Robert D. Oates's research while affiliated with Boston Medical Center and other places

Publications (114)

Article
While hundreds of knockout mice show infertility as a major phenotype, causative genic mutations of male infertility in humans remain rather limited. Here we report the identification of a missense mutation (D136G) in the X-linked TAF7L gene as a potential cause of oligozoospermia in men. The human aspartate (D136) is evolutionally conserved across...
Article
Klinefelter syndrome (KS) is a common disorder and almost every clinician in almost every sub-specialty of medicine will knowingly or unwittingly treat boys or men with a 47,XXY chromosomal constitution. Although there are numerous aspects of KS worthy of discussion, this contribution will focus specifically on the controversial, and as yet unresol...
Article
Full-text available
Purpose of Review Hormonal and surgical treatments for transgender individuals can severely impact reproductive potential. In this review, we discuss the role of fertility preservation in both male-to-female and female-to-male transgender patients. We focus on the effects of hormone replacement therapy on the gonads and discuss current methods and...
Article
Full-text available
Non-obstructive azoospermia accounts for 10–15% of male infertility, resulting in 60% of all cases of azoospermia and affecting about 1% of the male population. About 30% of these cases are due to Y chromosome microdeletions, chromosome abnormalities, or hormonal disorders. Pathogenic variants in genes on the sex chromosomes have key roles in sperm...
Article
Azoospermia describes up to 20% of males who are evaluated for infertility. While a small fraction of these cases can be explained by obstructive causes, the remainder will be due to factors intrinsic to the testis, such as spermatogenic dysfunction (Tournaye et al., 2017 [39]). In a subset of these patients, chromosomal and genetic anomalies will...
Article
Full-text available
Klinefelter syndrome can present as a wide spectrum of clinical manifestations at various stages in life, making it a chromosomal disorder with no standardized set of guidelines for appropriate management. Understanding the genetic and hormonal causes of this syndrome can allow physicians to treat each patient on a more individualized basis. The ti...
Article
This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.
Article
Full-text available
Background: Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or popula...
Article
As men age, medical and surgical diseases involving the genitourinary tract become more common. The conditions themselves, if not their treatments, can negatively impact the fertility potential of an affected man. Many older men maintain the desire to father children, so it is critical to understand the disturbed anatomy and physiology involved to...
Article
Full-text available
It is currently unclear whether an adolescent with 47,XXY Klinefelter syndrome will be better off having testicular sperm extraction (TESE) performed in an effort to ‘preserve fertility’ for the future or, alternatively, should be advised to simply wait until adulthood when he and his partner are ready to begin a family. This report will provide da...
Article
An accurate medical history and directed physical examination are essential in diagnosis of male infertility. We review the hormonal assessments and specific genetic analyses that are useful additional tests, and detail other evidence-based examinations that are available to help guide therapeutic strategies. By contrast with female infertility tre...
Article
Infertility is a widespread problem and a male contribution is involved in 20-70% of affected couples. As a man's fertility relies on the quantity and quality of his sperm, semen analysis is generally used as the proxy to estimate fertility or gain insight into the underlying reasons for infertility. Male reproductive impairment might result from f...
Article
In about one-half of adult Klinefelter syndrome (KS) patients, spermatozoa can be retrieved by means of testicular biopsy (TESE). Given the expected increase in the number of diagnosed KS patients owing to the use of noninvasive prenatal testing, the probable questions of young KS patients and their parents regarding future fertility, and the fact...
Article
Full-text available
Genome-wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X-linked meiosis-specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non-obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic...
Article
Sexual dysfunction and infertility are prevalent in the spina bifida (SB) population; however, the mechanism of how they affect a person with spina bifida is poorly understood. Additionally, the management of children with spina bifida becomes more difficult as they exit from pediatric institutes. The present study sought to evaluate sexual health...
Article
Ejaculatory dysfunction may occur after many different disorders ranging from traumatic spinal cord injury to diabetes mellitus. With an understanding of the many facets and nuances of the ejaculatory apparatus, both anatomic and neurologic, the well-versed clinician can proceed along a safe, efficient, and appropriate treatment algorithm to help a...
Article
Quantitative deficiencies in spermatogenesis, aberrations in spermatozoal ultramorphology, or defects in spermatozoal nuclear/DNA health may lead to male factor infertility. Rare situations present themselves when the clinical question of whether to harvest testis sperm, even when ejaculate sperm are available, arises. This chapter will try to prov...
Chapter
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have revolutionized the treatment of male factor infertility. However, it is still critically important to fully evaluate the male with a well-considered history, comprehensive physical examination, and appropriate hormonal and genetic assays in order to arrive at as precise a...
Article
Deletions involving the Y chromosome's AZFc region are the most common known genetic cause of severe spermatogenic failure (SSF). Six recurrent interstitial deletions affecting the region have been reported, but their population genetics are largely unexplored. We assessed the deletions' prevalence in 20,884 men in five populations and found four o...
Article
Once thought to be a chromosomal aberration associated with absolute sterility, Klinefelter syndrome may now be potentially treatable by testicular sperm retrieval coupled with intracytoplasmic sperm injection. With these therapeutic advances, azoospermic 47,XXY men now may have an opportunity for biological paternity. However, our knowledge of the...
Article
Assisted reproductive techniques have revolutionized the treatment of male reproductive failure, allowing biological fatherhood to be achieved by many men that nature would have never permitted. As we are able to help more and more couples with our therapies, the genetic basis of the man's spermatogenic, anatomical, or spermatozoal dysfunction need...
Article
When presented with an azoospermic patient, a thorough history and careful, considered physical examination often leads to a definite or presumptive diagnosis. An algorithmic, logical thought process is important to have in mind when embarking on the evaluation. Adjunctive laboratory tests, such as hormonal assays or genetic studies, are often comp...
Article
Male factor reproductive deficiency is wholly or ­partially contributory to the inability of many couples to achieve their goal of natural conception. As such, the evaluation of the male with history, physical examination, semen analyses, and other appropriate tests is mandatory when a couple presents with infertility. The failure to conceive shoul...
Article
Severe male factor infertility may have a presently identifiable genetic basis. Y chromosomal microdeletions (e.g., an AZFc microdeletion), karyotypic anomalies (e.g., Klinefelter Syndrome), and mutations in both alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be found, depending upon the etiology of the reproduct...
Article
Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) ch...
Article
Therapies for the treatment of severe male factor infertility have advanced well beyond our knowledge of the conditions we are treating. An intact Y chromosome is necessary for optimal spermatogenesis. It is imperative for the clinician to understand the molecular basis and clinical implications of anomalies that might afflict the Y chromosome. The...
Article
Evolving therapies have allowed the use of sperm from men with spermatogenic compromise, obstructive azoospermia, and sperm functional deficiency, enabling these men to procreate when unable to do so naturally. The genetic basis of only a portion of these conditions is known and research must be pursued into the genetic underpinnings of those that...
Article
What do we know about the genetic causes of reproductive failure in men who are otherwise healthy? What is the rationale for testing? What therapeutic and counseling interventions are most appropriate, based on the genetic diagnoses? Research and clinical experience are beginning to provide some answers.
Article
The human Y chromosome is replete with amplicons-very large, nearly identical repeats-which render it susceptible to interstitial deletions that often cause spermatogenic failure. Here we describe a recurrent, 1.8-Mb deletion that removes half of the azoospermia factor c (AZFc) region, including 12 members of eight testis-specific gene families. We...
Article
Full-text available
Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this delet...
Article
The most frequent known genetic causes of severe oligospermia (< 5 million sperm/ml) or azoospermia in men are Klinefelter's syndrome (KS), and deletions in the Y chromosome long arm (Yq). We aimed to compare the function of the pituitary-testicular axis in patients with severe oligospermia or azoospermia, idiopathic or associated with Y chromosome...
Article
Full-text available
Severe spermatogenic compromise may be the result of a Y-chromosomal deletion of the AZFc region. Prior studies are limited to relatively small numbers of AZFc-deleted men. In this study, we have fully characterized 42 infertile men with a Y chromosome microdeletion strictly confined to the AZFc region, and we report on 18 children conceived throug...
Article
It is widely believed that at least three nonoverlapping regions of the human Y chromosome-AZFa, AZFb, and AZFc ("azoospermia factors" a, b, and c)-are essential for normal spermatogenesis. These intervals are defined by interstitial Y-chromosome deletions that impair or extinguish spermatogenesis. Deletion breakpoints, mechanisms, and lengths, as...
Article
Full-text available
Limited mutation analysis for congenital bilateral absence of the vas deferens (CBAVD) has revealed only a minority of men in whom two distinct mutations were detected. We aimed to determine whether a more extensive mutation analysis would be of benefit in genetic counselling and prenatal diagnosis. We studied a cohort of 92 men with CBAVD using ma...
Article
To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patient...
Article
PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryoprese...
Chapter
Increased awareness of fertility issues and techno­ logic advances in the field of infertility have resulted in a major increase in the number of cou­ ples seeking treatment. Proper assessment and cor­ rection of male factors contributing to infertility is required as part of the complete evaluation for the infertile couple. A male factor can be id...
Chapter
Increased awareness of fertility issues and technologic advances in the field of infertility have resulted in a major increase in the number of couples seeking treatment. Proper assessment and correction of male factors contributing to infertility is required as part of the complete evaluation for the infertile couple. A male factor can be identifi...
Article
To describe a case involving the cryopreservation of testis tissue retrieved from a 15-year-old male teenager with Klinefelter's syndrome. Case report. An academic medical center. A 15-year-old boy with Klinefelter's syndrome. Microsurgical testis sperm extraction with cryopreservation of harvested tissue. Spermatozoa within testis tissue. Successf...
Article
Full-text available
Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping−sequencing process. A complex of three palindrom...
Article
To determine the presence or absence of the deleted in azoospermia (DAZ) gene clusters in the Y-bearing spermatozoa in semen of severely oligozoospermic men or in testicular biopsy samples of azoospermic men with somatic DAZ deletions. Prospective study. Academic hospital. Nineteen patients attending our clinics for therapeutic intracytoplasmic inj...
Article
An association between congenital bilateral absence of the vas deferens (CBAVD), normal renal anatomy and cystic fibrosis (CF) gene mutations is well established (CF/CBAVD). We postulate that unilateral renal agenesis (URA) and CBAVD (URA/CBAVD) may have a non-CF mutation-mediated genetic basis that leads to abnormal development of the entire meson...
Article
Men with cystic fibrosis (CF) have bilateral absence of the vas deferens causing an obstructive azoospermia that is not amenable to surgical correction. Advances in the field of reproductive medicine allow for the procurement of viable sperm and facilitate fertilization and pregnancy in couples where the man has CF. To describe patient anatomy and...
Article
Full-text available
Deletion of any of three regions of the human Y chromosome results in spermatogenic failure and infertility. We previously sequenced one of these regions, azoospermia factor a (AZFa) and found that it spanned approximately 800 kb. By sequence-tagged site (STS) content mapping, we roughly defined deletion breakpoints in two unrelated, azoospermic me...
Article
If your patient is unable to get pregnant because her partner has cystic fibrosis or congenital bilateral absence of the vas deferens, assisted reproductive technology offers a solution. But these disorders have genetic implications that you need to keep in mind when advising such couples.
Article
Full-text available
In humans, deletion of any one of three Y-chromosomal regions- AZFa, AZFb or AZFc-disrupts spermatogenesis, causing infertility in otherwise healthy men. Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked g...
Article
Testicular tissue extraction (TESE) to obtain spermatozoa for use with intracytoplasmic sperm injection (ICSI) has recently been employed in patients with non-obstructive azoospermia. Standard protocol is to retrieve a new sample of testis tissue on the day of oocyte recovery. Unfortunately, approximately 30% of men will possess no spermatozoa in t...
Article
Objectives: Epididymovasostomy is commonly performed at the most distal site of the epididymis where whole sperm are present within the lumen, regardless of their motility status. Although more fresh and motile sperm can be found more proximally within the epididymis, it is believed that the outcome of epididymovasostomy is better more distally. B...
Article
Full-text available
Some men with non-obstructive azoospermia harbour fully formed spermatozoa within their testicular tissue that can be used to achieve pregnancy via intracytoplasmic sperm injection (ICSI). Recently, Reijo et al. (1995) provided compelling evidence that the DAZ gene cluster is a strong candidate for one of the elusive azoospermia factors (AZF) locat...
Article
Hitherto, patients with testicular dysfunction and azoospermia had to resort to adoption, donor sperm insemination, or child-free living. The realization that a proportion of such men harbor spermatozoa in their testicular parenchyma, combined with the ability of intracytoplasmic sperm injection (ICSI) to effect pregnancy with single sperm, has pro...
Article
Azoospermia is often caused by factors that we cannot presently elucidate. However, our knowledge of the genetic bases of the varied etiologies of azoospermia is expanding rapidly. This information is critical in proper counseling of the couple who are employing some of the currently available and wonderous new technology to assist them in the ques...