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Sperm cryopreservation and in vitro fertilization/intracytoplasmic sperm injection in men with congenital bilateral absence of the vas deferens: A success story

2004; Elsevier BV; Volume: 82; Issue: 5 Linguagem: Inglês

10.1016/j.fertnstert.2004.05.079

1556-5653

Jennifer T. Anger, Gerald Wang, Stephen A. Boorjian, Marc Goldstein,

Assisted Reproductive Technology and Twin Pregnancy

In this study we evaluate the use of cryopreservation of sperm obtained at the time of surgical exploration in men with congenital bilateral absence of the vas deferens. We assess the impact of cryopreservation on pregnancy rates after IVF/intracytoplasmic sperm injection. Intraoperative cryopreservation of sperm at the time of microsurgical epididymal sperm aspiration in men with congenital bilateral absence of the vas deferens resulted in a 100% live delivery rate per couple, providing the highest pregnancy rates of any infertility treatment. In this study we evaluate the use of cryopreservation of sperm obtained at the time of surgical exploration in men with congenital bilateral absence of the vas deferens. We assess the impact of cryopreservation on pregnancy rates after IVF/intracytoplasmic sperm injection. Intraoperative cryopreservation of sperm at the time of microsurgical epididymal sperm aspiration in men with congenital bilateral absence of the vas deferens resulted in a 100% live delivery rate per couple, providing the highest pregnancy rates of any infertility treatment. Congenital bilateral absence of the vas deferens (CBAVD) is a relatively rare cause of male factor infertility that occurs in 1 in 1,000 men in the population (1Phillipson G. Petrucco O. Matthews C. Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection.Hum Reprod. 2000; 15: 431-435Crossref PubMed Scopus (48) Google Scholar). It is found in 1% of patients attending male infertility clinics (2Okada H. Yoshimura K. Fujioka H. Tatsumi N. Gotoh A. Fujisawa M. et al.Assisted reproduction technology for patients with congenital bilateral absence of the vas deferens.J Urol. 1999; 161: 1157-1162Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) and affects approximately 2% of men with azoospermia (2Okada H. Yoshimura K. Fujioka H. Tatsumi N. Gotoh A. Fujisawa M. et al.Assisted reproduction technology for patients with congenital bilateral absence of the vas deferens.J Urol. 1999; 161: 1157-1162Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 3Donat R. McNeill A. Fitzpatrick D. Hargreave T.B. The incidence of cystic fibrosis gene mutations in patients with congenital bilateral absence of the vas deferens in Scotland.Brit J Urol. 1997; 79: 74-77Crossref PubMed Google Scholar). Men with CBAVD have a form of obstructive azoospermia not amenable to surgical correction (4McCallum T.J. Milunsky J.M. Cunningham D.L. Harris D.H. Maher T.A. Oates R.D. Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes.Chest. 2000; 118: 1059-1062Crossref PubMed Scopus (66) Google Scholar) and must therefore rely totally on assisted reproduction to achieve pregnancy. Fertilization with intracytoplasmic sperm injection (ICSI) has greatly expanded the indications for cryopreservation of sperm in these men (5Palermo G. Joris H. Devroey P. Van Steirteghem A. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte.Lancet. 1992; 340: 17-18Abstract PubMed Scopus (2853) Google Scholar). In this study, we evaluated the outcomes associated with the use of cryopreserved epididymal sperm obtained at the time of microsurgical epididymal sperm aspiration (MESA) in men with obstructive azoospermia (OA) due to CBAVD. We assessed the impact of cryopreservation on pregnancy rates. The records of 30 consecutive men with OA due to CBAVD who underwent open MESA were retrospectively reviewed in accordance with the Helsinki Declaration of 1975 on human experimentation. Preoperatively, each had undergone a thorough history and physical examination followed by testing for the presence of a cystic fibrosis (CF) gene mutation. MESA was performed as described elsewhere (6Schlegel P.N. Berkeley A.S. Goldstein M. Cohen J. Alikani M. Adler A. et al.Epididymal micropuncture with in vitro fertilization and oocyte micromanipulation for the treatment of unreconstructable obstructive azoospermia.Fertil Steril. 1994; 61: 895-901PubMed Scopus (87) Google Scholar, 7Matthews G.J. Goldstein M. A simplified method of epididymal sperm aspiration.Urology. 1996; 47: 123-125Abstract Full Text PDF PubMed Scopus (22) Google Scholar). Sperm obtained intraoperatively were cryopreserved for subsequent IVF and ICSI. The intraoperative parameters that were analyzed included fluid volume, sperm concentration, motility, and number of vials stored. All cryopreserved specimens were tested for post-thaw motility. Patients were followed over time to evaluate the number of IVF/ICSI cycles performed in addition to pregnancy and delivery rates. The average patient age was 33.0 years, and the average partner age was 30.4 years. All patients had a diagnosis of CBAVD based on physical examination that was confirmed on surgical exploration. In the 24 men who had CF genetic data available, 11 were carriers of a CF mutation (46%), one had symptomatic CF, and 12 had no CF mutation. Of the 12 men with no mutation, one had congenital absence of the right kidney as demonstrated on ultrasound. At the time of MESA, an average of 6.1 vials were cryopreserved per patient. Each vial had an average volume of 1.1 mL including a media (range .5–2.5 mL), concentration of 29.0 million sperm/mL and motility of 37.1%. Of the 30 men, 13 were either followed up outside the United States, were lost to follow-up, or had not yet undergone IVF/ICSI cycles. Seventeen couples underwent 27 IVF/ICSI cycles at our institution (see Table 1). From these 27 cycles, 20 pregnancies occurred (74.1% pregnancy rate/cycle) and one couple miscarried, for a live delivery rate per cycle of 70.4% (19/27). The overall delivery rate per couple was 100%, with two couples undergoing two successful IVF cycles with deliveries. Deliveries included 12 singleton births, five sets of twins, and two sets of triplets. The total multiple birth rate was 36.8%.TABLE 1Results of microsurgical epididymal sperm aspiration with IVF/ICSI in couples with congenital bilateral absence of the vas deferens.No. of cycles per coupleNo. of pregnancies per coupleNo. of deliveries per couple11Singleton11Singleton11Twin41Singleton22Singleton, Twin11Twin11Singleton22Singleton, singleton21Triplet11Singleton11Triplet21Singleton22Miscarriage, singleton21Singleton21Singleton11Twin11TwinNote There were 27 total cycles, 20 total pregnancies, and 19 total deliveries, with 12 singletons, five sets of twins, and two sets of triplets (36.8% multiple births). Open table in a new tab Note There were 27 total cycles, 20 total pregnancies, and 19 total deliveries, with 12 singletons, five sets of twins, and two sets of triplets (36.8% multiple births). Whereas almost all men with CF have CBAVD, only a small proportion of men with CBAVD have a medical history of pancreatic insufficiency, respiratory disease, or chronic sinusitis; therefore it is considered a mild phenotype of CF (1Phillipson G. Petrucco O. Matthews C. Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection.Hum Reprod. 2000; 15: 431-435Crossref PubMed Scopus (48) Google Scholar, 8Oates R.D. Amos J.A. Congenital bilateral absence of the vas deferens and cystic fibrosis A genetic commonality.World J Urol. 1993; 11: 82-88Crossref PubMed Scopus (33) Google Scholar). To date, over 800 disease-causing mutations of the CF transmembrane conductance regulator (CFTR) gene have been identified (9Lewis-Jones D.I. Gazvani M.R. Mountford R. Cystic fibrosis in infertility: screening before assisted reproduction: opinion.Hum Reprod. 2000; 15: 2415-2417Crossref PubMed Google Scholar). Before ICSI, men with CBAVD and their female partners should be screened. If the female partner is found to be CF-positive on routine testing, the male partner must undergo the fullest possible investigation of the CFTR gene (9Lewis-Jones D.I. Gazvani M.R. Mountford R. Cystic fibrosis in infertility: screening before assisted reproduction: opinion.Hum Reprod. 2000; 15: 2415-2417Crossref PubMed Google Scholar). Lewis-Jones et al. emphasize the importance of screening the female partner because if she tests negative, then the couple's residual risk of having a child with CF or CBAVD will be reduced to 1:960 (9Lewis-Jones D.I. Gazvani M.R. Mountford R. Cystic fibrosis in infertility: screening before assisted reproduction: opinion.Hum Reprod. 2000; 15: 2415-2417Crossref PubMed Google Scholar). In men with OA due to various causes (10Janzen N. Goldstein M. Schlegel P. Palermo G. Rosenwaks Z. Hariprashad J. Use of electively cryopreserved microsurgically aspirated epididymal sperm with IVF and intracytoplasmic sperm injection for obstructive azoospermia.Fertil Steril. 2000; 74: 696-701Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), we have previously achieved pregnancy rates of 60.6% after MESA and IVF/ICSI. Our pregnancy rates in men with CBAVD alone are even better, with a 74% pregnancy rate per cycle. This high success rate is likely due to the fact that men with CBAVD have totally normal spermatogenesis, the only anomaly being the absent vas deferens. In addition, our population of couples with CBAVD had healthy wives with no female factors contributing to the couples' infertility. MESA is more costly and invasive than percutaneous epididymal sperm aspiration (PESA). Successful pregnancies have also been achieved using PESA and ICSI (11Meniru G.I. Gorgy A. Podsiadly B.T. Craft I.L. Results of percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection in two major groups of patients with obstructive azoospermia.Hum Reprod. 1997; 12: 2443-2446Crossref PubMed Scopus (22) Google Scholar) and have demonstrated no difference in fertilization and pregnancy rates between men with CBAVD and men who have undergone failed vasectomy reversals (11Meniru G.I. Gorgy A. Podsiadly B.T. Craft I.L. Results of percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection in two major groups of patients with obstructive azoospermia.Hum Reprod. 1997; 12: 2443-2446Crossref PubMed Scopus (22) Google Scholar). However, we prefer MESA to PESA because of the abundant high-quality sperm retrieved and the lower risk of contamination with blood cells. Although only a small number of motile spermatozoa are required for successful fertilization with ICSI (5Palermo G. Joris H. Devroey P. Van Steirteghem A. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte.Lancet. 1992; 340: 17-18Abstract PubMed Scopus (2853) Google Scholar), using MESA to obtain abundant high-quality sperm yields superior results. Abundant high-quality sperm can be cryopreserved in a single procedure for all future attempts at IVF/ICSI (10Janzen N. Goldstein M. Schlegel P. Palermo G. Rosenwaks Z. Hariprashad J. Use of electively cryopreserved microsurgically aspirated epididymal sperm with IVF and intracytoplasmic sperm injection for obstructive azoospermia.Fertil Steril. 2000; 74: 696-701Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). Concern exists surrounding the risk of transmission of CF gene mutations when IVF is used in these men. However, Shin et al. found that CBAVD was present in only 5% of brothers of men with CBAVD, consistent with incomplete penetrance for the CBAVD phenotype after inheritance of CF gene mutations (12Shin D. Gilbert F. Goldstein M. Schlegel P.N. Congenital absence of the vas deferens: incomplete penetrance of cystic fibrosis gene mutations.J Urol. 1997; 158: 1794-1798Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). For couples in which the man has CBAVD and the female partner tests negative for standard CFTR gene mutations, the maximum risk of having a child with CBAVD is less than 1% (12Shin D. Gilbert F. Goldstein M. Schlegel P.N. Congenital absence of the vas deferens: incomplete penetrance of cystic fibrosis gene mutations.J Urol. 1997; 158: 1794-1798Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Incomplete penetrance may account for a low prevalence of CBAVD in the population and may lower the risk of having a child with CBAVD for couples undergoing sperm retrieval and assisted reproductive techniques (12Shin D. Gilbert F. Goldstein M. Schlegel P.N. Congenital absence of the vas deferens: incomplete penetrance of cystic fibrosis gene mutations.J Urol. 1997; 158: 1794-1798Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). In a study by Phillipson et al., 60% of men with CBAVD carried a single CF gene mutation, 20% were compound heterozygotes, and 20% of men had no CF mutations (1Phillipson G. Petrucco O. Matthews C. Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection.Hum Reprod. 2000; 15: 431-435Crossref PubMed Scopus (48) Google Scholar). DeltaF508 is the most common mutation found (13Viville S. Warter S. Meyer J.M. Loriot M. Mollard R. Jacqmin D. Histological and genetic analysis and risk assessment for chromosomal aberration after ICSI for patients.Hum Reprod. 2000; 15: 1613-1618Crossref PubMed Scopus (26) Google Scholar). The presence of detectable CFTR gene mutations does not affect fertilization or pregnancy rates for men with CBAVD when IVF and micromanipulation are applied (1Phillipson G. Petrucco O. Matthews C. Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection.Hum Reprod. 2000; 15: 431-435Crossref PubMed Scopus (48) Google Scholar, 14Schlegel P.N. Cohen J. Goldstein M. Alikani M. Adler A. Gilbert B.R. et al.Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens.Fertil Steril. 1995; 64: 421-426PubMed Scopus (43) Google Scholar). Intraoperative cryopreservation of sperm at the time of MESA in men with CBAVD resulted in a 100% live delivery rate per couple after IVF/ICSI. Freezing multiple vials at one time can provide sufficient sperm for multiple future IVF/ICSI cycles, eliminating the need for repeated invasive procedures. These men have high-quality sperm and fertile wives, resulting in the highest pregnancy rates of any infertility treatment. It is important for physicians involved in the care of men with CF to convey the message that prospects for fatherhood are excellent with current technology (4McCallum T.J. Milunsky J.M. Cunningham D.L. Harris D.H. Maher T.A. Oates R.D. Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes.Chest. 2000; 118: 1059-1062Crossref PubMed Scopus (66) Google Scholar).