Drug-induced Infertility Research Articles

Rohypnol-induced sexual dysfunction is via suppression of hypothalamic-pituitary-testicular axis: An experimental study in rats.

Sexual activity is an essential part of reproductive functions and needed for the maintenance of fertility. Drugs, particularly substances of abuse, impair male reproductive function either by interrupting hormonal functions or through the nonhormonal pathways. This study evaluated the impact of Rohypnol use in sexual behaviour. Materials and methods: Thirty adult male Wistar rats of comparable weights (180-200g) were randomly allocated into three groups, the control and low-dose and high-dose Rohypnol-treated groups. The control group received 0.5ml of distilled water, while the low- and high-dose Rohypnol-treated groups received 2mg/kg b.w and 4mg/kg b.w of Rohypnol via oral lavage once daily for 28days. Rohypnol significantly increased mount latency, intromission latency, ejaculation latency and post-ejaculatory interval, as well as lowered mount frequency, intromission frequency and ejaculation frequency. Rohypnol-induced sexual dysfunction was found to be associated with significant suppression of circulatory follicle-stimulating hormone, luteinising hormone, testosterone and oestrogen. The present study reveals that Rohypnol induces sexual dysfunction through suppression of hypothalamic-pituitary-testicular axis. It also implicates Rohypnol as a potential candidate for drug-induced infertility.

Human umbilical cord perivascular cells prevent chemotherapeutic drug-induced male infertility in a mouse model

To study whether intratesticular (IT) administration of 2 sources of human umbilical cord perivascular cells (HUCPVC), rich and potent sources of mesenchymal stromal cells (MSC), before chemotherapy can prevent infertility in a mouse model. Two control groups of CD1 male mice without busulfan (BUS) administration (untreated and IT media injection groups) were included. Experimental groups included IT administration of media, first trimester (FTM) HUCPVCs or term HUCPVCs (n = 5 each) injected 3 days before BUS treatment (20 mg/kg). All groups were included in a mating time course study over 6 months. Preclinical study in a fertility center research laboratory. Not applicable. IT delivery of FTM or term HUCPVC before BUS treatment. Pregnancies, litter sizes, and gross morphology of offspring were monitored. Caudal epididymal sperm concentration, motility, and progressive motility were assessed by computer-assisted sperm analysis. Spermatogenesis was also assessed histologically in testicular tissue sections. FTM and term HUCPVC displayed an MSC-associated immunophenotype and expressed transcripts encoding paracrine factors known to regulate the testicular cell niche. IT administration of FTM and term HUCPVC before chemotherapy promoted the recovery of spermatogenesis and fertility compared with BUS-treated animals that received a media injection. Although the total number of pups sired over 6 months by males treated with FTM or term HUCPVC was reduced compared with untreated or media-injected controls, litter size and sperm parameters in fertile animals did not differ between control and cell-treated groups. HUCPVC represent a promising source of MSC-based therapy to prevent gonadotoxic chemotherapeutic drug-induced infertility.

CA 125 serum values in surgically treated endometriosis patients and its relationships with anatomic sites of endometriosis and pregnancy rate

Endometriosis is a benign gynecologic disease defined as the presence of functional endometrial glands and stroma outside the uterine cavity, causing dysmenorrhea, dyspareunia, menstrual irregularities, and infertility. Serum CA-125 measurement is now a consolidated method for diagnosing this condition, and its interpretation has posed a number of problems, particularly regarding utility in diagnosing minimal-mild endometriosis, whereas its value as a diagnostic aid in moderate-severe stages is well recognized. In our cohort, serum CA-125 values were significantly elevated in patients with ovarian and mixed endometriosis lesions (median levels 48 U/mL), compared with those who had exclusively extraovarian foci (median levels 27 U/mL), and so the correlation between this marker and the surgical and pathologic finding of ovarian and deep endometriosis was found to be statistically significant; however, the location did not affect the fertility rate.

Incidence of varicoceles in patients with ankylosing spondylitis evaluated by physical examination and color duplex sonography

Objectives. To assess the incidence of varicocele in ankylosing spondylitis (AS) in comparison to healthy age-matched controls. Methods. Twenty-one male patients with AS who were not taking disease-modifying antirheumatic drugs (eg, sulfasalazine, a well-known cause of drug-induced infertility) and age-matched healthy controls were evaluated with both physical examination and color duplex sonography for varicocele. The maximal vein diameters of pampiniform plexus and duration of reflux were recorded. Semen samples were also analyzed in both groups. Results. Patients with AS had a higher incidence of clinical varicoceles (52%) compared with the healthy age-matched controls (20%). On color Doppler examination, 12 patients (57%) had varicocele (3 bilateral and 9 on the left side) and 6 controls had varicocele on the left side. The patients with AS had significantly greater vein diameters of pampiniform plexus on the left and right side compared with the controls. Conclusions. The incidence of varicocele is increased in patients with AS, and its clinical relevance needs to be evaluated.

Drug-Induced Infertility and Sexual Dysfunction By Robert Forman, Susanna Gilmour-White, and Nathalie Forman (review)

Drug-Induced Infertility and Sexual Dysfunction By Robert Forman, Susanna Gilmour-White, and Nathalie Forman (review)

Testicular circulatory isolation in man: Comparison of radionuclide angiography with doppler evaluation

Testicular circulatory isolation (TCI) holds promise as a method to avoid drug-induced infertility in male patients about to receive cancer chemotherapy. Complete exclusion of blood flow to the testicle is essential to the success of this technique. We have compared the hand-held Doppler probe and radionuclide angiography (technetium-99m pertechnetate) as monitors of testicular blood flow in 10 patients subjected to unilateral TCI. When Doppler evaluation indicated that testicular circulation had been interrupted, the radionuclide angiogram uniformly confirmed and quantified this conclusion. These results validate the hand-held Doppler as an appropriate tool for assessing testicular blood flow in patients undergoing TCI.

Effects of carboplatin on the testis

In the present study, the influence of carboplatin [diammine(cyclobutane-1,1-dicarboxylato)platinum(II)], the main and most active representative of second-generation antitumour platinum complexes, on the morphology of the testes of male CF1 mice was investigated histologically by examining semithick sections. Carboplatin was administered in doses of 30, 60, or 120 mg/kg and applied as a single intraperitoneal injection. For comparison purposes, the parent compound cisplatin [cis-diamminedichloroplatinum(II)] was administered at equitoxic doses (3, 6 or 12 mg/kg). At various intervals between days 1 and 28 after treatment, the testes were removed and embedded in Epon. Both compounds effected severe structural alterations of Sertoli cells, disrupted the blood/testis barrier, and impaired the processes both of spermatogenesis and spermiohistogenesis. The structural damage in the testes following treatment with carboplatin was at least as pronounced as that occurring under the influence of equitoxic doses of cisplatin. Within a few days, the intercellular spaces around Sertoli cells widened, the tight contacts with neighbouring cells were disrupted, the cytoplasm of Sertoli cells disintegrated and their nuclei shrank. Numerous necroses, abnormal mitotic figures of spermatogenic cells and malformed spermatozoa appeared. Severe damage was evident on days 10-21 after treatment with carboplatin, the strength of the symptoms being clearly dependent on the dose applied. The first indications of ongoing recovery processes were detected on day 21 in the case of the low dose (30 mg/kg) or on day 28 following treatment with 60 mg/kg or 120 mg/kg. These results confirm that carboplatin is at least as toxic to the testes as cisplatin and that its substitution for cisplatin in clinical therapy does not diminish the problem of drug-induced infertility following platinum-based chemotherapy.

Drug-induced infertility.

Primary infertility may result from the use of various drugs. This phenomenon may be the result of an effect on the hypothalamic-pituitary-gonadal axis or a direct toxic effect on the gonads. Some of the drugs considered in this article demonstrate sex-related differences in their ability to cause infertility; there also may be age-related differences. The drugs described in this review, in regard to their association with the development of infertility, include various individual antineoplastic agents (cyclophosphamide, chlorambucil, busulphan, and methotrexate) and combinations of these chemotherapeutic drugs, glucocorticosteroids, hormonal steroids (diethylstilbestrol, medroxyprogesterone acetate, estrogen, and the constituents of oral contraceptives), antibiotics (sulfasalazine and co-trimoxazole), thyroid supplements, spironolactone, cimetidine, colchicine, marihuana, opiates, and neuroleptic agents.

Antifertility activities of 5-thio-D-glucose in mice and rats

5-Thio-D-glucose given orally to mice at 50 mg/kg/day for up to 49 days inhibited spermatogenesis and fertility, confirming an earlier report. Contrary to the earlier report, the antispermatogenic activity and the drug-induced infertility were only partially reversible as judged by mating trials and testicular morphology. A second experiment, designed to determine if the thiosugar had intrinsic antifertility activity under conditions in which the diabetogenic response was suppressed, showed that the antispermatogenic effect continued to be manifested when insulin (0.5 U/day)-treated rats were given 50 mg/kg/day 5-thio-D-glucose. We conclude that 5-thio-D-glucose is a partially reversible antifertility agent with some apparently intrinsic antispermatogenic activity independent of its effect on serum glucose concentrations.