To determine whether antioxidants improve male fertility, as measured by semen parameters and DNA fragmentation at 3 months and pregnancy resulting in live birth after up to 6 months of treatment, ...among couples with male factor infertility.
Multicenter, double-blind, randomized, placebo-controlled trial with an internal pilot study.
Nine fertility centers in the United States from December 2015 to December 2018.
Men (N = 174) with sperm concentration ≤15 million/mL, motility ≤40%, normal morphology ≤4%, or DNA fragmentation >25%, and female partners who were ovulatory, ≤40 years old, and had documented tubal patency.
Males randomly assigned to receive an antioxidant formulation (n = 85) containing 500 mg of vitamin C, 400 mg of vitamin E, 0.20 mg of selenium, 1,000 mg of l-carnitine, 20 mg of zinc, 1,000 μg of folic acid, 10 mg of lycopene daily, or placebo (n = 86). Treatment lasted for a minimum of 3 months and maximum of 6 months, and couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6.
Primary outcome was live birth; secondary outcomes included pregnancy within 6 months of treatment. For the internal pilot, the primary outcomes were semen parameters and sperm DNA fragmentation index after 3 months of treatment.
In the Males, Antioxidants, and Infertility (MOXI) study, after 3 months of treatment, the change in sperm concentration differed between the antioxidant group (median −4.0 interquartile range−12.0, 5.7 million/mL) and placebo group (+2.4 −9.0, 15.5 million/mL). However, there were no statistically significant differences between the two groups for changes in sperm morphology, motility, or DNA fragmentation. Among the 66 oligospermic men at randomization, sperm concentration did not differ at 3 months between the antioxidant and control groups: 8.5 (4.8, 15.0) million/mL versus 15.0 (6.0, 24.0) million/mL. Of the 75 asthenospermic men, motility did not differ at 3 months: 34% ± 16.3% versus 36.4% ± 15.8%. Among the 44 men with high DNA fragmentation, DNA fragmentation did not differ at 3 months: 29.5% (21.6%, 36.5%) versus 28.0% (20.6%, 36.4%). In the entire cohort, cumulative live birth did not differ at 6 months between the antioxidant and placebo groups: 15% versus 24%.
Antioxidants do not improve semen parameters or DNA integrity among men with male factor infertility. Although limited by sample size, this study suggests that antioxidant treatment of the male partner does not improve in vivo pregnancy or live-birth rates.
NCT02421887
El efecto de los antioxidantes en el factor masculino de infertilidad: ensayo clínico aleatorizado de hombres, antioxidantes e Infertilidad
Determinar si los antioxidantes mejoran la fertilidad masculina, según lo medido por los parámetros de semen y fragmentación del ADN a los 3 meses, y embarazo resultante en un nacido vivo después de 6 meses de tratamiento en parejas con infertilidad por factor masculino.
Ensayo multicéntrico, doble ciego, aleatorizado, controlado con placebo con un estudio piloto interno.
Nueve centros de fertilidad en los Estados Unidos desde diciembre del 2005 hasta diciembre del 2018.
Hombres (n= 174) con concentración de esperma ≤ 15 millones/ml, movilidad ≤ 4%, morfología normal ≤ 4%, o fragmentación del ADN > 25% y parejas femeninas las cuales eran ovulatorias, ≤ 40 años y tenían permeabilidad tubárica documentada.
Hombres asignados al azar para recibir una formulación antioxidante (n = 85) que contiene 500 mg de vitamina C, 400 mg de vitamina E, 0.20 mg de selenio, 1.000 mg de L-carnitina, 20mg de zinc, 1.000 ug de ácido fólico, 10 mg de licopeno diario o placebo (n= 86). El tratamiento duró un mínimo de 3 meses y un máximo de 6 meses y las parejas intentaron concebir naturalmente durante los primeros 3 meses y con citrato de clomifeno con inseminación intrauterina de la pareja femenina en los meses 4 a 6.
El primer resultado fue el nacimiento vivo, los segundos resultados incluyeron embarazo dentro de los 6 meses de tratamiento. Para el piloto interno, el primer resultado fueron los parámetros de semen e índice de fragmentación del ADN espermático después de 3 meses de tratamiento.
En el estudio Masculinos, Antioxidantes e Infertilidad (MOXI), después de 3 meses de tratamiento, el cambio en la concentración de esperma difirió entre el grupo antioxidante (mediana -4,0 rango intercuartil -12.0- 5,7 millones / mL) y el grupo placebo (+2,4 9,0- 15,5 millones / ml). Sin embargo, no hubo diferencias estadísticamente significativas entre los dos grupos para los cambios de morfología, motilidad o fragmentación del ADN espermático. Entre los 66 hombres oligospérmicos aleatorizados, la concentración de esperma no difirió a los 3 meses entre los grupos antioxidante y control: 8,5 (4,8- 15,0) millones / ml versus 15,0 (6,0- 24,0) millones / ml. De los 75 hombres astenospérmicos, la motilidad no difirió a los 3 meses: 34% ± 16,3% versus 36,4% ± 15,8%. Entre los 44 hombres con alta fragmentación del ADN, la fragmentación del ADN no difirió a los 3 meses: 29,5% (21,6% - 36,5%) versus 28,0% (20,6% - 36,4%). En toda la cohorte, la tasa acumulada de nacido vivo no difirió a los 6 meses entre los grupos de antioxidantes y placebo: 15% versus 24%.
Los antioxidantes no mejoran los parámetros de semen o integridad del ADN entre los hombres con infertilidad por factor masculino. Aunque limitado por el tamaño muestral, este estudio sugiere que el tratamiento de la pareja masculina con antioxidantes no mejora las tasas de embarazo o nacido vivo.
The testicular prosthesis can be an afterthought for providers when performing an orchiectomy for testicular cancer, torsion, atrophic testis, or trauma. However, data suggest that patients find the ...offer of a testicular prosthesis and counseling regarding placement to be extremely important from both a pragmatic and a psychosocial perspective. Only two-thirds of men undergoing orchiectomy are offered an implant at the time of orchiectomy and of those offered about one-third move forward with prosthesis placement. The relatively low acceptance rate is in stark contrast with high patient satisfaction and low complication rates for those who undergo the procedure. The most common postoperative patient concerns are minor and involve implant positioning, size, and weight. Herein, we provide an up-to-date review of modern preoperative evaluation, patient selection, expectation management, surgical technique, and expected outcomes for testicular prostheses.
A varicocele is an abnormal dilation of the pampiniform plexus of veins in the scrotum which begins at puberty in approximately 15% of males. Although common in the general population and often ...asymptomatic, varicoceles are associated with gonadal dysfunction including testicular atrophy, infertility, and hypogonadism in a subset of men diagnosed later in life. Because of the high prevalence and uncertain pathogenesis, definitive management guidelines for varicoceles diagnosed in the pediatric and adolescent population remain poorly defined. The varicocele is the most common etiology of male factor infertility, and treatment in the pediatric and adolescent population may improve semen quality and improve fecundity in adulthood. Evaluation of the pediatric and adolescent varicocele should include history, physical exam, and measurement of testicular volume with orchidometer or ultrasound. Testicular volume differentials and peak retrograde flow on Doppler ultrasonography are important factors in risk stratification of the pediatric varicocele population. Semen analysis and reproductive endocrine assessment should also be considered as part of the workup for adolescent patients. A variety of treatment approaches exist for varicocele, and while the microsurgical subinguinal approach is the gold standard for the adult population, it has yet to be confirmed as superior for the adolescent population. Referral to an andrologist for the adolescent patient with varicocele should be considered in equivocal cases. While active treatment of varicocele in the pediatric and adolescent population is controversial, it is clear that some untreated patients will suffer symptoms later in life, while overtreatment remains a concern for this large, vulnerable population. Therefore, surveillance strategies and improved accuracy in diagnosis of clinically important pediatric varicoceles prompting treatment are needed in the future.
European and North American guidelines recommend Y-chromosome microdeletion (YCM) screening in azoospermic and oligozoospermic men with sperm concentrations of <5 million sperm/ml; however, numerous ...studies have suggested that YCMs are rare when sperm concentrations are >1 million sperm/ml.
We systematically reviewed and meta-analyzed European and North American studies to determine the prevalence of a complete YCM in oligozoospermic men with sperm concentrations of >0–1, >1–5, and >5–20 million sperm/ml, and to determine whether 1 or 5 million sperm/ml is the most appropriate sperm concentration threshold for YCM screening.
A systematic review of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov was performed for studies assessing the prevalence of a complete YCM in oligozoospermic men in European and North American studies.
Thirty-seven studies were identified during a systematic review (n = 12 492 oligozoospermic men). All complete YCMs in oligozoospermic men were AZFc microdeletions. Eighteen studies contained data conducive to meta-analysis (n = 10 866 men). Comparing the pooled estimated prevalence by sperm concentration, complete YCMs were significantly more common in men with sperm concentrations of >0–1 million sperm/ml (5.0% 95% confidence interval {CI}: 3.6–6.8%) versus >1–5 million sperm/ml (0.8% 95% CI: 0.5–1.3%, p < 0.001). YCMs were similar in men with sperm concentrations of >1–5 and >5–20 million sperm/ml (0.8% 95% CI: 0.5–1.3% vs 0.5% 95% CI: 0.2–0.9%, p = 0.14).
In Europe and North America, the majority of YCMs occur in men with sperm concentrations of ≤1 million sperm/ml, with <1% identified in men with >1 million sperm/ml. Male infertility guidelines for North America and Europe should reconsider the sperm concentration screening thresholds to recommend testing for YCMs only for men with sperm concentrations of <1 million sperm/ml.
Complete Y-chromosome microdeletions (YCMs) are rare in men with >1 million sperm/ml. Routine screening for YCMs should occur only if sperm concentration is ≤1 million sperm/ml.
Complete Y-chromosome microdeletions (YCMs) are rarely found in men with sperm concentrations of 1–5 million sperm/ml. North American and European guidelines should be reconsidered, and clinicians do not need routine YCM screening if sperm concentrations are >1 million sperm/ml.
Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm ...retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 106 ml-1 vs 61.4 × 106 ml−1, P = 0.02) and total motile sperm count (2.9 million vs 11.4 million, P = 0.01). This difference was only predicted by homozygous delta F508 CFTR mutations (P < 0.05). The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction (70.0% vs 27.6%, P < 0.03) and lower fertilization rate with ICSI (32.5% vs 68.9%, P < 0.01). In conclusion, those with CF demonstrated lower sperm quality, greater difficulty with sperm retrieval, and worse ICSI outcomes compared with CBAVD-only patients. Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.
Controversy exists around the use of epididymal sperm for in vitro fertilization and intracytoplasmic sperm injection for couples with obstructive azoospermia, and the ability to reliably predict ...fertility outcomes with surgically extracted epididymal sperm remains limited. To provide additional clinical context, we sought to compare in vitro fertilization/intracytoplasmic sperm injection outcomes of epididymal sperm from couples with obstructive azoospermia to outcomes of couples using normal, ejaculated sperm.
We performed a case-control analysis of 40 couples who underwent office based epididymal sperm retrieval for obstructive azoospermia followed by in vitro fertilization/intracytoplasmic sperm injection compared with a control group of 38 female, age matched couples with no evidence of female factor infertility who underwent in vitro fertilization/intracytoplasmic sperm injection with normal, ejaculated sperm. Primary outcome was live birth on the initial embryo transfer.
Epididymal samples yielded a median total motile sperm count of 9.1 million, compared to 81 million for ejaculated sperm. On the primary embryo transfer fertilization rate (71% vs 77%, p=0.2), blastulation rate (48% vs 59%, p=0.09), clinical pregnancy rate (70% vs 58%, p=0.4), and live birth rate (58% vs 47%, p=0.4) did not differ between epididymal and ejaculated sperm groups.
For couples with a male partner with obstructive azoospermia epididymal sperm in vitro fertilization/intracytoplasmic sperm injection outcomes compare similarly with age matched controls undergoing in vitro fertilization/intracytoplasmic sperm injection using normal, ejaculated sperm. These results may help reproductive surgeons provide reassurance about the use of obstructed epididymal sperm as well as help guide discussions about anticipated outcomes of in vitro fertilization/intracytoplasmic sperm injection.
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