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Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation.

Frapsauce C, Ravel C, Legendre M, Sibony M, Mandelbaum J, Donadille B, Achermann JC, Siffroi JP, Christin-Maitre S - Hum. Reprod. (2011)

Bottom Line: Histology revealed severe hypospermatogenesis.Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed.Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy.

View Article: PubMed Central - PubMed

Affiliation: UPMC, AP-HP, Hôpital Tenon, Service de Biologie de la Reproduction, 75020 Paris, France.

ABSTRACT
DAX1/NR0B1 mutations are responsible for X-linked congenital adrenal hypoplasia (AHC) associated with hypogonadotropic hypogonadism (HH). Few data are available concerning testicular function and fertility in men with DAX1 mutations. Azoospermia as well as failure of gonadotrophin treatment have been reported. We induced spermatogenesis in a patient who has a DAX1 mutation (c.1210C>T), leading to a stop codon in position 404 (p.Gln404X). His endocrine testing revealed a low testosterone level at 1.2 nmol/l (N: 12-40) with low FSH and LH levels at 2.1 IU/l (N: 1-5 IU/l) and 0.1 IU/l (N: 1-4 IU/l), respectively. Baseline semen analysis revealed azoospermia. Menotropin (Menopur(®):150 IU, three times weekly) and human chorionic gonadotrophin (1500 IU, twice weekly) were used. After 20 months of treatment, as azoospermia persisted, bilateral multiple site testicular biopsies were performed. Histology revealed severe hypospermatogenesis. Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed. Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy. We report the first case of paternity after TESE-ICSI in a patient with DAX1 mutation, giving potential hope to these patients to father non-affected children. Furthermore, this case illustrates the fact that patients with X-linked AHC have a primary testicular defect in addition to HH.

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Related in: MedlinePlus

Seminiferous tubule sections showing (A) Sertoli cells only or an arrest of spermatogenesis at the spermatocyte stage (arrow) in most tubules, and (B) isolated tubules with very rare spermatids (arrow). Few normal Leydig cells were seen. Magnification ×400.
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DEQ372F2: Seminiferous tubule sections showing (A) Sertoli cells only or an arrest of spermatogenesis at the spermatocyte stage (arrow) in most tubules, and (B) isolated tubules with very rare spermatids (arrow). Few normal Leydig cells were seen. Magnification ×400.

Mentions: Hypogonadism was treated by testosterone enanthate (Androtardyl®: 250 mg intramuscularly, every 3 weeks). Six years later, as he desired paternity, a semen analysis was performed, which revealed azoospermia. Semen volume and semen pH were found to be normal. Spermatogenesis was therefore induced by gonadotrophins using menotropin (Menopur®:150 IU of FSH and 150 IU of LH, three times weekly) and human chorionic gonadotrophin (hCG: 1500 IU, twice weekly). One month later, his testosterone level reached 4 ng/ml. The treatment doses remained constant. After 20 months of treatment, testis volume reached 11 and 12 ml, for his right and left testis, respectively. However, azoospermia persisted. Consequently, bilateral testicular biopsies were performed. It was a blind, multiple-site biopsy. Very few spermatozoa were extracted from the right posterior fragment. Three straws were cryopreserved, each containing 100 motile spermatozoa. Histological examination revealed severe hypospermatogenesis. The diameter of the seminiferous tubules was either normal or reduced. Tubules were limited by a thickened basement membrane and contained mostly Sertoli cells and a few germ cells arrested at the spermatocyte stage (Fig. 2).Figure 2


Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation.

Frapsauce C, Ravel C, Legendre M, Sibony M, Mandelbaum J, Donadille B, Achermann JC, Siffroi JP, Christin-Maitre S - Hum. Reprod. (2011)

Seminiferous tubule sections showing (A) Sertoli cells only or an arrest of spermatogenesis at the spermatocyte stage (arrow) in most tubules, and (B) isolated tubules with very rare spermatids (arrow). Few normal Leydig cells were seen. Magnification ×400.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3037794&req=5

DEQ372F2: Seminiferous tubule sections showing (A) Sertoli cells only or an arrest of spermatogenesis at the spermatocyte stage (arrow) in most tubules, and (B) isolated tubules with very rare spermatids (arrow). Few normal Leydig cells were seen. Magnification ×400.
Mentions: Hypogonadism was treated by testosterone enanthate (Androtardyl®: 250 mg intramuscularly, every 3 weeks). Six years later, as he desired paternity, a semen analysis was performed, which revealed azoospermia. Semen volume and semen pH were found to be normal. Spermatogenesis was therefore induced by gonadotrophins using menotropin (Menopur®:150 IU of FSH and 150 IU of LH, three times weekly) and human chorionic gonadotrophin (hCG: 1500 IU, twice weekly). One month later, his testosterone level reached 4 ng/ml. The treatment doses remained constant. After 20 months of treatment, testis volume reached 11 and 12 ml, for his right and left testis, respectively. However, azoospermia persisted. Consequently, bilateral testicular biopsies were performed. It was a blind, multiple-site biopsy. Very few spermatozoa were extracted from the right posterior fragment. Three straws were cryopreserved, each containing 100 motile spermatozoa. Histological examination revealed severe hypospermatogenesis. The diameter of the seminiferous tubules was either normal or reduced. Tubules were limited by a thickened basement membrane and contained mostly Sertoli cells and a few germ cells arrested at the spermatocyte stage (Fig. 2).Figure 2

Bottom Line: Histology revealed severe hypospermatogenesis.Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed.Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy.

View Article: PubMed Central - PubMed

Affiliation: UPMC, AP-HP, Hôpital Tenon, Service de Biologie de la Reproduction, 75020 Paris, France.

ABSTRACT
DAX1/NR0B1 mutations are responsible for X-linked congenital adrenal hypoplasia (AHC) associated with hypogonadotropic hypogonadism (HH). Few data are available concerning testicular function and fertility in men with DAX1 mutations. Azoospermia as well as failure of gonadotrophin treatment have been reported. We induced spermatogenesis in a patient who has a DAX1 mutation (c.1210C>T), leading to a stop codon in position 404 (p.Gln404X). His endocrine testing revealed a low testosterone level at 1.2 nmol/l (N: 12-40) with low FSH and LH levels at 2.1 IU/l (N: 1-5 IU/l) and 0.1 IU/l (N: 1-4 IU/l), respectively. Baseline semen analysis revealed azoospermia. Menotropin (Menopur(®):150 IU, three times weekly) and human chorionic gonadotrophin (1500 IU, twice weekly) were used. After 20 months of treatment, as azoospermia persisted, bilateral multiple site testicular biopsies were performed. Histology revealed severe hypospermatogenesis. Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed. Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy. We report the first case of paternity after TESE-ICSI in a patient with DAX1 mutation, giving potential hope to these patients to father non-affected children. Furthermore, this case illustrates the fact that patients with X-linked AHC have a primary testicular defect in addition to HH.

Show MeSH
Related in: MedlinePlus