To describe a case of CBAVD due to a pathogenic variant in ADGRG2, detail the reproductive outcomes of the couple, and provide an up-to-date review of ADGRG2 variant pathophysiology as well as speculate on the mechanism by which defects in ADGRG2 function result in vasal agenesis. Review of the first reported case in the USA and expound on ADGRG2 dysfunction vis-à-vis male reproductive ductal anatomy. A pathogenic variant in ADGRG2 was the genetic etiology of CBAVD. The couple underwent sperm harvesting coupled with ICSI and delivered two daughters. Pathogenic variants in ADGRG2 are important to look for when CFTR analysis is negative and renal ultrasonography is normal.

Characterizing patient-reported outcomes is essential to informing perioperative counseling in gender-affirming genital surgery. This study used patient-reported outcomes to characterize gender congruence, genital self-image, and sexual function after gender-affirming vulvovaginoplasty. Transgender patients assigned male at birth at a single academic center were invited to complete a post-surgery survey. Of 157 patients who had undergone surgery between September 2016 and March 2022, 41 (26.1

Infertility impacts approximately one in six couples attempting to conceive; male factor is at least contributory, if not the sole basis, in 50 percent of these couples [1, 2]. Evaluation of the infertile male starts with the history, followed by the physical examination, and is coupled with semen analysis. The synthesis of this information may suggest inherited conditions (usually autosomal recessive) or de novo abnormalities resulting in an aberrant clinical or spermatozoal phenotype [3, 4]. These may be recognized chromosomal abnormalities, specific gene mutations, or qualitative factors that affect spermatogenesis and fertility potential. Identification of a specific genetic mishap may be informative for the patient and his overall health, for the couple and their therapeutic strategies and results, for the patient’s siblings and first-order relatives, and for the offspring that might be conceived. Although these aberrations may limit natural conception, technical innovations, coupled with the evolution of assisted reproductive technology (ART), may allow previously infertile/sterile couples to parent their own biological children. Helping couples also involves informing them, as best we can, the reasons for the infertility – the etiologies of the sperm defect, the basis for vasal agenesis, and the genetic underpinnings of the abnormally shaped sperm. Although thorough clinical evaluation of the infertile male has always been appropriate, proper genetic analysis and counseling may be equally as important. Male reproductive medicine, surgery, and genetics are inextricably intertwined. This chapter reviews the forms of male infertility that have had an identified genetic basis, summarizes the laboratory tests employed for diagnosis, and briefly discusses more recent salient issues, including concerns regarding the impact of paternal age. Three general subdivisions will be employed: genetic disorders affecting sperm production (in essence, quantitative); genetic disorders affecting sperm function (in essence, qualitative); and genetic disorders affecting sperm transport. This is a paradigm that is unusual but helps to provide a visual way of conceptualizing and compartmentalizing the various conditions discussed. Epigenetics, as it relates to male fertility/infertility, will be discussed in Chapter 6.

Although hundreds of knockout mice show infertility as a major phenotype, the 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 species, and its change to glycine (G) is predicted to be detrimental. Genetic complementation experiments in budding yeast demonstrate that the conserved aspartate or its analogous asparagine (N) residue in yeast TAF7 is essential for cell viability and thus its mutation to G is lethal. Although the corresponding D144G substitution in the mouse Taf7l gene does not affect male fertility, RNA-seq analyses reveal alterations in transcriptomic profiles in the Taf7l (D144G) mutant testes. These results support TAF7L mutation as a risk factor for oligozoospermia in humans.

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 unresolved, issue of whether it is advantageous to harvest testis tissue from peri-pubertal or adolescent boys with KS in a heroic effort to preserve that child’s chances of reproduction in his future adult life. What would be the rationale for that, how does the biology of spermatogenesis in the Klinefelter testis impact that decision, and what does the data show? The answer, assembled from a selection of seemingly disparate sources and directions, appears to be “No”. We do not have to advocate for an aggressive approach, we do not have to preemptively preserve future fertility. We can justifiably wait until adulthood with equivalent chances of success.

A Correction to this paper has been published: https://doi.org/10.1007/s10815-021-02257-3

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 spermatogenic failure. The co-occurrence of azoospermia and congenital cataracts ranges between 1 in 165,000 and 1 in 500,000. Our 28-year-old patient with normal intelligence and abnormally shaped teeth presented with both disorders. A microarray revealed a microdeletion at Xp23.13 with a whole NHS gene deletion as well as a contiguous deletion of two other genes [SCML1 and RAI2]. This observation represents the first report of non-obstructive azoospermia with congenital cataracts and a contiguous deletion of the SCML1 gene, a transcript of which is exclusively expressed in the testis. SCML1 is the putative culprit gene, which requires functional study or animal experiments. Our analysis of 60 known spermatogenesis failure-related genes by whole-exome sequencing revealed no other candidate. The Nance-Horan syndrome due to pathogenic variants in the NHS gene at Xp23.13 including whole gene deletion does not have azoospermia as a feature. Our report adds to the completeness of genetic counseling for an individual with azoospermia and congenital cataracts.

Purpose of ReviewHormonal 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 techniques available for fertility preservation. Moreover, we review the current literature on patient attitudes toward fertility preservation and existing barriers to care.Recent FindingsThe literature supports the notion that feminizing therapy negatively impacts spermatogenesis, as evidenced by impaired semen parameters. The degree of such decline lies on a spectrum and can be somewhat unpredictable. Similarly, masculinizing therapy with testosterone has variable effects on ovarian function, gynecologic organs, and future fertility potential. Further research is required to better elucidate the long-term effects of such therapies. Optimal timing for fertility preservation is in the postpubertal period prior to initiation of hormonal therapy. This is however not always possible. A multitude of barriers to pursuing fertility preservation exist, including lack of appropriate counseling, the potentially invasive nature of some fertility preservation methods, and the financial burden placed on the patients.SummaryFertility preservation in the transgender population remains poorly utilized. For transgender women, cryopreservation of sperm ideally is performed prior to initiation of hormone replacement therapy. Nonetheless, studies have shown that a degree of spermatogenesis is seen in some individuals without discontinuation of hormonal therapy. This could allow for less disruption, both physically and emotionally. Fertility preservation in transgender men remains invasive with oocyte retrieval as the main technique. Cessation of therapy, ovarian stimulation, and invasive testing has potential to be traumatic and enhance dysphoria. The possibility of fertility preservation at the time of gonadectomy is promising. Prepubertal fertility preservation is also on the horizon, though still experimental. Cost of preservation techniques and storage is currently prohibitive for many patients. Recent changes to state insurance mandates may soon make fertility preservation more accessible. Future research may demonstrate that fertility preservation is possible at the time of gender confirmation surgery, with the goal of being both effective and nontraumatic to the patient.

e1918 J Clin Endocrinol Metab, April 2020, 105(4):e1918–e1920 https://academic.oup.com/jcem doi:10.1210/clinem/dgz308 Abbreviations: ICSI, intracytoplasmic sperm injection; KS, Klinefelter syndrome; TESE, testis sperm extraction. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2019. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received 9 December 2019. Accepted 20 December 2019. First Published Online 26 December 2019. Corrected and Typeset 7 March 2020. Fertility Considerations in Adolescent Klinefelter Syndrome: Current Practice Patterns

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 timing of diagnosis and degree of symptoms can guide management. This report will provide an updated review of the clinical presentation at various stages in life and the implications for management.

LGBT HealthVol. 7, No. 1 Letter to the EditorDetection of Anal Cancer at the Time of Neovaginoplasty: Is There a Role for Anal Cancer Screening Before Gender-Affirming Genital Surgery in High-Risk Patients?James T. Rague, Robert D. Oates, Jaromir Slama, and Carl Streed JrJames T. RagueAddress correspondence to: James T. Rague, MD, Department of Urology, Boston Medical Center, Shapiro Suite 3B, 725 Albany Street, Boston, MA 02118 E-mail Address: james.rague@bmc.orgDepartment of Urology, Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, Robert D. OatesDepartment of Urology, Boston Medical Center, Boston, Massachusetts.Center for Transgender Medicine and Surgery, Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, Jaromir SlamaCenter for Transgender Medicine and Surgery, Boston Medical Center, Boston, Massachusetts.Department of Plastic Surgery, Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, and Carl Streed JrCenter for Transgender Medicine and Surgery, Boston Medical Center, Boston, Massachusetts.Department of Medicine, Boston Medical Center, Boston, Massachusetts.Search for more papers by this authorPublished Online:13 Jan 2020https://doi.org/10.1089/lgbt.2019.0128AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Detection of Anal Cancer at the Time of Neovaginoplasty: Is There a Role for Anal Cancer Screening Before Gender-Affirming Genital Surgery in High-Risk Patients?." LGBT Health, 7(1), pp. 68–69FiguresReferencesRelatedDetails Volume 7Issue 1Jan 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:James T. Rague, Robert D. Oates, Jaromir Slama, and Carl Streed Jr.Detection of Anal Cancer at the Time of Neovaginoplasty: Is There a Role for Anal Cancer Screening Before Gender-Affirming Genital Surgery in High-Risk Patients?.LGBT Health.Jan 2020.68-69.http://doi.org/10.1089/lgbt.2019.0128Published in Volume: 7 Issue 1: January 13, 2020Online Ahead of Print:December 6, 2019PDF download