Two-hundred and fifty-five boys between 6 and 20 months of age (mean 13 ± 3.9) with mono or bilateral cryptorchidism who received endocrinological and urological counseling and/or treatment were consecutively enrolled during the period 1987–1997 in an observational longitudinal cohort study. IRB approval is not available because the study consists of a cohort of patients consecutively selected but not randomized in the respective treatment group due to their young age and followed up for over 16-years. Exclusion criteria were previous hormonal or surgical treatments, concomitant chronic diseases, and genetic disorders. Patients were originally selected after medical consultation and counseling concerning the different available treatment options and were consequently treated according to the patient family preference after they approved and signed an informed consent. The options presented were long lasting hormonal therapy, surgical orchidopexy, hormonal therapy followed by surgery when the first was ineffective in determining complete testicular descent into the scrotum. Surgical treatment was performed by the same surgeon during a two-day hospital stay whilst medical therapy was administered at home according to a predefined treatment schedule. For all patients treated with hormonal therapy, human Chorionic Gonadotropin (hCG) was injected at the dosage of 1000 Units for 6 weeks and a repeated cycle of therapy again after 1 month, varying the treatment schedule based on patient weight (twice per week for babies with a body weight < 12 Kg and three times per week for babies with a body weight > 12Kg). A small number of parents decided not to submit their child to any pharmacological or surgical treatment for the risk of developing related adverse events.
Thereafter, all patients enrolled were clinically followed with repeated periodical outpatient clinic visits every two months for the first two years and then once a year until complete development of the testis, at the age of 18. Syndromic cases, boys with mobile testes or local recurrence in subjects with previously already descended testes were excluded from the study.
Patients were divided into 4 different groups according to the type of treatment received: group A received surgery; group B received hormonal therapy; group C received a combined sequential hormonal and surgical treatment; group D decided not to receive any treatment.
Treatments were not randomized but were assigned on patient family preference as well as on the need to be switched to surgery if unresponsive to the hormonal treatment alone.
Patients assigned to group A chose to be immediately treated by surgery. The procedure was performed under general anaesthesia with an inguino-scrotal access to the inguinal canal, dissection of spermatic chord with lisis of cremasteric muscle and fixation of the testis at the scrotum wall. Complications were recorded according to the Clavien Dindo classification .
Patients assigned to group B received hormonal treatment, according to the previously described schedule. Adverse events and adverse reactions were registered and classified according to the North Bristol NHS trust classification and adequately treated if necessary .
Group C included patients who initially received hormonal therapy but did not have a definite testis allocation in the scrotum and had undergone further surgical treatment.
Group D included subjects who decided to avoid the risks related to any kind of treatment although properly informed of the potential consequences of this choice on the fertility of the patient and the increased risk of developing testicular cancer.
192 out of 255 patients (76.4%) were available for further analyses concerning fertility. Testes location and size were recorded as well as the Follicular Stimulating Hormone (FSH), Testosterone (T) and Inhibin B circulating level. Patients were invited to collect semen for spermiogram testing at least 3 different times at a distance of at least one week between each test, recording as result the median value between the three samples taken.
Sperm analysis was conducted by two different biologists and information regarding sperm concentration, normal sperm cells number and sperm cell motility were collected according to the WHO 2010 international standards. .
All data regarding the testis volume measurement were calculated by Prader’s orchidometer.
Patients included in the “no treatment” group received additional medical consultation and scrotal ultrasound scan in order to monitoring the risk of testicular cancer onset.
Statistical analysis included the median values for the characteristics of patients included in different groups with different median follow-up periods.
Categorical data were described by absolute and relative frequency, continuous data by mean value and standard deviation. To compare quantitative factors (sperm concentration, progressive sperm motility, normal sperm morphology, inhibin B levels, FSH levels, testosterone levels and total testis volume) with different types of treatment (surgery, hormonal therapy, combined, no treatment)
ANOVA one-way was used followed by multiple comparisons with the Bonferroni method .
Significance was fixed at 0.05. All analyzes were carried out by SPSS v.26 technology.
Statement of Ethics
IRB approval is not available because this study consists of an observational longitudinal cohort study of patients consecutively selected (1987–1997), but not randomized in the respective treatment group due to their young age with a follow-up of over 16 years.