Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis

OBJECTIVE: To evaluate how varicocele repair (VR) impacts pregnancy (PRs) and live birth rates in infertile couples undergoing assisted reproduction wherein the male partner has oligospermia or azoospermia and a history of varicocele. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Azoospermic and oligospermic males with varicoceles and in couples undergoing assisted reproductive technology (ART) with IUI, IVF, or testicular sperm extraction (TESE) with IVF and intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Measurement of PRs, live birth, and sperm extraction rates. MAIN OUTCOME MEASURE(S): Odds ratios for the impact of VR on PRs, live birth, and sperm extraction rates for couples undergoing ART. RESULT(S): Seven articles involving a total of 1,241 patients were included. Meta-analysis showed that VR improved live birth rates for the oligospermic (odds ratio [OR] = 1.699) and combined oligospermic/azoospermic groups (OR = 1.761). Pregnancy rates were higher in the azoospermic group (OR = 2.336) and combined oligospermic/azoospermic groups (OR = 1.760). Live birth rates were higher for patients undergoing IUI after VR (OR = 8.360). Sperm retrieval rates were higher in persistently azoospermic men after VR (OR = 2.509). CONCLUSION(S): Oligospermic and azoospermic patients with clinical varicocele who undergo VR experience improved live birth rates and PRs with IVF or IVF/ICSI. For persistently azoospermic men after VR requiring TESE for IVF/ICSI, VR improves sperm retrieval rates. Therefore, VR should be considered to have substantial benefits for couples with a clinical varicocele even if oligospermia or azoospermia persists after repair and ART is required

Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

<p>Abstract</p> <p>Background</p> <p>Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.</p> <p>Methods</p> <p>Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.</p> <p>Results</p> <p>Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.</p> <p>Conclusions</p> <p>SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.</p

Color Doppler ultrasound imaging in varicoceles: Is the difference in venous diameter encountered during Valsalva predictive of palpable varicocele grade?

Objective: The clinical grading system for varicoceles is subjective and dependent on clinician experience. Color Doppler ultrasound (US) has not been standardized in the diagnosis of varicoceles. We aimed to determine if US measurement of varicocele could be predictive of World Health Organization (WHO) varicocele grade. Methods: Men who presented for either scrotal pain or infertility to a tertiary men's health clinic underwent physical examination, and varicoceles were graded following WHO criteria (0=subclinical, 1, 2, 3). US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver. Receiver operator characteristic curve analysis was used to determine if resting diameter, diameter during Valsalva, or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade. Threshold values for diameter were determined from these receiver operator characteristic curves. Results: A total of 102 men (50 with clinical varicocele and 52 with subclinical varicocele) were included. Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles (area under the curve [AUC]=0.67) with a diameter threshold of 3.0 mm (sensitivity 79%, specificity 42%). Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2 (AUC=0.57) with diameter threshold of 5.7 mm (sensitivity 71%, specificity 33%). For differentiating between Grades 2 and 3, diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm (sensitivity 71%, specificity 58%). Conclusion: Our results corroborate other studies that have shown a weak correlation between US and clinical grading. The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele. A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making