Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study

Abstract

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio ,10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic116 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic119 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400-1.290310 6 ml 21 ; P,0.01) and motility (medians: class A from 2% to 15%; P,0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.

The association of a probiotic with a prebiotic (Flortec, Bracco) to improve the quality/quantity of spermatozoa in infertile patients with idiopathic oligoasthenoteratospermia: a pilot study

“…Patients were not admitted to the study if any of the following criteria were present: refusal to participate in the study (5 patients); seminal white blood cell concentration >10 6 /mL or a positive seminal cultural analysis or positive urethral swab chlamydia test (6 patients); drug, tobacco, or alcohol abuse (8 patients); ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs) (3 patients); dropout during the course of the study (3 patients); previous cancer radiotherapy or chemotherapy (2 patients); palpable varicocoele (10 patients); X-ray exposure in the previous 8 months (3 patients); Y chromosome microdeletion (1 patient); and karyotype alterations (0 patients); T/E2 < 10 (4 patients) (Koscinski et al, 2007;Cavallini et al, 2013). Patients were not admitted to the study if any of the following criteria were present: refusal to participate in the study (5 patients); seminal white blood cell concentration >10 6 /mL or a positive seminal cultural analysis or positive urethral swab chlamydia test (6 patients); drug, tobacco, or alcohol abuse (8 patients); ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs) (3 patients); dropout during the course of the study (3 patients); previous cancer radiotherapy or chemotherapy (2 patients); palpable varicocoele (10 patients); X-ray exposure in the previous 8 months (3 patients); Y chromosome microdeletion (1 patient); and karyotype alterations (0 patients); T/E2 < 10 (4 patients) (Koscinski et al, 2007;Cavallini et al, 2013).…”

“…Eligible patients were those with normal semen appearance, consistency, liquefaction, volume, and pH. Patients were not admitted to the study if any of the following criteria were present: refusal to participate in the study (5 patients); seminal white blood cell concentration >10 6 /mL or a positive seminal cultural analysis or positive urethral swab chlamydia test (6 patients); drug, tobacco, or alcohol abuse (8 patients); ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs) (3 patients); dropout during the course of the study (3 patients); previous cancer radiotherapy or chemotherapy (2 patients); palpable varicocoele (10 patients); X-ray exposure in the previous 8 months (3 patients); Y chromosome microdeletion (1 patient); and karyotype alterations (0 patients); T/E2 < 10 (4 patients) (Koscinski et al, 2007;Cavallini et al, 2013).…”

“…Therapy for iOAT is commonly regarded to be empiric because iOAT has multiple origins (Cavallini et al, 2008) and, in current outpatient clinical practice, it is not possible to define the exact etiology of the spermatogenetic disorder of each iOAT patient. For the most part, the following therapies have been studied: aromatase inhibitors when total testosterone (T)/17-beta-2-estradiol (E2) is <10 (Cavallini et al, 2013), antioxidants (Showell et al, 2014), and follicle-stimulating hormone (FSH) (Garolla et al, 2014).…”

Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials

“…Crosschecking of the references and manual searches did not yield any additional studies for inclusion. Of these, three (Clark & Sherins, 1989;Gregoriou et al, 2012;Cavallini et al, 2013) studies met the inclusion criteria. Therefore, 42 further references were excluded from this review, as they were either case series or cross-sectional studies (Figure 1).…”

Microdissection Testicular Sperm Extraction

“…Another class of medication that has been used t o o p t i m i z e h o r m o n a l p a r a m e t e r s i n N O A a n d cryptozoospermia patients is aromatase inhibitors, such as anastrozole and letrozole. Although most studies were performed using anastrozole, which appears to have fewer side effects, one study comparing letrozole to placebo in cryptozoospermia and NOA patients suggested that letrozole may help enhance spermatogenesis with sperm return to the ejaculate in some NOA patients (24). Candidates for management with aromatase inhibitor include men with low serum testosterone (<300 ng/dL) and low testosterone: estradiol ratios (<10), in whom aromatase therapy has been suggested to enhance intratesticular testosterone levels and improve spermatogenesis (1,3,4).…”