Research at the UPMC Magee Center for Reproduction and Transplantation

This Institutional Review Board (IRB)-approved research protocol is open to males of any age who have:

• 2 testes.
• A newly diagnosed or recurrent disease or treatment (such as chemo or radiation) that puts them at significant risk for infertility.

This study is for:

• Young males who aren't yet producing mature sperm.
• Males who can't produce a semen sample.

In this study, we collect testicular tissues during surgery and allocate as follows:

• 75% we freeze and bank for your future reproductive use. Methods to use frozen testicular tissue in reproduction are still in development.
• 25% goes toward ongoing research to design technologies to produce sperm from the tissue (either inside or outside the body).

The research study will cover the costs of:

• Surgery.
• Testicular tissue processing and freezing.
• First year of frozen storage.

This IRB-approved research study is open to females who:

• Are under the age of 40.
• Have a newly diagnosed or recurrent disease or treatment (such as chemo or radiation) that puts them at significant risk for infertility.

This study is for:

• Young women who aren't yet producing mature eggs.
• Women who can't freeze their eggs.

In this study, we collect ovarian tissue during surgery and allocate as follows:

• 80% we freeze and bank for your future reproductive use. Methods to use frozen ovarian tissue in reproduction are currently experimental.
• 20% goes toward ongoing research to design technologies to produce eggs from the tissue.

This research study will cover the costs of:

• Surgery.
• Ovarian tissue processing and freezing.
• First year of frozen storage.

This IRB-approved research study is open to transgender females over 9 who:

• Have a diagnosis of gender dysphoria.
• Are receiving or planning to start gender-affirming treatments (hormone suppression or cross-sex hormones).
• Do not wish to delay or interrupt their gender-affirming treatments to avoid male puberty and sperm production.
• Have a referral for a fertility preservation consult from their PCP or care team.

This study of techniques is for young people who:

• Aren't yet producing mature sperm.
• Can't produce a semen sample.
• Or do not want to go through male puberty.

In this study, we collect testicular tissue during surgery and allocate as follows:

• 75% we freeze and bank for your future reproductive use. Methods to use frozen testicular tissue in reproduction are still in development.
• 25% goes toward ongoing research to design technologies to produce sperm from the tissue (either inside or outside the body).

The research study will cover the costs of:

• Surgery.
• Testicular tissue processing and freezing.
• First year of frozen storage.

This IRB-approved research study is open to transgender males over age 9 who:

• Have a gender dysphoria diagnosis.
• Are receiving or planning to start gender-affirming treatments (hormone suppression or cross-sex hormones).
• Do not wish to delay or interrupt their gender-affirming treatments to avoid female puberty and egg production to be retrieved and frozen.
• Have a referral for a fertility preservation consult from their PCP or care team.

This study is for young people:

• Who aren't yet producing mature eggs.
• Or do not want to go through female puberty to produce eggs.

In this study, we collect ovarian tissue during surgery and allocate as follows:

• 80% we freeze and bank for your future reproductive use. Methods to use frozen ovarian tissue in reproduction are still in development.
• 20% goes toward ongoing research to design technologies to produce mature eggs from the tissue.

This study will cover the costs of:

• Surgery.
• Ovarian tissue processing and freezing.
• First year of frozen storage.

This IRB-approved research study is open to women who:

• Are ages 18 to 45.
• Have previously frozen and stored ovarian cortical tissue that is available for transplantation back into their own body (autologous transplant).
• Have ovarian insufficiency.
• Are candidates for pregnancy (if that is the desired outcome).
• Have written clearance from the doctor treating the condition that caused the need for freezing ovarian tissue.

This study will investigate whether transplanted ovarian tissues can restore ovarian hormones, menstruation, and production of eggs to use for reproduction.

The research study will cover the costs of surgery to transplant the ovarian tissue.

This IRB-approved research study is open to males who:

• Have previously frozen and stored testicular tissue that is available for transplantation back into their own body (autologous transplant).
• Are at least Tanner stage 3 of puberty.
• Are in reasonably good health.
• Have written clearance from the doctor treating the condition that caused the need for freezing testicular tissue.

This study will investigate whether transplanted spermatogonial stem cells or testicular tissues can produce sperm that can be used for reproduction.

The research study will cover the costs of surgery and transplantation.

This IRB-approved research study is open to males who:

• Are over 18 years old
• Have two testicles.
• Have been diagnosed with azoospermia (no sperm in the ejaculate).

In this study, we flush the rete testis with liquid and examine the aspirate for sperm. The study will determine whether it's possible to retrieve sperm using this nonsurgical approach. In some cases, the study will compare the efficiency of this experimental method with standard options to retrieve sperm, such as testicular sperm extraction (TESE).

The research study will cover the cost of rete testis aspiration and the first year of frozen storage if sperm are recovered using the experimental method. The program will not cover costs of other standard sperm retrieval methods that may be conducted during the study visit.

This IRB-approved research study is open to males who are:

• Between the ages of 18 to 50.
• Scheduled to undergo chemotherapy treatment for a medical condition.
• Able to produce semen samples before starting chemotherapy and a week after starting chemotherapy.
• Have not previously received chemo or radiation.
• Do not have oligospermia (very low sperm counts in the ejaculate) or azoospermia (no sperm in the ejaculate).

In this study, we collect semen samples before and shortly after starting chemo and allocate as follows:

• 80% of the before chemo sample is banked for your future reproductive use.
• 20% of the before chemo sample goes toward research to determine the health and genetic integrity of sperm before chemo.
• 100% of the after-chemo sample goes toward research to determine the health and genetic integrity of sperm after starting chemo.

The research study will cover the costs of:

• Semen analysis.
• Sperm freezing.
• First year of frozen storage.

This IRB-approved research study is open to males who:

• Are ages 18 to 64.
• Have unexplained infertility.

In this study, we collect blood or saliva and conduct genomic sequencing to search for genetic causes of infertility.

The research study will cover the costs of:

• Blood/saliva collection.
• Shipment of blood/saliva samples to the research laboratory.

• Spermatogenic Gene Regulation and Infertility. NIH/NICHD P50 HD104454 (PI: Cohen, Project 2 Co-PI: Hwang) 2021-2026.
• Next-Generation Therapies for Fertility Preservation in Male Cancer Patients. NIH/NICHD R01 HD100197 (MPI: Orwig/Meistrich) 2020-2025.
• Genetics of Male Infertility: A Marker of Overall Health. NIH/NICHD P50 HD096723 (PI: Orwig, Project 1 Co-I: Hwang) 2019-2024.
• Reproductive Development from Gonads to Fetuses. NIH/NICHD T32 HD087194 (PI: Orwig) 2017-2022.
• Tri-Institutional Symposium on Reproductive Biology & Infertility (Tri-Repro). NIH/NICHD R13 HD102144 (MPI: Cohen, Bartolomei, Orwig) 2020-2025.
• CHOSE Project. Stem Cell Therapies for Male and Female Infertility: In-vitro Gametogenesis. Lucabella Foundation (MPIs: Clark, Hayashi, Orwig, Silber) 2019-present.
• Fertility Preservation for Transgender Patients. Anonymous Donor (PI: Orwig) 2019-2024.

Sperm deoxyribonucleic acid fragmentation: Predictors, fertility outcomes, and assays among infertile males. F&S Reports 2021;2:282-288. Rios JS, Coward RM, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, Krawetz SA, Usadi R, Baker VL, Sun F, Wild R, Smith JF, Santoro N, Zhang H, Steiner AZ.

Inclusion and diversity in oncofertility care. Journal of Adolescent and Young Adult Oncology 2021;10:120-126. Appiah L, Anazodo A, Salama M, Reinecke J, Rios JS, Sender L, Woodard TL.

Recent advances: Fertility preservation and fertility restoration options for males and females. Fac Rev 2021;10:55. Doungkamchan C, Orwig KE.

Testosterone therapy: Where do the latest guidelines agree and differ? Curr Opin Endocrinol Diabetes Obes 2020;27:397-403. Pelzman DL, Hwang K.

Progress in translational reproductive science: Testicular tissue transplantation and in vitro spermatogenesis. Fertility and Sterility 2020;113:500-509. Pelzman DL, Orwig KE, Hwang K.

Personalized medicine for the infertile male. The Urologic Clinics of North America 2020;47:523-536. Velez D, Hwang K.

Fertility preservation in boys: Recent developments and new insights (†). Human Reproduction Open 2020;2020:hoaa016. Goossens E, Jahnukainen K, Mitchell RT, van Pelt A, Pennings G, Rives N, Poels J, Wyns C, Lane S, Rodriguez-Wallberg KA, Rives A, Valli-Pulaski H, Steimer S, Kliesch S, Braye A, Andres MM, Medrano J, Ramos L, Kristensen SG, Andersen CY, Bjarnason R, Orwig KE, Neuhaus N, Stukenborg JB.

Single-cell rna sequencing of human, macaque, and mouse testes uncovers conser ved and divergent features of mammalian spermatogenesis. Developmental Cell 2020;54:529-547.e512. Shami AN, Zheng X, Munyoki SK, Ma Q, Manske GL, Green CD, Sukhwani M, Orwig KE, Li JZ, Hammoud SS.

Ovarian tissue cryopreservation as standard of care: What does this mean for pediatric populations? Journal of Assisted Reproduction and Genetics 2020;37:1323-1326. Nahata L, Woodruff TK, Quinn GP, Meacham LR, Chen D, Appiah LC, Finlayson C, Orwig KE, Laronda MM, Rowell EE, Anazodo A, Frias O, Rios JS, Whiteside S, Gomez-Lobo V, Dwiggins M, Childress KJ, Hoefgen HR, Levine JM, Jayasinghe Y, Moravek M.

Spermatogonial stem cell culture in oncofertility. The Urologic Clinics of North America 2020;47:227-244. David S, Orwig KE.

Spermatozoal large RNA content associated with semen characteristics, sociodemographic and lifestyle factors. PLOS One 2019;14:e0216584. Bianchi E, Boekelheide K, Sigman M, Braun JM, Eliot M, Hall SJ, Dere E, Hwang K.

Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science 2019;363:1314-1319. Fayomi AP, Peters K, Sukhwani M, Valli-Pulaski H, Shetty G, Meistrich ML, Houser L, Robertson N, Roberts V, Ramsey C, Hanna C, Hennebold JD, Dobrinski I, Orwig KE.

Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers. Human Reproduction (Oxford, England) 2019;34:966-977. Valli-Pulaski H, Peters KA, Gassei K, Steimer SR, Sukhwani M, Hermann BP, Dwomor L, David S, Fayomi AP, Munyoki SK, Chu T, Chaudhry R, Cannon GM, Fox PJ, Jaffe TM, Sanfilippo JS, Menke MN, Lunenfeld E, Abofoul-Azab M, Sender LS, Messina J, Klimpel LM, Gosiengfiao Y, Rowell EE, Hsieh MH, Granberg CF, Reddy PP, Sandlow JI, Huleihel M, Orwig KE.

Fertility preservation outcomes in adolescent and young adult feminizing transgender patients. Pediatrics 2019;144:e20183943. Barnard EP, Dhar CP, Rothenberg SS, Menke MN, Witchel SF, Montano GT, Orwig KE, Valli-Pulaski H.

Is in vitro organotypic culture the key to spermatogenesis of human immature testicular tissue? Fertility and Sterility 2018;110:1030-1031. Avellino GJ, Hwang K.

Fertility preservation for pediatric patients: Current state and future possibilities. The Journal of Urology 2017;198:186-194. Johnson EK, Finlayson C, Rowell EE, Gosiengfiao Y, Pavone ME, Lockart B, Orwig KE, Brannigan RE, Woodruff TK.