Post-treatment sperm cryopreservation practices in childhood and young adult cancer survivors.

RESEARCH QUESTION: What are current practices of post-treatment fertility preservation in male childhood cancer survivors (CCS) who have not benefitted from pre-therapeutic fertility preservation in France and other European countries? DESIGN: A survey was conducted of all fertility preservation centres in France (n = 30) and European fertility specialists (n = 9) in five European countries. Eight clinical cases and 40 questions were included to assess the effect of age at diagnosis, type of treatment (alkylating-agents, orchidectomy, testicular radiotherapy) and sperm parameters on the probability of a post-treatment fertility preservation proposal. Demographic characteristics of the responding practitioner were also collected. RESULTS: Post-treatment sperm cryopreservation was proposed by 100% of fertility specialists in cases of severe oligoasthenoteratozoospermia, 77-88% in cases of moderate oligoasthenoteratozoospermia and in 65-77% in cases of sperm motility and vitality impairment. In cases of normal sperm parameters, 27-54% of fertility specialists would propose post-treatment sperm cryopreservation. These results did not differ significantly according to the type of treatment received or to responder-related factors. Practices of European specialists were also guided by sperm parameter results; 44-67% of specialists responding that they would propose sperm cryopreservation in cases of moderate to severe sperm parameter alterations. CONCLUSION: Post-treatment semen analysis could be widely proposed to CCS who have not benefitted from pre-therapeutic fertility preservation. Post-treatment fertility preservation could be proposed in cases of persistent moderate to severe sperm parameter alterations. Guidelines would be important to homogenize practices and to encourage oncologists to refer CCS for fertility assessments.

Who cares about oligozoospermia when we have ICSI.

The value of assessing subfertile males with oligozoospermia is controversial due to prevailing notions that therapies are limited and ICSI may provide the couple with a baby without the need to explain the nature or cause of underlying male infertility. This article highlights that indiscriminately offering ICSI to oligozoospermic men is not free of potential adverse effects and does not grant subfertile men the best fertility pathway. Recent data support associations between oligozoospermia and poor male reproductive health, DNA and epigenetic damage in spermatozoa, and possible adverse health consequences to offspring. Many conditions affecting the testicles are capable of causing oligozoospermia (varicocele, genital infections, congenital and genetic defects testicular torsion/trauma, chronic diseases, inadequate lifestyle, occupational/environmental exposure to toxicants, drugs, cancer and related treatments, acute febrile illness, endocrine disorders, and iatrogenic damage to the genitourinary system). If oligozoospermia is detected, therapeutic interventions can improve sperm quantity/quality and the overall male health, ultimately resulting in better pregnancy outcomes even when ICSI is used. Fertility clinics are urged to engage male infertility specialists in diagnosing and treating oligozoospermia as a matter of best clinical practice. A well-conducted male infertility evaluation represents a unique opportunity to identify relevant medical and infertility conditions, many of which may be treated or alleviated. The andrological assessment may also help guide the optimal application of ICSI. The final goals are to positively impact the overall patient health, the couple's pregnancy prospects, and the offspring's well-being.

Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity.

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.

Clinical benefit for cryopreservation of single human spermatozoa for ICSI: A systematic review and meta-analysis.

BACKGROUND: Systematic reviews have focused on sperm recovery and post-thaw parameters after cryopreservation, but there is no information on the associated clinical outcomes. In recent years, an increasing number of studies have reported cryopreservation of a single sperm due to the importance of fertility preservation. OBJECTIVES: To assess whether the cryopreservation of single human spermatozoa improves clinical outcomes in patients with azoospermia or severe oligospermia. MATERIALS AND METHODS: We conducted an extensive literature search using the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science for relevant studies published through December 31, 2019. We calculated the pooled proportions of cryopreservation of a single human spermatozoon to assess the recovery, survival, fertilization, pregnancy, miscarriage, and delivery rates. Subgroup analyses were performed for the following covariates, (a) different carriers, (b) year of publication, and (c) source of sperm. RESULTS: We included 25 studies, which included 13 carriers. The pooled proportion of recovery rate of spermatozoa cryopreserved was 92% (95% CI, 87%-96%), and the survival, fertilization, pregnancy, miscarriage, and delivery rates were 76% (95% CI, 69%-83%), 63% (95% CI, 58%-67%), 57% (95% CI, 39%-74%), 12% (95% CI, 0%-33%), and 40% (95% CI, 12%-71%), respectively. Based on the subgroup analysis, the recovery and survival rates of frozen spermatozoa in a subgroup of different carriers were statistically significant. In the past decade, frozen single human spermatozoon technology has improved the recovery rates of frozen-thawed spermatozoa. However, the differences in clinical outcomes of frozen spermatozoa in subgroups of different sources of sperm were not statistically significant. DISCUSSION AND CONCLUSION: The techniques for single human spermatozoa are feasible and efficient and may benefit patients with severe oligospermia or azoospermia.

Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity / 亚洲男科学杂志(英文版)

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.

Is a contralateral testicular exploration required at microdissection testicular sperm extraction for men with nonobstructive azoospermia, cryptozoospermia or severe oligozoospermia?

OBJECTIVES: Men with nonobstructive azoospermia (NOA), cryptozoospermia and severe oligozoospermia are candidates for microdissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI). We sought to evaluate micro-TESE outcomes and the need for bilateral testicular exploration in the three groups of men. METHODS: We conducted a retrospective study of 233 consecutive micro-TESEs in men with nonobstructive azoospermia (n = 173), cryptozoospermia (n = 43) and severe oligozoospermia (n = 17). The decision to terminate the micro-TESE after a unilateral or bilateral testicular exploration was determined at the time of surgery and was based on the presence or absence of mature spermatozoa in the harvested micro-biopsies. Final assessment of sperm recovery, on the day of ICSI, was reported as successful (available spermatozoon for ICSI) or unsuccessful (no spermatozoon for ICSI). RESULTS: Unilateral testicular exploration resulted in successful sperm retrieval in 43% (75/173), 79% (34/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. Therefore, 57%, 21% and none of the men with NOA, cryptozoospermia and severe oligozoospermia, respectively, required a bilateral micro-TESE. Overall, micro-TESE resulted in successful sperm retrieval in 52% (90/173), 91% (39/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. CONCLUSION: Our data indicate that men with severe oligozoospermia are unlikely to require a bilateral testicular exploration at micro-TESE. Moreover, most cryptozoospermic men will have a successful sperm retrieval by micro-TESE with the majority of these patients requiring a unilateral exploration. In contrast, over 50% of the men with nonobstructive azoospermia will require a bilateral micro-TESE.

Testicular sperm extraction vs. ejaculated sperm use for nonazoospermic male factor infertility.

OBJECTIVE: To study the potential benefit of testicular sperm compared with ejaculated sperm for men with oligospermia. DESIGN: After exemption from institutional review board approval, we performed a retrospective cohort study using the Mayo Clinic Assisted Reproductive Technology database. SETTING: Single academic center. PATIENT(S): Couples with nonazoospermic male factor infertility (total motile sperm <25 million per ejaculate) undergoing intracytoplasmic sperm injection with sperm obtained by testicular sperm extraction (TESE) or ejaculated sperm between 2016 and 2019. INTERVENTION(S): In vitro fertilization, Intracytoplasmic sperm injection, TESE. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate. The secondary outcomes were fertilization rate, blastulation rate, pregnancy rate, and miscarriage rate. RESULT(S): Subjects in the two groups were similar in age, body mass index, and ovarian reserve. Baseline sperm parameters were similar in the two groups: total motile sperm (5.4 in the ejaculate sperm group vs. 3.6 million motile per ejaculate), except that baseline motility was higher in the group that used ejaculated sperm (40% vs. 29%). The total number of mature oocytes retrieved was similar in the two groups, but the use of TESE was associated with a 20% decrease in fertilization (60.0% vs. 80.6%) and half the number of blastocyst embryos (two vs. four) compared with ejaculated sperm. Compared with ejaculated sperm, use of TESE did not improve the miscarriage rate (11% vs. 9%) or the live birth rate (50.0% vs. 31.3%). CONCLUSION(S): Patients with male factor infertility and oligozoospermia did not have improved ICSI outcomes with the use of TESE samples compared with ejaculated sperm.

[Clinical observation of herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS for asthenospermia and oligospermia].

OBJECTIVE: To observe the clinical effect of herb-separated moxibustion on segmental conception vessel combined with low-frequency transcutaneous electrical acupoint stimulation (TEAS) for asthenospermia and oligospermia. METHODS: A total of 105 patients with asthenospermia and oligospermia were randomly divided into a combination group, a TEAS group and a medication group, 35 cases in each one. In the medication group, vitamin E capsules, coenzyme Q10 capsules，Wuzi Yanzong pills were taken. In the TEAS group, TEAS was applied at Shenshu (BL 23) and Pishu (BL 20), 2 Hz in frequency, 10-15 mA in intensity, once every 2 days, 30 min each time.On the base of the treatment as the TEAS group, herb-separated moxibustion on segmental conception vessel [Shenque (CV 8) to Zhongji (CV 3)] was applied in the combination group, once every 10 days. A total of 3 months were required in the 3 groups.Before treatment and 2, 3 months into treatment, the semen routine indexes (concentration, normal morphology rate, sperm motility), seminal plasma contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and TCM syndrome score were observed in the 3 groups, and the clinical efficacy was evaluated. RESULTS: Compared before treatment, except for the sperm morphology 2 months into treatment in the medication group, the semen routine indexes 2, 3 months into treatment were improved in the 3 groups (P<0.01), and the semen routine indexes 2, 3 months into treatment in the combination group were superior to the medication group and the TEAS group (P<0.01). Compared before treatment, the seminal plasma contents of SOD were increased and MDA were decreased 2, 3 months into treatment in the 3 groups (P<0.01), and the changes of the combination group were larger than the medication group and the TEAS group (P<0.01). Compared before treatment, the TCM syndrome scores 2, 3 months into treatment in the combination group, and 3 months into treatment in the medication group and the TEAS group were decreased (P<0.01). The TCM syndrome scores 2, 3 months into treatment in the combination group were lower than the medication group and the TEAS group (P<0.01). The total effective rates in the combination group, the medication group and the TEAS group were 85.7% (30/35), 68.6% (24/35) and 65.7% (23/35), the clinical efficacy of the combination group was higher than the medication group and the TEAS group (P<0.05). CONCLUSION: Herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS can improve semen routine, reduce sperm oxidative stress damage for patients with asthenospermia and oligospermia, and the clinical efficacy is better than the medication and TEAS.

Testicular Sperm Aspiration (TESA) or Microdissection Testicular Sperm Extraction (Micro-tese): Which Approach is better in Men with Cryptozoospermia and Severe Oligozoospermia?

OBJECTIVES: To evaluate and compare sperm retrieval outcomes by testicular sperm aspiration (TESA) and micro-dissection testicular sperm extraction (micro-TESE) in non-azoospermic men. METHODS: We conducted a retrospective study of 145 consecutive testicular sperm retrievals in men with cryptozoospermia (n = 56) or severe oligozoospermia (n = 84). The decision to perform a TESA or a micro-TESE was made after thorough discussion of the pros and cons of these procedures with the couple. Final assessment of sperm recovery, on the day of ICSI, was reported either as successful (available sperm for ICSI) or unsuccessful (no sperm for ICSI). RESULTS: Mean sperm concentration, sperm motility, testicular volume and serum FSH level of men undergoing TESA were not significantly different from those of men undergoing micro-TESE. In men with severe oligozoospermia (<5 million/ml), sperm recovery was successful in 95% (18/19) of those who underwent micro-TESE and in 92% (60/65) of those who underwent TESA (P > 0.05). In men with cryptozoospermia, sperm recovery was successful in 88% (42/48) of men who underwent micro-TESE and 25% (2/8) of men who underwent TESA (P < .001). CONCLUSIONS: These data indicate that in men with severe oligozoospermia, TESA and micro-TESE are equally successful sperm retrieval techniques. However, in men with cryptozoospermia, sperm retrieval rates are significantly higher with micro-TESE than TESA.

Two subsequent seminal productions: A good strategy to treat very severe oligoasthenoteratozoospermic infertile couples.

BACKGROUND: Sexual abstinence is considered one of the several factors that influence sperm quality. Recent studies show that a shortening of the abstinence period could be beneficial mostly in oligoasthenoteratozoospermic (OAT) patients. OBJECTIVE: Retrospective study to verify the efficacy of a second semen sample after a short abstinence to treat severe OAT infertile patients. MATERIALS AND METHODS: 127 couples treated between May 2014 and May 2018 were divided into two groups. Study Group 1 (75 cycles): severe OAT characteristics: count <0.2 × 106 /mL no progressive motility; count ≥0.2 × 106 /mL and no total or progressive motility; 0% normal morphology; a second semen sample was requested after abstinence of 2 h. Control Group 0 (52 cycles): normozoospermic or mild OAT; only one sample was requested. Intracytoplasmic sperm injection was utilized in all cases. RESULTS: All semen parameters were significantly different between Group 0 vs both samples of Group 1 (p < 0.001), excluding volume between Group 0 and 1st sample of Group 1 (p = 0.682). The comparison between 1st and 2nd samples from Group 1 showed significant differences in volume, total and progressive motility and morphology (p < 0.001, p < 0.001, p < 0.020) but not in total sperm count (p = 0.970). Fertilization, pregnancy rate/transfer, implantation and miscarriage rates were 85.9% and 61.1% (p < 0.001), 30.6% and 35.8% (p = 0.700), 17.5% and 24.0 (p = 0.292), 20.0% and 25.0% (p = 0.017) in Group 0 and Group 1 respectively. DISCUSSION AND CONCLUSION: The results show that a short abstinence in severe OAT patients allows us to obtain spermatozoa with better motility. The request for a second semen sample in couples with extreme semen parameters is a valid and simple strategy that helps to achieve the same probability of pregnancy compared to a Control Group. Furthermore, it allows us to utilize fresh spermatozoa avoiding the need to resort to cryopreserved reserves or testicular surgery.

Poor intracytoplasmic sperm injection outcome in infertile males with azoospermia factor c microdeletions.

OBJECTIVE: To explore whether the presence of azoospermia factor c (AZFc) microdeletions adversely affects intracytoplasmic sperm injection (ICSI) outcome. DESIGN: Retrospective cohort. SETTING: University hospital. PATIENT(S): A total of 293 patients with azoospermia or severe oligozoospermia AZFc deletions underwent 345 ICSI cycles, and 363 idiopathic patients with normal Y chromosome underwent 462 ICSI cycles. INTERVENTION(S): Testicular sperm aspiration, microdissection testicular sperm extraction. MAIN OUTCOME MEASURE(S): The main clinical outcome parameters were cumulative clinical pregnancy rate, cumulative live birth delivery rate, and no embryo suitable for transfer cycle rate. RESULT(S): Compared with the control group, the AZFc deletion group exhibited poorer ICSI outcome, with significant differences between the 2 groups for cumulative clinical pregnancy rate (45.39% vs. 67.49%; odds ratio [OR], 2.843; 95% confidence interval [CI]), cumulative live birth delivery rate (35.15% vs. 53.44%; OR, 2.234; 95% CI), no embryo suitable for transfer cycle rate (15.07% vs. 8.23%; OR, 0.565; 95% CI), fertilization rate (46.80% vs. 53.37%; adjusted ß, -0.074; 95% CI), implantation rate (28.63% vs. 31.26%; adjusted ß, -0.075; 95% CI) separately. The poor ICSI outcome of the AZFc deletion group was related to AZFc microdeletions by linear and logistic regression analyses. CONCLUSION(S): AZFc microdeletions adversely affect ICSI outcome; patients with AZFc deletion should be informed that they have reduced opportunities to be biological fathers.

Acupuncture for oligospermia and asthenozoospermia: A systematic review and meta-analysis.

BACKGROUND: Acupuncture is widely used for oligospermia and asthenozoospermia in China, but its effect is unclear. We aimed to determine the effectiveness and safety of acupuncture in treating oligospermia and asthenozoospermia. METHODS: An electronic search for randomized controlled trials evaluating acupuncture treatment in patients with oligospermia and asthenozoospermia published from database inception to October 2018 was conducted in PubMed, EMBASE, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database (VIP Database), the Wan-Fang Database, the China National Knowledge Infrastructure and the Cochrane Library. We established search terms related to 3 areas (oligospermia, asthenozoospermia, and acupuncture). Two authors independently screened all identified citations and extracted the data. The methodological quality of the included trials was assessed using the Cochrane criteria. RESULTS: Seven studies with a total of 527 subjects were screened according to inclusion and exclusion standards, and most of the studies had significant methodological weaknesses. Seven randomized controlled trials tested the effects of acupuncture compared with placebo acupuncture and conventional medications in patients with oligospermia and asthenozoospermia. The results of this study suggest that acupuncture alone has no clear superiority in improving sperm motility (standard mean difference [SMD] = 1.13, 95% confidence interval [CI]: -0.64 to 2.89), the sperm concentration (SMD = 0.32, 95% CI: 0.27-0.92) or semen volume compared with placebo acupuncture. No significant difference was found between acupuncture alone and conventional medications in improving sperm motility (SMD = -0.53, 95% CI: -2.54 to 1.48), the sperm concentration (SMD = -1.10, 95% CI: -1.48 to -0.72) or semen volume. However, adjuvant acupuncture may enhance the effect of medications on improving sperm motility (SMD = 4.10, 95% CI: 1.09-7.12) and the sperm concentration (SMD = 1.07, 95% CI: 0.739-1.40), but the study heterogeneity was too high to establish robust conclusions. CONCLUSION: These results suggest that the current evidence does not support acupuncture as an effective treatment for oligospermia and asthenozoospermia; therefore, acupuncture is not currently recommended as a treatment for these conditions. However, owing to the high risk of bias among the included studies, the evidence is limited, and more large-scale, high-quality clinical trials are needed in the future. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018083885.

A novel homozygous frameshift mutation in MNS1 associated with severe oligoasthenoteratozoospermia in humans.

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

Clinical observation of herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS for asthenospermia and oligospermia / 中国针灸

OBJECTIVE@#To observe the clinical effect of herb-separated moxibustion on segmental conception vessel combined with low-frequency transcutaneous electrical acupoint stimulation (TEAS) for asthenospermia and oligospermia.@*METHODS@#A total of 105 patients with asthenospermia and oligospermia were randomly divided into a combination group, a TEAS group and a medication group, 35 cases in each one. In the medication group, vitamin E capsules, coenzyme Q10 capsules，@*RESULTS@#Compared before treatment, except for the sperm morphology 2 months into treatment in the medication group, the semen routine indexes 2, 3 months into treatment were improved in the 3 groups (@*CONCLUSION@#Herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS can improve semen routine, reduce sperm oxidative stress damage for patients with asthenospermia and oligospermia, and the clinical efficacy is better than the medication and TEAS.

Downregulation of gene expression and the outcome of ICSI in severe oligozoospermic patients: A preliminary study.

Preimplantation embryo development might be influenced by a specific set of transcripts that are delivered to the oocyte by the sperm. The aim of the study was to determine the relationship between the level of selected transcripts in spermatozoa and preimplantation development of the embryos in couples with severe oligozoospermia undergoing intracytoplasmic sperm injection (ICSI) procedure. Therefore, we assessed messenger RNA (mRNA) levels of genes involved in fertilization events, oocyte activation, chromatin remodeling, and DNA repair in severe oligozoospermic compared with normozoospermic men as well as morphokinetic parameters of embryos using the time-lapse imaging system. mRNA profiling (44 genes), in mature sperm, was carried out with custom-designed 384-well TLDA Cards. The morphokinetic parameters of zygotes and embryos were recorded by using a time-lapse imaging system. The transcript levels of 21 genes were significantly decreased in the severe oligozoospermic group. Most were associated with fertilization events, oocyte activation and embryonic genome activation. Among them, mRNA of AKAP4 and PTK7 was greatly reduced, moreover, the transcripts of PLCζ and POU5F1, essential for OA and EGA, were not detected at all in patients with severe oligozoospermia. Moreover, the reduced expression of genes important for spermatogenesis, chromatin remodeling and DNA repair was also observed in this group. Time-lapse analysis revealed that fertilization failure occurred in 14% of retrieved oocytes and 90% of all degenerated embryos did not reach morula stage. This study provides preliminary results indicating a significant decrease in transcripts of genes important for spermatogenesis and early preimplantation development in the mature sperm of men with severe oligozoospermia.

Sperm source does not affect the ICSI outcome of patients with severely compromised spermatogenesis.

Patients with spermatogenic dysfunction may display sperm parameters ranging from extremely severe oligozoospermia (sperm count lower than 2 million/ml) to azoospermia. It has been proposed that, since these patients may have increased sperm DNA damage that could affect their ICSI outcome, the use of surgically retrieved testicular spermatozoa should be preferred to improve their chance of fathering their biological offspring. However, studies in this field have yielded conflicting results. The present study provides an updated assessment of this subject by comparing the ICSI outcome of 762 patients with nonobstructive azoospermia and 419 with sperm count lower than 2 million/ml (median sperm count 300,000/ml). Both groups were homogeneous for the number of retrieved and injected MII oocytes. No difference was seen in terms of fertilisation, clinical pregnancy and cumulative live birth rates. Only the number of injected MII oocytes was found to independently predict the live birth rate, even when adjusted for the number of transferred embryos (OR 1.10 (1.0-1.2, p = 0.038)). The results of the present study stand against the use of testicular spermatozoa in patients with extremely severe spermatogenic dysfunction with available spermatozoa in their ejaculate.

Novel micro-straw for freezing small quantities of human spermatozoa.

OBJECTIVE: To evaluate a novel micro-straw as an efficient, simple method for freezing a small number of human spermatozoa for intracytoplasmic sperm injection (ICSI). DESIGN: Prospective cohort study. SETTING: Sperm bank. PATIENT(S): Men with severe oligozoospermia or azoospermia undergoing a total of 143 ICSI cycles at the CITIC-Xiangya Hospital of Reproduction and Genetics from June 1, 2015, to June 31, 2019, and 20 donors at the Hunan Province Human Sperm Bank from 2001 to 2016. INTERVENTION(S): Analysis of sperm samples and clinical outcomes after sperm use. MAIN OUTCOME MEASURE(S): Clinical information, including number of motile sperm before and after freezing, freeze-thaw survival rates, two-pronuclear fertilization rates, clinical pregnancy, and early pregnancy loss rates after sperm use. RESULT(S): In the feasibility experiment using the micro-straw, we found a freeze-thaw survival rate of 73% ± 8.3% and no difference in normal sperm morphology, normal acrosome integrity, or DNA fragmentation index between the micro-straw and 1.8-mL cryotubes. The prospective cohort included 1,325 cases, and we collected sperm from testicular, epididymis, and ejaculation sources. We observed motile sperm in 1,294 (97.6%) of 1,325 frozen-thawed samples. Postthaw sperm were available for ICSI in 140 (97.9%) of 143 of cycles. The fertilization, cleavage, and high-quality embryo rates were 1,007 (81.7%) of 1,233; 995 (98.8%) of 1,007; and 537 (53.9%) of 995, respectively. Sixty-nine (49%) clinical pregnancies were achieved, and the miscarriage rate was 6 (8.6%) of 69. CONCLUSION(S): The micro-straw is suitable and clinically useful for the cryopreservation of small numbers of spermatozoa.

Nonsurgical Management of Oligozoospermia.

Male infertility secondary to oligozoospermia is surprisingly common. Although a majority of cases are idiopathic, oligozoospermia can be caused by endocrine dysfunction, anatomic abnormalities, medications, or environmental exposures. The work-up includes excluding reversible factors such as hormonal deficiency, medication effects, and retrograde ejaculation and identifying any underlying genetic syndrome and treating reversible medical causes. If no reversible cause is found, appropriate referrals to urology and assisted reproductive technology should be initiated. Lastly, clinicians should be aware of and respond to the psychological and general health ramifications of a diagnosis of oligozoospermia as part of the comprehensive care of men and couples struggling with a diagnosis of infertility.