Single men's attitudes towards posthumous use of their sperm cryopreserved due to illness in Israel.

BACKGROUND: Banking of frozen spermatozoa by single men opens the possibility of procreation long after their death. Requests for posthumous reproduction by the families of the deceased are growing, raising an ethical debate, especially when written instructions were not left by the patients and in cases of unplanned perimortem collection. The issue of the progenitors' intention to procreate after death is the key to ethically based decision-making in these cases. OBJECTIVES: To evaluate the attitude of single men cryopreserving spermatozoa before life-threatening medical situations towards post-mortem usage of their cryopreserved spermatozoa. MATERIALS & METHODS: Adult single men prior to sperm cryopreservation before cytotoxic therapy were asked to sign a structured form declaring their will and instructions for the usage of their cryopreserved spermatozoa in case of their demise. RESULTS: Four hundred fifty-two men of diverse ethnicity, religious and cultural backgrounds signed the form providing instructions for the use of their cryopreserved spermatozoa in case of mortality. Their age was 27.4 ± 8.06 years. Seven (1.5%) patients willed their spermatozoa for posthumous reproduction to a sibling, 22 (4.9%) to parents, and 26 (5.7%) to their informal female partners. The significant majority (n = 397; 87.8 %) of the single men were ordered to destroy their cryopreserved spermatozoa in case of their expiry. Note that, 26-39 years old men were less likely (81.8% vs. >90% in other ages) to order sperm destruction, as well as men with a poorer prognosis (83% vs. 90%). DISCUSSION: In this study group, most single men cryopreserving spermatozoa in the face of future life-threatening morbidity do so for their own future live parenthood, and are not interested in posthumous reproduction. CONCLUSION: Our results doubt the claim that single men who had an unplanned perimortem sperm collection can be universally presumed to have wished to father a child posthumously. Any claimed assumed consent in these cases should be considered for each case individually based on its specific circumstances.

Association between Hidradenitis Suppurativa and Abnormalities in Semen Parameters and Sexual Function: A Pilot Study.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting patients of reproductive age. Although HS shares risk factors with male infertility, only 1 epidemiological study has evaluated this association. To further evaluate this potential association, findings on semen and hormonal analysis, testicular ultrasound, and the International Index of Erectile Function (IIEF-15) were compared between 28 men attending a tertiary HS clinic during the period April 2019 to April 2021, and 44 healthy controls, spouses of infertile women undergoing semen evaluation before in vitro fertilization. Patients with HS were divided based on the absence or presence of gluteal and genital lesions. Patients with HS were younger than controls (median 27 vs 34 years, p < 0.0004) and had a higher proportion of smokers (86% vs 33%, p < 0.0001). Semen parameters in patients with gluteal-genital lesions, specifically those with severe scrotal involvement necessitating surgery, were lower than the WHO reference values and significantly lower than in patients without gluteal-genital lesions and controls. Erectile dysfunction was reported by 93% of patients with HS. These findings suggest that spermatogenesis and sexual function may be impaired in young men with HS. Therefore, multidisciplinary management of HS should include their evaluation to identify patients who might benefit from semen cryopreservation and sexual treatment.

Sugar Consumption Is Negatively Associated with Semen Quality.

Recently, in parallel to decrease in semen quality, the consumption of sugar has risen sharply. This provided the rationale to study the association between whole dietary sugar consumption and semen quality. Our aim was to investigate the association between sugar consumption and semen quality. The final cross-sectional study population (n = 280 of initial n = 593, after applying inclusion and exclusion criteria) attending routine semen analysis at sperm bank laboratory was subject to semen quality analysis according to WHO criteria (volume, sperm concentration, total sperm count, percentage total motility, and percentage normal morphology) and filled food frequency questionnaire (FFQ) and lifestyle questionnaire. Associations between consumed sugars and semen quality were analyzed using multivariate regression adjusted to relevant cofounders for 2 food components containing sugar including soft drinks (SoftD) and total added sugar to food products (SugProd). We found negative association between higher consumption of dietary sugar in all 2 dietary sub-categories and sperm concentration. Significant sperm concentration decrements of 18% and 23% were associated with SoftD median consumption of 0.2 drinks/day (IQR; 0.1-0.5 drinks/day). Significant sperm concentration decrements of 15% and 17% were associated with median SugProd consumption of 25 teaspoons of added sugar/day (IQR; 19-31 teaspoons of added sugar/day). In conclusion, our study findings demonstrate that sugar consumption is negatively associated with sperm concentration.

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer.

BACKGROUND: To assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors. PATIENTS AND METHODS: We retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis. RESULTS: Of 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease. CONCLUSION: The absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.

Does the time interval from the end of sperm processing to intrauterine insemination (lab-to-uterus time) affect treatment outcome?

BACKGROUND: Intra-uterine insemination is an essential component in the treatment of infertility. Success rates are dependent on clinical factors of the female partner, sperm quality, and preparation technique. The effect of the time interval between the end of sperm preparation in the lab, and its injection into the uterine cavity (lab-to-uterus time) is yet to be determined. AIM: To investigate the association between the lab-to-uterus time and the pregnancy rate. MATERIALS AND METHODS: Partner and donor spermatozoa intra-uterine insemination cycles were included. Preparation for intra-uterine insemination of partners' fresh ejaculate or donor thawed spermatozoa was identical. The time interval from the completion of this stage to the actual intra-uterine injection was recorded. The lab-to-uterus intervals were divided into groups A (0-29 min), B (30-59 min), C (60-89 min), and D (90-180 min). Pregnancy was defined as two adequate consecutive doubling levels of hCG and the pregnancy rates were compared between the groups. RESULTS: A total of 267 female patients (138 partner spermatozoa, 129 donors) who had 470 intra-uterine insemination cycles (218 partner spermatozoa, 252 donors) were included. No significant differences in pregnancy rates per treatment cycle were found between the four lab-to-uterus interval groups: A (n = 96 cycles; 16.7%), B (n = 217; 19.4%), C (n = 121; 16.5%), and D (n = 36; 36.1%). No difference was found in the pregnancy rates between partner and donor spermatozoa. In the case of fresh partner spermatozoa, the pregnancy rates for groups were as follows: A (n = 40 cycles, 20%); B (n = 94; 14.9%), C (n = 70; 17.1%), and D (n = 14; 35.7%) (NS). In the case of thawed donor spermatozoa, the pregnancy rates (per cycle) for groups were as follows: A (n = 56; 14.3%), B (n = 123; 22.8%), C (n = 51; 15.7%), and D (n = 22; 36.4)% (NS). CONCLUSIONS: The intra-uterine insemination outcome was not affected by the lab-to-uterus time interval. Extended waiting up to 3 h for insemination did not have any detrimental effect on pregnancy rates, regardless if partner or donor spermatozoa was used.

Dietary patterns are positively associated with semen quality.

OBJECTIVE: To study association of semen quality with a priori whole dietary pattern indexes, which reflect real-world dietary practices and the numerous combinations by which foods are consumed: Healthy Eating Index (HEI), Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet score (aMED), and Alternative Healthy Eating Index (AHEI). DESIGN: A cross-sectional single-center study. SETTING: Hospital fertility center and university. PATIENT(S): A total of 280 men attending fertility center from 2012 to 2015. INTERVENTION(S): Food frequency questionnaire (FFQ) and semen and sperm analysis. MAIN OUTCOME MEASURE(S): Food consumption with the use of FFQ and HEI, AHEI, aMED, DASH nutritional individual scoring indexes. Semen parameters, including semen volume, sperm concentration, motility, total count, and morphology. RESULT(S): Comparing the highest and lowest quartiles of the nutritional indexes, men in the highest quartiles of HEI, AHEI, aMed, and DASH indexes had significantly higher adjusted means of sperm concentration (by 10%, 45%, and 24% for HEI, AHEI, and DASH, respectively), normal sperm morphology (by 21% and 8% for AHEI and DASH, respectively), total sperm count (by 29% for AHEI), and sperm motility (by 6% and 11% for aMed and HEI, respectively). CONCLUSION(S): Adherence to any of the four dietary indexes is associated with better overall sperm quality, with AHEI best associated. Following our novel findings, we recommend using AHEI as a clinical and practical tool for public whole nutritional recommendation for semen quality.

Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments.

PURPOSE: To investigate if needle-immersed vitrification or slow-freezing yields better implantation results for human ovarian tissue and which method benefits more when combined with the "improvement protocol" of host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A. METHODS: Human ovarian tissue was preserved by needle-immersed vitrification or slow-freezing and transplanted into immunodeficient mice, either untreated (groups A and C, respectively) or treated with the improvement protocol (groups B and D, respectively). Grafted and ungrafted slices were evaluated by follicle counts, apoptosis assay and immunohistochemistry for Ki67 and platelet endothelial cell adhesion molecule (PECAM). RESULTS: Follicle number in the recovered grafts was limited. The number of atretic follicles was significantly higher after vitrification with/without the improvement protocol and slow-freezing than that after slow-freezing + the improvement protocol. Stroma cell apoptosis was the lowest in the group D. PECAM staining showed a peripheral and diffuse pattern in the group D (mostly normal follicular morphology) and a diffuse pattern in all other groups (few follicles, mostly atretic), with significantly higher diffuse levels in the vitrification groups. Ki67 staining was identified in all normal follicles. Follicles did not survive transplantation in the vitrification groups. CONCLUSIONS: Ovarian sample preparation with slow-freezing + the improvement protocol appears to yield better implantation outcomes than needle-immersed vitrification with/without the improvement protocol. The real quality of frozen tissue can be assessed only after grafting and not after thawing/warming.

Predictors of spermatogenesis in radical orchiectomy specimen and potential implications for patients with testicular cancer.

OBJECTIVE: To assess the ability of semen analysis and other patients' characteristics to predict the presence of spermatozoa in radical orchiectomy pathological specimen, and describe potential implications for patients with azoospermia and testis cancer. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital. PATIENT(S): A total of 214 consecutive patients with testicular cancer who underwent radical orchiectomy between 1997 and 2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory, and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with the presence of spermatozoa in the noninvolved ipsilateral testicular parenchyma. RESULT(S): Spermatozoa were found in the pathological specimen of 145 patients (67.8%). At multivariate analysis, increased tumor size was the only factor associated with lower rates of spermatozoa in the specimen. Mean tumor diameter was 4.06 cm, and spermatozoa were found in 83% and 49% of testes with tumor diameters <4 and ≥4 cm, respectively. Preoperative semen analysis records were available for 107 patients. Oligozoospermia, severe oligozoospermia, azoospermia, and cryptozoospermia were observed in 17 (16%), 18 (17%), 9 (8%) and 3 (3%) patients, respectively. Sperm concentration and motility were not associated with complete spermatogenesis. Seven of 12 patients (58%) with either azoospermia or cryptozoospermia had mature sperm in their pathological sections. CONCLUSION(S): Larger testicular cancers are associated with lower rates of spermatozoa in the ipsilateral testis. Given the substantial likelihood (∼60%) of spermatozoa to be present in the cancerous testis of patients with azoospermia and cryptozoospermia, concomitant oncologic testicular sperm extraction (TESE) can be considered in these selected patients.

Severe combined immunodeficiency (SCID): from the detection of a new mutation to preimplantation genetic diagnosis.

PURPOSE: To describe the identification of a new mutation responsible for causing human severe combined immunodeficiency syndrome (SCID). In a large consanguineous Israeli Arab family, this served as a diagnostic tool and enabled us to carry out preimplantation genetic diagnosis (PGD). We also demonstrated that PGD for homozygosity alleles is feasible. METHODS: We carried out genome-wide screening followed by fine mapping and linkage analysis in order to identify the candidate genes. We then sequenced DCLRE1C in order to find the familial mutation. The family was anxious to avoid the birth of an affected child, and therefore, because of their religious beliefs, PGD was the only option open to them. The embryos were biopsied at day 3, and a single blastomere from each embryo was analyzed by multiplex polymerase chain reaction for the SCID mutation and 5 additional polymorphic markers flanking DCLRE1C. RESULTS: Linkage analysis revealed linkage to chromosome 10p13, which harbors the DNA Cross-Link Repair Protein 1 C (DCLRE1C) ARTEMIS gene. Sequencing identified an 8 bp insertion in exon 14 (1306ins8) of DCLRE1C in all the affected patients; this causes an alteration in amino acid 330 of the protein from cysteine to a stop codon (p.C330X). One cycle of PGD was performed and two embryos were transferred, one homozygous wild-type and one a heterozygous carrier, and healthy twins were born. CONCLUSIONS: Identifying the familial mutation enabled us to design a reliable and accurate PGD protocol, even in this case of a consanguineous family.

Enhancement of bony in-growth to metal implants by combining controlled hydroxyapatite coating and heat treatment.

The rate of bony in-growth to heat-treated and controlled hydroxyapatite metal implants made of either titanium alloy (Ti-6Al-4V) or stainless steel (SS) 316L inserted to the medullar canal of the femur in rats was investigated. It was found that while partial coverage of hydroxyapatite (HA) did not cause a significant elevation of their bonding strength when compared with nonheated implants, HA, and heat treatment caused a significant (p < 0.01) elevation of 3.1-fold in the bonding strength of the implants to the host bone. A similar phenomenon to that found for the titanium alloy implants was found to be true for the SS implants as well. It is concluded that the novel approach presented in this article, that is, to heat treat implants as well as controlled partial coating of them by HA, prior to their insertion to host bone, produce an enhancement of bone growth to metal implants greater than utilization of each method alone. Our findings may be used to further enhance bony in-growth to metal implants in several clinical settings, producing avid implants with superior integration capabilities.