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Infertility, Male

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Genital Diseases, Male

Male Urogenital Diseases

Stem cell transplantation Testicular tissue grafting

Spermatogonial stem cell transplant and testicular tissue grafting is performed to produce sperm.

Spermatogonial Stem Cell Transplant and Testicular Tissue Grafting

Rachel Neelley

Kyle E Orwig, PhD

Spermatogonial stem cell transplantation through ultrasound guided rete testis injection and testicular tissue grafting will be performed for participants who have frozen testicular tissue prior to gonadotoxic therapy. The purpose of this study is to test the safety and feasibility of these transplant technologies and restore fertility for these participants.

Azoospermia (no sperm in ejaculated semen) impacts 1% of men in the general population and 15% of infertile men, which translates to 645,000 males between the ages of 20 and 50 (prime reproductive years) in the United States. Spermatogenesis arises from a population of spermatogonial stem cells in the testes that maintain continuous sperm production throughout a man's post-pubertal life. Diseases or medical treatments that compromise the stem cell pool and/or prevent the stem cells from differentiating can cause infertility. Adult men have the option to cryopreserve a semen sample prior to therapy but this is not an option for prepubertal patients who are not yet producing sperm. This study will test the safety and feasibility of two approaches to restore sperm production using previously cryopreserved testicular tissues, which contain spermatogonial stem cells.

The first approach is autologous transplantation of testicular cells, including spermatogonial stem cells, into the testis using ultrasound-guided rete testis injection. The second approach is autologous grafting of intact pieces of testicular tissue under the skin in the scrotum.

Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting

The investigators will publish individual participant data, after deidentification. The investigators will also report each individual participants data back to them. Participants will be identified with unique ID numbers. No identifiable information will be shared.

Rate of participants where sperm was found in semen analysis or testicular tissue analysis

Rate of participants diagnosed with cancer recurrence

Rate of infection, hospital readmission, re-operation occurs

University of Pittsburgh

Professor

Infections

Neoplasms

Virus Diseases

Papilloma

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

HPV exposure

Randa Akouri, Ph.D.

This observational study aims to investigate the presence of HPV DNA in semen samples from men undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. It focuses on understanding the impact of HPV on male fertility and embryo development following IVF/ICSI. The primary goal is to determine the prevalence of HPV-positive (HPV+) semen samples among men seeking infertility treatment with IVF/ICSI. Additionally, the study aims to compare semen characteristics between HPV-positive and HPV-negative (HPV-) samples and assess the embryological outcomes after IVF/ICSI in these two groups.

Participants in this study will include men receiving IVF/ICSI treatment and providing fresh ejaculated sperm at Sahlgrenska University Hospital in Gothenburg, Sweden, over one year. Those undergoing treatments with surgically extracted sperm, sperm freezing for fertility preservation, or planning treatments involving preimplantation genetic testing or egg donation will be excluded.

The study will involve analyzing HPV DNA in semen samples through PCR, utilizing the most effective method for HPV DNA detection previously identified in a pilot study. Sperm samples collected during infertility investigations and IVF/ICSI treatments will undergo gradient centrifugation to separate different components. A portion of the sperm sample will be preserved for PCR analysis to detect HPV DNA, while the rest will be used for IVF/ICSI procedures. The results from the PCR analyses will be correlated with semen characteristics and the outcomes of IVF/ICSI treatment. Furthermore, the samples will be stored for potential future analyses related to HPV-related biomarkers for up to 5 years at Biobank.

Infection with the human papillomavirus (HPV) represents one of the most widespread sexually transmitted diseases, affecting both genders. Over 100 types of HPV can cause infections in the skin or mucous membranes and are typically transmitted through skin-to-skin contact, vaginal or anal intercourse, as well as oral sex. Statistics indicate that between 50 and 80 percent of sexually active adults will experience genital HPV infections during their lifetime. These infections tend to be persistent, especially in men. Although most HPV infections are asymptomatic, they can lead to genital warts, dysplasia, cancer, infertility, and may impact the outcomes of in vitro fertilization (IVF). Despite extensive research on HPV-related conditions in women, there has been limited attention given to HPV-related conditions in men.

A systematic review and meta-analysis conducted in 2017, comprising 31 studies, revealed that the prevalence of HPV DNA in semen samples among men in the general population was 11.4%, rising to 20.4% among men with infertility. It remains unclear whether HPV localizes in seminal plasma or in cellular fractions of semen samples (such as sperm, epithelial cells, or leukocytes). Recent evidence has shown that HPV DNA can be found on the surface of sperm by binding to specific glycosaminoglycans (GAGs), such as syndecan-1, along the equatorial region of the sperm head. Additionally, a few in vitro studies have indicated that HPV DNA can be found inside sperm when mixed with the HPV virus. The potential effects of HPV on fertility are not yet fully understood. The presence of HPV infection in sperm has been associated with impaired sperm parameters, mainly sperm motility, and increased sperm DNA fragmentation. Existing evidence suggests a negative effect of HPV DNA in seminal plasma and/or on sperm on the number of live births and ongoing pregnancies, although the level of evidence remains limited. Considering that sperm is utilized in IVF, it is crucial to investigate the presence of HPV in seminal plasma and sperm in these men, as well as any potential consequences on embryo development following IVF.

The primary objective of this study is to assess the prevalence of HPV DNA in seminal plasma and/or on sperm in men undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments. Furthermore, the study aims to characterize semen parameters in men with HPV-positive (HPV+) and HPV-negative (HPV-) semen samples and analyze the embryological outcomes after IVF/ICSI in men with HPV+ semen samples compared to men with HPV- semen samples.

The secondary objectives include evaluating semen parameters such as volume, sperm concentration, and motility to determine if there are differences between men with HPV+ and HPV- semen samples. Additionally, the study aims to investigate whether the embryological outcome (fertilization rate, number of high-quality embryos) after IVF/ICSI treatment differs between men with HPV+ and HPV- semen samples.

Analyses of HPV DNA in seminal plasma and/or on sperm will be conducted using the method that has demonstrated the highest performance in detecting HPV DNA, based on a previously conducted pilot study. Sperm samples are typically provided at the Fertility Laboratory at the Department of Reproductive Medicine, SU, in conjunction with infertility investigations and IVF/ICSI treatments. Usually, up to 2 mL of ejaculated sperm sample undergo gradient centrifugation, separating motile sperm from seminal plasma, immotile sperm, squamous epithelial cells, leukocytes, and bacteria. A portion of the pellet containing motile sperm is used to analyze sample parameters, primarily concentration and motility. During IVF/ICSI treatments, parts of the sperm sample are utilized for egg fertilization while the remainder is discarded. Following gradient centrifugation, sperm samples are diluted with a preservation liquid (ThinPrep®, 1:2) and stored in a refrigerator for transport to the Clinical Microbiology Department (virological laboratory) at SU (once per week) for polymerase chain reaction (PCR) analysis. ThinPrep® is routinely used to preserve and fix cell samples for HPV analysis in women. In this study, the portion of the sperm sample typically discarded and not used for IVF treatment will be utilized for HPV DNA analysis using PCR. PCR is the method routinely employed at the Clinical Microbiology Department (virological laboratory) at SU for HPV DNA detection in cervical cell samples. Results from these analyses will be correlated with sample parameters and the embryological outcome following completed IVF/ICSI treatment. Once analyzed by PCR and upon the availability of material, the samples will be stored for 5 years at Biobank Väst for potential future analyses of HPV-related biomarkers.

Detection and Prevalence of Human Papillomavirus (HPV) in Seminal Plasma and/or on Sperm in Men Undergoing Treatment With IVF/ICSI.

Detection and Prevalence of Human Papillomavirus (HPV) in Seminal Plasma and/or on Sperm in Men Undergoing Treatment With IVF/ICSI in Southwestern Sweden: a Prospective Study.

Number of HPV + sperm samples among all recruited men undergoing infertility treatment with IVF/ICSI

Is semen volume different between men with HPV+ and HPV- semen samples?

Is sperm concentration different between men with HPV+ and HPV- semen samples?

Is sperm motility different between men with HPV+ and HPV- semen samples?

Is the fertilization rate (number of fertilized oocytes) after IVF/ICSI treatment different between men with HPV+ and HPV- semen samples?

Is the number of high-quality embryos(number of blastocysts developed after fertilization) after IVF/ICSI treatment different between men with HPV+ and HPV- semen samples?

Vastra Gotaland Region

Senior Consultant, M.D., Ph.D.

Participants will receive a standard of care fertility consult.

Participants will receive a standard of care fertility consult and will participate in a family-centered psychoeducational intervention consisting of completing a FP Decision Tool and participating in a guided discussion about responses and discrepancies identified in the FP Decision Tool.

The intervention will be administered by a trained interventionist. The interventionist will administer the digital FP Decision Tool to families in the intervention arm. The tool asks questions examining each AYA's thoughts or feelings regarding parenthood and fertility preservation. The parent version asks the same questions, plus additional questions asking the parent to rate their son's feelings on certain topics (i.e., whether their son wants to have a child, whether their son would be as happy with an adopted child versus a biological child). Items are coded based on the domains of the Health Belief Model (perceived benefits, perceived barriers, perceived threats, self-efficacy, and cues to action). Items are scored and the trained interventionist will facilitate a guided discussion based on the family's responses and discrepancies.

FP Decision Tool and Discussion

Leena Nahata, MD

Very little is known about how medical providers can help adolescent and young adults (AYAs) and their caregivers make decisions about fertility preservation (sperm banking) before beginning cancer treatment. The purpose of this study is to see if having a guided conversation about fertility preservation increases preservation rates and/or satisfaction with the decision among AYA males with cancer. The primary hypothesis is that compared to standard of care control group (routine fertility consult at diagnosis, n=20), AYAs in the intervention arm (routine fertility consult at diagnosis + FP Decision Tool and Facilitated Conversation by trained interventionist) will have higher rates of FP uptake. The secondary hypothesis is that families in the intervention group will report better FP decision quality compared to those in the control arm.

A rapidly growing population of male childhood cancer survivors are at risk for infertility and distress. As the number of male cancer survivors rises, it is essential to minimize treatment late effects. One of the most prevalent and significant complications among males is infertility, which can impair psychosocial development and reduce quality of life. National guidelines emphasize offering fertility preservation (FP) prior to initiation of cancer therapy, and sperm cryopreservation is an established and generally noninvasive FP method for pubertal males. Early research suggested only males receiving high doses of alkylating agents should bank sperm. However, variable sperm counts following equivalent doses of cyclophosphamide and scenarios in which patients have to move quickly from "low risk" treatments (which transiently impair sperm production) to "high risk" treatments, support the premise that all males receiving chemotherapy and/or gonadal radiation should consider FP at diagnosis. Despite studies showing \~50% of male childhood cancer survivors have fertility impairment, reports from many centers show only \~25% of pubertal males bank sperm prior to treatment. As survivors enter their reproductive years, many regret missed opportunities for FP and experience distress about potential infertility. Thus, interventions to improve FP uptake would have great potential for reproductive and psychological benefit.

Individual and family factors associated with sperm banking decisions remain poorly understood. Young age, cost, inadequate knowledge, and urgency to start treatment are common barriers to FP among AYA males with newly diagnosed cancer. As a result, most fertility counseling and FP interventions have targeted healthcare providers and systems or provider-patient interactions. While these are critical factors, less than half of male AYA advised about FP in a recent study actually banked sperm, indicating knowledge is not sufficient.

The purpose of this study is to test a decision tool and accompanying guided discussion as a method of improving decision making regarding FP, compared to a standard of care fertility consult.

Families will be randomly assigned to receive standard care or to receive standard care plus the investigator's study intervention. All families will then be followed for a year to assess outcomes.

Participants, the interventionist, and research staff will not be blinded.

Fertility Preservation in Male AYA With Cancer

Optimizing Fertility Preservation and Decision Quality in Male AYA With Cancer: A Family-centered Intervention

We do not plan on sharing individual participant data (IPD) with other researchers.

AYAs will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.

Caregivers will complete the six-item Brief Subjective Decision Quality (BSDQ) Questionnaire with total scores ranging from 1-7; higher scores indicate more satisfaction with their decision.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting	NCT04452305	Infertility, Ma... Cancer Autoimmune Diso...	Spermatogonial ...	-	University of Pittsburgh
Detection and Prevalence of Human Papillomavirus (HPV) in Seminal Plasma and/or on Sperm in Men Undergoing Treatment With IVF/ICSI.	NCT06161727	Human Papilloma... Infertility, Ma...	HPV exposure	18 Years - 60 Years	Vastra Gotaland Region
Fertility Preservation in Male AYA With Cancer	NCT04268004	Infertility, Ma...	FP Decision Too...	12 Years - 25 Years	Nationwide Children's Hospital
Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting	NCT04452305	Infertility, Ma... Cancer Autoimmune Diso...	Spermatogonial ...	-	University of Pittsburgh
Fertility Preservation in Male AYA With Cancer	NCT04268004	Infertility, Ma...	FP Decision Too...	12 Years - 25 Years	Nationwide Children's Hospital
Fertility Preservation in Male AYA With Cancer	NCT04268004	Infertility, Ma...	FP Decision Too...	12 Years - 25 Years	Nationwide Children's Hospital
Fertility Preservation in Male AYA With Cancer	NCT04268004	Infertility, Ma...	FP Decision Too...	12 Years - 25 Years	Nationwide Children's Hospital

Spots Global Cancer Trial Database for infertility, male