Fertility options after vasectomy: a cost-effectiveness analysis

Transcription

1 FERTILITY AND STERILITY '~v Vol. 67, No. 1, January Ct~pyright ' 1997 American Sf)eiety tbr Rep,'~Jductive Medicine Printed on acid-free paper in U. S. A. Fertility options after vasectomy: a cost-effectiveness analysis Christian P. Pavlovich, M.D.* Peter N. Schlegel, M.D.*iS The New York Hospital-Cornell Medical Center, and The Population Council, New York, New York Objective: To evaluate cost per delivery using two different initial approaches to the treatment of postvasectomy infertility. Design: Model of expected costs and results in the United States in Setting: Men with postvasectomy infertility, evaluated and treated at centers with experience in vasectomy reversal or sperm retrieval and ICSI. Patient(s): Men with postvasectomy infertility, with a female partner - 39 years of age. Intervention(s): 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. Main Outcome Measure(s): Cost per delivery, delivery rates. Result(s): Cost per delivery with an initial approach of vasectomy reversal was only $25,475. (95% confidence interval $19,609 to $31,339), with a delivery rate of 47%. However, the cost per delivery after sperm retrieval and ICSI was $72,521. (95% confidence interval $63,357 to $81,685 }, with an average of $73,146 for percutaneous or testicular sperm retrieval and $71,896 for surgical epididymal sperm retrieval. The delivery rate after one cycle of sperm retrieval and ICSI was 33c~. Conclusion(s): 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. Fertil Steril <~ 1997;67: Key Words: Sperm retrieval, vasectomy reversal, IVF, intracytoplasmic sperm injection, vasovasostomy Vasectomy is a safe and effective form of birth control that is used by up to 13% of all married couples in the United States (1). Vasectomy reversal subsequently is requested by 2% to 6% of men after the contraceptive procedure to restore their fertility (2). The high pregnancy rates (PRs) obtained with assisted reproduction in conjunction with sperm retrieval (3) have raised the question of whether vasectomy reversal is necessary. The most advanced assisted reproductive procedure for male factor infertility is intracytoplasmic sperm injection (ICSI), in which PRs from 18% to 41% per attempt have Received April 4, 1996; revised and accepted August 27, * James Buchanan Brady Foundation, Department of Urology, The New York Hospital-Cornell Medical Center. t The Population Council, Center for Biomedical Research. Reprint requests: Peter N. Schlegel, M.D., Room F-905A, Department of Urology, The New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, New York {FAX: ). been reported at different centers (4). Less invasive techniques for sperm retrieval, including percutaneous retrieval from the epididymis (5) and extraction of spermatozoa from the testis (6, 7) have stimulated the consideration of assisted reproduction as a primary treatment for all cases of postvasectomy infertility. Vasectomy reversal is very different from assisted reproduction with ICSI using retrieved spermatozoa. Vasectomy reversal involves an open scrotal surgical procedure and requires microsurgical expertise to achieve optimal results, but does not require treatment of the female partner for most couples (8, 9). Pregnancy after vasectomy reversal usually occurs after sexual intercourse, not assisted reproduction. As the interval of time after the vasectomy procedure increases, the risk of secondary epididymal obstruction increases. If epididymal obstruction is present, then a microsurgical vasoepididymostomy is required, after which sperm may not return to the ejaculate for 6 months to 2 years or longer Vol. 67, No. 1, January 1997 Pavlovich and Schlegel Postvasectomy infertility cost analysis 133

2 postoperatively (9). However, children will be conceived naturally after these procedures, and subsequent children may be born without additional intervention. Unlike vasectomy reversal, sperm retrieval with assisted reproduction involves procedures on both partners with their attendant risks of complications. Although sperm retrieval can be performed with minimal morbidity, the female partner must agree to extensive hormonal as well as procedural manipulation to have a chance at pregnancy. Given, these controversies in the management of men who are interested in having fertility restored after vasectomy, we analyzed the expected results of two different treatment approaches. The outcomes that we chose to evaluate were the delivery rates obtained and 1994 U.S. cost per delivery via assisted reproduction and sperm retrieval versus those achieved by vasectomy reversal alone. Overview of Model MATERIALS AND METHODS Models were created to estimate the average cost for delivery of at least one child for a couple with postvasectomy infertility in the United States. Each model used published data for pregnancy and delivery rates as well as costs of treatment at these centers. Where actual costs were not available, patient charges were used as costs. The definitions used for formulation of the model of costs per delivery after vasectomy reversal or sperm retrieval with ICSI are detailed below. Definitions Vasectomy Reversal Vasectomy reversal was defined as the procedure of performing a microsurgical reconstruction of the male reproductive tract to bypass the iatrogenically induced vasal obstruction of vasectomy and its subsequent effects, including epididymal obstruction. Therefore, the surgical procedures of microsurgical vasovasostomy or vasoepididymostomy would be required for vasectomy reversal. Sperm Retrieval For assisted reproduction after vasectomy, sperm must be retrieved from the testis, epididymis, or vas deferens. The most common published approach involves microsurgical epididymal sperm aspiration (3, 10-13). This procedure involves an open surgical approach with local or general anesthesia. Alternative approaches of epididymal or testicular sperm extraction may be less invasive, do not require mi- crosurgical skills, and often are performed under local anesthesia (3, 5-7). The results for percutaneous and testicular sperm retrieval were considered together. Because published success rates for sperm retrieval and ICSI were similar after vasectomy or in men with congenital absence of the vas deferens (12), series including both etiologies of obstruction were taken together. Intraeytoplasmic Sperm Injection A cycle of IVF was defined as the process of ovarian stimulation, monitoring of ovarian response with serial pelvic ultrasound evaluations and serum E2 determinations, oocyte retrieval via a transvaginal approach with ultrasound guidance, in vitro ICSI, and transfer of the fertilized oocytes (embryos). The micromanipulation technique of ICSI can be performed only during an IVF cycle. Intracytoplasmic sperm injection has been demonstrated to have clear superiority over IVF alone for the management of surgically retrieved epididymal sperm (11, 12). Because ICSI requires IVF so that eggs and sperm can be micromanipulated together in vitro, we will use the term ICSI instead of IVF and ICSI for simplicity and clarity. The outcome of live birth was chosen for two reasons. Although most reports of the success of assisted reproduction refer to pregnancies, the close observation of patients after IVF detects pregnancies that are reflected only as elevated serum 13-hCG levels tbiochemical pregnancy) or pregnancies that can be detected with an intrauterine fetal heart beat (clinical pregnancy) with subsequent spontaneous abortion. Pregnancy and Deliveo, Rates Contemporary IVF PRs were obtained from published data for IVF centers in the United States with experience in the application of ICSI t4/ to allow comparison with published microsurgical epididyreal sperm aspiration-icsi PRs 11-13). Data from the U.S, sites were confirmed by direct telephone contact with each IVF center and are collated in Table 1. A literature search was performed on CDP Colleague I CDP Technologies, New York, NYI using "vasectomy" and "reversal" as the key search words, for references in the English language. To evaluate expected PRs after vasectomy reversal, the proportion of patients who required bilateral microsurgical vasovasostorny (96%), unilateral vasovasostomy and contralateral vasoepididymostomy (3%), and bilateral microsurgical vasoepididymostomy (1%) for first-time vasectomy reversal were obtained from the single largest study of vasectomy reversal in the United States, the multicenter vasovasostomy study 134 Pavlovich and Schlegel Postvasectomy infertility cost analysis Fertility and Sterility '~

3 Table 1 Pregnancy Rates for Four ICSI Progn'ams in the United States* Center No. of cycles Clinical PRt Delivery rate A /163 (30.6} 27.6 B 91 28/91 (30.7} 27.6 C /229 (16.6) 17.7 D /227 (41.4} 37.0 Overall results /710 (29.6} (25 to 31}$ * Data adapted fi'om Schlegel (4~. t Values in parentheses are percentages. $ Values in parentheses are 95~ CIs. gxoup (8). All references and publicly available data were reviewed to detect any studies that may contribute additional data for evaluation of vasectomy reversal success rates. For microsurgical vasoepididymostomy, five of the largest contemporary treatment series from the United States were culled and used to estimate PRs for microsurgical vasoepididymostomy (14-18). For microsurgical vasovasostomy, results of the U.S. multicenter vasovasostomy study group (8) and a separate large series of consecutively treated patients (9) were used to estimate PRs for vasectomy reversal. Success rates were broken down further based on the time since vasectomy: <3 years, 3 to 8 years after vasectomy, 9 to 14 years after vasectomy, and > 15 years after vasectomy. Pretreatment Costs It was assumed that all men would require pretreatment evaluation before vasectomy reversal or sperm retrieval with an initial consultation (procedure code 99245), serum FSH (procedure code 83000), and T (procedure code 84403). For women, before an ICSI cycle, each IVF center proscribed a series of required evaluations. Because a single evaluation may allow preparation for two or three different ICSI procedures, the pretreatment costs were divided by three and added to the procedural cost for each ICSI cycle. Intracytoplasmic Sperm Injection Costs In vitro fertilization procedural costs were obtained from four well-known U.S. centers with published experience in ICSI for male factor infertility (4). Each center was contacted to obtain cost and PRs for contemporary ICSI procedures in It was assumed that the female partner would not require additional evaluation beyond that required by the IVF centers. The cost of male and female evaluation specifically for IVF required by each 1-VF center, as well as medications, monitoring, oocyte retrieval, laboratory fees (including ICSI), and transfer fees were all considered. The costs of IVF complications were adjusted, based on whether they occurred per pregnancy (e.g., obstetric complications) or per oocyte retrieval (e.g., pelvic hemorrhage, infection). The cost for treatment of complications was estimated based on available published data (4, 19, 20). The cost of IVF procedures was adjusted downward for failure of ovarian stimulation, based on published U.S. statistics for IVF cycle cancellation rates (21). Vasectomy Reversal and Sperm Retrieval Costs Vasectomy reversal and sperm retrieval fees were determined similarly by telephone survey of specialists who have published their results from the United States. Average anesthesia fees and ambulatory surgery charges also were obtained by telephone survey for the site where each surgeon performed vasectomy reversal procedures. Charges were obtained for microsurgical epididymal sperm aspiration, microsurgical vasovasostomy, and microsurgical vasoepididymostomy. For microsurgical epididymal sperm aspiration, anesthetic quotes were not available. Therefore, the 50th percentile national charge for anesthetic time (22) was applied to average anesthetic procedure time at one institution ( 11 ) to derive nationwide average costs of anesthesia for microsurgical epididymal sperm aspiration. The costs for a procedure were assumed to equal patient charges. Direct evaluation of cost per delivery was possible for each center performing vasectomy reversal, because both costs and PRs were available for each institution for vasectomy reversal. Cost per Delivery The only outcome of value to the treated couple is to achieve the delivery of one or more live children. Because multiple births are common after assisted reproductive interventions, we used the outcome of delivery, not the number of live births obtained. That is, achieving a live single birth for two different cotples is of much greater value as an outcome than achieving a twin birth for one couple. Therefore, we have used the outcome of live delivery to avoid confusion in considering multiple births separately. The total cost per live delivery was defined as the resultant costs of an intervention (vasectomy reversal versus ICSI with sperm retrieval)divided by the live delivery rate that can be attributed to the specific intervention. Pregnancy rates for ICSI were obtained for procedures primarily performed during 1994, so all charges were evaluated based on 1994 costs. Where ICSI success rates were discriminated by Vol. 67, No. 1, January 1997 Pavlovich and Schlegel Postvasectomy infertility cost analysis 135

4 female partner age, only results where the female age was <--39 years old were used. Adjustments of 10% spontaneous abortion rates were applied to clinical PRs when only the latter were available, based on previously published data for miscarriage rates after ICSI, to approximate delivery rates (4). This 10% spontaneous abortion rate also was applied to PRs reported after vasectomy reversal procedures to determine live delivery rates. Where ongoing and delivered pregnancies were reported together, it was assumed that ongoing and delivered pregrmncies were equivalent for ICSI results. After considering pretreatment evaluation costs, procedural costs, cost for treatment of complications, time lost from work, and delivery costs, the sum was added together and divided by the treatment-specific delivery rate for each treatment approach. Complications a~d Lost Work Time There are well-recognized complications of IVF as well as vasectomy reversal. In vitro fertilization is associated with the ovarian hyperstimulation syndrome, vaginal and pelvic hemorrhage after oocyte retrieval, pelvic infection, and multiple gestations ~4, 20). In addition, an increased risk of obstetric and pediatric complications has been observed, even after singleton pregnancies resulting from IVF. Estimates for complication rates were obtained from published data (20). Complications for vasectomy reversal were estimated based on published data and personal experience (Schlegel P, personal communication). Risks of vasectomy reversal primarily include bleeding, infection, testicular atrophy, and risks of anesthesia. The time out of work for recovery after vasectomy reversal and complications as well as 1VF-related obstetric complications were accounted for using a median income rate of $22,000 per year for women and $30,000 per year for men (U.S. Bureau of the Census, CD-ROM, "Income and Poverty, 1993.") Average obstetric, neonatal, and hospital costs for a singleton delivery, twin delivery, and triplet delivery were obtained from published costs (19). For each treatment, the proportion of attempts that would result in multiple gestation deliveries was estimated for ICSI (4). The delivery cost was obtained by factoring in the delivery rate and multiplicity of gestation. Statistical Analysis Cost per delivery figures were obtained by calculating average total costs and dividing by the specific delivery rate for each center. Average costs per delivery for each treatment were figured by weighting the cost per delivery at each center with the number of procedures performed at the center. Ninety-five percent confidence intervals (CI) then were calculated based on these data. Confidence intervals and other statistical evaluation was performed on Statgraphics computer software (Statistical Graphics.Corporation, Princeton, NJ). For ICSI costs, the charge at each IVF center was weighted based on the number of procedures performed in the published study to reflect more accurately charges per ICSI procedure in the United States. Pregnancy Rates RESULTS Vasovasostomy PRs varied <5c~ between six different centers and averaged 53% (95% CI 50%, to 54%) 8, 9)(Belker A, personal communication). Vasoepididymostomy PRs were 12%, 18c~, 27%, 42%, and 56%, with an arithmetic mean of 31%, but a weighted average PR of41% (95c~ CI 32% to 50%) (14-18). These data provided an overall vasectomy reversal PR of 52%, and an estimated live delivery rate of47% (95% CI 45% to 49%; Table 21 Microsurgical epididymal sperm aspiration PRs were 48%, 47%, and 36%,/11-13), with an average clinical PR of 44% and an estimated live delivery rate of 40%. Percutaneous sperm aspiration from the epididymis with ICSI has a published PR of 24% per attempt (5), whereas testicular sperm retrieval resulted in clinical pregnancies for 33 and 42c/c of attempts (6, 7), for an average PR of 33c~ and an estimated delivery rate of 30%. Overall, sperm retrieval and ICSI procedures had a mean weighted delivery rate per attempt of 33% (95% CI 26~ to 43%). Costs The average charge for vasectomy reversal (pretreatment evaluation, surgeon's fee, anesthetic, and associated ambulatory charges, weighted for the number of procedures performed at each center t8, 9, 14-18) was $6,938/Table 2), far greater than the 50th percentile surgical f~e for bilateral vasovasostomy reported in the United States, $1,385 (22). For microsurgical epididymal sperm aspiration, an average surgical fee of $3,000 was determined, and percutaneous aspiration of the testis or epididymis was assigned a procedure fee of $1,000. Anesthetic fees were $271 for microsurgical epididymal sperm aspiration, and ambulatory surgical fees for microsurgical epididymal sperm aspiration were $1,058. Costs of Complications Postoperative surgical complications occur in 1% to 2%, of all vasectomy reversal or microsurgical epi- 136 Pavlovich and Sehlegel Postvasectomy infertility cost analysis Fertility arid Sterility"

5 Table 2 Calculations for Cost per Delivery After Vasectomy Reve,'sal and Sperm Retrieval-ICSI Vasectomy reversal cost Sperm aspiration costs Bilateral vasovasostomy Bilateral vasoepididymostomy Percutaneous and testicular sperm,-etrieval-icsl Microsurgical epididymal sperm aspiration-icsi u.s.$ u.s.$ Pretreatmeat evaluation Surgical fee Anesthetic fee 6,782"t 13,051"t Ambulatory surgery fee Complication costs Lost work costs Delivery costs 4,726 3,686 ICSI-associated costs 0 0 Total costs 11,922 17,151 Cost per delivery*ll $24,838 $50,336 Range 16,021 to 31,096 40,672 to /, confidence interval 19,020 to 30,653 42,613 to 58,059 Vasectomy reversal Cost per delive~y*$ 25,475 Range 16,637 to 32, ~ confidence interval 19,609 to 31,339 U.S.$ U.S.$ ,000 3, ,058 54$ ,951 11,883 11,097 11,201 20,347 28,072 $73,146 $71,896 62,524 to 85,841 67,374 to 80, to 87,393 60,881 to 80,649 Sperm retrieval-icsi 72,521 62,524 to 85,841 63,357 to 81,685 * Weighted fro" the number of procedures reported for each center. -Includes pretreatment evaluation, surgical, anesthetic, and ambulatory surgical fees. $ Calculations for this figure are detailed in the Results section. Examples of the calculations for delivery and ICSI-associated costs ave provided in the Results section and in Table 3. II Cost per delivery for each treatment was calculated for individual centers providing the treatment and then combined as a weighted average. didymal sperm aspiration procedures with up to lc2 of procedures requiring re-exploration for hematoma or infection. Charges for re-exploration were assumed to include scrotal exploration (procedure code with a 50th percentile U.S. charge of $ ). In-hospital charges were assumed to double the ambulatory fee laveraged actual charges from four of the polled centers) for vasovasostomy because of the required overnight stay ($1,446 2 = $2,892/ per complication. Similar anesthetic charges to the vasovasostomy procedure ($1,435) were assumed for any re-exploration. An additional cost for 4 additional days of lost work are estimated at (4 days $15/h 8 h/d) $480. Total costs for treatment of a complication are estimated at ( , , ) $5,401; for each procedure, 1~ of $5,401 ($541 was assigned as the cost of complications. There are no published reports of hematoma requiring evacuation after percutaneous procedures on the testis or epididymis, although intratesticular hematomas are common. It may be that the rate of hematoma development requiring exploration after percutaneous fine needle aspiration of the testis is as high as 1:28 (4%) (Schlegel P, personal communication). Therefore, the risks and costs of complications after percutaneous sperm retrieval were assumed to be the same as after microsurgical epididymal sperm aspiration and vasectomy reversal. Lost Work Costs For each procedure involving scrotal exploration, 3 days of lost work were assumed for each man, based on the recovery requirements for similar procedures (4). For vasovasostomy, vasoepididymostomy, and microsurgical epididymal sperm aspiration, each man was assumed to have costs attributed to this lost work time of ($15/h 8 h/d 3 d) $360. Table 3 Effect of Different Delivery Rates on Cost of ICSI Assumed PR (q i Delivery costs IU.S.$1 Singleton 155q; I 1,624 2,166 Twin (35c/~) 3,984 5,313 Triplet { 10q; ~ 3,293 4,391 Total delivery costs Iu.s.$1 8,901 11,870 Weighted delivery costs (U.S.$~ 7,951" 11,8834 ICSI-associated costs I U.S.$1 ICSI procedure 11,818 11,818 Major maternal complications Minor maternal complications Time off work for multiple gestations Adjustment for failed stimulations -1,099-1,099 Total ICSI-associated cost per cycle (U.S.$) 11,122 11,201 Weighted ICSI-associated costs (U.S.$) 11,097" 11,201"~ * Weighted average figure obtained for centers reporting percutaneous and testicular sperm retrieval-icsi results. t Weighted average figure obtained for cente,-s reporting microsurgical epididymal sperm aspiration-icsi results. Vol. 67, No. 1, January 1997 Pavlovich and Schlegel Postvasectomy infertility cost analysis 137

6 This calculation was based on median male income in the United States, as indicated in the Materials and Methods section. Delivery Costs Overall inpatient charges for delivery of a singleton gestation were $9,845, whereas twin gestations increased the cost to $37,947 and triplet gestations cost an average of $109,765 (19). Forty-five percent of all ICSI pregnancies are multiple gestations, with 35% twin and 10% triplet or higher order prdgnancies (4). Therefore, for example, the cost per IVF cycle attributable to triplet gestations with an ICSI delivery rate of 30% was 0.30 x $109,765 x 0.10 = $3,293. The delivery cost attributable to twin gestations with an ICSI delivery rate of 30% was 0.30 z $37,947 x 0.35 = $3,984, and the delivery cost attributable to singleton gestations for an ICSI PR of 30% was 0.30 x $9,845 x 0.55 = $1,624. Delivery costs for an ICSI delivery rate of 30% were then ($3,293 + $3,984 + $1,624) $8,901 (Table 3). For naturally occurring pregnancies, multiple gestations are rare. Therefore, for example, the delivery cost attributable to pregnancies occurring naturally after each procedure of microsurgical vasovasostomy (with a delivery rate of 48%) was calculated as $9,845 x 0.48 = $4,726 (Tables 2 and 3). Intracytoplasmic Sperm Injection-Associated Costs The average ICSI procedural charge per cycle was $11,324, with individual center costs of $10,000, $10,492, $11,425, and $13,380, In addition, one third of the cost of required pretreatment evaluation of $1,482 ($494) was added to each cycle for a total of $11,818 (4). There are evaluable costs of known complications specific to IVF, in addition to the costs of multiple gestations, such as ovarian hyperstimulation and bleeding or infection after oocyte retrieval. Major maternal complications occur in 0.2% of cycles, with an estimated cost of $20,000 per complication. Minor maternal complications occur in 5~ of cycles, with an estimated cost of $2,500 per minor complication (20). Attributable costs of complications per IVF cycle are ($20,000 x 0.002) $40 and ($2,500 x 0.05) $125. Each multiple gestation resulted in maternal time lost from work. An average of 4 weeks duration of lost work time was applied for each cycle with multiple gestations (20), adjusted for delivery rates, as illustrated in Table 3. (For a 40% delivery rate; $11/ h x 40 h/wk x 4 wk 0.40 delivery/cycle x 0.45 multiple gestations/delivery = $317.) Failure of oocyte stimulation occurs in 12.4% of attempted cycles (21). Because failed stimulation results in a cancella- tion of the cycle, the cost per cycle was adjusted downward to account for the 75% of total IVF costs that are derived from the retrieval procedure and postretrieval treatment of IVF patients (20}. This adjustment was subtracted from ICSI procedural costs, costs of complications, and cost of time lost "from work to obtain the figure for ICSI-associated costs ($11,818 x x 0.75 = $1,099; Table 3). Intracytoplasmic sperm injection-associated costs and delivery costs were calculated for each center, because these values are dependent on the delivery rate at each center. To combine ICSI-associated costs and delivery costs from different centers, a weighted average was used to correct for the different number of procedures (vasectomy reversal, sperm retrieval) performed at each center (Table 2). Because of the weighting process, a weighted value for delivery costs and ICSI-associated costs may differ slightly from a single calculation that is based on an average delivery rate alone, as illustrated in Table 3. The effect of different delivery rates on delivery costs and ICSI-associated costs also is depicted in Table 3. Cost per Delivery and Delivery Rates The cost per delivery after vasectomy reversal included costs for bilateral vasovasostomy, as presented above, divided by delivery rate, and multiplied by 0.96, because only 96c~ of patients would have bilateral vasovasostomy (8). Similar calculations were performed for the 3~ of men who would require unilateral vasovasostomy and contralatera vasoepididymostomy, as well as the 1% of men who would require bilateral microsurgical vasoepididymostomy to obtain the total cost per delivery after vasectomy reversal. Therefore, cost per delivery after vasectomy reversal was calculated as [($24, ) + 1($24,838 + $50,336)/2 x 0.03] + ($50,336 x 0.01) = $25,475. The overall cost per delivery for sperm retrieval was calculated as a weighted average for each center publishing results on PRs after sperm retrieval-icsi. The cost per delivery after vasectomy reversal of $25,475 (95% CI $19,609 to $31,339) (Table 2) was far less than the overall $72,521 (95% CI $63,357 to $81,685) obtained for sperm retrieval and ICSI. For percutaneous or testicular sperm retrieval, the average cost per delivery was $73,146, whereas a cost per delivery of $71,896 was obtained after surgical sperm retrieval (microsurgical epididymal sperm aspiration) and ICSI. A range of costs per delivery after vasectomy reversal could be characterized further based on the interval after vasectomy (Table 4). Depending on the interval after vasectomy, the expected range of cost 138 Pavlovich and Schlegel Postvasectomy infertility cost analysis Fertili O, and Sterility'"

7 Table 4 Analysis of Effect of Time After Vasectomy on PRs and Cost per Delivery After Vasectomy Reversal Time after vasectomy PR Cost per delivery ' ~ U.:~.$ <3 years 68 20,594 3 to 8 years 48 25,072 9 to 14 years 40 28,118 --~ 15 years 27 36,915 per delivery after vasectomy reversal varied from $20,594 to $36,915 because of the increased prevalence of secondary epididymal obstruction with greater time after vasectomy. The average delivery rate achieved from a single intervention was 47% after vasectomy reversal and 33c~ after sperm retrieval and ICSI. Based on the technique for sperm retrieval, delivery rates were 40~ after microsurgical epididymal sperm aspiration-icsi and 30c~ after percutaneous or testicular sperm retrieval and ICSI. DISCUSSION Intracytoplasmic sperm injection has revolutionized the treatment of men with severe male factor infertility (4). Intracytoplasmic sperm injection also has been found to improve dramatically the results for treatment of men who require surgical sperm retrieval because of obstructive azoospermia (11, 12). Although traditional treatment of men with reconstructible obstructive azoospermia has involved microsurgical reconstruction, we felt that it would be timely to compare this traditional therapy with the results obtained after sperm retrieval and ICSI. To consider adequately the benefits of each procedure, we used both a cost analysis as well as crude delivery rates that could be expected after these interventions. A cost analysis is important, because any third party payer that decides to provide coverage for infertility treatment must consider all direct and indirect costs incurred by the initial treatment choice. Any model of medical treatment or costs may be subject to variability because of inaccuracies in the model. To most accurately reflect real costs, we used actual pregnancy and delivery rates obtained from published series of treated patients. Where adequate data were able to be gathered from U.S. treatments, those costs were used. Because very similar results are obtained in the United States and Europe for advanced fertility treatments (5-7, 11-13), European series also were used for pregnancy and delivery rates when inadequate U.S. data were available. To provide cost information applicable in the United States, we used a telephone survey of specialty cen- ters that had published their results of fertility treatment to avoid any bias in assigning average U.S. charges for assisted reproduction or microsurgical vasectomy reversal procedures. Calculation of 95% confidence intervals in this manuscript, as with similar multicenter evaluations of cost-effectiveness (20/, is dependent on the assumption that charges for different patients within an individual center are relatively uniform. The exact calculation of confidence intervals also assumes that data are distributed normally. To better describe the distribution of cost per delivery figures used in this manuscript, we included ranges as well as 95% confidence intervals. To validate the assumptions in our model of treatment for the couple after vasectomy, we have performed calculations of cost per delivery for vasectomy reversal versus sperm retrieval-icsi using a wide variety of different initial assumptions. This sensitivity analysis has demonstrated clearly that a dramatic improvement in cost per delivery as well as delivery rates is maintained for couples with postvasectomy infertility who chose vasectomy reversal over sperm retrieval-icsi. The nearly threefold decrease in cost per delivery with vasectomy reversal strongly supports the dramatic benefit for vasectomy reversal over sperm retrieval-icsi demonstrated in this study. Whereas recent Society for Assisted Reproductive Technology Registry data suggest a national average delivery rate of 17% per cycle for male factor infertility (21}, individual clinic results vary dramatically. A limited number of U.S. IVF clinics have documented high PRs after ICSI (4)(Table 1). To estimate most accurately the true cost of ICSI at a center that has favorable pregnancy results, we directly contacted these centers to obtain the fees that actually are charged to each patient. Data on charges were gathered by one individual with a significant background in medicine and infertility, as well as extensive practical experience in an IVF center. This assured an accurate compilation of all costs and charges for IVF: cost of medications, monitoring during ovarian stimulation, oocyte pick-up, and laboratory charges, as would be charged for a prospective patient. Previous estimates of national IVF charges in the United States have been $6,233 to $8,000 (20, 23). Our data clearly indicate that these prior published cost estimates do not reflect accurately the cost ($11,324) that a couple would incur with treatment at one of the documented successful treatment centers for ICSI in the United States. Similarly, the average charges for vasectomy reversal at the published centers in this study were far higher than one might expect from previously published national data on vasovasostomy fees (22). The relatively high procedural costs of ICSI are a Vol. 67, No. 1, January 1997 Pavlovich and Schlegel Postvasectomy infertility cost analysis 139

8 major component of the cost per delivery with sperm retrieval and ICSI. However, one cost that does not decrease as PRs improve is the cost of multiple gestations. As pregnancy and delivery rates increase, these costs increase as well. Without voluntary restraint or regulation of the number of embryos transferred during IVF, multiple gestations will continue. Unfortunately, multiple gestations routinely result in prematurity and its associated perinatal morbidity, with resulting high costs for neonatal care (19). These indirect costs of IVF often are not consrtered by infertility specialists or patients before the establishment of nmltiple gestations in the desperate venture to obtain a pregnancy. To limit multiple gestations, some countries have instituted national policies to limit the number of embryos that can be transferred. These measures allow a dramatic decrease in multiple gestations and associated perinatal morbidity and mortality 124). Transfer of more than three embryos does not increase the chance of a singleton pregnancy (25/. However, such multiple ETs do significantly increase the chance of multiple gestations. Previous cost analyses of ICSI for male factor infertility in the United States have shown that higher PRs do not dramatically decrease the cost per delivery with this treatment, in large part because of the high cost of multiple gestations 141. The risk of multiple gestations may limit application of this important technology. The initial treatment analysis in this paper does not provide for deliveries in all couples with a single procedure or treatment. However, sperm retrieval and cryopreservation is possible during microsurgical vasectomy reversal as well as microsurgical epididymal sperm aspiration. To avoid multiple procedures for sperm retrieval, it is necessary to make a concerted effort to acquire and freeze sperm during the vasectomy reversal procedure ( 3 ). This will allow nearly all couples to have a good opportunity to achieve a pregnancy and subsequent delivery, unless female factors prevent the successful application of ICSI. In the unusual case in which female factors would prevent a couple from having any chance of natural conception, then direct sperm aspiration with ICSI would be more appropriate than vasectomy reversal. The discovery and subsequent widespread application of ICSI has been of tremendous importance for the treatment &men with severe male infertility or who require surgical sperm retrieval. As with any new technology, the application of ICSI must find its appropriate place in the armamentarium of physicians who treat infertility. Unless microsurgical epididymal sperm aspiration results dramatically improve or ICSI procedural costs and multiple gestation rates decrease, vasectomy reversal will remain the primary recommended initial treatment for men who request re-establishment of fertility after vasectomy. Vasectomy reversal remains a highly successful and cost-effective treatment for men interested in restoration of fertility after vasectomy. Acknowledgments. The authors are indebted to Peggyann King, R.N., for telephone interviews and compilation of data on PRs and IVF costs. Important insight into anesthetic and ambulatory surgical billing practices was provided by Ms. I~-isten Adams of Cornell University Medical College. The authors also thank all of the centers that were forthcoming in providing information on their charges for fertility services. Appreciation is also extended to Martin L. Lesser, Ph.D., Di~4sion of Biostatistics at North Shore University Hospital, Manhasset, New York for his thoughtful contributions and independent statistical review of this manuscript. REFERENCES 1. National Health and Nutrition Examination Survey (U.S.). Epidemiologic Ibllowup study tnhanes). Hyattsville, MD: U.S. Department of Health and Human Services, Fenster H, McLoughlin MG. 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