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Cornell University
Weill Medical College

Cornell Institute for Reproductive Medicine

Center for Male Reproductive Medicine and Microsurgery

"State-of-the-Art Compassionate Care for the Infertile Couple"


What's New at 2003 AUA Meeting (Chicago, Illinois, May 2003)



State-of-the-art lectures (on the topics of Male Infertility Treatment)


Cost Comparison of Treatments For Male Infertility

Dr. Stanton C. Honig, New Haven, Connecticut


(State-of-the-art lecture on the topic of “Economic, Decision–making in Male Reproduction” was presented at the 2003 AUA meeting in Chicago on April 30, 2003. This article was originally published on AUANews, March 2003)

1.
Introduction
2. Varicocele Associated Infertility
3. Obstruction


1. Introduction:

Economic factors are important in all aspects of life. We are consumers always trying to maximize our goods per unit dollar spent. Historically, medical treatment has been evaluated purely on its success without respect to costs of therapy. However, quality of life issues in medicine such as infertility treatment have been reviewed as a commodity, evaluating costs, cost-benefit ratio and cost-effectiveness. With the advent of sophisticated assisted reproductive technologies (ART), there is increased awareness of success rates of competing therapies for infertility Treatment decisions are being based on a combination of success rates and economic factors. Limitations in health care dollars tend to limit access to medical treatment for certain non-life threatening areas of medicine such as infertility. Access to infertility and in vitro fertilization (IVF) is mandated by some states while other states have left these decisions to providers of health care.




Recent studies have applied analysis to male infertility treatment to determine the cost-effectiveness of specific treatments/live birth.1



2. Varicocele Associated Infertility:

Several studies have evaluated the most cost-effective option for varicocele associated male infertility. In 1997 Schlegel analyzed the cost of varicocelectomy versus IVF/intracytoplasmic sperm injection (ICSI).2 The cost per delivery after varicocelectomy was calculated to be $26,268 compared to $89,091 after IVF/ICSI (28% delivery rate) in 1994 dollars. The high costs of IVF/ICSI included initial male evaluation, delivery costs, complication costs, loss of work adjustments and multiple gestation costs. Even using higher published IVF/ICSI success rates (47%), the cost per delivery was still higher at $62,263 compared to varicocelectomy alone.

In another study of only treatment costs Comhaire found varicocele repair to be the least expensive option ($l,700/delivery) compared to intrauterine insemination (IUI) for 3 cycles $2,566/delivery) and IVF/ICSI ($11,667/delivery).3 The study was limited to only making comparisons based on procedure fees. The lower cost of varicocele repair was attributed to the lower fees associated with embolization and a pregnancy rate of 40% to 60%. Penson et al compared cost-effectiveness of 4 treatment strategies for varicocele related infertility, including observation, varicocelectomy followed by IVF if unsuccessful, gonadotropin stimulated IUI followed by IVF if unsuccessful (IUI/IVF) and immediate IVF.4 They concluded that from a health care payer's perspective, varicocele/IVF is preferable. The average cost per live delivery with the varicocele/IVF option was less expensive ($44,522) compared to the IUI/IVF option ($49,757) and immediate IVF ($64,422). Immediate IVF was the least cost-effective option from a health care payer perspective. With respect to patient perspective (excluding costs not usually paid for directly by the patient, such as obstetrical costs), costs for varicocele/IVF ($22,114) and IUI/P/F ($22,122) were almost equivalent with costs for immediate IVF ($33,686) significantly higher. The authors concluded that immediate IVF was never the most cost-effective option and varicocele repair was more cost-effective from the health care provider perspective.

Cayan et al examined preoperative and postoperative total motile sperm counts (volume x concentration x motile fraction) in 540 infertile men with varicoceles to determine whether varicocelectomy could lower needs for ART (patient might require IUI instead of IVF due to improvement in sperm quality with varicocelectomy).5 Of treated infertile men 40% had increased total motile sperm counts to down stage the level needed (ie ICSI to IVF, IUI or no treatment) and in more than half of them (overall 20%) semen quality improved for spontaneous pregnancy. The authors concluded that varicocelectomy has significant potential to not only downstage the level of ART, but also possibly obviate the need for ART and therefore pass on savings in treatment costs.



Pregnancy after varicocelectomy may take up to 1 year or more, which needs to be factored into cost-effective decision making. With ART couples need to be aware of the influence of delays in treatment, canceled cycles and the necessity of multiple cycles needed to achieve pregnancy which may lengthen time to delivery. In addition, for couples in whom the male partner undergoes varicocelectomy multiple natural pregnancies may occur afterwards, and the additional cost for repeated assisted reproduction to have another child may be avoided.


3. Obstruction:

In cases of vasectomy or other obstructive causes of azoospermia cost-effective decision making is necessary to determine whether to proceed with reconstruction or sperm retrieval combined with IVF/ICSI. Given the relatively high pregnancy rates (18% to 41%) obtained with ICSI combined with microsurgical epididymal sperm aspiration (MESA)/testicular sperm extraction (TESE),6,7 the role and necessity of microsurgical reconstruction have been questioned and have prompted cost-effective analysis comparing vasectomy reversal to sperm retrieval with assisted reproductive techniques.

Pavlovich and Schlegel8 published the first cost-effective comparison of vasovasostomy or vasoepididymostomy with sperm retrieval using MESA or percutaneous epididymal sperm aspiration (PESA)/TESE and ICSI. The cost per delivery after vasectomy reversal (delivery rate 47%) was $25,475, which was considerably lower compared to the $72,521 cost per delivery after sperm retrieval and ICSI (delivery rate 33% from pooled data). They also reported that the cost per delivery after microsurgical reconstruction increased as the interval from vasectomy (time from obstruction) increased. The cost per delivery was $20,594 for less than 3 years after vasectomy and $36,915 for greater than 15 years after vasectomy. Based on these data, which represent a health care provider standpoint, reconstruction was the more cost-effective option.

Heidenreich et al reported similar findings in cost-effective analysis comparing vasovasostomy versus MESA/TESE combined with ICSI for infertile German couples.9 Excluding the cost secondary to time out of work, the cost per live birth after vasovasostomy (pregnancy rate 52%) was US$2,508. The cost per live birth after MESA/TESE with ICSI cycle (pregnancy rate 24.5%) was higher at US$13,263. Kolettis and Thomas reported similar cost-effectiveness for vasoepididymostomy in men with mean obstructive intervals of 12 years. The cost per newborn was $31,099 (delivery rate 36%) compared to $51,024 using MESA with ICSI (delivery rate 29% from pooled data) despite vasoepididymostomies being more technically difficult and more expensive.10 Donovan et al also demonstrated that repeat microsurgical reconstruction is a cost-effective means of reestablishing fertility in men with previously failed vasectomy reversals.11 The cost per delivered baby for repeat vasectomy reversal was $14,892 (pregnancy rate 44%) versus a cost of $35,570 following MESA/ICSI (pregnancy rate 67%). Based on these costs, it was calculated that a pregnancy rate of 81% or a reduction in charges from $17,463 to $11 816 (assuming a constant success rate for ICSI) would be necessary to achieve a comparable cost per delivery.

Challenging the assumption that post-vasectomy infertile men with older female partners should seek IVF/ICSI as first line treatment rather than vasectomy reversal, Deck and Berger compared costs for vasectomy reversal versus TESE/ICSI in men with partners older than 37 years.12, 13 Using a 17% birth rate at $4,850 cost for vasectomy reversal, the cost per newborn was estimated at $28,530. In comparison, using an 8% birth rate with women older than 36 years (probably too low) the estimated cost per newborn for TESA/ICSI was $103,940. Based on these data, vasectomy reversals appear to be more cost-effective for men with ovulating partners older than 37 years. National pregnancy rates with ICSI in women older than 35 years are higher than percentages reported in this study, and so these rates are probably closer than reported. Generally speaking, it appears that in most cases reconstruction is still clearly the more cost-effective option. However, if IVF costs are lowered and significantly higher delivery rates are achieved with ICSI, then these options may become more cost competitive.

There are a significant number of other cost comparisons of treatments that will be discussed in my lecture in Chicago, including costs of missing a testis tumor by referring a male factor patient directly for IVF/ICSI, cost comparisons of the different sperm retrieval techniques of MESA, TESA and PESA, cost comparisons for different approaches to varicocele repair and cost issues related to sperm cryopreservation. Economic factors play a major role in the consideration of treatment options for male reproduction. The urologist is competing with the reproductive endocrinologist for treatments that will achieve pregnancies. Critical review of published data is necessary to determine which options are cost-effective for the patient, provider and health care system.

Reference:

1 Shins, D. and Honig, S. C.: Economics of treatments for male infertility. Urol Clin North Am, 29: 841, 2002.

2 Schlegel, P. N.: Is assisted reproduction the optimal treatment for varicocele associated male infertility? A cost-effective analysis. Urology, 49: 435, 1997

3 Comhaire, F.: Economic strategies in modern male subfertility treatment

4 Hum Reprod, 10S: 103, 1995

5 Penson, D. F., Paltiel, A. D. et al: The cost-effectiveness of treatment for varicocele related infertility. J Urol, 168: 2490,2002.

6 Cayan, S., Kardioglu, A., ErderW F.et al: Can varicocelectomy Significantly change the way couples use assisted reproductive technologies? J Urol, 165: 1264A, 2001

7 Schlegel, P. N., Palermo, G. P., Goldstein,M. et al: Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia. Urology, 49: 435, 1997

8 Zumbe, J., Beintker, M., Denil, J. et al:MESA and TESE: experiences of the German section of urological microsurgery. Andrologia, suppl., 28: 89, 1996

9 Pavlovich, C. P. and Schlegel, P. N.: Fertility options after vasectomy: a cost-effectiveness analysis. Fertil Steril, 67: 133,1997

10 Heidenreich, A., Altmann, P. and Engelmann, U. H.: Microsurgical vasovasostomy versus microsurgical epididymal sperm aspiration/testicular extraction of sperm combined with intracytoplasmic sperm injection. Eur Urol, 37:609,2000

11 Kolettis, P. N. and Thomas, A. J., Jr.: Vasoepididymostomy for vasectomy reversal: a critical assessment in the era of intracytoplasmic sperm injection. J Urol, 158: 467, 1997

12 Donovan, J. F., Jr., DiBaise, M., Sparks,A. E. T. et al: Comparison of microscopic epididymal sperm aspiration and intracytoplasmic sperm injection/invitro fertilization with repeat microscopic reconstruction following vasectomy: is second attempt vas reversal worth the effort? Hum Reprod, 13: 387, 1998

13 Deck, A. J. and Berger, R. E.: Should vasectomy reversal be performed in men with older female partners? J Urol, 163:105, 2000

(State-of-the-art lecture on the topic of “Economic, Decision–making in Male Reproduction” was presented at the 2003 AUA meeting in Chicago on April 30, 2003. This article was originally published on AUANews, March 2003)


State-of-the-art lectures (on the topics of Male Infertility Treatment)


Iatrogenic Cause of Male Infertility

Dr. Christopher G. Schrepferman, Louisville, Kentucky


(The State-of-the-art lecture on this topic was presented at the 2003 AUA meeting in Chicago, April 30, 2003. This article was originally published on AUANews, March 2003)

Currently there are an estimated 6 million infertile couples in the United States alone, representing about 10% of adults of reproductive age. With appropriate evaluation male reproductive dysfunction is identified as the sole or contributing cause of subfertility in 50% of these couples. A small but clinically important subset of male patients is rendered subfertile as a direct result of previous medical or surgical therapy While in some instances iatrogenic decrease in male fertility is unavoidable (eg chemotherapy for malignancy), it frequently can be prevented.

Patients diagnosed with testicular cancer represent a particularly high risk group for iatrogenic impairment of fertility At baseline they have a higher incidence of semen abnormalities due to the disease itself with or without a history of cryptorchidism.1 Depending on clinical stage and histological findings, some patients will require adjuvant chemotherapy and/or radiotherapy, both of which may cause severe oligoasthenospermia or azoospermia. Because this toxicity may be irreversible, an patients requiring adjuvant therapy should be offered cryopreservation of sperm before treatment.

Other patients with testicular cancer may require retroperitoneal lymphadenectomy (RPLND) as part of the treatment regimen. During node dissection postganglionic sympathetic nerve fibers arising from the hypogastric plexus may be damaged, resulting in ejaculatory dysfunction, typically anejaculation. Use of a modified template dissection has been shown to preserve ejaculation in 80% to 90% of patients,2 and a meticulous nerve sparing dissection in skilled hands may decrease the risk of anejaculation even further. The risk of postoperative ejaculatory dysfunction is highest in patients who have received chemotherapy or who have bulky adenopathy clinical conditions that significantly increase the technical difficulty of the nerve sparing dissection.

Post-RPLND ejaculatory dysfunction, most commonly anejaculation, is typically managed with electroejaculation (EEJ). Occasionally retrograde ejaculation may be converted to antegrade ejaculation with the use of oral sympathomimetic medications. EEJ specimen quality may be adequate for intrauterine insemination. However, the relatively low monthly pregnancy rate (about 15%) and the need for general anesthesia with each EEJ prompt many couples to proceed directly to in vitro fertilization, a considerably more expensive but often more effective therapy.

Iatrogenic decrease in fertility potential has also been reported in patients who have undergone inguinal surgery, most commonly herniorrhaphy Ischemic atrophy of the testis is rare in primary repairs (less than 1%) but occurs in 5% of recurrent hernia repairs.3 Vasal obstruction, either by transection or more often compression of the inguinal vas, is far more common than vascular insult. Vasal transection is rare and, if recognized, may be treated with immediate microsurgical reconstruction. Vasal compression may result from improper intraoperative handling, improper mesh placement or delayed fibrosis of the mesh. To date no long-term studies on adult mesh hernia repair have investigated the effect of mesh on the inguinal vas, although case reports of inguinal obstruction from mesh herniorrhaphy have been published.4 Unfortunately attempts at vasal reconstruction are frequently futile secondary to extensive mesh related fibrosis and resultant devascularization of the vas.

Injury to the inguinal vas during pediatric hernia repair has been more clearly studied. Unilateral vasal injury occurs in approximately 10% to 15% of patients based on the reported 2% incidence of azoospermia in patients with a history of bilateral hernia repair in childhood.3 Unless the vasal defects are inordinately long, inguinal exploration and microsurgical reconstruction can be accomplished in the majority of cases. Because many of these patients have had long-standing obstruction, some may also require concomitant scrotal vasoepididymostomy for secondary obstruction.

Other inguinal surgeries of childhood, including orchiopexy and hydrocelectomy, are rarely associated with vasal injury. Scrotal surgery, either pediatric or adult, may also decrease fertility potential in male patients. During hydrocelectomy the vas or epididymis may be damaged inadvertently during plication of the tunica vaginalis. Rarely, a spermatocele or epididymal cyst may obstruct the epididymis before intervention but surgical excision of these lesions increases the risk of scarring and subsequent obstruction. Spermatocelectomy should be delayed until the patient is certain he no longer desires fertility.

In addition to surgical complications, some medical interventions can also inadvertently decrease male fertility. As mentioned previously, chemotherapeutic agents may temporarily or permanently damage the germinal epithelium. Hormonal therapy, typically testosterone, is occasionally incorrectly prescribed in an effort to improve sperm production. Normal spermatogenesis is dependent on adequate intratesticular levels of testosterone and well regulated pulsatile gonadotropin release. Exogenous testosterone replacement is occasionally prescribed in a misguided effort to increase intratesticular testosterone and, therefore, improve sperm production. However, exogenous testosterone use will reliably inhibit follicle-stimulating hormone and luteinizing hormone secretion, greatly decreasing or eliminating sperm production. Testosterone therapy is never an appropriate intervention in patients being treated for infertility. In patients in whom azoospermia develops during testosterone therapy prompt cessation of the hormone usually results in resumption of sperm production. Patients who are severely hypogonadal, including those with hypogonadotropic hypogonadism, should be treated with injectable gonadotropins in an effort to restore testosterone and sperm production.

Preservation of fertility may not be a critical concern for many patients being treated for serious medical conditions, especially malignancy. Nevertheless, iatrogenic reduction in fertility potential can often be prevented. Careful attention to surgical detail during retroperitoneal, inguinal and scrotal procedures can prevent inadvertent injury to sympathetic nerve fibers, vas deferens or epididymis. Because chemotherapy and/or radiotherapy may result in permanent sterility, it is imperative to offer sperm cryopreservation to all men before starting therapy. Fortunately, recent advances in urological microsurgery and assisted reproductive technology allow patients with even the most severe iatrogenic decrease in fertility to achieve paternity.

Reference:

1 Carrol, P. R, Whitmore, W. F, Herr, H. W. et al: Endocrine and exocrine profiles of men with testicular tumors before orchiectomy. J Urol, 137: 420, 1987

2 Richie, J. P.: Clinical stage I testicular cancer: the role of modified retroperitoneal lymphadenectomy. J Urol, 144: 160, 990

3 Wantz, G. E.: Complications of inguinal hernia repair. Surg Clin North Am, 64: 287,1984

4 Seifman, B. D., Ohi, D. A., Jarow, J. P. et al: Unilateral obstruction of the vas deferens diagnosed by seminal vesicle aspiration. Tech Urol, 5: 113, 1999

(The State-of-the-art lecture on this topic was presented at the 2003 AUA meeting in Chicago, April 30, 2003. This article was originally published on AUANews, March 2003)


2003 AUA First Prize Winner of the Best Video Award

1. Microsurgical Intussusception Vasoepididymostomy: Tricks of the Trade (Marc Goldstein,M.D., Peter TK, Chan, M.D. and Philip S. Li, M.D.:Microsurgical, 2003 AUA Abstract # V1450)



2. Reviewing the Cover Page Article on the Journal of Urology, Vol.169,1924-1929, May 2003.“ Microsurgivcal vasoepididymostomy: A prospective random study of 3 intussusception techniques in rats ( Peter TK. Chan, Philip S. Li and Marc Goldstein)

[For reviewing full text of this article please click this picture or “Cover Page Article" to PDF file of this article (fulltext.pdf)]





MICROSURGICAL INTUSSUSCEPTION VASOEPIDIDYMOSTOMY: TRICKS OF THE TRADE

Marc Goldstein, M.D., New York, NY
Peter T Chan, M.D., Montreal, PQ, Canada
Philip S Li, M.D., New York, NY


Introduction and Objective: Microsurgical vasoepididymostomy is the most technically challenging procedure for the treatment of obstructive azoospermia. We present three techniques of intussusception microsurgical vasovasostomy that allow precise mucosal approximation and an atraumatic, leak-proof anastomosis.

Methods: The abdominal end of the vas is transected using a slotted-never-cutting clamp and an ultra-sharp micro-knife to provide a perfect transverse cut. In the triangulation technique, 3 double-armed 10-0 monofilament nylon sutures double-armed with 70 urn diameter fishhook shaped tapered needles are placed in a dilated epididymal tubule in a triangular fashion. In the two-suture technique, 2 sutures are placed in a transverse fashion in the epididymal tubule. In our new 2-suture longitudinal technique. 2 sutures are placed longitudinally in the tubule. To avoid collapse of the tubule due to leakage of fluid, each needle is left in the tubule without pulling through, until all needles are placed. Microdot-mapping technique is used by placing 6 evenly distributed microdots on the cut surface of the vas deferens for the 3 sutures technique and 4 for the 2 suture techniques, indicating the exit points of the mucosal sutures. The epididymal tubule is opened with a 15-degree microknife in the direction of the needles. The fluid is examined microscopically for sperm and cryopreservation. Upon tying the sutures, the epididymal tubule intussuscepts into the vasal lumen. The epididymal tunic and vasal sheath are approximated with 8-12 sutures of 9-0 nylon.

Results: The average operating time per anastomosis was 2 hours. The outcomes of the surgery in 54 consecutive men with obstructive azoospermia revealed a patency rate (sperm count > 10,000/ml) at 14 months post-op of 84%, with a crude pregnancy rate of 40%.

Conclusions: The advantages of the intussusception techniques over conventional end-side vasoepididymostomy are: 1) fewer micro-needles are required; 2) all needles can be easily placed in a distended epididymal tubule before opening. Furthermore, our longitudinal 2-suturc intussusception technique greatly simplifies the procedure and allows a larger epididymal luminal opening for anastomosis. Although a relative longer operating time and more meticulous techniques are required, a high patency rate and naturally conceived pregnancy rate are possible.

“This presentation is extremely well done with excellent visual presentation of the procedure. Congratulations on the production of this material. It is a first rate presentation!”
Arnold Belker, M.D.
Clinical Professor of Urology
Division of Urology
University of Louisville School of Medicine
Louisville, Kentucky


“These beautifully produced film are as close as you can get to being there, without actually sitting next to an experienced microsurgeon in the operating room.”
Zev Rosenwaks, M.D.
Revlon Distinguished Professor of Reproductive Medicine
Director of the Center for Reproductive Medicine and Infertility
The Weill Medical College of Cornell University


“This is the ideal way to illustrate how this operation is performed. Any experienced urologists or urologists in training can benefit greatly from this teaching series.”
E. Darracott Vaughan, M.D.
James J. Colt Professor of Urology and Chairman Emeritus of Urology
The Weill Medical College of Cornell University



For more information, please contact us at psli@med.cornell.edu.


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