Clinical Trial: Fertility Assessment in Patients With Klinefelter Syndrome
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Non-Invasive Methods to Maximize Fertility in Peri-Pubertal Patients With Klinefelter Syndrome
Brief Summary:
Klinefelter syndrome is characterized by primary testicular failure and progressive infertility. The objective of this study is to determine if sperm are present and can be observed in urine and semen samples of adolescent and young adult Klinefelter patients and to determine whether the presence of sperm correlates with physical and/or clinically obtained hormone measures of pubertal development.
This study was designed in order to answer the following questions:
- Is it possible to observe sperm in urine samples of adolescent and young adult Klinefelter patients?
- Is it possible to retrieve sperm for cryopreservation from semen samples of adolescent and young adult Klinefelter patients?
- Does the presence of sperm correlate with the physical and/or endocrine measures that are assessed during routine clinical evaluations of pubertal development in the KS patient population?
- If sperm retrieval is possible, what is the optimal age at which sperm retrieval should be attempted?
Detailed Summary:
Klinefelter Syndrome (KS) is a genetic condition in boys and men that results from having two X chromosomes and one Y chromosome. The incidence of the 47, XXY karyotype that defines the disorder ranges from 1:500 to 1:1000 in newborn males. The sexual development and fertility phenotypes of Klinefelter's syndrome include azoospermia (absence of sperm in the ejaculate), small firm testes, gynaecomastia (enlargement of breast tissue), low testosterone levels, and elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels that can have an important impact on the quality of life for these patients. Beginning with puberty, testicular biopsies from Klinefelter patients progressively show a degenerated testicular environment with Sertoli-cell-only tubules, sclerotic or hyalinized tubules, and interstitial Leydig cell hyperplasia. Nevertheless, scattered areas with focal spermatogenesis can be seen in Klinefelter men, and assisted reproductive techniques now offer hope for patients who wish to father their own biological children. In these cases, a surgical sperm recovery procedure called testicular sperm extraction (TESE) is performed to extract sperm for in vitro reproductive methods. Success rates for testicular sperm extraction in Klinefelter patients are consistently above 50% (50 - 72%) and are similar to the success rates reported for TESE in azoospermic patients without Klinefelter syndrome. Pregnancy rates and life births after intracytoplasmic sperm injection (ICSI) are similar in couples with or without KS, and babies fathered by KS patients have a normal karyotype. Previous studies in adult KS patients reported that sperm recovery rates were significantly lower after the age of 35. Therefore, it was suggested that surgical sperm recovery in younger (possibly pubertal) boys should be considered as an option to maximize the opportunity to preserve their fertility before becoming sterile. However, t
Sponsor: University of Pittsburgh
Current Primary Outcome: Presence of sperm in urine or semen. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will provide urine samples 1-2 times a year at the time of their routine visit with the endocrinologist. The presence of sperm will be analyzed.
Participants will also be given the opportunity to have their semen analysed for the presence of sperm 1-2 times a year at the time of their routine visit with the endocrinologist.
Participants will be followed until they reach age 26.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Longitudinal correlation of developmental and endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]Participants will be followed until they reach age 26. Thereafter, patients will be contacted once a year via phone to asses fertility/infertility issues and over all health.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure height.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure weight.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure body proportions.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure Tanner stages.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will examine the presence of gynecomastia.
- Correlation of developmental parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure and bilateral testicular size.
- Correlation of endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure testosterone (T).
- Correlation of endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure luteinizing hormone (LH)
- Correlation of endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure follicle-stimulating hormone (FSH).
- Correlation of endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time Frame: 1-2 times a year for an average of 7.4 years ]
Participants will be scheduled for a routine visit with the endocrinologist 1-2 times a year.
At each visit, the endocrinologist will measure serum anti-Mullerian hormone (AMH).
- Correlation of endocrine parameters with the presence or absence of sperm in urine and semen samples. [ Time&
Original Secondary Outcome: Same as current
Information By: University of Pittsburgh
Dates:
Date Received: May 26, 2015
Date Started: November 2015
Date Completion: October 2020
Last Updated: October 3, 2016
Last Verified: October 2016
