The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility.
Alkylating Agents ; Cryopreservation ; Drug Therapy ; Embryonic Stem Cells ; Fertility ; Fertility Preservation ; Germ Cells ; Gonads ; Hope ; Humans ; Induced Pluripotent Stem Cells ; Infertility ; Infertility, Male ; Male ; Methods ; Quality of Life ; Radiotherapy ; Spermatogenesis ; Spermatozoa ; Stem Cells ; Survival Rate ; Whole-Body Irradiation

Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeutic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for Hodgkin's disease, are particularly associated with subsequent infertility. Radiotherapy may also cause gonadal damage, most notably following direct testicular irradiation or total body irradiation. Because of the varied nature of the cytotoxic insult, it can be difficult to predict the likelihood of infertility in later life. Currently it is not possible to detect gonadal damage early due to the lack of a sensitive marker of gonadal function in the prepubertal age group. Semen cryopreservation is currently the only method of preserving fertility in patients receiving gonadotoxic therapy. This is only applicable to postpubertal patients and can be problematic in the adolescent age group. At present there is no provision for the prepubertal boy, although there are a number of experimental methods currently being investigated. By harvesting testicular tissue prior to gonadotoxic therapy, restoration of fertility could be achieved following treatment, either by germ cell transplantation or by in vitro maturation of the germ cells harvested. Alternatively, rendering the testes quiescent during cytotoxic treatment may protect the germ cells from subsequent damage. In addition to the many scientific and technical issues to be overcome prior to clinical application of these techniques, a number of ethical and legal issues must also be addressed to ensure a safe and realistic prospect for future fertility in these patients.
Antineoplastic Agents ; adverse effects ; Child ; Cryopreservation ; Ethics, Clinical ; Fertility ; Humans ; Infertility, Male ; etiology ; Male ; Neoplasms ; therapy ; Puberty ; Radiotherapy ; adverse effects ; Semen Preservation ; Testis

With advances in cancer treatment, more pediatric cancer patients have increased their life expectancy. Because cancer-related therapy causes various physical and psychological problems, many male survivors experience later problems with thyroid and sexual functions, and with growth. As outcomes have improved, more survivors need to maintain their reproductive function to maximize their long-term quality of life. Cancer and cancer-related treatment can impair fertility by damage to the testes, to the hypothalamic-pituitary-gonadal axis, or to the genitourinary organs. Prior radiation therapy to the testes, the use of alkylating agents, and central hypogonadism further impair fertility in male survivors of childhood cancer. Following any course of chemotherapy, peripubertal maturation, any testicular volume changes, and symptoms of androgen deficiency should be monitored systematically. If patients request fertility testing, spermatogenesis status can be evaluated either directly by semen analysis or indirectly by determination of the levels of testosterone/gonadotropins and by monitoring any changes in testicular volume. According to the patient's condition, semen cryopreservation, hormonal therapy, or assisted reproduction technologies should be provided.
Alkylating Agents ; Axis ; Cryopreservation ; Drug Therapy ; Fertility* ; Humans ; Hypogonadism ; Infertility ; Life Expectancy ; Male* ; Quality of Life ; Radiotherapy ; Reproduction ; Semen ; Semen Analysis ; Spermatogenesis ; Survivors* ; Testis ; Thyroid Gland

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.
Animals ; Antibodies ; Biopsy ; Castration ; Cats ; Contraception, Immunologic ; Fertility Agents ; Flagellin ; Gonadotropin-Releasing Hormone ; Humans ; Hypothalamus ; Infertility ; Male ; Salmonella typhimurium ; Sexual Maturation ; Spermatozoa ; Testis ; Testosterone ; Vaccination ; Vaccines

A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.
Adult ; Anabolic Agents ; therapeutic use ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Female ; Fertility Agents, Female ; therapeutic use ; Humans ; Male ; Mesterolone ; therapeutic use ; Oligospermia ; drug therapy ; etiology ; Pregnancy ; Pregnancy Outcome ; Sexual Maturation ; Sperm Count ; Testis ; drug effects ; pathology ; Testosterone ; therapeutic use

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Antioxidants ; Classification ; Clinical Protocols ; Diagnosis ; DNA ; Embryonic Structures ; Female ; Fertility ; Health Expenditures ; Humans ; Infertility ; Infertility, Male ; Male ; Membranes ; Ovum ; Oxidants ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; Reducing Agents ; Reproductive Health ; Semen ; Spermatozoa ; Subject Headings

Objective: To investigate whether the trigger effect of human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG) attributes to the treatment of unexplainable non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data about 282 cases of unexplainable NOA treated in the Maternity and Child Health Hospital of Guizhou Province from January 2010 to May 2017. All the patients underwent trigger treatment by intramuscular injection of hMG at 75 IU 3 times a week for 2 weeks, followed by hCG at 2 000 IU twice a week for another 2 weeks, and meanwhile took vitamin E, Levocarnitine and Tamoxifen as an adjunctive therapy. The treatment lasted 3－12 months. RESULTS: Fifty-eight of the 255 patients that completed the treatment were found with sperm in the semen after treatment, all with severe oligoasthenospermia. Forty-seven of the 58 cases received assisted reproductive technology (ART), of which 18 achieved clinical pregnancy. Semen centrifugation revealed no sperm in the other cases, of which 6 were found with epididymal sperm at epididymal and testicular biopsy after treatment and 3 of them achieved clinical pregnancy after ART. Sperm was found in the semen or at epididymal or testicular biopsy in 64 of the patients after treatment, with an effectiveness rate of 25.1%. CONCLUSIONS Trigger treatment by injection of hMG and hCG combined with adjunctive oral medication has a certain effect on unexplainable NOA.
Azoospermia ; drug therapy ; Chorionic Gonadotropin ; therapeutic use ; Drug Administration Schedule ; Epididymis ; Female ; Fertility Agents, Male ; therapeutic use ; Humans ; Injections, Intramuscular ; Male ; Menotropins ; therapeutic use ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Retrospective Studies ; Sperm Retrieval ; statistics & numerical data ; Spermatozoa ; Testis

OBJECTIVETo observe the therapeutic effect of Qilin Pills combined with clomiphene on idiopathic oligoasthenospermia.

METHODSWe randomly assigned 300 patients with idiopathic oligoasthenospermia to a trial (n = 156) and a control group (n = 144) to be treated with Qilin Pills (6 g, tid) combined with clomiphene (50 mg, qd) and clomiphene alone (50 mg, qd), respectively, both for a course of 12 weeks. Before and after 4, 8, and 12 weeks of medication, we determined sperm concentration, the percentages of grade a and grade a + b sperm, sperm motility, and the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), followed by evaluation of the clinical efficacy of Qilin Pills with the pregnancy rate in the patients' spouses as the secondaty therapeutic indexes.

RESULTSCompared with the baseline, both groups of patients showed remarkably improved semen parameters and hormone levels after treatment (all P < 0.01). After 4, 8, and 12 weeks of medication, statistically significant differences were observed between the trial and control groups in sperm concentration ([17.06 ± 2.24] vs [15.07 ± 2.48], [22.10 ± 2.65] vs [18.11 ± 2.97], and [28.13 ± 3.59] vs [21.21 ± 3.60] x 10(6)/mL, P < 0.01), the percentage of grade a sperm ([15.03 ± 2.39] vs [13.08 ± 2.51], [21.08 ± 3.16] vs [16.04 ± 3.05], and [28.08 ± 4.70] vs [20.14 ± 4.74]%, P < 0.01), the percentage of grade a + b sperm ([30.10 ± 5.07] vs [26.21 ± 3.96], [38.08 ± 5.64] vs [30.07 ± 4.80], and [48.04 ± 6.49] vs [35.28 ± 4.77]%, P < 0.01), sperm motility ([42.04 ± 4.86] vs [40.29 ± 4.19], [52.05 ± 5.58] vs [48.03 ± 4.40], and [65.03 ± 5.13] vs [56.67 ± 4.99]%), the FSH level ([7.75 ± 1.38] vs [7.20 ± 1.17], [10.83 ± 1.23] vs [9.10 ± 1.32], and [14.22 ± 0.84] vs [12.06 ± 1.45] IU/L, P < 0.01), the LH level ([10.05 ± 1.68] vs [9.18 ± 1.54], [13.96 ± 1.68] vs [11.99 ± 1.71], and [19.01 ± 2.42] vs [15.86 ± 2.08] IU/L, P < 0.01) and the T level ([19.19 ± 192] vs [18.34 ± 1.79] [21.06 ± 1.63] vs [20.06 ± 1.56], and [24.63 ± 1.06] vs [22.03 ± 1.49] nmol/L, P < 0.01). The pregnancy rate in the patients' spouses was significantly higher in the trial than in the control group at 4, 8, and 12 weeks (1.92 vs 0.69, 4.81 vs 3.47, and 11.54 vs 8.33%, P < 0.01). There were no statistically significant differences in drug tolerance between the two groups (P > 0.05). No obvious adverse reactions were observed.

CONCLUSIONQilin Pills combined with clomiphene can evidently improve the seminal quality and hormone level of oligoasthenospermia patients with no obvious adverse events. However, its long-term efficacy and tolerance deserve further clinical investigation.

Asthenozoospermia ; blood ; drug therapy ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fertility Agents ; therapeutic use ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Pregnancy ; Pregnancy Rate ; Semen ; Sperm Count ; Sperm Motility ; Spermatozoa ; Testosterone ; blood

OBJECTIVETo study the relationship between the positive antisperm antibody (AsAb) and nitric oxide (NO) content in blood of infertile patients and the therapeutic effect of integrative Chinese and western medicine (ICWM) treatment on the disease.

METHODSInfertile patients, 75 of AsAb positive and 68 of AsAb negative were selected to observe the mature partuient rate and abortion rate. Serum NO level were measured before treatment to observe the relationship between NO and positive AsAb. Patients were treated with ICWM and followed-up for five years.

RESULTSMean value of serum NO in patients with positive AsAb was significantly higher than that in fertile women, and there was no significant difference between patients with negative AsAb and fertile women (P < 0.01). In the 5 years after treatment, the mature partuient rate between the two groups showed insignificant difference (P > 0.05).

CONCLUSIONAsAb positive and NO level abnormal may interfere mutually, to intervent the reproductive process. ICWM therapy could effectively regulate auto-immunity and endocrine function, and make the infertile patients obtain satisfactory efficacy.

Adult ; Antibodies ; blood ; Dexamethasone ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fertility Agents, Female ; therapeutic use ; Humans ; Infertility, Female ; blood ; drug therapy ; immunology ; Male ; Nitric Oxide ; blood ; Phytotherapy ; Spermatozoa ; immunology

OBJECTIVETo explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.

METHODSSixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.

RESULTSDutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).

CONCLUSIONDutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.

Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism