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Outcome of donor versus husband insemination in couples with unexplained infertility treated by in vitro fertilization and embryo transfer
Vol. 61, No, 6, June 1994
FERTILITY AND STERILITY Copyright
00
Printed on acid-free paper in U. S. A.
1994 The American Fertility Society
Outcome of donor versus husband insemination in couples with unexplained infertility treated by in vitro fertilization and embryo transfer
Foad Azem, M.D.* Amnon Botchan, M.D.t Yuval Yaron, M.D.* Joseph B. Lessing, M.D.*:j:
Josef Har-toov, M.D.* Haim Yavetz, M.D.t Israel Yovel, M.D.* Ami Amit, M.D.*
Serlin Maternity Hospital, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To examine the IVF -ET outcome of couples with unexplained infertility treated by husband versus donor sperm. Design: A retrospective analysis of the IVF -ET outcome of couples with unexplained infertility treated by either husband or donor sperm and in a subgroup of patients treated simultaneously by husband and donor sperm. Setting: IVF Unit, Serlin Maternity Hospital, Tel Aviv, Israel. Patients: Couples diagnosed as having unexplained infertility underwent IVF at our Unit: included were 96 couples treated by husband insemination (group A), 27 couples who received donor insemination because of azoospermia (group B), and 8 couples who sought donor insemination after having previously failed IVF (group C). Results: No statistically significant difference was found between groups A and B regarding age of the females, duration of infertility, number of IVF cycles, fertilization rate, number of ETs, and pregnancy rate. Oocytes collected in group C were subdivided further into two groups: 45 were incubated with husband sperm and 46 were incubated with donor sperm. Fertilization rates were 46.6% and 50%, respectively. One pregnancy occurred. Conclusion: In couples with unexplained infertility who had undergone IVF-ET with husband insemination, the fertilization and pregnancy rates were similar to those of couples who were treated by donor sperm. Fertil Steril 1994;61:1088-91 Key Words: Donor, husband, insemination, IVF-ET, unexplained infertility
In a considerable proportion of infertile couples, there seems to be no explanation for their condition when standard methods of investigation are used. Such unexplained infertility may be the result of both male and female factors. Traditionally, the evaluation of male fertility has been based on se-
Received July 15, 1993; revised and accepted February 16, 1994. * In Vitro Fertilization/Embryo Transfer Unit. t Institute for the Study of Fertility. :\: Reprint requests: Joseph B. Lessing, M.D., IVF Unit, Serlin Maternity Hospital, P.O. Box 7079, Tel Aviv 61070, Israel (FAX: 972-3-6925687). 1088
Azem et al.
Donor versus husband sperm in IVF-ET
men analysis according to the World Health Organization (WHO) criteria (1). Recently, however, Check et a1. (2) have suggested that standard semen analysis frequently fails to identify sub fertile males, even when findings are normal according to light microscopy. Overstreet et a1. (3) found several types of in vitro human sperm dysfunction, including failure to bind to the zona pellucida, zona binding with failure to penetrate the zona, incomplete zona penetration, and poor sperm penetration into the ooplasm. They proposed that some men with "normal" semen and unexplained infertility had apparent dysfunction of gamete interaction. In the female, possible causes for unexplained Fertility and Sterility
infertility may include immunologic effects, such as the presence of autoantibodies (4), endometrial factors (5, 6), and possible factors associated with 00cytes (7). Trounson et al. (8) have shown that IVF results in patients with obstructed fallopian tubes, and those undergoing therapeutic donor insemination were superior to those of couples with unexplained infertility. This study was conducted to evaluate the role of sperm quality in unexplained infertility. For this purpose, we retrospectively analyzed the outcome in couples with unexplained infertility treated by IVF -ET in our Unit, by comparing those treated by donor sperm with those treated by husband sperm. Furthermore, in a third group of patients, the oocytes of each patient were allocated randomly to both donor and husband sperm, controlling for female factors.
MATERIALS AND METHODS
The study population consisted of couples in whom pregnancy failed to occur for ~2 years despite routine female evaluation that included: [1] normal endocrine profile (PRL, free-T 4' TSH, DHEAS, T, LH, and FSH); [2] biphasic BBT with ~ 12 days duration of the luteal phase and midluteal P > 10 ngjmL (31.8 nmoljL); [3] normal hysterosalpingography and laparoscopy; and [4] good postcoital test using either husband sperm or therapeutic donor insemination. The quality of sperm was assessed according to the WHO criteria (1). Husband sperm was used if found to be within the normal fertile range. Female partners of azoospermic men were treated by donor sperm. The study included three groups of patients undergoing IVF. Group A included 96 couples with unexplained infertility and apparent normospermy, as assessed by WHO criteria. Before IVF -ET, all these patients were treated by superovulation with clomiphene citrate (CC; Teva Pharmaceuticals Ltd., PetahTiqva, Israel) for at least five cycles and with hMG (Pergonal; Teva Pharmaceuticals Ltd.) and hCG (Chorigon; Teva Pharmaceuticals Ltd.) for at least another six cycles. In all these patients, oocytes retrieved for IVF were inseminated with husband sperm. Group B consisted of 27 couples with unexplained infertility and azoospermia. All patients previously had undergone at least six therapeutic donor inseminations, all properly timed with CC, and at least six therapeutic donor inseminations Vol. 61, No.6, June 1994
Table 1 Data From Couples* with Unexplained Infertility in Groups A and B
Duration of infertility (y)t:j: Age of femaleH Age of malet§
Group A husband insemination (n = 96)
Group B donor insemination (n = 27)
7.2 ± 4.6 32.7 ± 4.5 34.9 ± 5.3
6.4 ± 4.3 33.5 ± 4.5 27.3 ± 3.8
*n
= 123. t Values are means ± SD. :j: Intergroup differences are not statistically significant. § P < 0.000l.
with hMG but had failed to conceive. Oocytes retrieved from these patients were inseminated by donor sperm. According to the regulations of the Israeli Ministry of Health, donor sperm was quarantined for a period of ~6 months. Before use, donors were screened again for infectious diseases (hepatitis B surface antigen, antibodies for the human immunodeficiency virus). Cryopreservation and thawing, as well as insemination techniques, previously have been described (9). Group C included eight couples with unexplained infertility who sought donor insemination after previously failing three consecutive IVF-ET attempts, despite fertilization by husband sperm. Oocytes from each of these patients were distributed equally for insemination by both husband and donor sperm. Controlled ovarian hyperstimulation for IVF was performed in all patients using a standard protocol of hMG alone as described previously (10). Ovulation was induced with 10,000 IU hCG when follicles reached a mean diameter of 17 mm and serum E2 exceeded 800 pgjmL (conversion factor to SI units, 3.671). Oocyte retrieval was performed after 34 to 36 hours using an ultrasound-guided transvaginal approach. Embryo transfer was performed 2 to 3 days later, at a four- to eight-cell stage, using a Wallace catheter (H.G. Wallace Ltd., Colchester, Essex, United Kingdom). Blood samples for i3-subunit of hCG (i3-hCG) were drawn on days 12 and 16 after ET. In the event of pregnancy, transvaginal ultrasonography was performed at 6 and 8 weeks gestation to confirm clinical pregnancy. Biochemical pregnancies were not included in the study. Statistical analysis was performed with Tadpole software (Elsevier-BIOSOFT-1986, Cambridge, United Kingdom) using the X2 test, and paired t-test. All values are means ± standard deviation. Azem et al.
Donor versus husband sperm in IVF-ET
1089
Table 2 Results of IVF-ET Treatment in Patients With Unexplained Infertility in Groups A and B
No. of cycles initiated No. of ET cycles No. of oocytes*t No. of embryos*t Fertilization rate:j: § Pregnancy rate per ET First cycle:j: § All cycles:j: §
Group A husband insemination (n = 96)
Group B donor insemination (n = 27)
298 259 10.2 ± 6.3 3.9 ± 1.4 (66.3)
59 52 11.5 ± 5.9 3.2 ± 1.5 (69.1)
21 (25.0) 58 (22.4)
5 (20.8) 10 (19.2)
* Values are means
± SD. t Intergroup differences not statistically significant, Student's t-test. :j: Values in parenthesis are rates. § Intergroup differences not statistically significant, x2 test.
RESULTS
Table 1 summarizes the data relating to patients in groups A and B. No statistically significant differences were noted between the groups regarding age of the females and the duration of infertility. The donor males were significantly younger than the husband population. Table 2 summarizes the results of IVF treatment with husband sperm (group A) and donor sperm (group B). The cancellation rate in group A was 13.1% compared with 11.9% in group B and was not statistically significant. Likewise, no significant differences were noted for the mean number of oocytes retrieved, fertilization rate, or mean number of embryos transferred. Pregnancy rates did not differ significantly in either the first treatment or all cycles. Group C patients underwent one treatment cycle each. A total of 91 oocytes were retrieved. These were distributed equally for insemination by both husband and donor sperm. Of the 45 oocytes in semi nated with husband sperm, 21 were fertilized (46.6%). Of the 46 inseminated with donor sperm, 25 were fertilized (54.3%). A paired t-test showed no statistically significant difference. One pregnancy occurred in a patient who had 15 oocytes retrieved. Two of these were fertilized by husband sperm, and three were fertilized by donor sperm. According to the couple's request, only the former were transferred. DISCUSSION
The designation "unexplained infertility" is applied to couples who have failed to achieve preg1090
Azem et al.
Donor versus husband sperm in IVF-ET
nancy despite evaluations that uncover no obvious reasons for their infertility or to those who remain infertile despite correction of all detectable causes of infertility (11). Approximately 10% to 15% of infertile couples will be diagnosed eventually as suffering from this entity (12). Until recently, there were no known effective treatments for such couples. Although treatment-independent pregnancy occasionally occurs (13), many patients often pursue a more tangible mode of treatment. In recent years, the therapeutic options for alleviating infertility have increased dramatically and now include ovarian superovulation (14), IVF (15), GIFT, and zygote intrafallopian transfer. The use of these options for treating unexplained infertility is empiric and none have been shown to be superior to others. Apart from its therapeutic advantage, IVF also serves as a diagnostic tool as it helps to evaluate the fertilizability of the gametes. Such evaluation often reveals information unattainable by standard means for infertility evaluation. In a pioneering study, Trounson et al. (8) found normal embryo development among five of six patients who had had either occluded fallopian tubes or insemination with therapeutic donor insemination compared with none among nine patients with unexplained infertility. These results, in conjunction with others (3), suggest that standard semen analysis often may fail to identify subfertile males even when light microscopy findings ate normal. Contrary to the findings of Trounson et al. (8), our results showed no difference between husband and donor sperm with regard to fertilization and pregnancy rates in patients with unexplained infertility (groups A and B). Moreover, no difference in fertilization rates was noted in group C, in which oocytes were subdivided for insemination with either husband or donor sperm. Trounson et al. (8) used fresh, not frozen-thawed, sperm, which may explain the discrepancy. Our results may imply that, in couples with unexplained infertility, there is a decrease in sperm quality to an extent similar to that of frozen-thawed sperm. Indeed, in a previous study, we showed that fertilization rates in IVF were lower when frozen-thawed sperm in comparison with fresh sperm was used (9). Pregnancy rates, however, did not differ because an adequate number of transferred embryos compensated for this fact. Thus, unexplained infertility in some cases may be the result of occult male factor. On the other hand, the fertilization rate was lower somewhat in the study group, perhaps suggestive of an "egg factor" as well. Pregnancy rates in the study group Fertility and Sterility
were lower than in patients with tubal disease, which may be attributed either to decreased endometrial receptivity or to poor embryo quality, which also may underlie unexplained infertility. Intrinsic endometrial dysfunction may prevent embryo implantation and early development. Indeed, endometrial factors recently have been associated with unexplained infertility (16) and, at present, no satisfactory means exist by which to evaluate embryo quality. Perhaps the developing era of preimplantation diagnosis will resolve this issue in the future. In summary, our results show that, in couples with unexplained infertility treated by IVF, similar results are obtained whether husband or donor sperm is used. REFERENCES 1. Amann RP. A critical review of methods for evaluation of spermatogenesis from seminal characteristics. J Androl 1981;2:37-58. 2. CheckJH, Nowroozi K, Lee M, Adelson H, LatsoffD. Evalu· ation and treatment of a male factor component to unexplained infertility. Arch AndroI1990;25:199-211. 3. Overstreet JW, Yanagimachi R, Katz DF, Hayashi K, Hanson FW. Penetration of human spermatozoa into the human zona pellucida and the zona-free hamster egg: a study of fertile donors and infertile patients. Fertil Steril 1980;33:534-42. 4. Taylor PV, Campbell GM, Scott GS. Presence of autoantibodies in women with unexplained infertility. Am J Obstet Gynecol 1989;161:377-9. 5. Paulson RJ, Sauer MV, Lobo RA. Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril 1990;53:870-4.
Vol. 61, No.6, June 1994
6. Goswamy RK, Williams G, Steptoe PC. Decreased uterine reperfusion: a cause of infertility. Hum Reprod 1988;3:9559. 7. Ezra Y, Simon A, Laufer N. Defective oocytes: a new subgroup of unexplained infertility. Fertil Steril 1992;58:24-7. 8. Trounson AO, Leeton JF, Wood C, Webb J, Kovacs G. The investigation of idiopathic infertility by in vitro fertilization. Fertil Steril1980;34:431-8. 9. Yavetz H, Lessing JB, Niv Y, Amit A, Barak Y, Yovel I, et al. The efficiency of cryopreserved semen versus fresh semen for in vitro fertilization/embryo transfer. J In Vitro Fert Embryo Transf 1991;8:145-8. 10. Barak Y, Lessing JB, Amit A, Kogosowski A, Yovel I, David MP, et al. The development of an efficient ambulatory in vitro fertilization (IVF) and embryo transfer (ET) program using ultrasonically guided oocyte retrieval. Acta Obstet Gynecol Scand 1988:67:585-8. 11. Templeton AA, Penney GC. The incidence, characteristics and prognosis of patients whose infertility is unexplained. Fertil Steril 1982;37:175-82. 12. Crosignani G, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. Hum Reprod 1991;7:953-8. 13. Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment independent pregnancy among infertile couples. N Engl J Med 1983;309:1201-6. 14. Fisch P, Casper RF, Brown SE, Wrixon W, Collins JA, Reid RL, et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril 1989;51:828-33. 15. Lessing JB, Amit A, Barak Y, Kogosowski A, Gruber A, Y ovel I, et al. The performance of primary and secondary unexplained infertility in an in vitro fertilization-embryo transfer program. Fertil Steril 1988;50:903-5. 16. Graham RA, Seif MW, Aplin SD, Li TC, Cooke ID. Rogers AW, et al. An endometrial factor in unexplained infertility. Br Med J 1990;300:1428-31.
Azem et al.
Donor versus husband sperm in IVF-ET
1091
FERTILITY AND STERILITY Copyright
00
Printed on acid-free paper in U. S. A.
1994 The American Fertility Society
Outcome of donor versus husband insemination in couples with unexplained infertility treated by in vitro fertilization and embryo transfer
Foad Azem, M.D.* Amnon Botchan, M.D.t Yuval Yaron, M.D.* Joseph B. Lessing, M.D.*:j:
Josef Har-toov, M.D.* Haim Yavetz, M.D.t Israel Yovel, M.D.* Ami Amit, M.D.*
Serlin Maternity Hospital, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To examine the IVF -ET outcome of couples with unexplained infertility treated by husband versus donor sperm. Design: A retrospective analysis of the IVF -ET outcome of couples with unexplained infertility treated by either husband or donor sperm and in a subgroup of patients treated simultaneously by husband and donor sperm. Setting: IVF Unit, Serlin Maternity Hospital, Tel Aviv, Israel. Patients: Couples diagnosed as having unexplained infertility underwent IVF at our Unit: included were 96 couples treated by husband insemination (group A), 27 couples who received donor insemination because of azoospermia (group B), and 8 couples who sought donor insemination after having previously failed IVF (group C). Results: No statistically significant difference was found between groups A and B regarding age of the females, duration of infertility, number of IVF cycles, fertilization rate, number of ETs, and pregnancy rate. Oocytes collected in group C were subdivided further into two groups: 45 were incubated with husband sperm and 46 were incubated with donor sperm. Fertilization rates were 46.6% and 50%, respectively. One pregnancy occurred. Conclusion: In couples with unexplained infertility who had undergone IVF-ET with husband insemination, the fertilization and pregnancy rates were similar to those of couples who were treated by donor sperm. Fertil Steril 1994;61:1088-91 Key Words: Donor, husband, insemination, IVF-ET, unexplained infertility
In a considerable proportion of infertile couples, there seems to be no explanation for their condition when standard methods of investigation are used. Such unexplained infertility may be the result of both male and female factors. Traditionally, the evaluation of male fertility has been based on se-
Received July 15, 1993; revised and accepted February 16, 1994. * In Vitro Fertilization/Embryo Transfer Unit. t Institute for the Study of Fertility. :\: Reprint requests: Joseph B. Lessing, M.D., IVF Unit, Serlin Maternity Hospital, P.O. Box 7079, Tel Aviv 61070, Israel (FAX: 972-3-6925687). 1088
Azem et al.
Donor versus husband sperm in IVF-ET
men analysis according to the World Health Organization (WHO) criteria (1). Recently, however, Check et a1. (2) have suggested that standard semen analysis frequently fails to identify sub fertile males, even when findings are normal according to light microscopy. Overstreet et a1. (3) found several types of in vitro human sperm dysfunction, including failure to bind to the zona pellucida, zona binding with failure to penetrate the zona, incomplete zona penetration, and poor sperm penetration into the ooplasm. They proposed that some men with "normal" semen and unexplained infertility had apparent dysfunction of gamete interaction. In the female, possible causes for unexplained Fertility and Sterility
infertility may include immunologic effects, such as the presence of autoantibodies (4), endometrial factors (5, 6), and possible factors associated with 00cytes (7). Trounson et al. (8) have shown that IVF results in patients with obstructed fallopian tubes, and those undergoing therapeutic donor insemination were superior to those of couples with unexplained infertility. This study was conducted to evaluate the role of sperm quality in unexplained infertility. For this purpose, we retrospectively analyzed the outcome in couples with unexplained infertility treated by IVF -ET in our Unit, by comparing those treated by donor sperm with those treated by husband sperm. Furthermore, in a third group of patients, the oocytes of each patient were allocated randomly to both donor and husband sperm, controlling for female factors.
MATERIALS AND METHODS
The study population consisted of couples in whom pregnancy failed to occur for ~2 years despite routine female evaluation that included: [1] normal endocrine profile (PRL, free-T 4' TSH, DHEAS, T, LH, and FSH); [2] biphasic BBT with ~ 12 days duration of the luteal phase and midluteal P > 10 ngjmL (31.8 nmoljL); [3] normal hysterosalpingography and laparoscopy; and [4] good postcoital test using either husband sperm or therapeutic donor insemination. The quality of sperm was assessed according to the WHO criteria (1). Husband sperm was used if found to be within the normal fertile range. Female partners of azoospermic men were treated by donor sperm. The study included three groups of patients undergoing IVF. Group A included 96 couples with unexplained infertility and apparent normospermy, as assessed by WHO criteria. Before IVF -ET, all these patients were treated by superovulation with clomiphene citrate (CC; Teva Pharmaceuticals Ltd., PetahTiqva, Israel) for at least five cycles and with hMG (Pergonal; Teva Pharmaceuticals Ltd.) and hCG (Chorigon; Teva Pharmaceuticals Ltd.) for at least another six cycles. In all these patients, oocytes retrieved for IVF were inseminated with husband sperm. Group B consisted of 27 couples with unexplained infertility and azoospermia. All patients previously had undergone at least six therapeutic donor inseminations, all properly timed with CC, and at least six therapeutic donor inseminations Vol. 61, No.6, June 1994
Table 1 Data From Couples* with Unexplained Infertility in Groups A and B
Duration of infertility (y)t:j: Age of femaleH Age of malet§
Group A husband insemination (n = 96)
Group B donor insemination (n = 27)
7.2 ± 4.6 32.7 ± 4.5 34.9 ± 5.3
6.4 ± 4.3 33.5 ± 4.5 27.3 ± 3.8
*n
= 123. t Values are means ± SD. :j: Intergroup differences are not statistically significant. § P < 0.000l.
with hMG but had failed to conceive. Oocytes retrieved from these patients were inseminated by donor sperm. According to the regulations of the Israeli Ministry of Health, donor sperm was quarantined for a period of ~6 months. Before use, donors were screened again for infectious diseases (hepatitis B surface antigen, antibodies for the human immunodeficiency virus). Cryopreservation and thawing, as well as insemination techniques, previously have been described (9). Group C included eight couples with unexplained infertility who sought donor insemination after previously failing three consecutive IVF-ET attempts, despite fertilization by husband sperm. Oocytes from each of these patients were distributed equally for insemination by both husband and donor sperm. Controlled ovarian hyperstimulation for IVF was performed in all patients using a standard protocol of hMG alone as described previously (10). Ovulation was induced with 10,000 IU hCG when follicles reached a mean diameter of 17 mm and serum E2 exceeded 800 pgjmL (conversion factor to SI units, 3.671). Oocyte retrieval was performed after 34 to 36 hours using an ultrasound-guided transvaginal approach. Embryo transfer was performed 2 to 3 days later, at a four- to eight-cell stage, using a Wallace catheter (H.G. Wallace Ltd., Colchester, Essex, United Kingdom). Blood samples for i3-subunit of hCG (i3-hCG) were drawn on days 12 and 16 after ET. In the event of pregnancy, transvaginal ultrasonography was performed at 6 and 8 weeks gestation to confirm clinical pregnancy. Biochemical pregnancies were not included in the study. Statistical analysis was performed with Tadpole software (Elsevier-BIOSOFT-1986, Cambridge, United Kingdom) using the X2 test, and paired t-test. All values are means ± standard deviation. Azem et al.
Donor versus husband sperm in IVF-ET
1089
Table 2 Results of IVF-ET Treatment in Patients With Unexplained Infertility in Groups A and B
No. of cycles initiated No. of ET cycles No. of oocytes*t No. of embryos*t Fertilization rate:j: § Pregnancy rate per ET First cycle:j: § All cycles:j: §
Group A husband insemination (n = 96)
Group B donor insemination (n = 27)
298 259 10.2 ± 6.3 3.9 ± 1.4 (66.3)
59 52 11.5 ± 5.9 3.2 ± 1.5 (69.1)
21 (25.0) 58 (22.4)
5 (20.8) 10 (19.2)
* Values are means
± SD. t Intergroup differences not statistically significant, Student's t-test. :j: Values in parenthesis are rates. § Intergroup differences not statistically significant, x2 test.
RESULTS
Table 1 summarizes the data relating to patients in groups A and B. No statistically significant differences were noted between the groups regarding age of the females and the duration of infertility. The donor males were significantly younger than the husband population. Table 2 summarizes the results of IVF treatment with husband sperm (group A) and donor sperm (group B). The cancellation rate in group A was 13.1% compared with 11.9% in group B and was not statistically significant. Likewise, no significant differences were noted for the mean number of oocytes retrieved, fertilization rate, or mean number of embryos transferred. Pregnancy rates did not differ significantly in either the first treatment or all cycles. Group C patients underwent one treatment cycle each. A total of 91 oocytes were retrieved. These were distributed equally for insemination by both husband and donor sperm. Of the 45 oocytes in semi nated with husband sperm, 21 were fertilized (46.6%). Of the 46 inseminated with donor sperm, 25 were fertilized (54.3%). A paired t-test showed no statistically significant difference. One pregnancy occurred in a patient who had 15 oocytes retrieved. Two of these were fertilized by husband sperm, and three were fertilized by donor sperm. According to the couple's request, only the former were transferred. DISCUSSION
The designation "unexplained infertility" is applied to couples who have failed to achieve preg1090
Azem et al.
Donor versus husband sperm in IVF-ET
nancy despite evaluations that uncover no obvious reasons for their infertility or to those who remain infertile despite correction of all detectable causes of infertility (11). Approximately 10% to 15% of infertile couples will be diagnosed eventually as suffering from this entity (12). Until recently, there were no known effective treatments for such couples. Although treatment-independent pregnancy occasionally occurs (13), many patients often pursue a more tangible mode of treatment. In recent years, the therapeutic options for alleviating infertility have increased dramatically and now include ovarian superovulation (14), IVF (15), GIFT, and zygote intrafallopian transfer. The use of these options for treating unexplained infertility is empiric and none have been shown to be superior to others. Apart from its therapeutic advantage, IVF also serves as a diagnostic tool as it helps to evaluate the fertilizability of the gametes. Such evaluation often reveals information unattainable by standard means for infertility evaluation. In a pioneering study, Trounson et al. (8) found normal embryo development among five of six patients who had had either occluded fallopian tubes or insemination with therapeutic donor insemination compared with none among nine patients with unexplained infertility. These results, in conjunction with others (3), suggest that standard semen analysis often may fail to identify subfertile males even when light microscopy findings ate normal. Contrary to the findings of Trounson et al. (8), our results showed no difference between husband and donor sperm with regard to fertilization and pregnancy rates in patients with unexplained infertility (groups A and B). Moreover, no difference in fertilization rates was noted in group C, in which oocytes were subdivided for insemination with either husband or donor sperm. Trounson et al. (8) used fresh, not frozen-thawed, sperm, which may explain the discrepancy. Our results may imply that, in couples with unexplained infertility, there is a decrease in sperm quality to an extent similar to that of frozen-thawed sperm. Indeed, in a previous study, we showed that fertilization rates in IVF were lower when frozen-thawed sperm in comparison with fresh sperm was used (9). Pregnancy rates, however, did not differ because an adequate number of transferred embryos compensated for this fact. Thus, unexplained infertility in some cases may be the result of occult male factor. On the other hand, the fertilization rate was lower somewhat in the study group, perhaps suggestive of an "egg factor" as well. Pregnancy rates in the study group Fertility and Sterility
were lower than in patients with tubal disease, which may be attributed either to decreased endometrial receptivity or to poor embryo quality, which also may underlie unexplained infertility. Intrinsic endometrial dysfunction may prevent embryo implantation and early development. Indeed, endometrial factors recently have been associated with unexplained infertility (16) and, at present, no satisfactory means exist by which to evaluate embryo quality. Perhaps the developing era of preimplantation diagnosis will resolve this issue in the future. In summary, our results show that, in couples with unexplained infertility treated by IVF, similar results are obtained whether husband or donor sperm is used. REFERENCES 1. Amann RP. A critical review of methods for evaluation of spermatogenesis from seminal characteristics. J Androl 1981;2:37-58. 2. CheckJH, Nowroozi K, Lee M, Adelson H, LatsoffD. Evalu· ation and treatment of a male factor component to unexplained infertility. Arch AndroI1990;25:199-211. 3. Overstreet JW, Yanagimachi R, Katz DF, Hayashi K, Hanson FW. Penetration of human spermatozoa into the human zona pellucida and the zona-free hamster egg: a study of fertile donors and infertile patients. Fertil Steril 1980;33:534-42. 4. Taylor PV, Campbell GM, Scott GS. Presence of autoantibodies in women with unexplained infertility. Am J Obstet Gynecol 1989;161:377-9. 5. Paulson RJ, Sauer MV, Lobo RA. Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril 1990;53:870-4.
Vol. 61, No.6, June 1994
6. Goswamy RK, Williams G, Steptoe PC. Decreased uterine reperfusion: a cause of infertility. Hum Reprod 1988;3:9559. 7. Ezra Y, Simon A, Laufer N. Defective oocytes: a new subgroup of unexplained infertility. Fertil Steril 1992;58:24-7. 8. Trounson AO, Leeton JF, Wood C, Webb J, Kovacs G. The investigation of idiopathic infertility by in vitro fertilization. Fertil Steril1980;34:431-8. 9. Yavetz H, Lessing JB, Niv Y, Amit A, Barak Y, Yovel I, et al. The efficiency of cryopreserved semen versus fresh semen for in vitro fertilization/embryo transfer. J In Vitro Fert Embryo Transf 1991;8:145-8. 10. Barak Y, Lessing JB, Amit A, Kogosowski A, Yovel I, David MP, et al. The development of an efficient ambulatory in vitro fertilization (IVF) and embryo transfer (ET) program using ultrasonically guided oocyte retrieval. Acta Obstet Gynecol Scand 1988:67:585-8. 11. Templeton AA, Penney GC. The incidence, characteristics and prognosis of patients whose infertility is unexplained. Fertil Steril 1982;37:175-82. 12. Crosignani G, Walters DE, Soliani A. The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. Hum Reprod 1991;7:953-8. 13. Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment independent pregnancy among infertile couples. N Engl J Med 1983;309:1201-6. 14. Fisch P, Casper RF, Brown SE, Wrixon W, Collins JA, Reid RL, et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril 1989;51:828-33. 15. Lessing JB, Amit A, Barak Y, Kogosowski A, Gruber A, Y ovel I, et al. The performance of primary and secondary unexplained infertility in an in vitro fertilization-embryo transfer program. Fertil Steril 1988;50:903-5. 16. Graham RA, Seif MW, Aplin SD, Li TC, Cooke ID. Rogers AW, et al. An endometrial factor in unexplained infertility. Br Med J 1990;300:1428-31.
Azem et al.
Donor versus husband sperm in IVF-ET
1091