[Epidemio-clinical and seminal profile of the man consulting for the desire to procreate: current situation in Lubumbashi, in the Democratic Republic of Congo]. / Profil épidémio-clinique et séminal de l'homme consultant pour désir de procréation: état des lieux à Lubumbashi, en République Démocratique du Congo.

Introduction: in Lubumbashi, as in upscale areas where explorations of fertility are very clever, the spermogram remains the essential analysis in the diagnosis of male infertility. This is the cause of 40% of couple infertility. The spermogram is the first step in identifying seminal abnormalities. The objective of this study was to determine the epidemiological-clinical and seminal profile of the man consulting for the desire to procreate in Lubumbashi. Methods: this was a cross-sectional study. We received 202 subjects in Lubumbashi, whose spermogram was performed from August 1st, 2020 to July 31st, 2021. The semen parameters were studied and interpreted according to WHO standards (2010) with studies of factors associated with their disturbance. Bivariate and multivariate analyzes had been carried out. The statistical significance threshold was set at p < 0.05. Results: the epidemiological-clinical profile of the respondents was as follows: the most represented age group was 30 to 39 years; infertility was primary in 80.69% of cases; the duration of the desire for paternity was 2 years at most in 44.55% of cases. The sperm abnormalities found were: oligozoospermia (40.09%), azoospermia (11.38%), asthenozoospermia (18.31%) and teratozoospermia (10.39%). Oligozoospermia was significantly associated with varicocele (ORa = 10.9 [3.0-39.5]; p < 0.0001), genital infection (ORa =2.7 [1.0-7, 2]; p = 0.041) and obesity (ORa = 2.6 [1.0-7.9]; p = 0.020) while azoospermia was the cure for inguinal hernia (ORa = 4.2 [1.0-17.2]; p = 0.049) and malnutrition (ORa =6.0 [1.2-29.7]; p = 0.027). Asthenozoospermia was significantly associated with the age group of 40 to 49 years (ORa = 6.6 [1.2-37.4]; p = 0.034), tobacco (ORa =7.5 [2.7 -21.0]; p = 0.000), undernutrition (ORa = 7.7 [1.0-61.9]; p = 0.045) and overweight (ORa =3.8 [1.3-11, 5]; p=0.019). Teratozoospermia was significantly associated with smoking (ORa = 5.6 [1.8-17.7]; p = 0.003) and overweight (ORa =5.3 [1.2-23.3]; p = 0.027). Conclusion: more than half of the respondents had, of the three main fertility parameters, at least one that was disturbed. Sperm count was the most affected parameter. Alcohol, tobacco, genital infection and malnutrition were the most common risk factors for the abnormalities observed.

Contribution to a better analysis of spermatic and ultrasound testicular parameters in the follow-up of male infertility at the Histology Embryology Cytogenetic Laboratory of Cheikh Anta Diop University (UCAD).

INTRODUCTION: In Senegal, marital infertility is a real problem for society. We undertook the study of this subject to make an analysis of the spermatic parameters of the infertile Senegalese man and to better understand the impact of testicular morphological anomalies on male fertility. PATIENTS AND METHODS: We conducted a cross-sectional, descriptive, retrospective study of 100 infertile patients followed at the Histology-Embryology-Cytogenetics laboratory of UCAD in Dakar, during the year 2020. Sperm parameters, presence of varicocele, and testicular volume were evaluated in our patients. RESULTS/DISCUSSION: The mean age of the patients was 35.17±8.7 years. A history of sexually transmitted infections was found in 57% of patients. The mean duration of infertility was 5.67±3.2 years. The mean sperm count was 14,871,230/ml±4,950,000. Necrospermia was the most frequent abnormality found (60%), followed by asthenospermia (51%). The high rate of necrospermia could be explained by the high frequency of sexually transmitted infections. Other abnormalities were oligospermia (48%, including 09% cryptospermia), azoospermia (19%), teratospermia (19%), and hypospermia (13%). The predominance of azoospermia and oligospermia should prompt a search for a genetic predisposition in these subjects. The mean testicular volume was 10.3±4.9 cc on the right and 9.5±4.8 cc on the left. A single or bilateral varicocele was found in 43% of subjects. Patients with azoospermia and teratospermia were associated with testicular hypotrophy with a significant value (p=0.04). CONCLUSION: Overall, the senegalese man consulting for infertility is a young adult, married for an average of 5 years. Necrospermia is the most frequently found anomaly. The severity of both qualitative and quantitative abnormalities should lead to a systematic search for a genetic origin. The etiological research of infertile patients must be done within a multidisciplinary framework to propose better management of these patients.

Homozygous SPAG6 variants can induce nonsyndromic asthenoteratozoospermia with severe MMAF.

BACKGROUND: Multiple morphological abnormalities of the sperm flagella (MMAF) is a subtype of severe asthenoteratozoospermia with poorly understood genetic etiology. SPAG6 is a core axonemal component that plays a critical role in the formation of cilia and sperm flagella. Previous studies have reported that mutations in SPAG6 cause primary ciliary dyskinesia (PCD), but the association between SPAG6 gene variants and the MMAF phenotype has not yet been described. METHODS: We performed whole-exome sequencing (WES) in two unrelated Han Chinese men with MMAF. Sanger sequencing was used to validate the candidate variants. Routine semen analysis was carried out according to the WHO guidelines (5th Edition). Sperm morphology was assessed using modified Papanicolaou staining. Scanning and transmission electron microscopy (S/TEM) was performed to observe the ultrastructural defects of the sperm flagella. Western blot analysis and immunofluorescence (IF) of spermatozoa were performed to examine the expression of SPAG6 protein. Assisted fertilization with intracytoplasmic sperm injection (ICSI) was applied. RESULTS: Two homozygous SPAG6 variants were identified by WES and Sanger validation in two patients with MMAF phenotype (F1 II-1: c.308C > A, p. A103D; F2 II-1: c. 585delA, p. K196Sfs*6). Semen analysis showed progressive rates of less than 1%, and most of the spermatozoa presented MMAF by Papanicolaou staining. TEM revealed that the overall axonemal ultrastructure was disrupted and primarily presented an abnormal "9 + 0" configuration. No other PCD-related symptoms were found on physical examination and medical consultations, as well as lung CT screening. The level of SPAG6 protein was significantly decreased in the spermatozoa, and IF analysis revealed that SPAG6 staining was extremely weak and discontinuous in the sperm flagella of the two patients. Notably, F1 II-1 and his wife conceived successfully after undergoing ICSI. CONCLUSIONS: Our research provides new evidence for a potential correlation between SPAG6 variants and the MMAF phenotype.

Combined transvaginal and transabdominal oocyte retrieval in a patient with an ectopic ovary and unicornuate uterus.

OBJECTIVE: To report the utility of combined transvaginal and transabdominal oocyte retrieval in a patient with an ectopic ovary and unicornuate uterus. DESIGN: Video case report with demonstration of oocyte retrieval technique. SETTING(S): University-affiliated fertility center. PATIENT(S): A 35-year-old woman, gravida 0, with a 6-month history of infertility who presented to our center for fertility evaluation. Hysterosalpingography revealed a left unicornuate uterus and patent left fallopian tube magnetic resonance imaging and laparoscopy showed a right ectopic ovary located in the upper abdomen. Her partner was a 36-year-old male with isolated teratozoospermia. The couple did not conceive with intrauterine insemination. INTERVENTION(S): Ovarian stimulation for in vitro fertilization (IVF). Transvaginal retrieval of oocytes from the right ovary was not deemed possible due the anatomic location of the ovary, intervening blood vessels, and limited mobility of the ovary. Institutional review board approval was not required for this case report as per our institution's policy; patient consent was obtained for publication of the case. MAIN OUTCOME MEASURE(S): Transabdominal retrieval of oocytes from the right ovary and transvaginal retrieval of oocytes from the left ovary. RESULT(S): The couple underwent two IVF cycles. Nine oocytes were retrieved during the first IVF cycle: seven transabdominal (right ovary) and two transvaginal (left ovary). All oocytes were mature, and five blastocysts were cryopreserved. Eight oocytes were retrieved during the second IVF cycle, of which five oocytes were retrieved transabdominally from the right ovary, and three oocytes were retrieved transvaginally from the left ovary. All oocytes were mature, and four blastocysts were cryopreserved. A single thawed embryo was transferred in the natural menstrual cycle, which resulted in the live birth of a full-term baby boy weighing 2,410 grams. CONCLUSION(S): The current case highlights the safety and feasibility of combined transvaginal and transabdominal oocyte retrieval in patients with an ectopic ovary located in the upper abdomen.

Macrozoospermia associated with mutations of AURKC gene: first case report in Latin America and literature review / Macrozoospermia asociada con mutaciones del gen AURKC: primer caso clínico en Latinoamérica y revisión de la bibliografía

A Chilean 35-year-old male patient with a history of primary infertility made an appointment at the Unit of Reproductive Medicine at Clínica Las Condes, Santiago, Chile. Multiple semen analyses revealed abnormal sperm morphology as the most prevalent finding. Multiflagellated and macrocephalic spermatozoa were observed and indicated a possible macrozoospermic phenotype. The constant presence of abnormal sperm morphology led the scope of the study to include Aurora Kinase C (AURKC) gene sequencing. The patient was diagnosed with a homozygous mutation of this gene. The mutation was detected in exon 6, type c.744C>G+/+ (P.Y248*) variant. As previously described in the Human Gene Mutation Database (HGMD), this pathogenic variant is associated with macrozoospermia. Although this mutation is not the most frequently observed, it is the first of its kind reported in Latin America

Un chileno de 35 años con antecedentes de infertilidad primaria consultó en la Unidad de Medicina Reproductiva de la Clínica Las Condes, Santiago, Chile. Múltiples espermiogramas revelaron una morfología anormal de los espermatozoides como la anomalía más relevante. Se observaban espermatozoides multiflagelados y macrocefálicos, lo que indicaba un fenotipo de macrozoospermia. La uniformidad del patrón observado condujo a ampliar el enfoque del estudio hacia la secuenciación del gen cinasa Aurora C (AURKC). Al paciente se le diagnosticó una mutación homocigota de este gen. La mutación fue detectada en el exón 6, con la variante c.744C>G+/+ (P.Y248*). Como se ha descrito anteriormente en la Base de Datos de Mutaciones de Genes Humanos (HGMD), esta variante patogénica se asocia a macrozoospermia. Aunque esta mutación no es la que se observa con más frecuencia, es la primera de su tipo notificada en Latinoamérica

Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent respiratory infections, nasosinusitis, tympanitis, and/or male infertility, all of which can severely impair the patient's quality of life. Multiple morphological abnormalities of the sperm flagella (MMAF) is one type of severe teratozoospermia and results from a variety of flagellar defects. In this study, we conducted whole-exome sequencing to identify and evaluate the genetic lesions in two patients with potential PCD and MMAF. Biallelic mutations in exon 10, c.983G>A; p.(Gly328Asp), and exon 29, c.3532G>A; p.(Asp1178Asn), of the CFAP74 (NM_001304360) gene were identified in patient 1 (P1), and biallelic mutations in exon 7, c.652C>T; p.(Arg218Trp), and exon 35, c. 4331G>C; p.(Ser1444Thr), of the same gene were identified in patient 2 (P2). Bioinformatic analysis suggested that these variants may be disease causing. Immunofluorescence confirmed that CFAP74 was absent in these patients' sperm samples. Intracytoplasmic sperm injection (ICSI) was carried out for P1, and his wife became pregnant after embryo transfer and gave birth to a healthy baby. To the best of our knowledge, this study is the first to identify the importance of CFAP74 in potential PCD and MMAF, contributing to the genetic diagnosis of these disorders and helping to predict pregnancy outcomes relevant in in vitro fertilization.

Impact of Abnormal Sperm Morphology on Live Birth Rates Following Intrauterine Insemination.

PURPOSE: We evaluated the live birth rate and the prevalence of congenital anomalies in couples undergoing intrauterine insemination with abnormal sperm morphology (less than 4% normal forms). MATERIALS AND METHODS: We retrospectively reviewed intrauterine insemination outcomes from January 2012 to March 2015. Patients who were found to have an ultrasound confirmed clinical pregnancy were contacted to determine the live birth rate and the prevalence of congenital abnormalities. We used chi-square analysis to assess categorical variables and the Student t-test to assess continuous variables. Logistic regression was done to assess the odds of achieving pregnancy and the risk of spontaneous abortion while assessing female age, the total motile count and sperm morphology. RESULTS: In 984 intrauterine insemination procedures performed in a total of 501 couples we found no difference in the ultrasound clinical pregnancy rate in couples with sperm morphology less than 4% vs 4% or greater (12.3% vs 13.6%, p=0.59). We collected live birth and birth abnormality data on 95 of the 130 couples with ultrasound confirmed clinical pregnancy for a 73% response rate. We found no difference in the live birth rate or the spontaneous abortion rate after an ultrasound confirmed clinical pregnancy in couples with abnormal sperm morphology (less than 4% normal forms). There was also no increased risk of birth abnormalities for patients with abnormal sperm morphology. CONCLUSIONS: Abnormal sperm morphology impacted neither the pregnancy rate nor the live birth rate in couples undergoing intrauterine insemination. These results can be used to reassure couples who undergo intrauterine insemination that there is a minimal impact of abnormal sperm morphology on the live birth rate and the prevalence of birth abnormalities.

Relationship between sperm DNA damage with sperm parameters, oxidative markers in teratozoospermic men.

OBJECTIVE: This study was aimed at determining the extent of sperm nuclear DNA damage in patients with isolated teratozoospermia and examining its relationship with oxidative stress. STUDY DESIGN: Semen samples from 60 patients with isolated teratozoospermia and 30 normozoospermic donors were examined. DNA damage was evaluated by the COMET assay. Seminal antioxidant activities (Superoxide dismutase; Glutathione peroxidase; Catalase), iron and malondialdehyde concentrations were measured spectrophotometrically. RESULTS: Sperm DNA damage; malondialdehyde and iron levels were more elevated in studied groups than controls. Nevertheless, the antioxidant enzyme activity obtained was significantly lower in the group of patients with teratozoospermia compared to the controls. Sperm DNA damage was positively correlated to malondialdehyde and seminal iron level while reduced seminal antioxidant status was negatively associated with sperm DNA breaks. Interestingly, we noted that sperm DNA damage; lipid peroxidation, iron level, and impaired antioxidant status were negatively correlated to normal sperm morphology. CONCLUSION: These findings may explain the complex biological relationship between teratozoospermia, oxidative stress, and DNA damage. In fact, an impaired seminal antioxidant status and an increased seminal level of both lipid peroxidation and iron can affect sperm nuclear integrity resulting in DNA breaks and can be associated with poor sperm morphology.

Role of Sperm Morphology in Deciding Between Various Assisted Reproduction Technologies.

Sperm morphology has long been used as a clinical tool in the assessment of men with infertility. In the past, high percentages of abnormal sperm have been associated with lower pregnancy rates. However, significant intra- and interlaboratory variation has been found for sperm morphology assessment and several recent meta-analyses have demonstrated that sperm morphology is no longer predictive of lower pregnancy rates when using assisted reproduction technology (ART). As the validity of the test and the predictive nature of sperm morphology are no longer as robust as before, clinicians should not rely on percentage thresholds for normal sperm when deciding on which ART to opt for. Instead, clinicians should base ART decisions on other reproductive factors.

Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice.

The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for ß-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis.

[Teratozoospermia and karyopathological abnormalities in epithelial urogenital tract cells in male shift workers with varicocele in oil fields of the north of Siberia].

THE PURPOSE OF THE RESEARCH: The aim of this work was to study associations between varicocele and the various types of karyopathologic abnormalities in epithelial urogenital tract cells or teratozoospermia in oil field shift workers of the north of Siberia. MATERIALS AND METHODS: We examined 139 male individuals in several oil field of the north of Tomsk and Tyumen regions. The examined individuals were divided in 4 groups: 1) driller-workers with varicocele; 2) driller-workers without varicocele; 3) oil field administrative staff with varicocele, and 4) oil field administrative staff without varicocele. Samples of both the sperm ejaculate and the epithelial urogenital tract cells were obtained from all the individuals for microscopic assay. RESULTS: It was found that the frequencies of both the teratozoospermia and the various karyopathologic abnormalities in epithelial urogenital cells were significantly higher in the workers with varicocele compared to all the other groups. There were correlations between karyopathologic abnormalities in epithelial urogenital cells and teratozoospermia in both the driller-workers with varicocele and the oil field administrative staff with varicocele. However, the frequencies of damaged cells in this workers group were significantly higher than the ones in the administrative staff with varicocele, which can be associated with the genotoxic effects of work conditions at oil fields of the north of Siberia. CONCLUSIONS: From the data it was concluded that the increased frequencies of the abnormalities in the epithelial urogenital cells and the sperm in the driller-workers with varicocele may be associated with both the diseases endogenous factor and the genotoxic effects of work conditions at the oil fields.