Peter Braude

• BSc MB BCh MA PhD FRCOG FMedSci FSB DPMSA
• Professor Emeritus at King's College London

In January 1979, Robert Edwards and Patrick Steptoe delivered a lecture detailing the ten-year clinical and scientific research programme that led to the birth of Louise Brown, the first baby born utilising IVF. This thoroughly-researched book provides both a full annotated transcript of the lecture as well as recorded reminiscences from those who...

Background: Older people are more likely to have a stoma postabdominal surgery than younger people. Few studies have examined the effect of a stoma on older people. The aim of this review was to explore the effect of a stoma on functional independence of an older person. We explored secondary outcomes of poststoma formation length of hospital stay...

No profession should be more involved in the debate about Germline Genome Editing than the members of the Royal College of Obstetricians and Gynaecologists, the Royal College of Midwives, and the practitioners of new reproductive technologies, for the safety of future generations is in their hands. After all, it is our profession which has been the...

For many practitioners of in vitro fertilisation (IVF) today, it must be hard to comprehend the disdain and disgust with which the introduction of IVF as therapy for infertility was greeted. The ethical and legal wrangling about human reproductive cloning and the current debate over trans‐generational (germline) genome editing gives a small flavour...

Preimplantation genetic screening for aneuploidy continues to excite disagreement, discussion and confusion in the field of reproductive medicine. This commentary provides a contribution to the ongoing debate.

Mitochondria are essential cytoplasmic organelles that generate energy (ATP) by oxidative phosphorylation and mediate key cellular processes such as apoptosis. They are maternally inherited and in humans contain a 16,569-base-pair circular genome (mtDNA) encoding 37 genes required for oxidative phosphorylation. Mutations in mtDNA cause a range of p...

Assisted reproduction, including preimplantation genetic diagnosis has been subject to statutory regulation in the UK since 1991 under terms of the Human Fertilisation and Embryology Act (1990). The law in the rest of Europe is varied but changing in favour of allowing PGD. In general, sex selection for non-medical purposes is outlawed, unlike the...

Progress and improvements in preimplantation genetic testing historically have been driven by technological advance. Powerful new genetic technologies are being applied to PGT before their nuances or consequences are fully understood. The potential for discovering genome-wide information by techniques such as next generation sequencing raises parti...

Preimplantation genetic diagnosis (PGD) is a rapidly advancing field of reproductive genetics. With the significant improvements achieved over the last few years in the understanding of many genetic diseases and in the techniques of molecular genetic testing, new genetic diseases are being added to the list of conditions amenable to PGD almost on a...

The Guy’s Centre for Preimplantation Genetic Diagnosis (PGD) is the largest and most successful of the HFEA licensed centres that offer PGD in the UK. This book grew out of a number of courses that we ran at Guy’s on the understanding, requirements and practical implications of setting up or running a PGD service in the UK. These courses have been...

To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. Randomized controlled trial. Tertiary referral fertility units. Women with previous poor ovarian response undergoing IVF. One hundred eleven women were randomized to the long GnRH agonist, short agonist, an...

This review considers why and how embryos are selected for transfer and with what consequences. It concludes that: (i) current selection methods are inadequate or at least inadequately subjected to evidential scrutiny; (ii) decisions about number of embryos should be based not solely on input (numbers transferred) but on the likelihood of the trans...

We respond to Dr Fishel's commentary on evidenced-based medicine in assisted reproduction and the role of the UK's National Health Service. We agree that proper randomised clinical trials are not easy to set up or execute. Recruitment is also challenging but requires that all personnel involved in the study, clinicians, embryologists and nurses, ag...

Despite increasing interest in other stem cell types including induced pluripotent stem cells (iPSC), human embryonic stem cells (hESC) remain the gold standard pluripotent cell type. Clinical use of hESC is now being explored in a number of phase I clinical trials, including safety trials for spinal cord injury (Geron, started October 2010) and ma...

The protocols described here are comprehensive instructions for deriving human embryonic stem (hES) cell lines in xeno-free conditions from cryopreserved embryos. Details are included for propagation, cryopreservation and characterization. Initial derivation is on feeder cells and is followed by adaptation to a feeder-free environment; competent te...

Background aims: Human embryonic stem (hES) cells hold great potential for cell therapy and regenerative medicine because of their pluripotency and capacity for self-renewal. The conditions used to derive and culture hES cells vary between and within laboratories depending on the desired use of the cells. Until recently, stem cell culture has been...

The European Union Tissues and Cells Directive requires screening of tissue and cell donors for infective organisms to prevent inter-patient transmission. The Directive includes the unique term partner donation, which refers to "donation of reproductive cells between a man and a woman who declare that they have an intimate physical relationship". I...

We assessed the outcomes of ovarian stimulation in a two-day egg collection (EC) week with preimplantation genetic diagnosis (PGD) cycles (N = 307) compared to a five-day EC week with conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (N = 2,417). The mean (SD) age of women undergoing PGD was 34 (3.97) and 35 (3....

To compare the outcome of transfer of thawed blastocysts frozen on either day 5 or day 6 after in vitro fertilisation. Cohort observational study. Tertiary assisted conception unit in London, UK. Six hundred and forty-two consecutive nondonor programmed thawed blastocyst transfer (TBT) cycles. High-grade blastocysts were frozen on day 5 (n = 314) o...

Debate exists regarding the effect of raised BMI on the outcome of pregnancies after assisted reproduction technology. We assessed the effect of BMI on the risk of miscarriage in women conceiving following single blastocyst transfer (SBT) after controlling for confounding factors. Fresh and cryo-thawed cycles of SBT that resulted in a pregnancy bet...

Multiple pregnancy (MP) is widely recognized as the single biggest risk to children born as a result of assisted reproduction treatment. There is an emerging trend in Europe and Canada to promote single-embryo transfer (SET). In this issue, Gleicher argues that twin pregnancies should not be seen as an unfavourable outcome of assisted reproduction...

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.

Should be systematically reported so that lessons can be learnt and appropriate action taken

The prospect of using mitochondrial gene replacement to conceive children free of mitochondrial disease highlights the need for a sound ethical framework for reproductive genetic technology, say Annelien Bredenoord and Peter Braude

In 2005, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium published a set of Guidelines for Best Practice PGD to give information, support and guidance to potential, existing and fledgling PGD programmes. Subsequent years have seen the introduction of new technologies as well as the evolution of current techniques....

The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scalin...

There are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers. We conducted a systematic review and meta-analysis of controlled studies to compare pregnancy outcomes following transfer of thawed blastocysts that were frozen either on Day 5 or Day 6 following...

Introduction: Corifollitropin alfa is a new recombinant gonadotropin with sustained follicle stimulating activity that has been proven in the Engage trial (Devroey et al. 2009) to provide equally high ongoing pregnancy rates compared with daily recombinant follicle-stimulating hormone (rFSH). As the ultimate goal of controlled ovarian stimulation...

Abstract Introduction: The success of IVF/ICSI cycles depends on satisfactory ovarian response to stimulation. The number of oocytes collected per stimulation cycle has been used among other parameters to assess adequate response in controlled ovarian stimulation with gonadotrophins. However, the optimal number of retrieved oocytes that maximises c...

Introduction: For parthenogenetic blastocyst formation, oocytes can be artificially activated by different physical and chemical stimuli. The main disadvantage of most parthenogenetic activating agents is that they cause a single rise in cytosolic Ca2 + concentrations, different from the Ca2 + oscillations seen during fertilization. In order to im...

Introduction: This paper reports from a multidisciplinary, ethnographic study exploring the views, values and practices (the ethical frameworks) drawn on by professional staff in assisted conception units and stem cell laboratories in relation to embryo donation for human embryonic stem cell (hESC) research in the UK. The continued widespread supp...

Introduction Unexplained recurrent miscarriage (RM) is extremely stressful for women and effective treatment is eagerly awaited. Aspirin and (low-molecular-weight) heparin are being used increasingly, even though evidence to support its use is not available. In the ALIFE study we investigated whether aspirin combined with low-molecular-weight hepar...

Preimplantation genetic diagnosis using whole genome amplification and a haplotyping approach (PGH) was first described in 2006 and suggested as an efficient alternative to single-cell PCR for monogenic disorders. DNA from single cells was amplified using multiple displacement amplification; the resulting products were then tested using disease-spe...

To demonstrate the feasibility of establishing a successful pregnancy for a carrier of a balanced Y;autosome translocation. Four locus-specific fluorescence in situ hybridization (FISH) probes, informative for the translocation, were identified and tested on peripheral lymphocyte metaphase chromosomes and interphase preparations from the translocat...

The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile...

Objective. To assess the success rates of PGD cycles performed in a 2-day egg collection (EC) week programme compared to those with IVF/ICSI cycles performed in a 5-day EC week programme. Methods. Analysis of all conventional IVF/ICSI and PGD cycles in a tertiary referral centre between January 2006 and March 2009. Results. A consecutive series of...

Background: Herlitz junctional epidermolysis bullosa (HJEB) is a severe, life-threatening, autosomal recessive blistering skin disease for which no cure is currently available. Prenatal diagnosis for couples at risk is feasible through fetal skin biopsy or analysis of DNA extracted from chorionic villi, but these methods can be applied only after...

Since the derivation of the first human embryonic stem cell (hESC) line in 1998, there has been substantial interest in the potential of these cells for regenerative medicine and cell therapy and in the use of hESCs carrying clinically relevant genetic mutations as models for disease research and therapeutic target identification. There is still a...

Complete hydatidiform moles have a diploid chromosome constitution, generally with only paternal genetic material present (diandry). Diandric complete moles are thought to arise either by fertilization of an anucleate oocyte by two spermatozoa or, more commonly, doubling of a single sperm genotype. Molar pregnancies are usually sporadic, and may be...

Bilateral uterine artery embolisation (UAE) is being increasingly adopted as a non-surgical treatment for fibroids The main reason women give for wishing to avoid surgery is the desire to retain their fertility potential However, there is virtually no data about how uterine artery embolisation (UAE) affects fertility In an attempt to provide some i...

Sickle cell disease (SCD) is a clinically significant hemoglobinopathy with increasing global incidence. We describe our experience of using pre-implantation genetic diagnosis (PGD) for the prevention of SCD at a tertiary referral centre in London. Between January 2002 and December 2007, of 78 at-risk couples referred for PGD treatment, 12 couples...

An elective single-embryo transfer (SET) policy has not been applied to preimplantation genetic diagnosis (PGD) for inherited genetic disorders because of concerns regarding post-thaw survival of biopsied embryos. Our objective was to evaluate the survival and pregnancy potential of embryos biopsied for PGD at the cleavage stage and cryopreserved a...

An unfortunate group of women, often in their mid- to late 30s, find themselves in the position of being perimenopausal prematurely. For a few, this may occur because of loss of oocytes due to chemotherapy or autoimmune disease. However, for the majority, the reason for the low ovarian reserve is unclear, perhaps simply having fewer oocytes colonis...

Human embryonic stem cells (hESCs), derived from human blastocysts, hold a great promise for regenerative medicine, drug development and basic research in developmental biology. Moreover, hESC lines that carry a clinically relevant inherited defect, monogenic or chromosomal, present an important tool for research into the pathophysiology of these d...

Embryos surplus to therapeutic requirements following preimplantation genetic diagnosis can be used to derive human embryonic stem cell (hESC) lines carrying mutations significant to human disease. These cells provide a powerful in vitro tool for modelling disease progression in a number of cell types as well as having the potential to revolutionis...

There has been continued substantial interest from both scientists and the public in the therapeutic and scientific potential of stem cells since the first isolation of human embryonic stem cells (hESC) in 1998.1 Pluripotent hESCs derived from the inner cell mass of preimplantation embryos following fertilisation in vitro (IVF) have been well studi...

The internet is a frequently used source of information for infertile couples. Previous studies suggested that the quality of health information on the internet is poor. The aim of this study was to assess the quality of websites providing information on infertility and its management in the UK. Differences between website types and affiliations we...

To examine the relationship between endometrial thickness and outcome of medicated frozen-thawed embryo replacement (FER) cycles. A retrospective observational study. Assisted conception unit at a university hospital. All patients who underwent an FER cycle between 1997 and April 2006 and met the inclusion criteria. For endometrial preparation, a d...

To examine the clinical pregnancy rate (CPR) and multiple pregnancy rate (MPR) in a large in vitro fertilisation (IVF) programme before and after the introduction of single blastocyst transfer (SBT) strategy in a selected group of women. A 3-year pre- and postintervention study. A tertiary reproductive medicine and assisted conception unit in a Lon...

One response of the UK research community to the public sensitivity and logistical complexity of embryo donation to stem cell research has been the formation of a national network of 'human embryonic stem cell coordinators' (hESCCO). The aim of hESCCO is to contribute to the formation and implementation of national standards for hES cell derivation...

Key content Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis and termination of affected pregnancies. PGD for late‐onset and susceptibility conditions requires careful consideration on a case‐by‐case basis. PGD for sex selection for nonmedical reasons is prohibited in the UK. The use of PGD is expanding and its ethica...

We tested the hypothesis that restricting comparison of the live birth rate following in vitro fertilisation (IVF) treatment in those couples having their first IVF cycle in whom the female is under 35 years of age and has a normal follicle-stimulating hormone level would improve the validity of comparing IVF clinics' success rates. We analysed all...

Many randomized trials have evaluated the use of various pituitary suppression regimens to improve outcome of poor responders undergoing IVF treatment. A systematic review was conducted of the trials of gonadotrophin-releasing hormone (GnRH) agonist long regimen, GnRH agonist short regimen, GnRH antagonist regimen, as well as other pituitary suppre...

The introduction of intracytoplasmic sperm injection (ICSI) in 1992 has dramatically changed the management of severe male infertility. In severe male infertility, live birth rates with ICSI are superior to those with other non-donor treatments. In non- male infertility, however, pregnancy rates are not better with ICSI than with in vitro fertiliza...

Detection of genetic diseases before implantation for couples at risk helps ensure healthy children, but testing for aneuploidy does not improve the chances of live birth in normal infertile women, say Peter Braude and Frances Flinter

The development and implementation of new methods in human embryonic stem cell (hESC) research is fraught with difficulties, not least of which is the highly variable reporting of the number and quality of embryos used to derive hESC lines. Without a clear minimum information convention among the derivation teams, understanding and comparing deriva...

Following the early demise of their first child with Herlitz junctional epidermolysis bullosa (HJEB) a couple wished to consider prenatal testing. An immediate option would be fetal skin biopsy (FSB), a technique available for over 25 years, based on transmission electron microscopy and immunohistochemical analysis of laminin-332 expression, lookin...

Poor response to ovarian stimulation with exogenous gonadotrophins occurs in 9–24% of women undergoing in vitro fertilisation (IVF) treatment, which represents an estimated 4000–10,000 women per year in the UK. Poor responders often have their treatment cycle cancelled because of expected poor outcome. One treatment strategy that may influence outc...

Assisted hatching (AH) was developed as a possible solution to repeated implantation failure. The aim of this analysis was to examine the relationship between the morphology of embryos in a previous cycle on outcome in a subsequent cycle with AH. A total of 175 AH cycles performed after previous failed ART without hatching were divided into group A...

To report on our experience with preimplantation genetic diagnosis (PGD) cycles performed for serious genetic disease in relation to the clinical factors affecting outcome. Retrospective review of data from a single centre. Tertiary referral PGD centre in a London teaching hospital. The PGD cycles included 172 cycles for chromosome rearrangements,...

Bacterial contamination of the transfer catheter during embryo transfer is associated with poor clinical outcomes. Antibiotics at the time of embryo transfer may improve outcomes. We evaluated the effect of co-amoxiclav on the rates of bacterial contamination of transfer catheters and clinical pregnancy. On the day of oocyte collection, 350 patient...

This study aimed to evaluate the effect of small intramural fibroids on the cumulative pregnancy, ongoing pregnancy, live birth and implantation rates after three IVF/ICSI attempts. The first three treatment cycles of women enrolled for IVF/ICSI over a 12-month period were analysed. Only patients with small (<or=5 cm) intramural fibroids not encroa...

Preimplantation genetic haplotyping (PGH) proof-of-principle was demonstrated by multiple displacement amplification (MDA) of single buccal cells from a female donor and genotyping using 12 polymorphic markers within the dystrophin gene; the known paternal genotype enabled identification of the paternal haplotype in the MDA products despite 27% all...

Skin fragility-ectodermal dysplasia syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the desmosomal protein, plakophilin 1. Clinically, there may be considerable morbidity from extensive skin erosions and painful fissures on the palms and soles. In the absence of any specific treatment, prenatal diagnosis is an op...

The desire to improve in vitro fertilization (IVF) results has led clinicians to replace more than 1 embryo in the uterus. As a result, multiple births have increased over the last 2 decades to epidemic proportions, exposing the field of assisted conception to justified criticism. This review aims to ensure that physicians involved in the field of...

"A conflict of interest seems to exist between short term advantages with more pre-embryos for transfer (i.e. better immediate results, lower direct costs, and fewer treatment episodes), and long term disadvantages (i.e. high cost of prematurity hospital care and increased risks for children of mortality and morbidity)."

Introduction Since its first clinical use, pre-implantation genetic testing (PGT) has become increasingly available as a method of detecting genetic disorders before pregnancy is established. Based on a difference of purpose, PGT can be classified as either pre-implantation genetic diagnosis (PGD) or pre-implantation genetic screening (PGS). PGD wa...