P-007 Surgical sperm retrieval rate in men with Klinefelter syndrome is associated with testicular volume - but not with body constitution or Sertoli cell markers
Authors: Fedder J , Milton A  M , Jessen E , Gravholt C  H , Skakkebæk A , Mamsen L  S , Andersen C  Y , Johannsen E  M , Eskildsen T  V , Blach K 
Published: July 2024

Abstract

Study question
Do sperm retrieval and pregnancy rates in men with Klinefelter syndrome (KS) depend upon sperm retrieval method, age, testicular volume, body weight, and hormone concentrations?

Summary answer
Successful sperm retrieval was significantly associated with total testicular volume but not with sperm retrieval method, age, body weight, BMI, FSH, inhibin-B or AMH.

What is known already
Testicular sperm can be retrieved from approximately 40% of men with KS, resulting in an average pregnancy rate of 16%. The sperm retrieval rate seems to be unrelated to the age of the man and to preoperative FSH-levels. A decrease in testosterone concentration is usually observed 3 months after surgery. Possible negative effects of testosterone substitution therapy prior to surgery and the predictive value of body constitution, testicular volume and the Sertoli cell markers, AMH and inhibin-B, for sperm retrieval success in KS men are only partly known.

Study design, size, duration
A total of 14 KS patients underwent subcapsular orchiectomy and 34 KS patients underwent m-TESE at Centre of Andrology & Fertility Clinic, Odense University Hospital. Pre-surgery examination included ultrasonography of the testicles, genetic analyses (standard chromosome analysis and screening for Y microdeletions and CFTR variants) and hormone analyses (including FSH, LH, testosterone, estradiol, prolactin, TSH, AMH, inhibin-B). Testosterone, LH, and FSH were also measured 3 months after surgery.

Participants/materials, setting, methods
Forty-three men had a 47,XXY karyotype, while 5 (2 from the subcapsular group and 3 from the m-TESE group) had a mosaic karyotype including 47,XXY. Subcapsular orchiectomy was performed unilaterally, while m-TESE was usually performed bilaterally. To avoid freezing the sperm retrieved, oocytes from the female partner was aspirated and vitrified after FSH-stimulation according to our usual IVF protocols. Oocytes were thawed on the day of sperm retrieval and embryos transferred in estrogen-progesterone stimulated cycles.

Main results and the role of chance
Sperm were obtained in 19 (40%) of the 48 men with KS. In 10 couples (21%) pregnancy was obtained and 7 women (15%) gave birth to at least one child resulting in ten children (6 girls and 4 boys), while one pregnancy is still ongoing. In the group who had a subcapsular orchiectomy, 5 (36%) had sperm retrieved, and pregnancy was obtained in 3 (20%) cases. Two gave birth to a child, while the third woman have had several abortions, most likely due to large fibromyomas of the uterus. In the m-TESE group 14 (41%) had sperm retrieved, and pregnancy was obtained in 7 (21%) cases. Five women (15%) gave birth to 8 children, while 1 pregnancy is still ongoing and the seventh experienced an early pregnancy loss. Furthermore, 3 couples have still not embryos transferred. Sperm were found in 3 men (60%) with mosaic karyotype. Sperm retrieval success was significantly associated with testicular volume (mean total testicular volumes of 3.4 mL vs. 2.3 mL; p &lt; 0.01) but not with age, height, body weight, BMI or preoperative FSH, inhibin-B or AMH levels. Testosterone levels measured 3 months after the surgery, did not differ between men irrespective of surgical method.

Limitations, reasons for caution
The numbers of patients are limited and randomized studies with sufficient power are difficult to perform. AMH and inhibin-B, were only measured in the m-TESE group.

Wider implications of the findings
In KS patients, sperm retrieval and pregnancy rates were similar irrespective of the sperm retrieval method. Also serum testosterone 3 months postoperatively and cosmetic results experienced by patients were similar. Multicenter studies and larger studies are needed to provide more detailed information of the potential predictors for successful sperm retrieval.

Trial registration number
Not applicable