiency, embryonic development and clinical outcome after the biopsy of one or two blastomeres for preimplantation genetic diagnosis.

Background: Preimplantation genetic diagnosis or screening (PGD, PGS) involves embryo biopsy on Day 3. Opting for one- or two-cell biopsy is a balance between the lowest risk for misdiagnosis on the one hand and the highest chance for a pregnancy on the other hand.

Methods: A prospective controlled trial was designed and 592 ICSI cycles were randomly assigned to the one-cell (group I) or the two-cell group (group II).

The analysis of one or two blastomeres for PGD using fluorescence in-situ hybridization.

Background: The analysis of one or two blastomeres for PGD using fluorescence in-situ hybridization (FISH) is debated. The proportion of analysable embryos, false negatives, false positives, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and efficiency were evaluated when one or two blastomeres were analysed.

Methods: Embryos of patients having PGD for aneuploidy screening were assigned non-randomly to two groups: group I (n = 413), more slow cleaving embryos with one nucleus for analysis, and group II (n = 1366), regularly cleaving embryos with two nuclei for analysis.

The importance of aneuploidy screening in reciprocal translocation carriers.

The purpose of this study is to investigate the aneuploidy rate and the mosaicism of chromosomes not involved in reciprocal translocations. Aneuploidy screening (AS) (13, 16, 18, 21 and 22) was performed as a re-analysis on fixed blastomeres from 126 embryos already analysed in preimplantation genetic diagnosis (PGD) cycles of eight female and five male reciprocal translocation carriers who had not achieved a pregnancy. A successful diagnosis for AS was achieved in 91.

Single-cell chromosomal imbalances detection by array CGH.

Genomic imbalances are a major cause of constitutional and acquired disorders. Therefore, aneuploidy screening has become the cornerstone of preimplantation, prenatal and postnatal genetic diagnosis, as well as a routine aspect of the diagnostic workup of many acquired disorders. Recently, array comparative genomic hybridization (array CGH) has been introduced as a rapid and high-resolution method for the detection of both benign and disease-causing genomic copy-number variations.

Preimplantation genetic diagnosis for aneuploidy screening in women older than 37 years.

Objective: To provide background information about the average aneuploidy and implantation rates of older patients after IVF with preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) when the patients are subdivided into age categories; and to compare pregnancy outcome data after PGD-AS in this group of patients with a similar control group.

Design: Retrospective clinical study.

Setting: Patients in an academic reproductive medicine unit.

Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages.

Objective: To determine the aneuploidy rate in embryos of women with idiopathic recurrent miscarriages and to evaluate whether preimplantation genetic diagnosis for aneuploidy screening could be a feasible approach to improve the possibility of successful pregnancy in these couples.

Design: Prospective cohort study.

Setting: Tertiary university referral center.

Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial.

Background: It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART).

Methods: A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS.

Klinefelter syndrome: expanding the phenotype and identifying new research directions.

Purpose: The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities.

Methods: This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings.

Results And Conclusions: The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency.