Infertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa; (3) time - to consider the available "treatment window", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic.
Azoospermia ; Female ; Fertilization in Vitro/methods* ; Humans ; Infertility, Male/therapy* ; Male ; Prevalence ; Reproductive Techniques, Assisted ; Sperm Injections, Intracytoplasmic/methods* ; Spermatozoa

Azoospermia/therapy* ; Female ; Humans ; Male ; Microdissection ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; Sperm Motility ; Sperm Retrieval ; Spermatozoa ; Testis

The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.
Azoospermia/therapy* ; China ; Female ; Humans ; Infant, Newborn ; Male ; Oligospermia/therapy* ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Sperm Injections, Intracytoplasmic/methods* ; Sperm Retrieval ; Spermatogenesis ; Spermatozoa

Advances in the oncology field have led to improved survival rates. Consequently, quality of life after remission is anticipated, which includes the possibility to conceive children. Since cancer treatments are potentially gonadotoxic, fertility preservation must be proposed. Male fertility preservation is mainly based on ejaculated sperm cryopreservation. When this is not possible, testicular sperm extraction (TESE) may be planned. To identify situations in which TESE has been beneficial, a systematic review was conducted. The search was carried out on the PubMed, Scopus, Google Scholar, and CISMeF databases from 1 January 2000 to 19 March 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed in selecting items of interest. Thirty-four articles were included in the systematic review, including 15 articles on oncological testicular sperm extraction (oncoTESE), 18 articles on postgonadotoxic treatment TESE and 1 article on both oncoTESE and postgonadotoxic treatment TESE. Testicular sperm freezing was possible for 42.9% to 57.7% of patients before gonadotoxic treatment and for 32.4% to 75.5% of patients after gonadotoxic treatment, depending on the type of malignant disease. Although no formal conclusion could be drawn about the chances to obtain sperm in specific situations, our results suggest that TESE can be proposed before and after gonadotoxic treatment. Before treatment, TESE is more often proposed for men with testicular cancer presenting with azoospermia since TESE can be performed simultaneously with tumor removal or orchiectomy. After chemotherapy, TESE may be planned if the patient presents with persistent azoospermia.
Child ; Humans ; Male ; Azoospermia/therapy* ; Testicular Neoplasms/therapy* ; Quality of Life ; Spermatozoa ; Testis ; Syndrome ; Sperm Retrieval ; Retrospective Studies

OBJECTIVE: To analyze the clinical treatment results of male infertility caused by Y chromosome azoospermia factor c region(AZFc) deletion after synchronous micro-dissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) and to guide the treatment of infer- tile patients caused by AZFc deletion. METHODS: The clinical data of infertile patients with AZFc deletion who underwent synchronous micro-TESE in Peking University Third Hospitalfrom January 2015 to December 2019 were retrospectively analyzed. The clinical outcomes of ICSI in the patients who successfully obtained sperm were followed up and we compared the outcomes between the first and second synchronous procedures, including fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate and live birth rate. RESULTS: A total of 195 male infertile patients with AZFc deletion underwent micro-TESE. Fourteen patients were cryptozoospermia and their sperms were successfully obtained in all of them during the operation, and the sperm retrieval rate (SRR) was 100%(14/14). The remaining 181 cases were non obstructive azoospermia, and 122 cases were successfully found the sperm, the SRR was 67.4%(122/181). The remaining 59 patients with NOA could not found mature sperm during micro-TESE, accounting for 32.6% (59/181). We followed up the clinical treatment outcomes of the patients with successful sperm retrieved by synchronous micro-TESE and 99 patients were enrolled in the study. A total of 118 micro-TESE procedures and 120 ICSI cycles were carried out. Finally 38 couples successfully gave birth to 22 male and 22 female healthy infants, with a cumulative live birth rate of 38.4% (38/99). In the fresh-sperm ICSI cycle of the first and second synchronous operation procedures, the high-quality embryo rate, clinical pregnancy rate of the fresh embryo transfer cycle and live birth rate of the oocyte retrieve cycle were 47.7% vs. 50.4%, 40.5% vs. 50.0%, and 28.3% vs. 41.2%, respectively. The second operation group was slightly higher than that of the first synchronous operation group, but there was no significant difference between the groups. CONCLUSION Male infertility patients caused by AZFc deletion have a high probability of successfully obtaining sperm in testis through micro-TESE for ICSI and give birth to their own offspring with their own biological characteristics. For patients who failed in the first synchronous procedure, they still have the opportunity to successfully conceive offspring through reoperation and ICSI.
Azoospermia/therapy* ; Chromosome Deletion ; Chromosomes, Human, Y ; Female ; Humans ; Infertility, Male/therapy* ; Male ; Pregnancy ; Retrospective Studies ; Semen ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development ; Sperm Injections, Intracytoplasmic/methods* ; Sperm Retrieval ; Spermatozoa ; Testis

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11
Adult Germline Stem Cells/metabolism* ; Animals ; Azoospermia/genetics* ; Infertility, Male/therapy* ; Male ; Mice ; Mutation/genetics* ; Spermatogenesis/genetics*

Sperm cryopreservation has been widely used in assisted reproduction, but conventional techniques are not suitable for the cryopreservation of small numbers of sperm. The application of the single sperm cryopreservation technique has significantly improved the clinical treatment of cryptozoospermia and non-obstructive azoospermia. Ever since Cohen et al first developed the method of single sperm cryopreservation in 1997, constant efforts have been made to develop the carriers for this technique. In this review, we mainly discuss the existing methods and clinical outcomes of single sperm cryopreservation.
Azoospermia ; therapy ; Cryopreservation ; methods ; Heterozygote ; Humans ; Male ; Oligospermia ; therapy ; Reproduction ; Semen Preservation ; methods ; Spermatozoa

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.
Adult ; Azoospermia/therapy* ; Follicle Stimulating Hormone/blood* ; Humans ; Male ; Microdissection ; Oligospermia/pathology* ; Predictive Value of Tests ; Sensitivity and Specificity ; Sertoli Cell-Only Syndrome/pathology* ; Sperm Maturation ; Sperm Retrieval ; Spermatozoa ; Testis/pathology* ; Threshold Limit Values

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.
Adolescent ; Adult ; Age Factors ; Azoospermia ; Cryopreservation ; Drug Therapy ; Humans ; Japan/epidemiology* ; Male ; Middle Aged ; Neoplasms/epidemiology* ; Semen Analysis ; Semen Preservation/methods* ; Sperm Banks/statistics & numerical data* ; Surveys and Questionnaires ; Testicular Neoplasms/epidemiology* ; Treatment Outcome ; Young Adult

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