Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update / 亚洲男科学杂志(英文版)

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.

Effects of clomiphene citrate on seminal parameters in idiopathic oligospermia: a single blinded prospective randomized controlled trial

Background: About 15% married couples face problem of infertility of which male factor is implicated in 20% of them. In about 30% infertile men no causative factor is found and the condition is termed “Idiopathic”. They are often treated by empirical medications or Assisted Reproductive Technologies (ART) although success in few; our present study is carried on effects of clomephene citrate on seminal parameters in idiopathic oligospermia.Methods: This single blinded prospective randomized controlled trial was conducted at the infertility clinic with 200 idiopathic oligospermic men (sperm count <15 millions/ ml of ejaculate) after fulfilling inclusion and exclusion criteria and were alternately allocated into two equal groups - “Group C” receiving clomephene citrate tablets and “ Group P” receiving placebo after concealment. Semen analysis data were collected at baseline and every month and three months of completion of treatment and were summarized by routine descriptive statistical analysis.Results: The demographic characteristics like mean age is comparative in both groups but duration of infertility of >2 years is more in group C than group p (4.3±3.06 versus 4.1±2.57). The semen volume, spermatozoa count, sperm motility and not normal form are all increased after three months of treatment in group C as are biochemical parameters like total testosterone and serum FSH, LH and as also pregnancy rate (22% versus 4%).Conclusions: This study showed clomiphene citrate treatment protocol is inexpensive, relatively safe and easy to administer and improves semen volume, sperm count and sperm motility but not sperm morphology by increasing serum testosterone, FSH and LH in male and resulting in improved pregnancy rate in female partners.

Semen analysis and sperm function parameters in patients with infertility in Navi Mumbai and Panvel region

Background: Although semen analysis is routinely used to evaluate male partner in infertile couples, infertility and problems of impaired fecundity have been a concern through ages and is also a significant clinical problem today, which affects 8-12% of couples worldwide. Aim of the study was to study different semen parameters in male factor infertility (MFI) and thus increasing the awareness regarding same.Methods: This is cross sectional study conducted between period of September 2016 to December 2018. Semen of 150 patients were studied and results were analysed as per recent WHO (2010) criteria.Results: The present study included 150 patients whose age ranged from 24 to 51 years. Patients were divided into different age groups and sperm count was studied in each group. Abnormal sperm morphology was studied with respect to sperm head, neck, tail defects and combined defects. Sperm deformity index (SDI) and Teratozoospermic index (TZI) were calculated. Other parameters including semen volume, pH, liquefaction time, sperm vitality and motility were also studied which showed significant variations. Conclusions: Although semen analysis is first and most informative investigation for evaluation of male factor infertility, studying individual semen parameters and sperm function and increasing its awareness in general population especially in developing countries is equally important. Besides, it is necessary to acknowledge its limitation with respect to collection, processing, evaluation and biological variation of samples. Also, a normal semen analysis may not prove successful fertility potential of an individual.

Role of Measurement of Reactive Oxygen Species in Semen Sample of Patients with Male Factor Infertility and Treatment with Antioxidants in Patients with High ROS Levels

Introduction: It is a known fact that human sperms, producereactive oxygen species in small amounts, which is usefulfor normal functioning of the sperm mainly sperm oocyteinteraction acrosome reaction and capacitation. Recentresearch has shown that this ROS in increased amounts is acause of male infertility.Material and methods: It is a prospective control trial todetermine the abnormal pattern of reactive oxygen speciesin semen sample of patients with male factor infertility andto determine the effects of antioxidants in semen sampleof patients with high ROS in semen sample. 150 patientswere selected who were undergoing IVF treatment. Patientswere divided into three groups according to the severity ofabnormality in the semen analysis. The ROS levels of all thepatients were measured and compared with 50 normal fertiledonors. The patients whose ROS levels was found to be highwere then given antioxidants for 2 months and their ROSlevels in semen measured for improvement.Results: The ROS levels were significantly high in all thethree groups compared to fertile donors. The patients withhigh R0S levels were then treated with antioxidants and it wasseen that all the three groups had significant improvement intheir ROS levels.Conclusion: So, to conclude it is hence proved by my studythat ROS level measurement is useful for patients with malefactor infertility and the use of antioxidants significantly helpsin reducing ROS levels in semen.

Chronic epididymitis and Grade III varicocele and their associations with semen characteristics in men consulting for couple infertility / 亚洲男科学杂志(英文版)

Chronic epididymitis and varicocele are frequently observed genital disorders in men consulting for couple infertility, but their impact on semen characteristics at the time of infertility consultation is still a matter of debate. We investigated 652 male partners of couples who had their first infertility consultation between 1999 and 2015 in Argentina. Men with chronic epididymitis (n = 253), Grade III varicocele (n = 106), and both conditions (n = 125) were compared with a control group (n = 168) composed of men without these disorders or any other recognized causes of male infertility. We showed that men who presented isolated chronic epididymitis were more likely to have high percentages of low sperm motility and abnormal sperm morphology as well as a high number of white blood cells. Men with isolated Grade III varicocele had low sperm production and motility and an increased percentage of abnormal sperm morphology. Finally, men who simultaneously presented chronic epididymitis with Grade III varicocele had a low sperm motility and increased percentage of abnormal sperm morphology as well as a high number of white blood cells. Physical examination of the genital organs may identify common disorders, potentially involved as causal factors of patient's infertility. These disorders are associated with specific seminal profiles that should help in identifying the best treatment from the available therapeutic options, effectiveness, safety, and allowing as much as possible natural conception.

Chronic epididymitis and Grade III varicocele and their associations with semen characteristics in men consulting for couple infertility / 亚洲男科学杂志(英文版)

Chronic epididymitis and varicocele are frequently observed genital disorders in men consulting for couple infertility, but their impact on semen characteristics at the time of infertility consultation is still a matter of debate. We investigated 652 male partners of couples who had their first infertility consultation between 1999 and 2015 in Argentina. Men with chronic epididymitis (n = 253), Grade III varicocele (n = 106), and both conditions (n = 125) were compared with a control group (n = 168) composed of men without these disorders or any other recognized causes of male infertility. We showed that men who presented isolated chronic epididymitis were more likely to have high percentages of low sperm motility and abnormal sperm morphology as well as a high number of white blood cells. Men with isolated Grade III varicocele had low sperm production and motility and an increased percentage of abnormal sperm morphology. Finally, men who simultaneously presented chronic epididymitis with Grade III varicocele had a low sperm motility and increased percentage of abnormal sperm morphology as well as a high number of white blood cells. Physical examination of the genital organs may identify common disorders, potentially involved as causal factors of patient's infertility. These disorders are associated with specific seminal profiles that should help in identifying the best treatment from the available therapeutic options, effectiveness, safety, and allowing as much as possible natural conception.

IMSI versus ICSI for male factor infertility: A meta-analysis / 中华男科学杂志

<p><b>Objective</b>To evaluate the efficacy and safety of intracytoplasmic morphologically selected sperm injection (IMSI) versus intracytoplasmic sperm injection (ICSI) in in vitro fertilization (IVF) for couples with male factor infertility.</p><p><b>METHODS</b>Using the Cochrane system evaluation method, we searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and SinoMed and manually searched the reference lists of the included studies and relevant reviews for randomized controlled trials (RCT) comparing ICSI and IMSI published from 1992 to July 2017. We performed a meta-analysis on the included literature with the RevMan 5.3 software and subgroup analyses due to the prominent clinical heterogeneity of the patients.</p><p><b>RESULTS</b>Of the 280 articles retrieved, 8 RCTs were included, involving 1 741 IVF cycles (842 cycles of IMSI versus 899 cycles of ICSI). There was no evidence for any significant difference between IMSI and ICSI in the live birth rate in the subgroup of infertility induced by pure male factors (RR = 1.31, 95% CI: 0.68－2.51; very low quality evidence from 1 RCT with 77 cycles) but an association of IMSI with an increased clinical pregnancy rate (RR = 1.46, 95% CI: 1.02－2.07; low quality evidence from 4 RCTs with 813 cycles), nor was there any evidence for that in the live birth rate (RR = 0.88, 95% CI: 0.60－1.31; low quality evidence from 1 RCT with 255 cycles) or clinical pregnancy rate (RR = 1.03, 95% CI: 0.86－1.23; moderate quality evidence from 3 RCTs with 851 cycles) in the subgroup of infertility caused by accompanying male factors.</p><p><b>CONCLUSIONS</b>The evidence is of low quality for the association of IMSI with an increased rate of clinical pregnancy and is not sufficient to support the routine use of IMSI in IVF for male factor infertility.</p>

Fragmentación del ADN espermático e infertilidad masculina / Fragmentation of sperm DNA and male infertility

La integridad del ADN de los espermatozoides, es un indicador importante de la fertilidad, se utiliza como una variable adicional para evaluar, junto al espermograma, la calidad de una muestra seminal. En el presente trabajo se describen algunos aspectos de interés relacionados con la fragmentación del ADN espermático, cuya etiología es multifactorial y está relacionada con factores intrínsicos, como el empaquetamiento anormal de la cromatina durante la espermiogénesis, la apoptosis defectuosa antes de la eyaculación y la producción excesiva de especies reactivas del oxígeno; y con factores extrínsecos, como son los cambios en los hábitos de vida, la exposición a agentes tóxicos, así como la edad avanzada. La fragmentación está asociada al deterioro de las variables seminales, además afecta la fertilidad natural y la realizada por tratamientos de reproducción asistida, por lo que la implementación en los laboratorios de Andrología, de la tecnología para detectar si el ADN de los espermatozoides está íntegro o fragmentado, incorpora un nuevo conocimiento en el estudio de los hombres con trastornos de fertilidad, lo que contribuye a mejorar el diagnóstico y pronóstico de la infertilidad masculina. Para realizar este trabajo se revisaron 122 artículos, de los cuales 84 cumplieron con los criterios de calidad esperados. La búsqueda se realizó a través de los buscadores habituales(AU)

Sperm DNA´s integrity is an important indicator of fertility and it is used as an additional variable to evaluate the quality of a seminal sample, together with the spermogram. This paper describes some interesting aspects related to the fragmentation of sperm DNA, whose etiology is multifactorial and is related to intrinsic factors, such as the abnormal packing of chromatin during spermiogenesis, defective apoptosis before ejaculation, and the excessive production of oxygen´s reactive species; and with extrinsic factors, such as changes in life habits, exposure to toxic agents, as well as aging. Fragmentation is associated with the deterioration of seminal variables, it also affects natural fertility and that produced by assisted reproduction treatments, so the implementation in the andrology laboratories of the technology to detect if the DNA of the sperm is intact or fragmented incorporates a new knowledge in the study of men with fertility disorders, which contributes to improve the diagnosis and prognosis of male infertility. To carry out this work, 122 articles were reviewed, of which 84 met the expected quality criteria. The search was made through the usual search engines(AU)

Inseminación intrauterina o fertilización in vitro en factor masculino

Se presentan los argumentos a favor y en contra para indicar inseminación intrauterina homóloga versus fertilización in vitro/ICSI en parejas infértiles con factor masculino. Las variables que influyen en los resultados de ambas técnicas deben ser consideradas al momento de la elección, velando por la proporcionalidad de los tratamientos indicados así como la relación costo/beneficio.

Arguments for and against intrauterine insemination versus in vitro fertilization/ICSI in cases of infertile couples with male factor are discussed. Several variables influencing the results must be considered prior to indicating the technique, including cost-benefit and proportionality of the therapy.

The low frequency of Y chromosome microdeletions in subfertile males in a Sinhalese population of Sri Lanka.

Aims: This study was designed to determine the prevalence of azoospermia factor (AZF) microdeletions on the Y chromosome in Sri Lankan Sinhalese infertile men with azoospermia and severe oligozoospermia. Settings and Design: The patient group was 207 karyotypically normal infertile Sinhalese males. Materials and Methods: The presence of 13 sequence-tagged site (STS) markers in the AZF region was tested using multiplex polymerase chain reaction (M-PCR). One hundred and twenty unselected men were also studied as a control group. Results: Three (1.5%) had classic Y chromosome microdeletions in the AZFc sub-region. Conclusions: These results suggest a much lower Y chromosome microdeletion frequency than previously thought, even among a strictly selected group of sub-fertile males in Sri Lanka.

Detection of Adeno-associated Virus from Semen Suffering with Male Factor Infertility and Having Their Conception Partners with Recurrent Miscarriages

Adeno-associated virus (AAV) and human papillomavirus (HPV) DNAs were found in abnormal quality semen, early abortus and female genital tissues. It was suggested that they might cause male infertility and miscarriages. This study was performed to determine the detection rate of these viruses in the semen and to assess the relationship between the presence of virus and male factor infertility and recurrent miscarriages. Sixty-three of 99 recruited male were included in this study according to the completeness of follow-up and the sample availability. Fourteen male with normal reproductive capacity were allocated to control group, 15 male with abnormal results in semen analysis were grouped as male factor infertility (MF) group, and 34 male whose spouses have had history of repeated spontaneous abortions were designated as repeated miscarriage (RM) group. AAV and HPV were detected in semen by polymerase chain reaction. The detection rate of AAV in the MF infertility group and RM group was 60.0% and 50.0%, respectively, while 14.3% in the control group (p < 0.05). However, the differences in the detection rate of HPV were not statistically significant among groups. These results suggest that AAV could be related to repeated miscarriages and male infertility.

Successful treatment of severe male factor infertility in Jamaica with intracytoplasmic sperm injection / Tratamiento exitoso de la infertilidad severa por factor masculino en Jamaica mediante inyección de esperma intracitoplasmático

OBJECTIVES: To examine the impact of intracytoplasmic sperm injection (ICSI) on the treatment of subfertile couples in Jamaica. METHOD: A review of the outcome of treatment cycles for infertile couples that underwent in-vitro fertilisation (IVF) and ICSI from 2003-05 at the Hugh Wynter Fertility Management Unit (HWFMU) of the University of the West Indies. Fertilisation and pregnancy rates for the cycles as well as the factors determining the success of the procedure were reviewed. SPSS 11.1 was used to do statistical calculations. RESULTS: Ninety-six ICSI cycles were done from January 1, 2003 to December 31, 2005. For couples with previous poor or no fertilisation in a standard IVF group (n = 12), the fertilisation rate was 72%; for those with substandard semen (n = 73), the fertilisation rate was 77.5%, for those with semen retrieved by surgical sperm method (n = 11), the fertilisation rate was 59%. The resulting live births were 0%, 12.5% and 27.3% respectively. There was a statistically significant impact ofage on pregnancy rates as the mean age ofthe females in the previously poor or no fertilisation in a standard IVF group (39.08 ± 5.14) was greater than those of the substandard semen group (35.93 ± 4.22) ]p = 0.023[ as well as the group with surgical sperm retrieval (32.82 ± 6.65) ]p = 0.019[. CONCLUSION: With ICSI, the fertilisation and pregnancy rates in Jamaica are comparable to international rates regardless of the cause of infertility. However, the age of the female partner does have a significant impact on the pregnancy rate following ICSI.

OBJETIVO: Examinar el impacto de la inyección de esperma intracitoplasmático (IEIC) en el tratamiento de las parejas subfértiles en Jamaica. MÉTODO: Se realizó un examen del resultado de los ciclos de tratamiento para las parejas infértiles que recurrieron a la fertilización in vitro (FIV) y a la IEIC de 2003 a 2005 en la Unidad de Tratamiento de la Fertilidad Hugh Wynter del Hospital Universitario de West Indies (HWFMU). Se examinaron las tasas de fertilización y embarazos en todos los ciclos así como los factores que determinan el éxito del procedimiento. Se usó el programa SPSS para realizar los cálculos estadísticos. RESULTADOS: Se realizaron noventa y seis ciclos de IEIC del 1ero de enero de 2003, al 31 de diciembre de 2005. Para parejas con ninguna o pobre fertilización en un grupo estándar de FIV (n - 12), la tasa de fertilización fue 72%; para aquellos con semen subestándar (n = 73), la tasa de fertilización fue 77.5%; para aquellos con semen recuperado mediante recuperación quirúrgica de esperma (n = 11), la tasa de fertilización fue 59%. Los nacimientos vivos resultantes fueron 0%, 12.5%, y 27.3% respectivamente. Hubo un impacto estadísticamente significativo de la edad sobre las tasas de comembarazo, ya que la edad promedio de las hembras en la fertilización previamente pobre o sin fertilización en un grupo FIV estándar (39.08 ± 5.14) fue mayor para las del grupo de semen subestándar (35.93 ± 4.22) ]p = 0.023[ así como las del grupo con recuperación quirúrgica del esperma (32.82 ± 6.65) ]p = 0.019[. CONCLUSIÓN: Con el uso de IEIC, las tasas de fertilización y embarazo en Jamaica, son comparables a las tasas internacionales, independientemente de cual sea la causa de la infertilidad. Sin embargo, la edad de la pareja hembra no tiene un impacto significativo sobre la tasa de embarazo una vez aplicada la IEIC.

Possible role of male factors in recurrent pregnancy loss.

Objective : To evaluate various causes possibly contributing towards recurrent pregnancy loss (RPL), particularly male factors. Prospective study of 75 couples with history of RPL who were investigated for genetic, anatomic, immunological, infective and systemic causes in both partners. Functional sperm capacity was assessed by the Hypo-osmotic swelling test (HOS), Acrosomal Reaction (AR), Nuclear condensationdecondensation test (NCD) and Seminal Total Leukocyte Count (TLC) along with semen analysis. Twenty male volunteers with recently proven fertility were also included for detailed sperm morphology and sperm functions test as controls. Amongst male partners 3(4%) had varicocele, 23(30.6%) had infection, 1(1.3%) immunological and 1(1.3%) had genetic abnormality. Sperm motility, viability and sperm function tests were significantly lower in the RPL group as compared to the control group (P=0.000). Male factor might be a possible contributing factor towards RPL. Both the partners should be evaluated and treated simultaneously in order to achieve desirable outcome.

Analysis of Strict Morphology of Human Spermatozoa / 대한산부인과학회잡지

The proportion of male factor infertility due to quantitative and qualitative sperm disorders is approximately 50-60% in infertile couples. In IVF-ET, lower or failed fertilization of oocytes usually results from subnormal count of total motile sperms, but this may occur in infertile couples even with normal sperm count. It has been suggested that some functional defects in sperms are responsible for lower or failed fertilization. Routine semen analysis based on numerical background has limits for the assessment of fertilization capacity of sperm in infertile males, and the andrologic test for the prediction of fertilization capacity must be objective, repeatable, quick, economic, and easily applicable for the clinical settings. The purposes of this study were to develop the analysis method of strict morphology of sperm using the strict criteria as a simple, inexpensive and useful test of sperm fertilization capacity, to establish the normal fertile range and the cut-off value of strict morphology, and to evaluate the validity of strict morphology as a prognostic indicator of fertilization capacity in IVF-ET. In establishing the effectiveness of strict morphology of sperm, ROC curve was used. Among the various thresholds for the prediction of fertilizing ability, normal morphologic value 10.0 corresponding to the value with higher sensitivity and lesser false positive rates was determined as a cut-off value. Using this cut-off point, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of strict morphology for the prediction of fertilization capacity was 73.9%, 81.0%, 80.6%, and 72.7%, respectively. To evaluate the clinical validity of strict morphology as a prognostic indicator of fertilization capacity, this cut-off point was applied to 133 patients undergoing IVF-ET. For the prediction of fertilization rate >30% in IVF-ET, the sensitivity, specificity, PPV, and NPV was 77.3%, 77.8%, 87.2%, and 63.6%, respectively. In conclusion, the strict morphology of sperm is one of the most simple and useful test for the assessment of fertilization capacity of sperm and the prediction of IVF-ET outcomes in infertile couples.

Microassisted Fertilization of Human Oocytes with Intracytoplasmic Sperm Injection in In VitroFertilization Program / 대한산부인과학회잡지

In spite of much progress in in vitro fertilization and embryo transfer(IVF-ET) program,the pregnancy rate remains at 20~30%, and the endometrial implantation rate per embryotransferred at 10%. Although IVF-ET is widely applied in the treatment of coupleswith male factor infertility, it may fail in many infertile couples with normal semen parameters,and certain couples cannot be accepted for standard IVF-ET due to unfertilization orextremely low fertilization rate of oocytes. Recently, several procedures of microassistedfertilization(MAF) using micromanipulation have been introduced, and pregnancies and birthshave been obtained after intracytoplasmic sperm injection(ICSI).This clinical study was performed to develop and establish ICSI as an effective procedureof MAF in infertile couples who could not be accepted for standard IVF-ET becauseof extremely impaired semen characteristics(Group A) and because of failure in fertilizationof extremely low fertilization rate of oocytes with the conventional fertilization technique inthe previous IVF-ET cycles(Group B). From March, 1995 to December, 1996, a total of 114cycles of IVF-ET with ICSI in 65 infertile patients were included in study group, and theoutcomes of ICSI were analyzed according to fertilization rate, cumulative embryo score(CES), and pregnancy rate.In Group A, 34 patients were evaluated with semen score such as number of totalmotile sperms, and then divided into 4 groups accordingly. In 62 ICSI cycles, the numberof oocytes retrieved after controlled ovarian hyperstimulation(COH) was 12.4+/-6.8, and thenumber of oocytes optimal for ICSI procedure was 8.8+/-5.5. The fertilization rate of 65.7+/-23.6% could be obtained after ICSI. The number of embryos transferred was 4.4+/-2.2 withthe mean CES of 50.5+/-34.3 in ICSI cycles. The overall pregnancy rate was 24.2%(15/62)per cycle and 44.1%(15/34) per patient. There were no significant differences in the pregnancyrates among 4 groups. Although more mature oocytes were retrieved, the fertilizationrate was significantly lower in Group A-1 compared with Group A-IV. However, semenscore did not clearly affect the outcomes of ICSI in couples with severe male factor infertility.In Group B, the number of oocytes retrieved after COH was 10.5+/-6.1 in 49 previouscycles, and 10.8+/-5.7 in 52 ICSI cycles. In ICSI cycles, the number of oocytes optimal forICSI procedure was 8.5+/-5.1 with the fertilization rate of 72.4+/-22.5%. The number ofembryos transferred was 1.4+/-2.4 in previous cycles, and 4.7+/-1.8 with the mean CES of 50.4+/-29.9 in ICSI cycles. In ICSI cycles, the overall pregnancy rate was 30.8%(16/52) percycles and 51.6%(16/31) per patients.In conclusion, MAF of human oocytes with ICSI is a promising fertilization method forIVF-ET patients, especially with few spermatozoa for the conventional methods of in vitroinsemination and with the past history of failure in fertilization or low fertilization rate inthe previous cycles, and ICSI using micromanipulation procedures applied to human oocyteswill provide a range of novel techniques which may dramatically improve the pregnancy ratein IVF-ET program and contribute much to the effective management of infertile couples.