Disorders of Sex Development: A Multidisciplinary Team Approach to Clinical Care and Research

March 19, 2020

Disorders of sex development (DSD) are characterized by divergence between chromosomal, gonadal, and phenotypic sex associated with atypical development of the internal and/or external reproductive systems. Individuals affected by a DSD can present during infancy, childhood, or adolescence. In some instances, individuals are ascertained by prenatal testing. 

These disorders may encumber pubertal development and future fertility. At UPMC Children’s Hospital of Pittsburgh, health care for these individuals involves a multidisciplinary integrated team approach. Team members include pediatric endocrinology, pediatric urology, genetics, gynecology, reproductive endocrinology, pathology, and behavioral health experts. The team’s mission focuses on developing individualized plans of care specific for each patient and family.

Selma Feldman Witchel, MD, professor of pediatrics and director of the Pediatric Endocrinology Fellowship Program, leads the pediatric endocrine component of this team. The DSD Multidisciplinary Team meets monthly to discuss specific cases and review novel scientific discoveries. She and her team members also are engaged in research activities. 

“The patients affected by these complex disorders require a high level of expertise. A multidisciplinary approach is essential to promote healthy outcomes and high quality of life for our patients,” says Dr. Witchel. 

Fertility Preservation for Pediatric Patients: Considerations, Options, and the Advancing Science

Fertility preservation options are rapidly advancing for pediatric patients on numerous fronts. At UPMC Children’s, clinicians such as Dr. Witchel and her colleagues are on the forefront of advancing programs for fertility preservation for patients with DSD and for transgender patients. In collaboration with colleagues such as Kyle Orwig, PhD, professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences and Director of the Fertility Preservation Program in Pittsburgh, and clinicians such as Marie N. Menke, MD, MPH, director of the Division of Reproductive Endocrinology and Infertility in the Department of Obstetrics, Gynecology and Reproductive Sciences at UPMC Magee-Womens Hospital, Dr. Witchel has helped transgender patients navigate the confusing world of fertility.

“We counsel all our DSD and gender dysphoria patients about future fertility options and fertility preservation. At present, minimal evidence-based data exists in the medical literature on this subject, but this area is rapidly evolving,” says Dr. Witchel.

Drs. Witchel, Menke, and Orwig have collaborated on several studies in the recent past that have dealt with fertility preservation for transgender children and adolescents.

In February 2019, Dr. Witchel and UPMC Magee colleagues Stephanie S. Rothenberg, MD, and Dr. Menke published their experience with “Oocyte Cryopreservation in a Transgender Male Adolescent” in the New England Journal of Medicine. This publication described their work with a transgender male adolescent. The authors highlighted the challenges of the fertility preservation options currently available for patients who have not completed natal puberty.

“Through our multidisciplinary approach, we were able to successfully retrieve and preserve a small number of mature eggs that one day may allow this individual to have biological children,” explains Dr. Witchel. “It is too early to know the feasibility of achieving the goal of fertility preservation for all individuals. Importantly, the science has rapidly advanced and experimental protocols are underway in the UPMC system.” 

Other patients with DSD may benefit from this approach. Patients with Klinefelter syndrome or other disorders of sex development may benefit from similar fertility preservation techniques and protocols. 

“Right now, for some of these patients, we can preserve the potential to have children in the future.” says Dr. Witchel. “Nevertheless, many questions remain unanswered regarding future fertility derived from frozen tissue samples.” 

Collaborative work between UPMC Children’s and UPMC Magee regarding fertility preservation in adolescent and young adult feminizing transgender patients were published in the September 2019 issue of the journal Pediatrics. Importantly, this study of 11 transfemales showed that semen cryopreservation was a viable fertility preservation option for these individuals; semen preservation may also be possible for individuals who have already started gender affirming therapies. However, additional studies will be needed in the future to determine the specific protocols to preserve the most viable sperm.

References and Further Reading

Berklite L, Witchel SF, Yatsenko SA, Schneck FX, Reyes-Múgica M. Early Bilateral Gonadoblastoma Associated With 45,X/46,XY Mosaicism: The Spectrum of Undifferentiated Gonadal Tissue and Gonadoblastoma in the First Months of Life. Pediatr Dev Pathol. 2019 Jul-Aug; 22(4): 380-385.

Yatsenko SA, Witchel SF. Genetic Approach to Ambiguous Genitalia and Disorders of Sex Development: What Clinicians Need to Know. Semin Perinatol. 2017 Jun; 41(4): 232-243.

Tas E, Sebastian J, Madan-Khetarpal S, Sweet P, Yatsenko AN, Pollock N, Rajkovic A, Schneck FX, Yatsenko SA, Witchel SF. Familial Deletion of the HOXA Gene Cluster Associated With Hand-Foot-Genital Syndrome and Phenotypic Variability. Am J Med Genet A. 2017 Jan; 173(1): 221-224.

Rothenberg SS, Witchel SF, Menke MN. Oocyte Cryopreservation in a Transgender Male Adolescent. N Engl J Med. 2019 Feb 28; 380(9):886-887. 

Barnard EP, Dhar CP, Rothenberg SS, Menke MN, Witchel SF, Montano GT, Orwig KE, Valli-Pulaski H. Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients. Pediatrics. 2019 Sep; 144(3). pii: e20183943.