Bibliography with Summary of Articles Referenced about Vasectomy Reversals – 2023 Update

This is an expanded bibliography of key academic articles with a brief summary and conclusions of the key concepts from each of the articles, peer-reviewed papers, books and presentations referenced in this website, compiled, written and summarized by vasectomy reversal authority, professor and microsurgeon Sheldon H. F. Marks MD.

Please note that these summaries often use actual phrases, sentences or complete paragraphs and data taken directly from the PubMed abstract, poster, published article, or book. We are not claiming original authorship of these works. The purpose of these summaries is to provide additional authoritative evidence to support the information provided throughout this website and to allow for up-to-date and accurate shared decision-making with one’s partners and doctors about vasectomy related topics, so that couples can make an intelligent, informed decisions.

These summaries are arranged by category alphabetically and then within each category by the first author’s last name, according to standard bibliography guidelines. Additional references are included for those that are interested in doing more research.

The articles, posters, book and abstracts that are written or coauthored by Dr. Marks, Dr. Burrows, Matthew Marks, MS (our andrologist) or others here at the International Center for Vasectomy Reversal and the Arizona Andrology Lab and Cryobank, which are arranged by the author’s name in italics.

COVID19 and Sperm, Fertility, Banking and Testosterone

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis Justin K Achua, Kevin Y Chu , Emad Ibrahim , Kajal Khodamoradi , Katiana S Delma, Oleksii A Iakymenko , Oleksandr N Kryvenko , Himanshu Arora , Ranjith Ramasamy. World J Mens Health. 2020 Nov 3. doi: 10.5534/wjmh.200170.

Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J., Bruce H. First Case of 2019 Novel Coronavirus in the United States. N. Engl. J. Med. [Internet] 2020;382(10):929–936

Salam A.P., Horby P.W. The Breadth of Viruses in Human Semen. Emerging Infectious Diseases. 2017;23(11):1922–1924. doi: 10.3201/eid2311.171049.

Anesthesia Complications

Apfel, C.C., Philip, B.K., Cakmakkaya, O.S. et al, Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology. 2012;117:475–486. The authors conducted a prospective multicenter study of 2,170 adults undergoing general anesthesia at ambulatory surgery centers in the United States from 2007 to 2008 and found that 10% of patients experienced postoperative nausea and vomiting. 37% of ambulatory surgical patients suffered from post-discharge nausea and vomiting (PDNV). Those at higher risk included independent predictors of female gender, age less than 50 yrs, history of nausea and/or vomiting after previous anesthesia, opioid administration in the post-anesthesia care unit, and nausea in the post-anesthesia care unit. These at risk patients would benefit from long-acting prophylactic measures.

Devereaux, P.J., Xavier, D., Pogue, J. et al, Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154:523–528. This cohort study of 8351 patients at 190 centers in 23 countries examined the characteristics and short-term outcome of perioperative myocardial infarction (MI), which can occur after general anesthesia with noncardiac surgery. Most patients with a perioperative MI will not experience ischemic symptoms. This study reviewed the risks of an MI and associated complications including death.

Gan, T.J., Meyer, T.A., Apfel, C.C. et al, Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2007;105:1615–1628. This article reviews the evidence-based reference guidelines formulated by a multidisciplinary international panel for the management of postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. These guidelines identify risk factors for PONV with recommended techniques for reducing baseline risks and treatment of PONV.

Harris M, Chung F. Complications of general anesthesia. Clin Plast Surg. 2013 Oct;40(4):503-13. This article reviews some of the more common and serious complications of general anesthesia to include cardiopulmonary risks such as pulmonary aspiration of gastric contents, cardiac arrhythmias, strokes and heart attacks as well as anesthetic drug reactions, kidney damage, malignant hyperthermia, dental damage and rare anesthesia awareness.

Kluger, M.T., Short, T.G. Aspiration during anaesthesia: a review of 133 cases from the Australian Anaesthetic Incident Monitoring Study (AIMS). Anaesthesia. 1999;54:19–26. The authors looked at 240 incidents of vomiting/regurgitation with 133 cases of aspiration during anesthesia. Aspiration was reported twice as often in elective compared with emergency surgery, with 56% of incidents taking place during induction of anaesthesia. Death ensued in five cases, all of whom had significant co-morbidities. Aspiration remains an important anaesthetic-related morbidity.

Newland MC, Ellis SJ, Peters KR, Simonson JA, Durham TM, Ullrich FA, Tinker JH. Dental injury associated with anesthesia: a report of 161,687 anesthetics given over 14 years. J Clin Anesth. 2007 Aug;19(5):339-45. This article reviews a case-control study at a tertiary-care university hospital from August of 1989 and December 31, 2003 to determine the frequency, outcomes, and risk factors for dental injury related to anesthesia. 78 patients with dental injury were identified. Eighty-six percent of dental injuries were discovered by the anesthesia provider. Maxillary incisors were the most frequently injured teeth. The most commonly reported injuries were enamel fracture, loosened or subluxated teeth, tooth avulsion, and crown or root fracture, more common in patients with poor dentition or reconstructive work, whose tracheas were moderately difficult or difficult to intubate.

Pandit, J.J., Cook, T.M., Jonker, W.R. et al, A national survey of anaesthetists (NAP5 Baseline) to estimate an annual incidence of accidental awareness during general anaesthesia in the UK. Anaesthesia. 2013;68:343–353. The researchers used a questionnaire to 7125 anesthesia providers in 329 hospitals throughout the U.K. to determine the number of new cases of accidental awareness for a calendar year, and also to estimate how many cases they had experienced during their careers. There were 153 new cases of accidental awareness notified to respondents in 2011, an estimated incidence of 1:15 414, lower than the 1-2:1000 previously reported in prospective clinical trials. Almost half the cases (72, 47%) occurred at or after induction of anaesthesia but before surgery, with 46 (30%) occurring during surgery and 35 (23%) after surgery before full recovery.

Wagener, G., Brentjens, T.E. Renal disease: the anesthesiologist’s perspective. Anesthesiol Clin. 2006;24:523–547. This is a comprehensive review of the impact of surgery and anesthesia on renal function. The authors describe physiologic responses to anesthetic issues and consequences. Surgery causes the release of catecholamines, renin, angiotensin, and AVP that lead to a redistribution of renal blood flow and a decrease in GFR. Additionally, general anesthesia often results in some degree of hypotension and depressed cardiac output, which further reduces renal perfusion and potentially jeopardizes renal function. Acute renal failure in the perioperative period is associated with a high morbidity and mortality. It is imperative to maintain euvolemia, normotension, and cardiac output, and to avoid nephrotoxic agents to optimize renal blood flow and renal perfusion as the best prevention of renal dysfunction.

Walsh, S.R., Tang, T., Wijewardena, C. et al, Postoperative arrhythmias in general surgical patients. Ann R Coll Surg Engl. 2007;89:91–95. A literature search was performed to look at new-onset arrhythmias are a common problem following major non-cardiac surgery. This review examines the available literature to establish the incidence and significance of new-onset arrhythmias following major non-cardiothoracic surgery. The available data suggest that new-onset arrhythmias affect about 7% of patients following major non-cardiothoracic surgery. These arrhythmias are often associated with other underlying complications.

Antisperm Antibodies

Carbone DJ Jr, Shah A, Thomas AJ Jr, Agarwal A. Partial obstruction, not antisperm antibodies, causing infertility after vasovasostomy. J Urol 1998;159(3):827-830. This study showed that the presence of antisperm antibodies are not a significant factor in persistently infertile men post-reversal with low sperm quality. Repeat vasectomy reversal appears to be the most successful treatment option in this setting to restore normal fertility after vasectomy.

Marks M, Perkins A, Russell H, Burrows P, Marks S. Antisperm antibodies: prevalence, patterns and impact on natural conception following vasectomy reversal. Fertil Steril 2013;100(3): S375. This study looked at sequential antibody testing after vasectomy reversals and found no patterns or prevalence. Some men had high levels, some low, many fluctuated from test to test, suggesting a single test to be of no value. In addition, many men with very high and even 100% antibody binding were able to father children, with no benefit or harm noted vs. others with low or no antibodies. Significant levels of ASA were seen in 53% of vasectomy reversal patients and were not predictable based on age, obstructive interval or surgical method. IgG antibody binding levels did not have an impact on those that achieved natural conception following vasectomy reversal.

Marks SHF. Vasectomy Reversal: Manual of Vasovasostomy and Vasoepididymostomy. New York; Springer; 2018. This book is a step-by-step manual of how to prepare for and perform state-of-the-art microsurgical techniques used by leading experts, as well as intra-op and post-reversal dilemmas and care to maximize results. Special attention is given to microscopic interpretation of the vasal fluid as well as various options and issues with vasovasostomy and vasoepididymostomy.

Newton RA. IgG antisperm antibodies attached to sperm do not correlate with infertility following vasovasostomy. Microsurgery 1998;9(4):278-280. The sperm of 12 men after vasovasostomy were tested for antisperm antibodies. The researchers found that no significant difference in the level of antisperm antibodies could be found between the fertile group and the infertile group.

Banking of Sperm

Boyle KE, Thomas AJ, Jr, Marmar JL, Hirshberg S, Belker AM, Jarow JP. Sperm harvesting and cryopreservation during vasectomy reversal is not cost effective. Fertil Steril. 2006; 85:961-4. This multicenter study, including university hospitals and private practices, looked at costs and whether sperm harvesting and cryopreservation at the time of vasectomy reversal vs. sperm harvesting at the time of IVF only if the patient remained azoospermic after vasectomy reversal. They found for institutions that charge for banking, it is not cost-effective to pay extra for sperm retrieval at the time of the reversal. Of note, ICVR does not charge any extra fees for sperm retrieval with cryopreservation and the first year of banking.

Glazier DB, Marmar JL, Mayer E, Gibbs M, Corson SL. The fate of cryopreserved sperm acquired during vasectomy reversals. J Urol. 1999; 161:463-6 SE. This review looked at the use and outcomes of intraoperative sperm banking specimens during vasectomy reversal in patients with the intention to maintain these as insurance for possible future intracytoplasmic sperm injection. The authors noted that intraoperative collection and cryopreservation of epididymal and testicular sperm are recommended during vasectomy reversal surgery. This is especially important for require bilateral vasoepididymostomy to bank sperm at reversal.

Schrepferman CG, Carson MR, Sparks AE, Sandlow JI. Need for sperm retrieval and cryopreservation at vasectomy reversal. J Urol. 2001; 166:1787–9. This study reviewed 84 consecutive vasectomy reversals. Sperm was retrieved at reversal in 15 of 46 vasovasostomy (none used), 11 of 18 vasoepididymostomy (3 used) and 13 of 20 vasovasostomy with vasoepididymostomy (none used) cases. Only 8% of men with banked sperm eventually used it for assisted reproductive techniques. The authors did not recommend routine sperm retrieval for cryopreservation in men who undergoing vasovasostomy on both sides because of the high success rates, though for men with a bilateral vasoepididymostomy they suggest to bank sperm at reversal. In men who undergo vasovasostomy with vasoepididymostomy they suggested the decision should be based on preoperative counseling and intraoperative findings.

Complications of Vasectomy

Adams CE, Wald M. Risks and complications of vasectomy. Urol Clin North Am 2009; 36:331-6. Vasectomy is considered a safe and effective procedure for permanent contraception. Complications from vasectomy are relatively rare and usually minor in nature with the immediate risks to include infection, hematoma, and pain. Complications seldom lead to hospitalization or aggressive medical management. Technique is surgeon dependent; however, certain techniques, such as fascial interposition, decrease the rates of vasectomy failure.

Li SQ, Goldstein M, Zhu J, Huber D. The no‐scalpel vasectomy. J Urol. 1991;145:341‐344. Dr. Li and colleagues describe a new method of delivering the vas deferens and performing a vasectomy which was developed and used in China since 1974. This method eliminates the scalpel, results in fewer complications to include hematomas and infections, and leaves a smaller wound that closes spontaneously than the conventional incision technique. The reported incidence of hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States. The disadvantage of the technique is the learning curve for hand-on training and number of cases necessary to gain proficiency. However, the advantages for surgeons and patients will improve the care of patients and using this technique and enhance the popularity of vasectomy.

Lowe G. Optimizing outcomes in vasectomy: how to ensure sterility and prevent complications. Transl Androl Urol. 2016 Apr; 5(2): 176–180. Improvements in technique have led to a decreased failure rate and fewer complications, although significant variations in technique exist. Use of cautery occlusion with or without fascial interposition appears to have the least vasectomy failures. A no-scalpel approach lowers the risk of hematoma formation, infection and bleeding post-operatively. Incorporating these principles may allow the physician to optimize outcomes in vasectomy.

Consent Pre-Reversal

Kovac JR, Lipshultz LI. Factors to consider for informed consent prior to vasectomy reversal. Asian J Androl. 2016 May-Jun;18(3):372. This is commentary by the authors on the summary article by Drs. Patel and Smith about the preoperative work-up for patients undergoing vasectomy reversal (VR). This review describes factors that help predict success such as surgeon skill/experience, shorter obstructive interval, a partner’s positive fertility history and younger female age. They suggest that the pre-surgical discussion of vasectomy reversal should include other options for having children after vasectomy such as IVF as well as a review of the pros and cons of sperm retrieval at the time of VR and cryopreservation. The authors ask why, with all the research available, do some physicians still feel comfortable only offering a vasovasostomy (VV), irrespective of the microscopic characteristics of the vasal fluid, and that patients are done a disservice by not being offered the options of both procedures. Although the introduction of the operative microscope has significantly improved patency rates with VR, a small minority of physicians still routinely perform only macroscopic reconstruction. All these issues should be discussed preoperatively, and informed consent should be obtained during the initial patient consultation.

Cost Effectiveness of 1 vs 2 Layer Reversal

Nyame YA, Babbar P, Almassi N, Polackwich AS, Sabanegh E. Comparative cost‐effectiveness analysis of modified 1‐layer versus formal 2‐layer vasovasostomy technique. J Urol. 2016;195:434‐438. The authors performed a retrospective analysis to determine the cost benefits of a modified 1-layer vasovasostomy compared to a formal 2-layer vasovasostomy. Of the 106 men who underwent bilateral vasovasostomy from 2010 to 2015 at a single institution, 81.1% (86) had a formal and 18.9% (20) had a modified 1-layer repair. The modified 1-layer closure resulted in a significantly shorter operative time, lower microsuture cost and lower overall operative cost compared to formal 2-layer repair (all p <0.05). There were no statistically significant differences in semen parameters between the 2 techniques at the first postoperative visit, though both were at approximately 90% success, well below the 99.5 % that we can see with a multilayer closure.

Female AMH and FSH Levels

Depmann M, Broer SL, Eijkemans MJC, va Rooij IAJ, Scheffer GJ, Heimensem J, Mol BW. Anti-Mullerian hormone does not predict time to pregnancy: results of a prospective cohort study. Gynecol Endocrinol. 2017 Aug;33 (8):644-648. This prospective study looked to see if ovarian reserve tests (ORTs) can predict time to pregnancy. In 102 pregnancy planners followed for 1 year, or until ongoing pregnancy occurred, after cessation of contraceptives. A baseline measurement of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) was conducted. Correcting for female age, the authors found no predictive effect of AMH, basal FSH or the AFC for time to ongoing pregnancy They concluded that baseline AMH, AFC or FSH levels do not predict time to pregnancy.

Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, Baird DD. Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. JAMA. 2017 Oct 10;318(14):1367-1376. The goal of this paper was to determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. This review of 750 women who are in the fertile reproductive years (30 to 44 years old) found that despite the lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential (low serum antimüllerian hormone AMH levels and high urinary FSH levels) which are used to indicate low ovarian reserve. This usually suggests problems with IVF success, though were not associated with reduced fertility when compared with matched women who had normal ovarian reserve. The authors do not support the use of the FSH or AMH blood tests to assess natural fertility.

Female Factors that Influence Conception Success

Deck AJ, Berger RE. Should vasectomy reversal be performed in men with older female partners? J Urol 2000;163(1):105-6. Many doctors still assume that men with older female partners who seek treatment of post-vasectomy infertility should undergo in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) rather than vasectomy reversal. This study reviewed IVF/ICSI success rates and costs with advancing maternal age compared to outcomes and costs for vasectomy reversal in men with older partners. Median male age was 46 years (range 37 to 67) and median female age was 40 years (range 38 to 48). Vasectomy reversal appears to be cost-effective to achieve fertility in men after vasectomy with ovulating partners older than 37 years.

Hinz S, Rais-Bahrami S, Kempkensteffen C, Weiske WH, Schrader M, Magheli A. Fertility rates following vasectomy reversal: importance of age of the female partner. Urol Int 2008;81(4):416-20. This study looked at the influence of maternal age on pregnancy rates with 212 male partners following vasectomy reversal. With the tendency in women towards delayed childbirth, the increased use of vasectomy as means of family planning, and advances in reproductive techniques, this issue is very important for patient counseling. Maternal age of >or=40 years is an independent predictor of a lower rate of pregnancy following vasectomy reversal but still compared favorably to published pregnancy rates following intracytoplasmatic sperm injection (IVF with ICSI) in patients older than 40. Therefore, the authors conclude that vasectomy reversal should be the treatment of choice for patients with advanced maternal age desiring reinstated fertility following vasectomy.

Kim SW, Ku JH, Park K, Son H, Paick JS. A different female partner does not affect the success of second vasectomy reversal. J Androl. 2005;26(1):48–52. The aim of this study was to determine whether the pregnancy rate with the same female partner or younger partners was higher compared with different or older partners after undergoing repeated vasectomy reversal. The authors did not observe a significant difference in the pregnancy rate between patients with the same or a different female partner. Partner age was the only independent predictor for pregnancy. Patients with a partner less than 35 years old had a 4.1-fold greater chance of pregnancy than those with a partner 35 years old or older. Their findings suggest that repeat microsurgical vasectomy reversal still remains a reasonable choice for patients with different female partners. However, it should be considered that the likelihood of achieving pregnancy after repeat vasectomy reversal may decrease with advancing age of the female partner.

High Surgical Volumes and Outcomes

Aikoye A, Harilingam M, Khushal A.The impact of high surgical volume on outcomes from laparoscopic (totally extra peritoneal) inguinal hernia repair. J Clin Diagn Res 2015;9(6): PC15-6. This study looked at outcomes of laparoscopic hernia repair in 100 consecutive patients over time by a single surgeon as this technique has a steep learning curve for the surgeon, with proficiency and outcomes dependent on experience. Those surgeries performed by surgeons with significant experience had fewer complications as compared to those is the early surgical period. This confirmed that a higher surgical volume improved the proficiency of the surgeon and resulted in reduced risks and complications.

IVF vs. Vasectomy Reversal

Donovan JF, Jr, DiBaise M, Sparks AE, Kessler J, Sandlow JI. Comparison of microscopic epididymal sperm aspiration and intracytoplasmic sperm injection/in-vitro fertilization with repeat microscopic reconstruction following vasectomy: is second attempt vas reversal worth the effort. Hum Reprod. 1998;13(2):387–93. The authors performed microscopic reconstruction in 18 men following failed microscopic vasectomy reversal. They compared the cost efficiency of repeat vasectomy reversal to that for MESA combined with ICSI/in-vitro fertilization (ICSI/IVF). The cost of male partner procedures (vasectomy reversal, MESA) was based on physician and hospital charges, while the cost of ICSI/IVF included preparation of the female partner (medications and physician charges) and procedures (physician and hospital charges including oocyte retrieval, micromanipulation, and embryo transfer). Couples attempting to overcome infertility caused by vasal obstruction should be informed that vas reconstruction remains a cost-effective means of re-establishing fertility even in men who have previously failed vasectomy reversal.

Pavlovich CP, Schlegel PN. Fertility options after vasectomy: a cost-effectiveness analysis. Fertil Steril. 1997;67(1):133–41. This study evaluated cost per delivery using two different initial approaches to the treatment of postvasectomy infertility with a female partner < or = 39 years of age, treated at centers with experience in vasectomy reversal or sperm retrieval and IVF/ICSI. Initial microsurgical vasectomy reversal was compared with retrieved epididymal or testicular sperm. Actual treatment charges, complication rates, and pregnancy and delivery rates obtained in the United States were used for cost per delivery analysis. The most cost-effective approach to treatment of postvasectomy infertility is microsurgical vasectomy reversal. This treatment also has the highest chance of resulting in delivery of a child for a single intervention.

Shridharani A, Sandlow JI. Vasectomy reversal versus IVF with sperm retrieval: which is better? Curr Opin Urol 2010; 20:503-9. This paper reviews the advances in assisted reproductive technologies (ART), specifically sperm retrieval techniques for intracytoplasmic sperm injection (ICSI) coupled with in-vitro fertilization (IVF), as well as refinements in microsurgical reconstruction have led to improved outcomes and cost-effectiveness. Microsurgical reconstruction of the vas has remained a cost-effective, reliable and effective means of restoring fertility in the majority of men who have previously undergone vasectomy when the reconstruction is performed by an experienced microsurgeon.

IVF/ICSI Risks and Complications

Kissin DM, Zhang Y, Boulet SL, Fountain C, Bearman P, Schieve L, Yeargin-Allsopp M, Jamieson DJ. Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children. Human Reproduction. 2015;30(2):454–465. The authors performed a population-based retrospective cohort study to look at whether assisted reproductive technology (ART) treatment factors or infertility diagnoses were associated with autism among ART-conceived children. This study suggests that the incidence of autism diagnosis in ART-conceived children with fresh embryo transfer cycles during the first 5 years of life was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF, and lower when parents had unexplained infertility (among singletons) or tubal factor infertility (among multiples) compared with other types of infertility. This study provides additional evidence of the association between some types of ART procedures with autism diagnosis. Additional research is required to explain the increased risk of autism diagnosis with ICSI use, as well as studies on the effectiveness and safety of ICSI.

Kulkarni AD, Jamieson DJ, Jones HW, Jr, Kissin DM, Gallo MF, Macaluso M, Adashi EY. Fertility treatments and multiple births in the United States. N Engl J Med. 2013;369(23):2218–2225. This 2013 study looked at the trends in and magnitude of the contribution of fertility treatments to the increase in multiple births. The authors estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during IVF (P<0.001) and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF (P<0.001). Over the past four decades, the increased use of fertility treatments in the United States has been associated with a substantial rise in the rate of multiple births. The rate of triplet and higher-order births has declined over the past decade in the context of a reduction in the transfer of three or more embryos during IVF.

Mainigi M, Rosenzweig JM, Lei J,. Mensah V, Thomaier L, Talbot CC Jr, Olalere D, Ord T, Rozzah R, Johnston MV, Burd I.Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes. Reprod Sci. 2016;23(6):785–794. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. The authors studied the peri-implantation environment and its effects on brain development, utilizing a mouse model with and without superovulation to examine the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring.

Pontesilli M, Painter RC, Grooten IJ, van der Post JA, Mol BW, Vrijkotte TG, Repping S, Roseboom TJ. Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood. Reprod Biomed Online. 2015;30(3):258–267. This article reviews the effects of artificial reproductive techniques and subfertility on cardiovascular and metabolic profiles of children aged 5-6 years using data from the Amsterdam Born Children and their Development study. At the age of 5-6 years, fasting glucose levels were higher among children conceived through ovulation induction and IVF-ICSI compared with those of children of fertile couples. Subfertility and conception through ovulation induction and IVF-ICSI each contributed to aspects of an adverse cardiovascular and metabolic profile in childhood.

Qin J, Sheng X, Wu D,. Gao S, Yang T, Wang H. Adverse Obstetric Outcomes Associated With In Vitro Fertilization in Singleton Pregnancies. Reproductive Sciences. 2016;0(0) 1933719116667229. This prospective cohort study compared the obstetric outcomes of women treated with in vitro fertilization (IVF), women with indicators of subfertility but without assisted reproductive technologies, and fertile women with singleton pregnancies. 1260 eligible mothers were recruited into the IVF group, 1899 into the subfertile group, and 2480 into the fertile group. Compared to the fertile group, gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature rupture of membranes, anemia in pregnancy, preterm birth, low birth weight, perinatal mortality and congenital malformations were increased in the IVF group.

Qin J-B, Sheng X-Q, Wu D,. Gao SY, Yang TB, Wang H. Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2016:1–17. The aim of this meta-analysis review is to estimate the worldwide prevalence of adverse pregnancy outcomes (APOs) associated with IVF/ICSI singleton pregnancies. Fifty-two cohort studies, with 181,741 IVF/ICSI singleton births and 4,636,508 spontaneously conceived singleton births, were selected for analysis. Among IVF/ICSI singleton pregnancies, there were increased risks for preterm birth, very preterm birth, low birth weight, very low birth weight, small for gestational age, perinatal mortality, and congenital malformations. The IVF/ICSI singleton pregnancies have higher prevalence of adverse pregnancy outcomes compared with those conceived naturally. Significant differences in different continents, countries, income groups, and type of assisted conception were found.

Sandin S, Nygren K, Iliadou A, Hultman CM, Reichenberg A. Autism and mental retardation among offspring born after in vitro fertilization. JAMA. 2013;310(1):75–84. This population-based retrospective cohort study examined the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. Swedish national health registers were used to assess offspring born between 1982 and 2007 for a clinical diagnosis of autistic disorder or mental retardation. Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. This study suggested that the incidence of autism diagnosis in ART-conceived children during the first 5 years of life was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF, and lower when parents had unexplained infertility (among singletons) or tubal factor infertility (among multiples) compared with other types of infertility.

Seggers J, Haadsma ML, La Bastide-Van Gemert S, Heineman MJ, Middelburg KJ, Roseboom TJ, Schendelaar P, Van den Heuvel ER, Hadders-Algra M. Is ovarian hyperstimulation associated with higher blood pressure in 4-year-old IVF offspring? Part I: multivariable regression analysis. Human Reproduction. 2014;29(3):502–509. This prospective, assessor-blinded follow-up study of 194 children was designed to assess if ovarian hyperstimulation, the in vitro procedure, or a combination of these two negatively influence blood pressure (BP) and anthropometrics of 4-year-old children born following IVF. Higher systolic blood pressure (SBP) were found in 4-year-old children born following conventional IVF with ovarian hyperstimulation compared with children born following IVF without ovarian hyperstimulation. Increasing evidence suggests that IVF, which has an increased incidence of preterm birth and low birthweight, is associated with higher BP and altered body fat distribution in offspring but the underlying mechanisms are largely unknown. These findings are in line with other studies describing adverse effects of IVF on cardiometabolic outcome, but this is the first study suggesting that ovarian hyperstimulation, as used in IVF treatments, could be a causative mechanism.

Scherrer U, Rimoldi SF, Rexhaj E, Stuber T, Duplain H, Garcin S, de Marchi SF, Nicod P, Germond M, Allemann Y, Sartori C. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation. 2012;125(15):1890–1896. These researchers assessed systemic and pulmonary vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children. Carotid-femoral pulse-wave velocity was significantly faster and carotid intima-media thickness was significantly greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher in ART than in control children. Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself.

Sullivan-Pyke CS, Senapati S, Mainigi MA, Barnhart, KT,. In Vitro Fertilization and Adverse Obstetric and Perinatal Outcomes. Semin Perinatol. 2017 Oct; 41(6): 345–353. This article reviews many of the serious potential complications associated with IVF obtained via a literature search. The authors note that even though most IVF-conceived children are healthy, IVF has also been associated with adverse obstetric and perinatal outcomes as well as congenital anomalies. There is also literature suggesting an association between IVF and neurodevelopmental disorders as well as potentially long-term metabolic outcomes. The main issue with adverse outcomes is the higher risk of multiple gestations in IVF, but studies have shown that singleton IVF pregnancies still have a higher incidence of adverse outcomes compared to unassisted singleton pregnancies. Infertility itself may be an independent risk factor. Possible complications of IVF include hypertensive disorders of pregnancy such as gestational hypertension, preeclampsia, and eclampsia. Gestational diabetes (GDM) has also been studied as an increased outcome in IVF pregnancies because it predisposes to a higher risk of hypertension in pregnancy, fetal macrosomia, operative delivery, and cesarean delivery. There also appears to be an increased risk of preterm delivery in children conceived after IVF. Abnormalities in birth weight, particularly low birth weight, have been associated with IVF. Many studies have highlighted a concern for potentially increased risks of congenital defects and rare imprinting disorders in IVF pregnancies. Cerebral palsy (CP), autism and autism spectrum disorders (ASD) incidence was higher in the ICSI-conceived children compared to IVF-conceived children, even after adjusting for male factor infertility. There is evidence that at least some IVF-conceived children may be at increased risk for cardiometabolic disorders including insulin resistance, higher blood pressure, and higher body fat percentage compared to children conceived without medical assistance. The data suggests that, independent of subfertility or infertility, as the number of manipulations to the embryos increases, the risk of adverse effects including long term outcomes may increase.

Tararbit K, Houyel L, Bonnet D, De Vigan C, Lelong N, Goffinet F, Khoshnood B. Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. European Heart Journal. 2011;32(4):500–508. The authors reviewed data from the Paris Registry of Congenital Malformations on 5493 cases of CHD and 3847 malformed controls for which no associations with ART were reported in the literature to estimate the risk of congenital heart defects (CHD) associated with assisted reproductive technologies (ART), specifically inductors of ovulation only, in vitro fertilization, and intracytoplasmic sperm injection. Assisted reproductive technologies were specifically associated with significant increases in the odds of malformations of the outflow tracts and ventriculoarterial connections and of cardiac neural crest defects and double outlet right ventricle. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.

IVF Trends for Post-Vasectomy Fertility

Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015 Jan 20;313(3):255-63. This paper is a retrospective cohort study using data on fresh IVF and ICSI cycles reported to the US National Assisted Reproductive Technology Surveillance System during 1996-2012. Intracytoplasmic sperm injection (ICSI) is increasingly used in patients without severe male factor infertility without clear evidence of a benefit over conventional in vitro fertilization (IVF). To assess national trends and reproductive outcomes for fresh IVF cycles (embryos transferred without being frozen) following the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use. Among fresh IVF cycles in the United States, ICSI use increased from 36.4% in 1996 to 76.2% in 2012, with the largest relative increase among cycles without male factor infertility. Compared with conventional IVF, ICSI use was not associated with improved post-fertilization reproductive outcomes, irrespective of male factor infertility diagnosis.

Lifestyle and Fertility

Drobnis EZ, Nangia AK. Male Reproductive Functions Disrupted by Pharmacological Agents. Adv Exp Med Biol. 2017; 1034:13-24. The authors reviewed medications that disrupt male reproductive functions. Many medications can affect the hypothalamic-pituitary-gonad axis, acting as endocrine disrupting chemicals (EDCs) with impaired testosterone production and/or spermatogenesis. An increase in circulating prolactin levels is a common adverse medication effect resulting in lower gonadotropin and testosterone secretion. Drugs can also have direct toxicity on the seminiferous tubule epithelium, including effects on Leydig cells, Sertoli cells, or germ cells. In some cases, spermatogenesis can be severely impaired. Even after ejaculation, exposure to seminal plasma can alter sperm function, and some drugs may affect sperm at this stage.

Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM. The relationship between male BMI and waist circumference on sperm quality data from the LIFE study. Hum Reprod 2014;29(2):193-200. This population-based prospective cohort of 501 couples attempting to conceive looked at the relationship between body size as measured by body mass index (BMI) and increased waist circumference, physical activity and semen parameters of the male partners of couples attempting to become pregnant. Researchers reported that obesity is associated with a higher likelihood of having a low ejaculate volume, low sperm concentration and low total sperm count.

Eisenberg ML. Invited Commentary: The Association between Marijuana Use and Male Reproductive Health. 2015 Am J Epidemiol 2015 Sep 15;182(6):482-4. Dr. Eisenberg commented on the Gunderson paper, noting that this article provides important information for patients and providers regarding the negative impact of marijuana use on semen quality. Although the benefit of marijuana cessation on recovery is uncertain, further study on the impact of marijuana use on male reproductive health is encouraged.

Gundersen TD, Jorgensen N, Andersson AM, Bang AK, Nordkap L, SkakkebaekNE, Priskorn L, Juul A, Jensen TK. Association between use of marijuana and male reproductive hormones and semen quality: a study among 1215 healthy young men. Am J Epidemiol 2015 Sep 15;182(6):473-81. The researchers analyzed data from a pre-military questionnaire, an exam and blood samples of 1,215 young Danish men aged 18-28 years. The questionnaire included information on marijuana and recreational drug use during the past 3 months (no use, use once per week or less, or use more than once per week). A total of 45% had smoked marijuana within the last 3 months. Regular marijuana smoking more than once per week was associated with lower sperm concentrations and a lower total sperm count. They reported that the use of marijuana more than once per week reduced the sperm concentration by 52% and total sperm count by 55% The conclusion was that marijuana use may be contributing to poor semen quality.

Jensen TK, Gottscchau M, Madsen JO, Andersson AM, Lassen TH, Skakkebaek NE, Swan SH, Priskorn L, Juul A, Jorgensen N. Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open 2014;4(9): e005462. This cross-sectional population-based study looked at the association in 1221 18-28-year-old Danish men between three measures of alcohol consumption (recent, typical/habitual, binging), semen quality and serum reproductive hormones. The authors considered normal sperm and levels of reproductive hormones (follicle-stimulating hormone FSH, luteinizing hormone LH, testosterone, sex hormone binding globulin SHBG, estradiol E2, free testosterone and inhibin B. This study suggests that even modest habitual alcohol consumption of more than 5 drinks per week had adverse effects on semen counts and quality although the most negative associations were seen in men who consumed more than 25 drinks per week. Alcohol consumption was also linked to lower testosterone levels. The authors conclude that young men trying to conceive should avoid habitual alcohol intake.

Jurewicz J, Radwan M, Sobala W, Ligocka D, Radwan P, Bochenek M, Hanke W. Lifestyle and semen quality: role of modifiable risk factors. Syst Biol Reprod Med. 2014 Feb;60(1):43-51. The purpose of this study was to determine if there was any relationship between exposure to modifiable lifestyle factors and main semen parameters, sperm morphology, and sperm chromatin structure to suggest an adverse effect on human reproductive health. A total of 344 men who attended an infertility clinic with normal or slightly low sperm concentration were asked many questions about their lifestyle. The results of the research suggest that lifestyle factors may affect semen quality. They found a negative association between increased body mass index (BMI) and semen volume, drinking red wine 1-3 times per week was negatively related to sperm abnormalities, using a cell phone more than 10 years decreased the percentage of motile sperm cells and men who wore boxer shorts had a lower percentage of sperm abnormalities and sperm with DNA damage. Being active and drinking coffee had a positive association with sperm motility.

Kesari KK, Agarwal A, Henkel R. Radiations and male fertility. Reprod Biol Endocrinol. 2018 Dec 9;16(1):118. This is a review of the data to look at the impact of ionizing and non-ionizing radiations on sperm development and male infertility. This review focuses on radiation from cell phones, laptops, Wi-Fi and microwave ovens, as these are the most common sources of non-ionizing radiations. From a literature review, it is clear that radiofrequency electromagnetic fields (RF-EMF) have deleterious effects on sperm parameters (to include sperm count, morphology and motility), affects the endocrine system, and produces toxicity, instability and oxidative stress on the DNA. This review includes protective measures for these radiations and recommendations. The study concludes that the RF-EMF may induce oxidative stress with an increased level of reactive oxygen species, which may lead to male infertility.

Marks M, Perkins A, Burrows P, Marks S. Body mass index does not predict for intraoperative findings or post-operative outcomes with vasectomy reversal. Andrology 2012;33(Suppl2):35. This was a retrospective analysis of 405 consecutive patients spanning two years that underwent surgery at our specialized vasectomy reversal clinic to look at BMI, age, years since vasectomy, surgical technique (VV: vasovasostomy or VE: vasoepididymostomy or VV/VE), intraoperative vasal fluid (volume, consistency) and sperm quality assessment, and maximum total motile sperm count in post−operative semen analysis. To assess the effect of BMI on intraoperative findings and post−operative outcomes, subjects were split into 3 groups based on the values of BMI categories: normal weight (BMI 18.5−24.9), overweight (BMI 25−29.9) and obese (BMI 30 or greater). The underweight category was not included due to a sample size of one. No significant differences were found between the three categories or the data assessed. All three categories had similar distributions for each parameter. The majority of subjects in each category had moderate, watery intraoperative fluid with complete or complete motile sperm and a return of sperm to the ejaculate. The range of average maximum total motile sperm per ejaculate was from 41.8 to 53.0 million with no significant difference between the BMI categories. The patient’s BMI did not predict connection type or vasectomy reversal success.

Pacey AA, Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Cherry NM. Participating Centres of Chaps-UK. Modifiable and non-modifiable risk factors for poor sperm morphology. Hum Reprod. 2014 Aug;29(8):1629-36. This study in 318 men throughout the UK with poor sperm morphology and unsuccessful attempts to father a child over 12 months, showed that other than summer months and the use of marijuana, most common lifestyle choices are not associated with poor sperm morphology. It is important to note that this study did not look at sperm counts or motility. This study supports the fact that many studies claim that a man’s lifestyle can affect sperm morphology, the authors believe that the evidence is weak with studies often underpowered and poorly controlled. This study showed that there was not any significant association with body mass index (BMI), type of underwear, smoking or alcohol consumption or having a history of mumps.

Perkins AR, Burrows PJ, McCauley TC, Ax RL and Marks SF. Smoking decreases pregnancy rates of vasectomy reversal patients. 64th Ann. Mtng. Amer. Soc. Reprod. Med. 2008. Abstract. The purpose of this retrospective study was to determine patency and pregnancy rates of 1955 vasectomy reversal (VR) patients that smoked compared to nonsmoking VR patients. Patients were considered smokers if they smoked three or more cigarettes a day, used chewing tobacco or smoked cigars on a daily basis. The smoking group consisted of 13% (253/1955) of patients that underwent a VR. The type of surgery performed for each group was similar. Data included smoking status, obstructive interval, surgical method (vasovasostomy [VV] or vasoepididymostomy [VE]), patency and pregnancy rate. Patency was examined for each group and return of motile sperm to the ejaculate did not differ, though pregnancy rates for each group demonstrated a significant difference, as nonsmokers had a pregnancy rate of 43% (527/1220) and smokers had a pregnancy rate of 35% (57/162).

Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Pacey AA, Cherry NM; Participating Centres of Chaps-uk. Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study. Hum Reprod. 2012 Sep;27(9):2799-806. This research analyzed 939 men in the UK to see if various lifestyle factors had any positive or negative impact on sperm motility or sperm concentration. They found that most common lifestyle choices had little effect on sperm counts or motility. The authors did find that a history of prior testicular surgery, manual labor and not wearing loose underwear did hurt motility and sperm counts. They did not find any significant association of low sperm counts or motility with smoking alcohol consumption, the use of recreational drugs, a high BMI or having a history of mumps or fever.

Rao M, Zhao XL, Yang J, Hu SF, Lei H, Xia W, Zhu CH. Effect of transient scrotal hyperthermia on sperm parameters, seminal plasma biochemical markers, and oxidative stress in men. Asian J Androl. 2015 Jul-Aug;17(4):668-75. In this experimental prospective study, the researchers aimed to analyze the effect of transient scrotal heating (hyperthermia) on the male reproductive organs, to look at sperm parameters, semen plasma biochemical markers, and oxidative stress, to evaluate whether different frequencies of heat exposure cause different degrees of damage to spermatogenesis. Two groups of volunteers (10 per group) received testicular warming in a 43°C water bath 10 times, for 30 min each time: group 1: 10 consecutive days; group 2: once every 3 days. Sperm parameters, epididymis and accessory sex gland function, semen plasma oxidative stress and serum sex hormones were tested before treatment and in the 16-week recovery period after treatment. The authors concluded from the data that transient scrotal hyperthermia seriously, but reversibly, negatively affected the spermatogenesis, oxidative stress may be involved in this process. In addition, intermittent heat exposure more seriously suppresses the spermatogenesis compared to consecutive heat exposure.

Rossi BV, Abusief M, Missmer SA. Modifiable Risk Factors and Infertility: What are the Connections? Am J Lifestyle Med. 2014;10(4):220-231. The authors summarize much of the literature on the impact of modifiable lifestyle choices and fertility. Many couples initiate lifestyle changes to increase their fertility and chances of pregnancy. The authors note that there is conflicting data on many of the dietary factors studied, though there is strong data to support that alcohol and tobacco can reduce fertility. Some studies show that elevated body mass index (BMI) and obesity in both men and women reduces pregnancy rates. There is a growing body of research on environmental toxin exposures and reproductive health, which should be used to guide couples to healthy lifestyle choices.

Sharma R, Biedenharn KR, Fedor JM, Argawal A. Lifestyle factors and reproductive health: taking control of one’s fertility. Reprod Biol Endocrinol. 2013 Jul 16; 11:66. This article looked at modifiable lifestyle habits that have been shown to influence overall health and well-being and have a significant impact on fertility. These include the age when a couple tries to start a family, nutrition, weight, exercise, psychological stress, environmental and occupational exposure that can impact on fertility. Habits such as cigarette smoking, illicit drug use, and alcohol and caffeine consumption have been shown to negatively influence fertility. Others positive behaviors such as exercise, healthy nutrition and avoidance of known toxic substances such as tobacco, alcohol and marijuana may be beneficial.

Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2014;(12):CD007411. This is a Cochrane review of 48 published randomized controlled trials (RCTs) in 4179 subfertile men to evaluate the effectiveness and safety of oral supplementation with antioxidants for subfertile male partners in couples seeking fertility assistance. Approximately 5 % of men are subfertile, with 30% to 80% of male subfertility cases from the damaging effects of oxidative stress on sperm. The primary outcome looked at was live birth; secondary outcomes included clinical pregnancy. A limitation of this review was that there were two different groups of trials with different endpoints: 3 that reported on the use of antioxidants and the effect on live birth and clinical pregnancy, and 25 trials that reported on sperm parameters as their primary outcome. The evidence of these studies was graded as ‘very low’ to ‘low.’ This review reported that there is low quality evidence from only four small randomized controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates and increase clinical pregnancy rates.

van Dongen J, Tekle FB, van Roijen JH. Pregnancy rate after vasectomy reversal in a contemporary series: influence of smoking, semen quality and post-surgical use of assisted reproductive techniques. BJU Int. 2012 Aug;110(4):562-7. This research looked to determine the influence of smoking, postoperative semen characteristics and the use of an assisted reproductive technique (ART) on pregnancy rate outcomes in a contemporary series of 162 men undergoing vasectomy reversal. The literature indicates that success rates (i.e. patency and pregnancy rates) are dependent primarily on the obstructive interval since vasectomy and the age of the female partner. Looking at the influence of preoperative data (including smoking) and semen parameters indicates that a significant influence of post-surgical sperm motility impacts on time to first pregnancy. The use of assisted reproductive techniques, when natural pregnancy failed, was successful in ≈50% of couples who attempted this procedure. A clear and significant association between sperm motility and the probability of conception was found, whereas smoking, female age and time since vasectomy appeared to have no influence on natural pregnancy outcome in this patient cohort.

Lion Vasectomy Reversal

O’Brien R. Lion cubs born in Chile after world first veterinary procedure. https://www.reuters.com/article/us-chile-lion-idUSKBN1802FD. This was an article that appeared in the newspapers about a urologist in Chile that performed a successful vasectomy reversal on an African Lion. As written by Reuters: Two baby lion cubs were presented to the public at a zoo in Chile on Thursday, born after a pioneering veterinary procedure that involved a reversed vasectomy of their father. The cubs’ mother “Masai” became pregnant after the father “Maucho” underwent the procedure, which vets at Buin Zoo in the suburbs of Santiago, Chile, said took months of planning and a five-hour operation. “This is the first successful reversal of a lion vasectomy reported in the world,” said Marcelo Marconi, a urology specialist who joined the zoo vet team to lead the procedure. “It gives a way of preserving and maintaining a species in a zoo.”

Microsurgical Vasectomy Reversal Training

Akanksha Mehta, Philip S Li. Male infertility microsurgical training Asian J Androl. 2013 Jan; 15(1): 61–66. This is a review of microsurgical training for urologists and clinical andrologists specializing in male infertility. Success in male infertility microsurgery is heavily dependent on the surgeon’s microsurgical skills. Laboratory-based practice to enhance microsurgical skills improves the surgeon’s confidence, and reduces stress and operating time, benefiting both the patient and the surgeon. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. The role of emerging techniques, such as robotic-assisted microsurgery, is also discussed.

Li PS, Ramasamy R, Goldstein M. Male Infertility Microsurgical Training. In: Sandlow JI, editor. Microsurgery for Fertility Specialists New York; Springer; 2012. The authors of each chapter review specific topics in urologic microsurgery and training, which is among the most technically and mentally challenging of surgical procedures. Most male infertility microsurgeries are performed under 10–25× magnification. Under the operating microscope, tiny movements are magnified by 15–40×. There are few surgical fields where outcomes are so dependent on technical performance in the operating room. Success in male infertility microsurgery is therefore heavily dependent on the quality and extent of practice and training in the microsurgical laboratory.

Mini-Incision Vasectomy Reversal

Grober ED, Jarvi K, Lo KC, Shin E. Mini-incision vasectomy reversal using no-scalpel vasectomy principles: efficacy and postoperative pain compared with traditional approaches to vasectomy reversal. J.Urology. 2011;77:602–6. The researchers evaluated the efficacy and postoperative morbidity of a mini-incision vasectomy reversal (MIVR) using no-scalpel vasectomy principles compared with traditional incisional approaches to vasectomy reversal (VR). They reviewed 164 patients undergoing consecutive VR using the no-scalpel vasectomy principles and instruments. Semen analyses were obtained at 3-month intervals postoperatively until pregnancy was achieved. Motile sperm in the ejaculate after VR defined patency. The results showed that MIVR did not compromise patency outcomes or semen parameters compared with more traditional approaches to VR and results in less pain during the early period of recovery after surgery and quicker functional recovery.

Jarvi K, Grober ED, Lo KC, Patry G. Mini-incision microsurgical vasectomy reversal using no-scalpel vasectomy principles and instruments. Urology. 2008;72:913–5. This article highlights the techniques for a mini-incision microsurgical vasectomy reversal to reduce the surgical risks and postoperative recovery. Application of the no-scalpel vasectomy principles and instruments have allowed the doctor to minimize the scrotal incision (generally to </=1 cm after closure) without compromising the quality of reversal or the operative time.

Nomograms for Predicting Vas Reversal Results

Fenig DM, Kattan MW, Mills JN, Gisbert M, Yu C, Lipshultz LI. Nomogram to preoperatively predict the probability of requiring epididymovasostomy during vasectomy reversal. J Urol. 2012;187:215‐218. The authors evaluated 271 patients prospectively to create a nomogram to predict the probability of requiring epididymovasostomy for men who underwent primary vasectomy reversal during a 5-year period. Time to reversal and a sperm granuloma were selected as important predictors of epididymovasostomy. Epididymovasostomy can be preoperatively predicted based on years since vasectomy and a granuloma on physical examination. The authors suggest that urologists use this nomogram to better inform patients of the potential need for epididymovasostomy and whether specialist referral is needed.

Hsiao W, Goldstein M, Rosoff JS, et al. Nomograms to predict patency after microsurgical vasectomy reversal. J Urol. 2012;187:607‐612. This is a retrospective review of 548 patients who underwent microsurgical vasectomy reversal to create predictive nomograms. Surgery was considered successful if sperm concentration was 100,000 or more sperm per ml, total count was 100,000 or more sperm per ejaculate, motile sperm were present and there was no evidence of subsequent failure. Two nomograms to predict patency were generated, one for preoperative counseling and a second for postoperative counseling. The factors with the largest effect on patency were average testicular volume and obstruction duration. The factor with the least effect was the presence of sperm granuloma. These nomograms may prove useful to guide further treatment decisions.

Kavoussi PK, Bird ET. Validation of a vasoepididymostomy predictor model: is vasoepididymostomy truly predictable preoperatively? Fertil Steril. 2009;92:180‐181. This prospective study was performed to validate a vasoepididymostomy (VE) predictor nomogram. A previously published VE predictor model was then applied to 115 consecutive reversal patients using the fibrin glue technique. Predicted outcomes were analyzed with respect to outcomes with consideration of actual procedures performed. The maximum follow-up was 30 months, with a median follow-up of 16 months. Forty patients who would have been predicted to require VE on one or both sides by the predictor model actually underwent vasovasostomy (VV) bilaterally. Follow-up data were available in 62% of these patients, of which 88% were patent and 52% have achieved pregnancies thus far. The authors concluded that a predictor model designed to identify which patients need VE versus those who will need simply VV is not a reliable predictor in their patient population of patients undergoing a fibrin glue vasectomy reversal.

Parekattil SJ, Kuang W, Agarwal A, Thomas AJ. Model to predict if a vasoepididymostomy will be required for vasectomy reversal. J Urol. 2005;173:1681‐1684. The authors performed a retrospective review of 483 patients who underwent vasectomy reversal to devise a model to preoperatively predict the need for a vasoepididymostomy (VE) when performing a vasectomy reversal. The data on 393 vasovasostomies and 90 vasoepididymostomies were reviewed. Patient age and time since vasectomy were the only significant independent predictors of VE. The model was designed tested on a separate randomly selected 50 patient group and found to be 100% sensitive in detecting patients requiring VE with a specificity of 58.8%.

Obstructive Interval and Vasectomy Reversal Success Rates

Maghelia A, Rais-Bahrami S, Kempkensteffen C, Weiske WH, Miller K, Hinz S. Impact of obstructive interval and sperm granuloma on patency and pregnancy after vasectomy reversal. Int J Androl. 2010 Oct 1;33(5):730-5. The objective of this study was to determine the effect of the obstructive interval and the presence of a sperm granuloma on vas patency and pregnancy rate following vasectomy reversal analyzing data from 334 patients with complete follow-up. There were significant associations between the obstructive interval and procedure performed as well as with patient age. Patients with longer obstructive intervals were more often older and more likely to have a vaseoepididymostomy performed. There was no association between the presence of a sperm granuloma or the length of the obstructive interval with post-operative vas patency and pregnancy rates. The only independent predictor of post-operative fertility was age of the female partner.

Marks SHF, Burrows PJ, Cropp AR, Ax RL, McCauley TC. Obstructive interval should not be a deterrent in vasectomy reversal. Androl 2008; March/April (Suppl):21. The purpose of this study was to evaluate compliancy of vasectomy reversal (VR) patients at our reversal only specialty center. 389 patients were retrospectively evaluated for their compliance with an advised post-operative SA. Patients were considered compliant if a pregnancy or SA result was reported. Non-compliant patients were contacted to assess their reason for failed compliance. The responses from the non-compliant patients were grouped into five categories: 1) “busy schedule;”2) “assumed VR successful;”3) “uninterested in fertility outcome;”4) “results left to faith;”5) “could not locate local laboratory.” 85% of VR patients were compliant. The non-compliant group consisted of 15% of VR patients. Non-compliant patients were on average 4.4 years older than compliant patients.

Mui P, Perkins A, Burrows PJ, Marks SF, Turek PJ. The need for epididymostomy at vasectomy reversal plateaus in older vasectomies: a study of 1229 cases. Andrology 2014;2(1):25-9. We wrote this paper with Dr. Turek when we both realized that we had a significant number of successful reversals on men many years from vasectomy, with results better than was suggested by older papers. In this review of 1229 patients, we looked to define how the need for EV at reversal changes with time after vasectomy through a retrospective review of consecutive reversals performed by three surgeons over a 10-year period. Post-operative patency rates, total spermatozoa and motile sperm counts in younger (<15 years) and older (>15 years) vasectomies were assessed. The rate of unilateral (VE/VV) or bilateral VE increased linearly in vasectomy intervals of 1-22 years at 3% per year but plateaued at 72% in vasectomy intervals of 24-38 years. The need for VE at reversal increases with time after vasectomy, but contrary to conventional thinking, this relationship is not linear and plateaus at 22 years after vasectomy.

Oxidative Stress and Sperm

Bisht S, Dada R. Oxidative stress: Major executioner in disease pathology, role in sperm DNA damage and preventive strategies. Front Biosci (Schol Ed). 2017 Jun 1;9:420-447. The authors reviewed the role of oxidative stress (OS) in a wide array of diseases such as neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and cancer. OS is caused by an imbalance in production of Reactive Oxygen Species (ROS) and antioxidant defenses in the cell which results in the damage of cellular components, inactivate essential metabolic enzymes and disrupt signal transduction pathways. OS induces peroxidative damage to the sperm plasma membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes dysregulation in levels of mRNAs/transcripts. OS induced pathologies are caused by endogenous and exogenous factors, the majority of which, are modifiable. Antioxidant supplementation could help in relieving OS, however, its long-term usage may disrupt the intricate oxidation-reduction balance and can lead to “Reductive Stress.”Adoption of simple lifestyle interventions may relieve OS and can also aid in its management. This may improve overall quality of life (QOL) and can reduce prevalence of OS induced diseases.

Wright C, Milne S, Leeson H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod Biomed Online. 2014 Jun;28(6):684-703. This is a review of the issues and concerns with DNA fragmentation from oxidative stress on male factor fertility. DNA fragmentation is an important factor and a robust indicator of fertility potential in the etiology of male infertility. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Ideally oxidative stress and so DNA fragmentation should be minimized where possible. Endogenous and exogenous factors that contribute to oxidative stress are reviewed, and in many cases are easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple’s chances of conception either naturally or via assisted reproduction.

Paternal Age and Fertility

Almeida S, Rato L, Sousa M, Alves MG, Oliveira PF. Fertility and Sperm Quality in the Aging Male. Curr Pharm Des. 2017 Nov 28;23(30):4429-4437. The authors have written an up-to-date review to discuss the molecular mechanisms involved in the alteration of the reproductive function in aging men, with a focus on the functioning of the reproductive axis and what are the major effects of aging in spermatogenesis. They also address how aging affects sperm quality and possible causes underlying sperm dysfunction with special emphasis in oxidative stress. Older men exhibit notable disturbances in the reproductive axis, with steroidogenesis being impacted much more than spermatogenesis. The endocrine changes, together with morphological and functional alternations of the aging testis, result in decreased testosterone production. Nonetheless, studies are needed to scrutinize the impact of age versus age-induced dysfunction of the reproductive axis. Furthermore, the multiple effects of aging on the acquisition of sperm motility, on sperm morphology and concentration indicate that the quality of spermatozoa may decline over time.

Jennings MO, Owen RC, Keefe D, Kim ED. Management and counseling of the male with advanced paternal age. Fertil Steril. 2017 Feb;107(2):324-328. The authors performed a systemic review of 42 sources from the literature and societal guidelines to address questions that couples with a male of advanced paternal age may ask: They found that the many questions were answered separately by the supporting literature, though societal guidelines still did not provide best-practice guidelines to address issues with advanced paternal age.

Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol. 2015 Apr 19;13:35. This paper is a review of the literature looking at effect of paternal ageing on fertilization and reproduction including semen quality and reproductive function. They note that the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease, negative effects on sperm quality and testicular functions. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny.

Post-Vasectomy Reversal Care

Davies N, Papa N, Ischia J, Bolton D, Lawrentschuk N. Consistency of written post-operative patient information for common urological procedures. ANZ J Surg. 2015 Dec;85(12):941-5. This study analyzed the consistency of procedure-specific written post-operative advice provided to patients in Australia. 209 post-operative handouts for 7 common urological procedures were obtained from a selection of Australian hospitals and practicing urologists’ websites. These were examined for consistency of post-operative information, advice and readability. Most addressed expected symptoms and when to seek medical attention. Many also covered post-op care. The researchers found significant variability in written post-operative advice, usually at a grade level higher than recommended. Duration of expected symptoms and timing for resuming normal activities were the most common sources of discordance between handouts. They recommend that individual surgeons and hospitals provide specific and tailored advice directly to their own patients, written at a grade level suitable for the majority to understand.

Maatman TJ, Aldrin L, Carothers GG. Patient noncompliance after vasectomy. Fertil Steril. 1997; 68:552–555. This retrospective chart review looked at the rate of compliance with postvasectomy follow-up instructions to confirm sterility. Postvasectomy follow-up instructions were given to the patient both verbally and in writing. The records of 1,892 consecutive patients undergoing vasectomy were reviewed, and the results of semen analyses were noted to determine the rate of compliance with postvasectomy follow-up instructions.

Murphy R, Perkins A, Marks MB, Burrows PJ, Marks SF. Post Vasectomy Reversal Semen Analysis Compliancy. Andrology 2012;33(Suppl2):42.  The purpose of this study was to evaluate compliancy of 389 vasectomy reversal patients for follow-up semen analysis at our specialty center. Despite the significant out-of-pocket expense, not all patients followed-up with a semen analysis (SA) as requested to ensure success of the procedure. Patients were considered compliant if a pregnancy or SA result was reported. Non-compliant patients were contacted to assess their reason for failed compliance. The responses from the non-compliant patients were grouped into five categories: 1) “busy schedule;”2) “assumed VR successful;”3) “uninterested in fertility outcome;”4) “results left to faith;”5) “could not locate local laboratory.” Non-compliant patients were on average 4.4 years older than compliant patients. The results from this study indicate that 15% of VR patients fail to comply with the advised post-operative semen analyses, which ensures success of the procedure, despite the high out-of-pocket expense of the reversal.

Perkins A, Marks MB, Burrows PJ, Marks SF. Anti-Inflammatory Treatment for Asthenozoospermia Following Microsurgical Vasectomy Reversal. Presented at American Society of Andrology 38th Annual Meeting, San Antonio, Texas: April 13-17, 2013. This retrospective chart review looked at the role of anti-inflammatory medications for the management of patients with suboptimal postoperative semen parameters following a vasectomy reversal in 526 men at our center. Patients with <15 million motile sperm in the ejaculate received a regimen of 20mg Prednisone daily for 7 days followed by 6 weeks of a non−steroidal anti−inflammatory (NSAID), 600mg Ibuprofen three times daily or 200mg Celebrex once daily with a recheck a semen analysis 6 weeks into treatment. Analyzed data included obstructive interval, patient age, partner age, surgery connection, patency, time to first semen analysis, pre− and post−treatment total motile sperm count. Among 526 patients treated with the anti−inflammatory protocol 78% responded with improvements in total motile counts on follow−up semen analyses and 22% showed no improvement. Response rate among bilateral VV patients was 85%, among VV/VE patients was 75% and among bilateral VE patients was 59%. Further analysis of non−responders revealed 61% failed to comply with protocol and 39% complied. This suggests that the medical anti-inflammatory therapy appears to benefit patients with suboptimal semen parameters.

Vas Reversal Practice Patterns

Crain DS, Roberts JL, Amling CL. Practice patterns in vasectomy reversal surgery: results of a questionnaire study among practicing urologist. J Urol 2004;171(1):311-5. This paper summarizes the results of a 20-question survey to assess the practice patterns of community and academic urologists with respect to surgical technique, follow-up care, patient selection and the definition of success. A total of 1,508 questionnaires were mailed and 622 completed questionnaires were returned. Of the respondents 367 (59%) indicated that they perform vasectomy reversals, including 29 (8%) who were fellowship trained in infertility, 86 (23%) who were affiliated with residency training and 252 (69%) who practiced in a community setting. As expected, on average fellowship trained urologists performed more reversals yearly than academic or community urologists (26.4, 12.2 and 7, respectively). An average of 8 anastomotic sutures were placed in 2 layers but significant differences existed between fellowship trained urologists, and their academic and community counterparts. Most urologists (71%) defined their success by the presence of sperm in the ejaculate.

Post Vasectomy Pain Syndrome (PVPS)

Horovitz D, Tjong V, Domes T, Lo K, Grober ED, Jarvi K. Vasectomy reversal provides long‐term pain relief for men with the post‐vasectomy pain syndrome. J Urol. 2012;187:613‐617. This is a review of the demographics and outcomes of vasectomy reversal in the treatment of men with the post-vasectomy pain syndrome. Three urologists in Toronto, Ontario performed 23 vasectomy reversals between January 2000 and September 2010 for treatment of post-vasectomy pain syndrome. Of these men who underwent 14 vasovasostomies 13 completed a telephone conducted questionnaire for a response rate 56%. After vasovasostomy improvement of pain occurred in 93% (13 of 14) and 50% were rendered pain-free with an average improvement in pain intensity scores of 65% (p <0.005). Of the men 15% (2 of 13) had a recurrence of pain to baseline but overall 79% (11 of 14) had a durable positive response. Quality of life was significantly improved after vasovasostomy (p <0.005) and 93% (13 of 14) of the patients said they would undergo the same operation again. The authors conclude that a vasovasostomy is an effective treatment modality for the post-vasectomy pain syndrome, with durable long-term improvement in pain intensity and quality of life.

Leslie TA, Illing RO, Cranston DW, et al. The incidence of chronic scrotal pain after vasectomy: a prospective audit. BJU Int 2007; 100:1330-3. The authors looked at scrotal pain before and after 625 vasectomies performed by 9 surgeons. Only four men (0.9%) described severe pain after vasectomy impacting their quality of life, with 15% describing new onset of discomfort by 7 months.

Myers SA, Mershon CE, Fuchs EF. Vasectomy reversal for treatment of the post-vasectomy pain syndrome. J Urol 1997; 157:518-20. This is a review of the records of 32 patients who underwent vasovasostomy or epididymovasostomy for the treatment of post-vasectomy pain syndrome. 27 of 32 men had resolution of pain after the reversal. They conclude that a vasectomy reversal has a high rate of success for relief of the post-vasectomy pain syndrome and should be considered a good option for the treatment of the post-vasectomy pain syndrome.

Parekattil SJ, Cohen MS. Robotic microsurgery 2011: male infertility, chronic testicular pain, postvasectomy pain, sports hernia pain and phantom pain. Curr Opin Urol. 2011 Mar;21(2):121-6. The authors examine the use of new robotic microsurgical procedures to treat chronic testicular, post-vasectomy or groin pain, to include vasectomy reversal, varicocelectomy, microsurgical denervation of the spermatic cord. The addition of this new technology should improve outcomes for the management of these pain issues.

Sinha V, Ramasamy R. Post-vasectomy pain syndrome: diagnosis, management and treatment options. Transl Androl Urol. 2017 May; 6(Suppl 1): S44–S47. This paper is a discussion of post-vasectomy pain syndrome which can impact on 1-2% of vasectomy patients, described as chronic testicular pain for greater than three months after the vasectomy. Post-vasectomy pain syndrome (PVPS) is diagnosis of exclusion and may be caused by direct damage to spermatic cord structures, compression of nerves in the spermatic cord via inflammation, back pressure from epididymal congestion, or scarring and perineural fibrosis. Treatment should begin with the most noninvasive options first and then progress towards surgical management if symptoms persist. Noninvasive therapies described include acupuncture, pelvic floor therapy and pharmacologic options.

Smith-Harrison LI, Smith RP. Vasectomy reversal for post-vasectomy pain syndrome. Transl Androl Urol. 2017 May; 6(Suppl 1): S10–S13. This article is a review of post-vasectomy pain and the use of reversals as an effective treatment. This paper examines vasectomy reversals as a surgical option for men who fail conservative or medical management for post-vasectomy pain syndrome (PVPS).

Tandon S, Sabanegh E., Jr. Chronic pain after vasectomy: a diagnostic and treatment dilemma. BJU Int 2008; 102:166-9. This paper is a review the diagnostic and therapeutic features of chronic testicular pain, postvasectomy pain syndrome (PVPS). They note that although early pain lasting for a few weeks is fairly common after vasectomy (present in up to 30% of men), long‐term pain requiring some kind of intervention or surgical therapy occurs in up to one in 1000 men. This article reviews vasal anatomy and physiology, clinical presentations, nonsurgical treatments such as conservative (scrotal elevation/support; thermal therapy, i.e. heat or cold as needed for comfort; limiting activity (no lifting/sexual activity restrictions): medical therapies, e.g. NSAIDs, narcotic analgesics, antibiotics, neuroleptic drugs, spermatic cord nerve block, biofeedback or a psychiatric evaluation as well as surgical intervention to include excision of any sperm granuloma, epididymectomy, spermatic cord denervation, reversal of the vasectomy (vasovasostomy/vasoepididymostomy) and orchidectomy.

Redo Vasectomy Reversals

Fox M. Failed vasectomy reversal: is a further attempt using microsurgery worthwhile? BJU Int. 2000; 86:474–8. The authors reviewed a series of 28 redo reversal patients with failure of a first vasectomy reversal over a 10-year period using a microsurgical technique using a two-layer technique. Results of post-operative semen analysis at 3-6 months and paternity were compared with those of 137 men with primary microsurgical vasovasostomy showing that sperm was successfully restored to the ejaculate in 16 of 28 (57%) and successful fertilization was reported in 32%. The interval between vasectomy and reversal surgery was relevant to the outcome, with four out of four men having sperm in the ejaculate within 5 years and three achieving paternity. The overall results of the redo reversals were not significantly different from those after primary microsurgical reversal surgery. Microscopic vasovasostomy after previous obstructive failure provides the patient with a further reasonable chance of becoming fertile, even with success after a prolonged period.

Hernandez J, Sabanegh ES. Repeat vasectomy reversal after initial failure: overall results and predictors for success. J Urol. 1999; 161:1153–6. The authors performed a retrospective review of the treatment outcomes for repeat microsurgical vasectomy reversal in 41 men following a prior failed vasectomy reversal (s) and described predictors for success. 20 men underwent bilateral (16) or unilateral (4) vasoepididymostomy, 11 with underwent bilateral (7) or unilateral (4) vasovasostomy and 10 who had undergone unilateral vasoepididymostomy with contralateral vasovasostomy. The mean obstructive interval was 10.6 years with patency and pregnancy rates of 79 and 31%, respectively. Mean total motile sperm count for successful redo reversals was 38.0 million. In this series, previous conception with the current partner was predictive of future conception after redo reversal. Urologists performing repeat vasectomy reversal must be familiar with microsurgical techniques, since almost three-quarters of patients will require at least unilateral vasoepididymostomy. Microsurgical reconstruction following failed vasectomy reversal is associated with high patency and moderate pregnancy rates at short-term follow-up.

Hollingsworth MR, Sandlow JI, Schrepferman CG, Brannigan RE, Kolettis PN. Repeat vasectomy reversal yields high success rates. Fertil Steril. 2007;88(1):217–9. This is a retrospective review of the author’s experience with repeat vasectomy reversals looking at the post-operative patency and natural pregnancy rates. Their data demonstrated that repeat vasectomy reversal is a valid option in patients with a failed initial reversal, although the suitability of repeat reversal should be based on the obstructive interval, the original reversal, the experience of the reversal surgeon, and any female factors, as well as the couple’s wishes.

Matthews GJ, McGee KE, Goldstein M. Microsurgical reconstruction following failed vasectomy reversal. J Urol. 1997; 157:844–6. The authors reviewed redo microsurgical reconstruction outcomes following a failed vasectomy reversal with 64 repeat vasectomy reversals (52 redo and 12 redo redo procedures) performed on 57 men. They felt that complete failure of a vasectomy reversal was usually a result of unrecognized epididymal obstruction. Late failure following initial patency suggests a compromised anastomosis. Of men with absolute azoospermia (initial or complete procedure failures) following vasovasostomy, 74% required 1 or more vasoepididymostomies, compared to 24% of men with initially patent vasovasostomies (late failures). Repeat vasectomy reversals result in patency and pregnancy rates somewhat lower than previously reported for unselected vasovasostomy and vasoepididymostomy. Because stenosis rates are greater following reoperation, intraoperative and postoperative sperm cryopreservation is recommended.

Paick J-S, Park JY, Park DW, Park K, Son H, Kim SW. Microsurgical vasovasostomy after failed vasovasostomy. J Urol. 2003;169(3):1052–5. This paper analyzed the results of a repeat microsurgical vasovasostomy in 62 cases after a failed initial vasovasostomy to identify predictors of surgical outcome. Regardless of the intraoperative observation of sperm in the vasal fluid bilateral microsurgical 2-layer vasovasostomy was performed when surgically possible. Of these 62 patients 60 (97%) underwent bilateral (58) or unilateral (2) vasovasostomy and 2 (3%) underwent unilateral vasovasostomy with contralateral epididymovasostomy. The overall patency and pregnancy rates achieved were 92% and 57%, respectively, and the natural birth rate was 52%. Increased age of the wife proved a negative prognostic factor for pregnancy. This study suggests that a compromised anastomosis after the previous surgery is the most common cause of failed vasovasostomy. We recommend that microsurgical vasovasostomy should be performed preferentially in failed vasovasostomy cases.

Pasqualotto FF, Agarwal A, Srivastava M, Nelson DR, Thomas AJ. Fertility outcome after repeat vasoepididymostomy. J Urol. 1999;162(5):1626–8. The authors looked 18 patients who underwent repeat vasoepididymostomy to determine whether repeat surgical reconstruction after failed vasoepididymostomy is effective or whether they should undergo sperm retrieval for IVF with ICSI. The patency rates according to the levels of the redo epididymal anastomosis were 66.7, 62.5 and 100% in the caput, corpus and cauda, respectively. After repeat vasoepididymostomy two-thirds of men have sperm in the semen. Aspiration of motile sperm and cryopreservation from the epididymal tubule were possible in 11 of 18 cases at repeat vasoepididymostomy, so the authors recommend banking at the time of the redo surgery. It appears worthwhile to offer patients repeat vasoepididymostomy after a failed initial procedure.

Perkins A, Burrows P, McCauley T, Ax R, Marks, SF, Redo Vasectomy Reversal Intra-Operative Findings Indicate Incorrect Initial Reversal Technique. American Society for Reproductive Medicine 64th Annual Meeting, San Francisco, California, November 8-12, 2008. The purpose of this retrospective analysis by our team was to evaluate the etiology of failed vasectomy reversals and assess the success rate of redo vasovasostomy (VV) or vasoepididymostomy (VE) surgery at our VR clinic, where 10% (222/2268) of VR surgeries were redo cases. Bilateral VV was performed 57% (119/208) of the time for redo patients. The remainder of the patients received a unilateral VV and a unilateral VE (VV/VE) or a bilateral VE, 25% (51/208) and 18% (38/208) respectively. Redo VR patients had a patency of 89% (161/181) with an average of 41 million motile sperm per ejaculate and a pregnancy rate of 43% (77/181). We concluded from the data that: 1) our success of redo VR confirms prior published success rates, reaffirming redo VR as a viable option after failed VR; 2) in 28% of redo VR, a VE was indicated when an initial VV was performed. We attribute the initial failure of the remaining 72% redo patients that received VV to intravasal scarring or technical reasons.

Robot-Assisted Vasectomy Reversals

Brahmbhatt JV, Gudeloglu A, Liverneaux P, Parekattil SJ. Robotic microsurgery optimization. Arch Plast Surg. 2014 May;41(3):225-30. The authors review many of the new advances and adjunctive surgical instrumentation with outcomes for robotic microsurgery. Specifically they highlight tools for enhanced optical magnification, micro-Doppler sensing of small vessels, vein mapping capabilities, hydro-dissection, micro-ablation technology, and confocal microscopy to provide imaging at a cellular level.

Kavoussi PK. Validation of robot-assisted vasectomy reversal. Asian J Androl. 2015 Mar-Apr;17(2):245-7. This article is a retrospective chart review from a single VR center of men who underwent either robot-assisted VR (RAVR) or microsurgical VR (MVR) by a single fellowship trained microsurgeon between 2011 and 2013. Fifty-two men who were interested in VR were counseled and given the option of RAVR versus MVR. Twenty-seven men elected to have MVR while 25 men elected RAVR. These included vasovasostomies and vasoepididymostomies in both groups, as well as redo VRs in men who had failed previous VR attempts by other surgeons. There was no statistically significant difference between the microsurgical group and the robot-assisted group, respectively, in overall patency rates (89% vs 92%), 6 weeks post-VR mean sperm concentrations (28 million ml-1 vs 26 million ml or total motile counts (29 million vs 30 million), or mean operative times (141 min vs 150 min). Transitioning from MVR to RAVR is feasible with comparable outcomes.

Kavoussi P, Calixte N, Brahmbhatt J, Parekattil S. Robot‐assisted microsurgery for chronic orchialgia. Transl Androl Urol. 2017;6:S6‐S9. This article is a summary of a literature search on the use of robot assisted vasectomy reversals for post-vasectomy pain syndrome, also called chronic orchialgia. First line management of chronic orchialgia is conservative treatment; however, in men who fail conservative therapy, surgical intervention may be indicated. Microsurgery has been the mainstay for surgical treatment of chronic orchialgia, but the implementation of robotics to microsurgery lends itself particularly to surgical treatment of chronic orchialgia. Current surgical therapies in which robot assistance have been applied to microsurgery include microsurgical denervation of the spermatic cord, varicocelectomy, and vasectomy reversal.

Kavoussi PK, Harlan C, Kavoussi KM, Kavoussi SK. Robot-assisted microsurgical vasovasostomy: the learning curve for a pure microsurgeon. J Robot Surg. 2018 Oct 31. The objective of this retrospective chart review was to evaluate the learning curve for a microsurgeon’s first 100 RAVVs transitioning to robot-assisted microsurgical vasovasostomy (RAVV). Cases were stratified into four groups by 25 case intervals. Postoperative mean sperm concentrations in the initial semen analyses after RAVV are consistent over time. For a single microsurgeon not formally trained in robotic microsurgery, 75 RAVV cases were required to optimize and plateau in anastomosis times and 75 cases were required to optimize operative times.

Parekattil SJ, Gudeloglu A, Brahmbhatt J, et al. Robotic assisted versus pure microsurgical vasectomy reversal: Technique and prospective database control trial. J Reconstr Microsurg. 2012;28:435–44. This study provides the first clinical prospective control trial of robotic assisted versus pure microsurgical vasovasostomy (MVV) and vasoepididymostomy (MVE). The use of robotic assistance for vasectomy reversal may provide the microsurgeon with improved visualization, elimination of tremor, and decreased fatigue and obviate the need for a skilled microsurgical assistant. The use of robotic assistance in microsurgical vasovasostomy and vasoepididymostomy may have benefit over MVV and MVE with regards to decreasing operative duration and improving the rate of recovery of postoperative total motile sperm counts based on this study.

Trost L, Parekattil S, Wang J, Hellstrom WJ. Intracorporeal robot‐assisted microsurgical vasovasostomy for the treatment of bilateral vasal obstruction occurring following bilateral inguinal hernia repairs with mesh placement. J Urol. 2014;191:1120‐1125. The authors describe a robotic assisted surgical approach to manage iatrogenic inguinal vasal obstruction. The robotic approach offers novel opportunities to the operating surgeon, including performing microsurgical anastomoses in traditionally challenging locations. They describe an intracorporeal, robot-assisted, microsurgical 2-layer anastomosis vasovasostomy for iatrogenic vasal obstruction that was not amenable to standard microscopic repair. Semen analysis 8 weeks after the procedure demonstrated a successful result. These results demonstrate the feasibility of the procedure and highlight unique aspects of the robotic approach, which may offer advantages over the traditional microscope in select cases.

Semen Analysis

Burrows PJ, Schrepferman CG, Lipshultz LI. Comprehensive office evaluation in the new millennium. Urol Clin North Am. 2002 Nov;29(4):873-94. The book chapter reviews the comprehensive office-based evaluation of male-factor infertility to include a risk assessment in the patients past and current medical history, identification of pertinent physical examination findings, and correct assessment of laboratory data. The authors also address the increased the urologist’s ability to use functional tests of sperm function to expand on routine semen analysis testing.

World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. 2010. This comprehensive manual for andrology and fertility laboratories defines the guidelines, techniques and standards used around the world for the laboratory processing, examination and interpretation of a semen analysis.

Sperm Granuloma

Maghelia A, Rais-Bahrami S, Kempkensteffen C, Weiske WH, Miller K, Hinz S. Impact of obstructive interval and sperm granuloma on patency and pregnancy after vasectomy reversal. Int J Androl 2010;33(5):730-5. This study looked at the effect of the obstructive interval and the presence of a sperm granuloma in 334 patients on vasal patency and pregnancy rate following vasectomy reversal. They found that patients with longer obstructive intervals were more often older and more likely to have a vasoepididymostomy (VE) performed. They found no association between the presence of a sperm granuloma or the length of the obstructive interval with post-operative vas patency and pregnancy rates. They did find what others have shown that the age of the female partner is a predictor of pregnancy after reversal.

Schmidt SS. Spermatic granuloma: an often-painful lesion. Fertil Steril 1979 Feb;31(2):178-81. Sperm granulomas are localized inflammatory masses which frequently occur at the site of vasectomy as a result of sperm leaking into surrounding tissues. Although some are often silent, others can be agonizingly painful. A series of 154 granulomas was presented. Of these, 83 were symptomatic and 63 required surgery for relief of pain.

Sperm Kinetics after Reversals

Perkins A, Marks M, Burrows P, Marks S. Sperm kinetics following vasectomy reversal. Androl 2012;33(Suppl2):42. This is the summary of a poster that we presented at an American Society of Andrology meeting where we conducted a retrospective analysis of records from 33 subjects that underwent a bilateral vasovasostomy and then had a monthly semen analysis, specifically to look at the standard length of time a patient can expect for their sperm counts to return to a target of at least 10 million motile. The average years from vasectomy to reversal for the study group was 8 years (range 1−20) and average age at the time of VR was 40 years (range 30−57). All patients produced motile sperm in at least one semen analysis (SA) by the third test, 112 days, with 88% (29/33) ejaculating over 10 million motile sperm. The highest total count and total motile were reported on average within the sixth month (182 days) post operatively with 117 million and 61 million respectively. Within the six-month observation period 42% (14/33) of the subjects reported a pregnancy. Most patients that undergo bilateral vasovasostomy can expect sperm return on the first analysis one month post−operatively with a gradual increase in sperm kinetics and a 42% pregnancy rate in the first six months.

Sperm Morphology

Ombelet W, Dhont N, Thijssen A, Bosmans E, Kruger T. Semen quality and prediction of IUI success in male subfertility: a systematic review. Reprod Biomed Online. 2014 Mar;28(3):300-9. The authors performed a literature search of 983 papers, of which only 55 studies fulfilled the inclusion criteria, to review many of the variables that may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample and the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies leaving an urgent need for better studies to answer this question.

Shabtaie SA, Gerkowicz SA, Kohn TP, Ramasamy R. Role of Abnormal Sperm Morphology in Predicting Pregnancy Outcomes. Curr Urol Rep. 2016 Sep;17(9):67. This review discusses the evaluation of sperm morphology for prognosis in assisted reproductive techniques such as intrauterine insemination and in vitro fertilization with or without intracytoplasmic sperm injection. The authors also address the evaluation of a patient with teratozoospermia seeking fertility treatment. They note that the evaluation of strict morphology for predicting successful pregnancy has been controversial, though remains a common component of semen analysis and justification to encourage couples to proceed directly to IVF/ICSI.

Success of Vas Reversals and the Marks Vas Cutting Forceps

Bolduc S, Fischer MA, Deceuninck G, Thabet M. Factors predicting overall success: a review of 747 microsurgical vasovasostomies. Can Urol Assoc J 2007;1(4):388-94. The authors performed a retrospective analysis of 747 modified 1-layer microsurgical vasovasostomy (VV) procedures performed between 1984 and 2000 to determine outcomes and predictors of Vas-to-Vas connection success. The overall patency rate was 86% and pregnancy rates were 33% and 53% at 1 and 2 years after primary VV, respectively. Preoperative factors associated with successful outcome and pregnancy included shorter obstructive interval and same female partner (p < 0.05). Intraoperative factors predicting success included the use of surgical clips instead of suture at vasectomy, the presence of a sperm granuloma, the presence and quality of vasal fluid, and the presence and quality of sperm in vasal fluid. This study confirms the effectiveness of VV for vasectomized men who wish to father children. It also demonstrates that preoperative and intraoperative factors can be predictive of the VV outcome.

Crosnoe LE, Kim ED, Perkins AR, Marks MB, Burrows PJ, Marks SH. Angled vas cutter for vasovasostomy: technique and results. Fertility and Sterility. 2014;101(3):636-639. In this retrospective chart review, we described the technique and results of bilateral vasovasostomy at our vasectomy reversal center using a new 3-mm vas cutting forceps angled at 15° for vasal transection. Men who underwent a bilateral vasovasostomy by a single surgeon (SHM) between 2001 and 2012 and had a minimum of one semen analysis postoperatively or a reported natural conception. Before September 14, 2010, a straight-edge 90° vas cutter was used on all vasovasostomy connections; 375 men received a bilateral vasovasostomy and met follow-up criteria. Beginning on September 14, 2010, an angled cutter was used on all vasovasostomy patients, with 194 men meeting the exclusion criteria. A minimum of 1 × 10(6) sperm reported on a postoperative semen analysis, or a reported natural conception was used to establish patency. The overall vasovasostomy patency rate using the 15° angled vas cutter was 99.5% and was 95.7% using the straight 90°vas cutter. The development of an angled vas cutter provides an increased surface area for vasal wound healing to allow for larger tissue diameter for better healing, resulting in high patency rates after vasovasostomy.

Namekawa T, Imamoto T, Kato M, Komiya A, IchikawaT . Vasovasostomy and vasoepididymostomy: Review of the procedures, outcomes, and predictors of patency and pregnancy over the last decade. Reprod Med Biol. 2018 Oct; 17(4): 343–355. This article reviews database searches the surgical techniques, outcomes, and predictors of postoperative patency and pregnancy, with a focus on articles that have reported over the last 10 years. High patency and pregnancy rates are reported by experienced surgeons using microsurgical techniques over the past decade. The reported mean patency rate was 87% and the mean pregnancy rate was 49% for a patient following microscopic VV and/or VE for vasectomy reversal. Recently, robot‐assisted techniques were introduced and have achieved a high rate of success. As the VE is a more technically challenging procedure than the VV, patients who need a VE should be referred to an experienced VE surgeon.The predictors and predictive models of postoperative patency and pregnancy also have been reported. The obstructive interval, presence of a granuloma, and intraoperative sperm findings predict postoperative patency. These factors also predict postoperative fertility. In addition, the female partner’s age and the same female partner correlate with pregnancy after surgery.

Silber SJ, Grotjan HE. Microscopic vasectomy reversal 30 years later: a summary of 4010 cases by the same surgeon. J Androl 2004;25(6):845-859. This review of 4010 patients that underwent a microscopic vasectomy reversal between 1975 and 2003 by 1 surgeon at a single institution. Of these, 1735 were successfully contacted to obtain reliable long‐term data. A total of 1556 (89.7%) were able to establish a pregnancy in their female partner, resulting in 2111 pregnancies. When there was no sperm in the vas fluid at the time of vasectomy reversal, vasoepididymostomy was performed rather than vasovasostomy. A total of 1581 patients underwent bilateral vasovasostomy; 1184 underwent vasoepididymostomy on one side and vasovasostomy on the other side; and 1139 underwent bilateral vasoepididymostomy. Of patients undergoing vasovasostomy, 2.1% had no sperm in the ejaculate postoperatively, and 10.3% of patients undergoing bilateral vasoepididymostomy had no sperm in the ejaculate postoperatively. On average a patency rate of 96.2% in the total group of patients was achieved. When the vasectomy was less than 10 years prior to reversal, the patency rate was 98%. When the vasectomy was 10 or more years prior to reversal, the patency rate was 93%. Among all the patients, 77.7% had sperm counts greater than 5 million/mL postoperatively. Among patients undergoing bilateral vasovasostomy and those undergoing bilateral vasoepididymostomy, 92.5% and 84.3% eventually achieved a pregnancy, respectively. The pregnancy rate did not differ with patients that had a sperm count of greater than 5 million sperm/mL. The pregnancy rate for less than 5 million sperm/mL was 78.3% and when there was greater than 5 million sperm/mL the pregnancy rate was 91.9%. Although the duration of time between vasectomy and vasectomy reversal had an impact on pregnancy rate, the greatest impact was the age of the wife.

Among wives under age 30 at the time of the vasectomy reversal, 94.2% established a pregnancy, but only 61.1% of wives age 40 or older established a pregnancy. They concluded that microsurgical vasectomy reversal is preferable to sperm retrieval and intracytoplasmic sperm injection (ICSI), since the pregnancy rate appears to be higher with this technique than with sperm retrieval and ICSI. It does not appear that sperm antibodies or testicular damage are likely to account for failure to achieve pregnancy after vasectomy reversal. Rather, it is likely to be related to partial or complete obstruction following surgery, or to the fertility of the female partner.

Yumura Y, Tsujimura A, Imamoto T, et al. Nationwide survey of urological specialists regarding male infertility: results from a 2015 questionnaire in Japan. Reprod Med Biol. 2017;17:44‐51. This paper investigated the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan between April 2014 and March, 2015. The authors contacted 47 clinical specialists in male infertility who had been certified by the Japan Society for Reproductive Medicine. The participating clinicians were sent a questionnaire regarding information on their infertile patients and the number and success rates of male infertility operations that had been performed in their practice. Thirty-nine specialists returned the questionnaire and provided information regarding 7268 patients. The patency rates with vasovasostomy and epididymovasostomy were 81.8% and 61.0%, respectively. Surgical outcomes for infertile male patients are favorable and can be of great clinical benefit for infertile couples.

Testosterone and Fertility

Coward RM, Mata DA, Smith RP, Kovac JR, Lipshultz LI. Vasectomy reversal outcomes in men previously on testosterone supplementation therapy. Urology. 2014 Dec;84(6):1335-40. This article is a retrospective review of six out of 265 men on testosterone supplementation therapy before vasectomy reversal from 2010 to 2013, looking at the preoperative management and outcomes of vasectomy reversal (VR) in men with a history of testosterone supplementation therapy (TST). Nine vasovasostomies and 3 epididymovasostomies were performed. Patency was 83% after a median follow-up of 6.4 months and was 100% in men undergoing at least 1 vasovasostomy. Spontaneous pregnancy was achieved by 50% during the follow-up period. Testicular salvage medical therapy may play a role in the preoperative management of VR in men with prior TST. VR after TST can have outcomes comparable to those in the general population.

Kovac JR, Scovell J, Ramasamy R, Rajanahally S, Coward RM, Smith RP, Lipshultz LI. Men regret anabolic steroid use due to lack of comprehension regarding the consequences on future fertility. Andrologia 2015 Oct;47(8):872-8. The authors examined whether men with anabolic-steroid-induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic-androgenic steroids (AAS) and what their reasons were for this regret. An anonymous, prospective survey was distributed to 382 men seeking follow-up treatment for hypogonadism. Prior AAS use was confirmed by self-report, and men were categorized based upon whether they regretted (R) or did not regret (NR) their use of AAS. 15.2% expressed regret over AAS use. Those men who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility. Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%). A lack of awareness regarding the negative long-term effects on fertility was the primary factor related to regret of AAS use in men with ASIH.

Twins, Fertility and Vasectomy Reversals

Hall JG. Twinning. Lancet. 2003 Aug 30;362(9385):735-43. This paper is review of twinning with a discussion of the frequency and complications in twin pregnancies and long-term outcomes. Artificial reproductive technologies have led to a pronounced rise in numbers of dizygotic and monozygotic twins. Although spontaneous dizygotic twinning is clearly associated with increased concentration of follicle-stimulating hormone and ovulation of more than one egg, causes of monozygotic twinning remain elusive. Monozygotic twinning seems to represent an anomaly in itself, with an increased number of spontaneous abortions and structural congenital anomalies. Both monozygotic and dizygotic twins have growth rates that slow at 30 weeks in utero and might be programmed both developmentally and biochemically earlier in pregnancy to have different responses at birth and after birth compared with singletons.

McNamara HC, Kane SC, Craig JM, Short RV, Umstad MP. A review of the mechanisms and evidence for typical and atypical twinning. Am J Obstet Gynecol. 2016 Feb;214(2):172-191. The authors review the literature on the mechanisms for twinning and disorders of twin gestations as well as cases of atypical twinning and the reexamination of the fundamental theories to explain twin gestations. The authors also address atypical twinning to include the phenomena of chimeric twins, phenotypically discordant monozygotic twins and mirror-image twins. Refinements in the modeling of early embryonic development in twin pregnancies may have significant clinical implications.

Vasoepididymostomy (VE)

Chan PT. The evolution and refinement of vasoepididymostomy techniques. Asian J Androl. 2013; 15:49–55. Dr. Chan reviews the indications, evolution and techniques for microsurgical vasoepididymostomy (VE) for obstructive azoospermia secondary to epididymal obstruction Although alternative management such as epididymal or testicular sperm aspiration in conjunction with intracytoplasmic sperm injection is feasible, various studies have established the superior cost-effectiveness of VE as a treatment of choice. Microsurgical VE is considered one of the most technically challenging microsurgeries. Its success rate is highly dependent on the skills and experience of the surgeons. Various techniques have been described in the literature for VE. The author describes a new technique known as longitudinal intussusception VE (LIVE) in which the epididymal tubule is opened longitudinally to obtain a larger opening to allow its tubular content to pass through the anastomosis, with preliminary data demonstrating a patency rate of over 90%.

Chan PT, Brandell RA, Goldstein M. Prospective analysis of outcomes after microsurgical intussusception vasoepididymostomy. BJU Int. 2005; 96:598–601. This paper reviews a prospective analysis from 1998 to 2003 of 68 out of 324 patients with obstructive azoospermia. Vasoepididymostomy is considered the most challenging reconstructive microsurgery in urology. The mean age was 39.8 years for the men and 31.8 years for their partners with the median duration of obstruction was 18.8 years; and 37% of patients had had previous failed attempts at reconstruction. The overall patency (>10 000 sperm/mL) rate was 84% (53/63). A favorable patency and pregnancy rate can be achieved using microsurgical intussusception vasoepididymostomy. Microsurgical reconstruction of the reproductive tract should be primary therapeutic method in cases of azoospermia from epididymal obstruction.

Chawla A, O’Brien J, Lisi M, Zini A, Jarvi K.Should all urologist performing vasectomy reversal be able to perform vasoepididymostomies if required? J Urol 2004;172(3):1048- 50. This study is a retrospective review the records of 22 patients who had undergone redo vasectomy reversal from January 1999 to September with a minimum follow-up of 2 years. The authors looked at the potential causes for vasectomy reversal failure in patients who had undergone VV without an attempt at VE. Despite the general consensus that an epididymal obstruction may occur following a vasectomy and that some men should undergo vasoepididymostomy (VE) rather than vasovasostomy (VV), the practice of many urologists has been to offer only VV for vasectomy reversal. This study indicates that a large proportion of men (48%) have an epididymal obstruction as the etiology for vasectomy reversal failure. The authors recommend that all surgeons offering vasectomy reversals be able to offer VE if required based on intraoperative findings to serve the patient adequately as well as his partner and their future fertility.

Ostrowski KA, Tadros NN, Polackwich AS, McClure RD, Fuchs EF, Hedges JC. Factors and practice patterns that affect the decision for vasoepididymostomy. Can J Urol. 2017 Feb;24(1):8651-8655. The authors used a questionnaire to determine the factors used by leaders performing microsurgical vasectomy reversal to make the decision between vasovasostomy (VV) and vasoepididymostomy (VE). This was sent to all members of the Society for the Study of Male Reproduction (SSMR), a male reproduction subspecialty society of the AUA. Sixty-seven surgeons responded to the questionnaire, of which 72% of members performed less than 50 vasectomy reversals per year. Also, 71% of members stated that less than 20% of their vasectomy reversals are vasoepididymostomies. When evaluating epididymal fluid at the time of reversal, 87% would perform a VE for pasty fluid, 66% with creamy fluid without sperm heads and 55% with no or scant fluid. With respect to banking sperm, 36% take sperm or testicular tissue at the time of VE while 37% sometimes take sperm mostly depending on the couple’s preference. The Berger end-to-side with intussusception VE technique is used by the majority of members (78%).

Vasovasostomy (VV)

Belker AM, Thomas AJ Jr, Fuchs EF, Konnak JW, Sharlip ID. Results of 1,469 microsurgical vasectomy reversals by the vasovasostomy study group. J Urol. 1991;145:505‐511. This landmark study from almost 30 years ago reviewed 1,469 men who underwent microsurgical vasectomy reversal procedures during 9-year period at 5 institutions. Of 1,247 men who had first-time procedures sperm were present in the semen in 865 of 1,012 men (86%) who had postoperative semen analyses, and pregnancy occurred in 421 of 810 couples (52%) for whom information regarding conception was available. Rates of patency (return of sperm to the semen) and pregnancy varied depending on the interval from the vasectomy until its reversal. If the interval had been less than 3 years patency was 97% and pregnancy 76%, 3 to 8 years 88% and 53%, 9 to 14 years 79% and 44% and 15 years or more 71% and 30%. When sperm were absent from the intraoperative vas fluid bilaterally and the patient underwent bilateral vasovasostomy rather than vasoepididymostomy, patency occurred in 50 of 83 patients (60%) and pregnancy in 20 of 65 couples (31%). Repeat microsurgical reversal procedures were less successful. A total of 222 repeat operations produced patency in 150 of 199 patients (75%) who had semen analyses and pregnancy was reported in 52 of 120 couples (43%).

Chen XF, Wang HßX, Liu YD, et al. Clinical features and therapeutic strategies of obstructive azoospermia in patients treated by bilateral inguinal hernia repair in childhood. Asian J Androl. 2014;16:745‐748. This article reviews the role of vasectomy reversal for the management of azoospermia after childhood inguinal herniorrhaphy, a common cause of seminal tract obstruction. Vasovasostomy (VV) can be used to reconstruct the vas deferens and restore the sperm for natural pregnancy. From July 2007 to June 2012, a total of 62 patients, with history of childhood inguinal herniorrhaphy and diagnosed as obstructive azoospermia were treated in the author’s center. The overall patency rate and natural pregnancy rate were 56.5% (35/62) and 25.8% (16/62), respectively. 30.6% (19/62) of the patients underwent bilateral VV and unilateral or bilateral vasoepididymostomies due to ipsilateral epididymal obstruction with the patency and natural pregnancy rate decreasing to 63.2% (12/19) and 26.3% (5/19). 21.0% (13/62) of the patients merely underwent vasal exploration without reconstruction due to failure to find distal vasal stump, etc. This study indicates that microsurgical reanastomosis is an effective treatment for some patients with seminal tract obstruction caused by childhood inguinal herniorrhaphy.

Dickey RM, Pastuszak AW, Hakky TS, Chandrashekar A, Ramasamy R, Lipshultz LI. The evolution of vasectomy reversal. Curr Urol Rep 2015;16(6):40. The authors review the evolution of the techniques of vasectomy reversal from macrosurgical to the current microscopic and robotic technologies. They describe how urological microsurgery has consistently implemented advanced techniques and state-of-the art technology with continued refinement to provide for even more favorable outcomes following vasectomy reversal.

Fox M. Vasectomy reversal—microsurgery for best results. Br J Urol 1994;73(4):449-53. This study looked at series of 103 consecutive patients to determine whether microsurgery achieves a better result in vasectomy reversal than other macroscopic techniques. The method used in all patients was a modification of a two-layer anastomotic technique. In the first 49 patients 8/0 Vicryl was used macroscopically to create a two-layer anastomosis whereas in 54 patients 10/0 Ethilon was used microscopically. The rate of sperm in the semen was highest at 94% in those in whom the microscopic technique had been used. The additional time and effort required for a microsurgical approach to vasovasostomy were worthwhile to obtain patency and fertility rates which were superior to those of other techniques.

Kirby EW, Hockenberry M, Lipshultz LI. Vasectomy reversal: decision making and technical innovations. Transl Androl Urol. 2017 Aug; 6(4): 753–760. The aim of this article is to provide a detailed description of the operative and perioperative procedures and decision-making employed by surgeons performing state-of-the-art vasectomy reversals VRs. Reversals are a complex microsurgical procedure requiring up-to-date intraoperative decision-making, surgical technique, and postoperative management to achieve high success rates.

Marks SHF. Vasectomy Reversal: Manual of Vasovasostomy and Vasoepididymostomy. New York; Springer; 2018. This recently published textbook outlines for physicians, nurses, surgical assists and anyone involved with vasectomy reversals, the step-by-step details on the thought processes and technical “how to” perform a state-of-the-art vasectomy reversal, with chapters on pre-op issues and care, intra-op techniques, decision-making, challenges and post-reversal dilemmas, care and management.

Nalesnik JG, Sabanegh ES Jr. Vasovasostomy: multiple children and long-term pregnancy rates. Curr Surg. 2003 May-Jun;60(3):348-50. This is a retrospective examination of 73 patients that were at least 4 years out from vasovasostomy to determine the long-term patency and pregnancy rates after vasovasostomy and the likelihood of having more than 1 child after this procedure. Using questionnaires, from a population of 73 patients with proven prior fertility, 43 could be contacted for data collection. Only thirteen (33%) desired more than 1 child at the time of vasectomy reversal. After vasovasostomy in patients with a vasal obstructive interval of 7 years, up to 45% of couples may achieve pregnancy and up to 35% could go on to conceive a second child. Vasovasostomy remains a highly effective option for restoration of fertility in vasectomy patients, while offering the opportunity for multiple pregnancies with only a single intervention.

Owen ER. Microsurgical vasovasostomy: a reliable vasectomy reversal. Aust N Z J Surg. 1977;47:305‐309. This is a pioneering paper describing early research in vasectomy reversals. Optimal results of repair of a severed tube can be expected when a meticulous atraumatic microsurgical technique is based on a detailed knowledge of the anatomy and function of the tube. A reliable vas repair after vasectomy involves the avoidance of leakage or scarring in a tube of which the ends differ in internal diameter from 1 mm to 0-2 mm and in which the inner mucosal layer is difficult of access because of its solid muscular core surround. In addition, the healing will only occur without massive scarring and the nerve supply will only return if the blood supply can be retained as close as possible to the anastomosis. The technique described was first researched in the Macaque monkey and requires considerable microsurgical expertise. It has proved reliable in that 98% of the first 50 patients showed sperms in their ejaculates three months after operation, with a 62% pregnancy rate after an operation on one side only. The vasectomies had been performed up to 13 years before, and one can only conclude that a routine scrotal vasectomy should not be considered irreversible.

Ramasamy R, Mata DA, Jain L, Perkins AR, Marks SH, Lipshultz L. Microscopic visualization of intravasal spermatozoa is positively associated with patency after bilateral microsurgical vasovasostomy. I. Andrology. 2015 May;3(3):532-5. We performed a retrospective review of the pre-operative and intraoperative factors associated with successful patency following bilateral microsurgical vasovasostomy (VV) in 1331 men between 2006 and 2013. Vasal fluid was examined intraoperatively for gross quality (i.e., clear or opaque and creamy/thick) and for the presence of spermatozoa on microscopy (i.e., whole spermatozoa, sperm fragments, or azoospermia). Overall, 1307 patients achieved post-operative patency (98%) while 24 remained obstructed (2%). Only microscopic examination of the intravasal fluid for the presence of spermatozoa (bilateral or unilateral whole spermatozoa vs. sperm parts/azoospermia) at the time of VV was significantly associated with post-operative patency. Identification of bilateral or unilateral sperm fragments vs. azoospermia was also associated with increased odds of post-operative patency Identification of whole spermatozoa in the vasal fluid at the time of VV was positively associated with post-operative patency. This study’s findings stress the need for intraoperative microscopy to aid in post-operative patient counseling.

Schwarzer JU. Vasectomy reversal using a microsurgical three-layer technique: one surgeon’s experience over 18 years with 1300 patients. Int J Androl 2012;35(5):706-13. This paper highlights the technique and the results of microsurgical vasectomy reversal -vasovasostomy (VV) and epididymovasostomy (EV) in a three-layer technique in a single-centre study over 18 years. End-to-end VV was only performed if spermatozoa had been demonstrated at the epididymal stump of the vas. In all other cases, EV was carried out in a preocclusive region of the epididymal tubule. The outpatient procedure of refertilization was associated with a very low complication rate, which underlines its minimal-invasive character. The follow-up rate was 71%, the overall patency rate was 89% and the pregnancy rate was 59%. Secondary azoospermia was only observed in 1% of the patients. In relation to the intervals of obstruction, the patency and pregnancy rates were higher after short-term obstruction than after long-term obstruction. Correspondingly, higher success rates were found after VV than after EV. This is understandable because the probability for indication of EV increases with longer periods of obstruction. Good clinical results are achieved with this strategy, as evidenced by pregnancy rates and semen analyses.

Scovell JM, Mata DA, Ramasamy R, et al. Association between the presence of sperm in the vasal fluid during vasectomy reversal and postoperative patency: A systematic review and meta-analysis. Urology 2015; 85:809-13. The authors investigated the association between the presence of sperm in the vasal fluid during vasectomy reversal (VR) and postoperative patency using a meta-analysis of the literature reporting on the association between the presence of sperm in the intraoperative vasal fluid (ie, whole or parts vs none) and patency (ie, patent or not) after microsurgical vasovasostomy for men with obstructive azoospermia due to vasectomy. Only four case series and 2 retrospective cohort studies of a total of 1293 eligible patients were identified. The mean obstructive interval was 7.1 years. The postoperative patency was 4.1 times higher given the presence of intravasal sperm or sperm parts as opposed to their absence at the time of VR. The presence of whole sperm or sperm parts in the vasal fluid during VR is positively associated with postoperative patency.

Silber SJ. Microscopic vasectomy reversal. Fertil Steril. 1977;28:1191‐1202. This article is a review of more than 300 patients undergoing microscopic vasovasostomy that have been carefully studied in an effort to determine the factors which affect the recovery of fertility after an accurate microscopic reanastomosis. The over-all pregnancy rate in an unselected group of early patients was 71%. Recovery of fertility correlated with the return of normal sperm counts and with the quality of seminal fluid in the vas deferens on the testicular side of the obstruction at the time of vasovasostomy. The three most important factors influencing return of fertility after vasovasostomy are (1) a meticulous microscopic technique for reconnection, (2) the duration of time the vas deferens has been obstructed, and (3) the presence of absence of a sperm granuloma at the site of the vasectomy, venting the long-term pressure buildup which otherwise would occur. The presence of a sperm granuloma at the vasectomy site generally ensured the presence of good quality sperm in the vas fluid at the time of vasovasostomy and the recovery of a good sperm count postoperatively. If all three of these factors are favorable, vasectomy should be reversible for most patients.

Silber SJ. Perfect anatomical reconstruction of vas deferens with a new microscopic surgical technique. Fertil Steril. 1977;28:72‐77. This is a review of early results with a new, two-layer microscopic technique for anastomosis of the vas deferens, using an operating microscope and ultrafine suture, reveal that patency of the vas deferens can be achieved in virtually every case. Normal sperm counts can be achieved in up to 95% of patients. Failure with conventional techniques is usually due to continuing partial obstruction. Thus, while success is also good 10 years after vasectomy, it is not as predictable. Previous failure with a conventional operation does not limit success with a reoperation using the microscopic two-layer technique. Operations on 200 patients since this original study are confirming these early results.

Vitamin and Supplement Risks

Hoek J, Koster MPH, Schoenmakers S, Willemsen SP, Koning AHJ, Steegers Régine EAP, Steegers-Theunissen PM. Does the father matter? The association between the periconceptional paternal folate status and embryonic growth. Fert Stert. February 2019. Volume 111, Issue 2, Pages 270–279. The authors looked at a total of 511 singleton pregnancies, with 303 conceived spontaneously and 208 after in vitro in a prospective periconceptional cohort study to study the association between periconceptional paternal folate status and embryonic growth trajectories in early pregnancy at a Single tertiary hospital. Found that in spontaneously conceived pregnancies (and not IVF), both low and high periconceptional paternal folate status are associated with reduced embryonic growth. These data underline the importance of paternal folate status during the periconception period.

Mohan A, Lahiri A. Herbal medications and plastic surgery: a hidden danger. Aesthetic Plast Surg. 2014 Apr;38(2):479-81. The authors review the risks and concerns with the use of herbal medications with surgery. They note that patients and many health care practitioners are often unaware of the adverse side effects of herbal medicines and supplements. In addition, because many of these herbal supplements are available over the counter, many patients do not disclose these when listing medications to health care providers. Many supplements are known to have anticoagulant, cardiovascular, and sedative effects. Commonly, questions about herbal medicines are not routinely asked in clinics, and patients do not often volunteer such information. With the number and awareness of complementary medications increasing, their usage among the population is likely to increase. The authors recommend specific questioning about the use of complementary medications and discontinuing such medications before surgery.

Wong WW, Gabriel A, Maxwell GP, Gupta SC. Bleeding risks of herbal, homeopathic, and dietary supplements: a hidden nightmare for plastic surgeons? Aesthet Surg J. 2012 Mar;32(3):332-46. This paper provides a comprehensive review of many of the risks of commonly used complementary and alternative medicines, which can increase complications of surgical bleeding. Because herbal products, homeopathic medicines, and dietary supplements are widely used and despite their “natural” characteristics, these remedies have the potential to cause bleeding in patients who undergo surgery. This review focuses on 19 herbs, three herbal formulas, two herbal teas, and several other supplements that can cause bleeding perioperatively and postoperatively. They note that surgeons should screen all patients and educate them on the possible dangers associated with these treatments.

This reference bibliography was reviewed, edited and updated on January 1, 2023, by Dr. Sheldon Marks.