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Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles
Assisted reproductive technology FERTILITY AND STERILITY
Vol. 61, No.5. May 1994
Printed on acid-free paper in U. S. A.
Copyright Il:! 1994 The American Fertility Society
Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles
Shlomo Lipitz, M.D.* Jaron Rabinovici, M.D. Mordechai Goldenberg, M.D.
David Bider, M.D. Jehoshua Dor, M.D. Shlomo Mashiach, M.D.
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, and The Sackler School of Medicine, Tel-Aviv, Israel
Objective: To determine whether complete failure of fertilization of oocytes in couples with mechanical infertility during the first IVF cycle indicates a poor prognosis for subsequent IVF cycles. Design: A retrospective study of 172 cycles of IVF in 50 couples with mechanical infertility and complete failure of fertilization during their first IVF trial. Setting: In vitro fertilization unit of the Sheba Medical Center. Patients: Fifty couples undergoing one to eight cycles of IVF for mechanical infertility. Main Outcome Measure(s): Fertilization rate of retrieved oocytes and pregnancy rate. Results: Of the initial 50 couples, 44 underwent additional IVF cycles, and 43 (97.7%) achieved fertilization during the second or third cycle. Twenty-four patients conceived during the study period as a result ofIVF. Conclusions: Complete failure of fertilization in couples with mechanical infertility does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. Complete failure of fertilization during the first cycle of IVF in couples with mechanical infertility is accompanied by a good prognosis for subsequent cycles. Fertil Steril 1994;61:863-6 Key Words: IVF, mechanical infertility, failure of fertilization
Complete failure of fertilization is a frustrating experience for couples undergoing IVF. After successful oocyte retrieval, failure to achieve fertilization of any of the retrieved oocytes can occur in approximately 10% to 20% of all IVF cycles (1-3). Failure of fertilization occurs approximately twice as often in couples with male infertility diagnosed by classic criteria than in couples with normal sperm parameters (3). In addition, the lower rate of fertilization in couples with abnormal sperm parameters often implies a poor prognosis for future IVF cycles (4, 5).
Received August 2, 1993; revised and accepted January 7, 1994. * Reprint requests: Shlomo Lipitz, M.D., Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer 52621, Israel (FAX: 972-3-535-2081). Vol. 61, No.5, May 1994
In our IVF program at the Sheba Medical Center, complete fertilization failure occurs in 8%, 48%, and 22% of all treatment cycles of couples with tubal infertility, male infertility, and unexplained infertility, respectively (6). We showed previously that complete failure of fertilization during the initial IVF attempt in couples with male infertility or with unexplained infertility is associated with decreased oocyte fertilization rates and repeated complete failures of fertilization in subsequent IVF cycles (6, 7). These findings indicate that initial complete failure of fertilization in some couples with male infertility or with unexplained infertility may result from a chronic pathology of sperm-oocyte interaction. Little is known about the clinical significance of fertilization failure during the first IVF cycle in coupIes with mechanical infertility and normal semen Lipitz et al.
Complete failure of fertilization in IVF
863
parameters and whether this initial failure of fertilization signifies a previously undiagnosed pathology. Therefore, the aim of this retrospective study was to examine the results of 172 IVF cycles in 50 couples with mechanical infertility after complete failure of fertilization in their first IVF trial. Specifically, we wanted to examine whether complete failure of fertilization in these couples recurred during subsequent IVF cycles and if not, whether the oocyte fertilization rate during these subsequent cycles was different from that observed with other causes of infertility.
MATERIALS AND METHODS
We carried out a retrospective file search of our computerized data base that contains all clinical and laboratory records of patients who underwent IVF between 1984 and 1990. The search algorithm aimed to identify those couples in whom mechanical infertility was diagnosed either by hysterosalpingography and/or by laparoscopy before IVF. Only those couples were included in this study in whom no retrieved oocytes were fertilized during the first IVF -ET treatment cycle. In all treatment cycles, only the husband's semen was used. In all cases, semen analysis before and during any IVFET treatment cycle was found to be normal according to the criteria of the World Health Organization (8). In each case, the diagnosis of mechanical infertility had been reached after the following tests were found to be within the normal range. Female tests: regular menses; biphasic body temperature; luteal phase serum P; PRL; LH; FSH; and thyroid hormones. Male tests: repeated sperm analyses; bacteriological cultures; testicular volume; LH; FSH; T; repeated postcoital tests. The diagnosis of mechanical infertility was based on a pathologic hysterosalpingography verified by a subsequent laparoscopy. The treatment and monitoring protocols used for IVF-ET were described previously (9, 10). The term "first IVF cycle" refers to the initial IVF cycle with complete failure of fertilization. The subsequent cycles are numbered consecutively, for example, second IVF cycle refers to the cycle after the initial, unsuccessful cycle. The patients were neither specifically encouraged nor discouraged to repeat cycles. Repetition of the cycle depended on the expressed desire of the patients. Micromanipulation or chemical treatments were not used in subsequent cycles. The stimulation protocols were simi864
Lipitz et al.
Complete failure of fertilization in IVF
lar. Pregnancy was defined as fetal heart rate motion on ultrasound. Data were analyzed by nonparametric methods. Correlation between the number of fertilized 00cytes during the different IVF cycles was determined by Kendall's rank correlation coefficient test. Results are expressed as mean ± SEM. Significance was assumed at P s 0.05.
RESULTS
Fifty couples with mechanical infertility failed to fertilize 397 oocytes during the first IVF cycle (Tables 1, 2). Forty-four couples (88%) underwent one cycle, 30 underwent two cycles, 19 underwent three cycles, 14 underwent four cycles, 8 underwent five cycles, 4 underwent six cycles and 3 underwent eight additional cycles of IVF-ET (Table 1). The pregnancies that occurred during the study period and the combined cumulative pregnancy rate (PR) for the study population are shown in Table l. Twenty-four of the initial 44 couples conceived as a result of IVF during the study period after their first failed IVF cycle, that is, the IVF-related PR per couple was 54.5%, and the PR per cycle was 14%. Thirteen pregnancies resulted in deliveries, that is, the take home baby rate per cycle was 7.6%. Number of IVF Cycles Needed to Overcome Complete Failure of Fertilization
All 43 couples who elected to undergo at least two more IVF cycles achieved fertilization in at least one subsequent cycle. One couple did not retry after two initial failures. Most of the "first-time" fertilizations (79.5%) occurred during the second IVF cycle and the rest during the third IVF cycle. Among the 35 couples who achieved fertilization
Table 1 In Vitro Fertilization Cycles, Pregnancies, and Cumulative PR After Failure of Fertilization During the First IVF Cycle*
Cycle
No. of IVF cycles
IVF -related pregnancies
Cumulative IVF-related PR
1 2 3 4 5 6 7 8
50 44 30 19 14 8 4 3
0 7 4 4 6 2 0 1
0 0.16 0.27 0.43 0.67 0.75 0.75 0.84
* This table includes all IVF cycles during the study period.
Fertility and Sterility
Table 2
Estradiol Levels and Number of Oocytes Retrieved and Fertilized During 1VF Cycles
Oocytes retrieved
Fertilization rate
Oocytes fertilized
%
First cycle (n = 50) Second cycle (n = 44) Third cycle (n = 30) Fourth cycle (n = 19) Fifth cycle (n = 14) Sixth cycle (n = 8) Seventh cycle (n = 4) Eight cycle (n = 3)
397 340 234 144 91 55 26 19
(7.9 (7.7 (7.8 (7.5 (6.5 (6.8 (6.5 (6.3
± ± ± ± ± ± ± ±
1.1) [1 to 22]t
0.9) [1 to 25] 0.6) [2 to 18] 0.7) [2 to 15] 0.7) [2 to 13] 0.6) [2 to 14] 0.8) [3 to 10] 1) [2 to 7]
* Conversion factor to S1 unit, 3.671.
during the second cycle, seven pregnancies that resulted in seven singleton deliveries at term were recorded (Table 1). Of the nine couples who again failed to achieve fertilization during the second IVF cycle, eight underwent a third trial. During this third cycle all eight women achieved fertilization, and one woman conceived and delivered at term. It is noteworthy that complete failure of fertilization did not recur in any of the 30 couples who underwent three or more cycles of IVF. Failure of Fertilization in the First Cycle Is Not a Predictor of Decreased Fertilization During Subsequent IVF Cycles in Couples with Mechanical Infertility
The 44 couples underwent 122 subsequent IVF cycles after the initial failed cycle. The overall rate of oocyte fertilization during the IVF cycles that followed the unsuccessful first cycle was 70.5% compared with 67.6% in all couples with mechanical infertility (11). The fertilization rates were similar for the individual cycles, that is, 71.7%, 67.5%, and 75% for the second, third, and fourth cycles, respectively (Table 2). Further, mean E 2 levels were similar in all cycles (Table 2).
DISCUSSION
The results of our study indicate that complete failure of fertilization in couples with mechanical infertility does not persist during subsequent IVF cycles. All 43 couples who elected to undergo at least two more IVF cycle achieved fertilization in at least one subsequent cycle. One couple did not retry after two initial failures. Because all of the firsttime fertilizations occurred during the second and Vol. 61, No.5, May 1994
244 158 108 63 38 17 13
(5.5 (5.2 (5.6 (4.5 (4.7 (4.2 (4.3
± ± ± ± ± ± ±
0 1.8) [0 to 14] 1.2) [0 to 11] 1.5) [1 to 10] 0.9) [1 to 9] 1) [2 to 8] 1.1) [2 to 8] 0.7) [1 to 6]
0 71.7 67.5 75 69.2 69 65.3 68.4
E2 levels on day ofhCG pg/mL*
1,112 1,085 1,099 1,153 1,170 1,200 1,095 1,132
± ± ± ± ± ± ± ±
496 462 399 452 394 512 405 408
t Values are total number with means ± SE oocytes per couple in parentheses and ranges in brackets.
third IVF cycle, at least two additional IVF cycles should be performed after primary failure of fertilization in these couples before considering other diagnoses or other treatment options. Our data indicate that initial complete failure of fertilization during the first IVF cycle in couples with mechanical infertility is not associated with decreased oocyte fertilization rates in subsequent cycles (Table 2). In this study, after the first failed IVF cycle complete failure of fertilization recurred only in 9 of the 122 subsequent IVF cycles. Complete failure of fertilization did not recur in any of the 78 cycles ofthe 30 couples who underwent three or more cycles of IVF. Further, the overall oocyte fertilization rate during the subsequent cycles was 70.5%, and this rate compares favorably with our experience and with the experience of others. The results of this study and of previous studies (6, 7) seem to indicate that initial complete failure of fertilization carries a different prognosis in couples with mechanical infertility than in those with male or unexplained infertility. We reported previously on the fertilization rates of couples with male infertility after at least one previous IVF cycle resulted in complete failure of fertilization (7). Of all couples with male infertility, 81.2% achieved fertilization in a subsequent cycle, but the mean oocyte fertilization rate during these subsequent cycles was decreased (47.7%) and complete failure of fertilization recurred in subsequent cycles (7). In another study on initial complete failure of fertilization in couples with unexplained infertility, we showed that most couples (81.1%) achieved fertilization during the two subsequent treatment cycles (6). However, in these couples with unexplained infertility, initial failure of fertilization also was accompanied by decreased oocyte fertilization rate in subsequent cycles. Thus, we concluded that in these Lipitz et al.
Complete failure of fertilization in IVF
865
cases initial complete failure of fertilization may serve as an indicator of an underlying undiagnosed pathology of oocyte and sperm interaction (6). The results ofthe present study indicate that in contrast to couples with either male or unexplained infertility, initial complete failure of fertilization in couples with mechanical infertility is associated with an excellent prognosis for subsequent IVF cycles. This suggests that complete failure of fertilization in most couples with mechanical infertility occurs due to acute, nonrepetitive reasons such as, inadequate ovarian stimulation and laboratory techniques. In conclusion, the results of this study indicate that complete failure of fertilization during the first IVF cycle in couples with mechanical infertility does not necessarily recur during subsequent IVF cycles. Nearly all couples (97.7%) will achieve fertilization during the first two subsequent treatment cycles. In these subsequent IVF cycles, a normal oocyte fertilization rate and a normal PR can be expected.
REFERENCES 1. Trounson A, Wood C. In vitro fertilization results, 1979-82 at Monash University, Queen Victoria and Epworth Medical Centers. J In Vitro Fert Embryo Transf 1984;1:42-7. 2. Molloy D, Harrison K, Breen T, Hennessey J. The predic-
866
Lipitz et al.
Complete failure of fertilization in IVF
3.
4.
5.
6.
7.
8.
9.
10.
11.
tive value of idiopathic failure to fertilize on the first in vitro fertilization attempt. Fertil Steril 1991;56:285-9. Barlow P, Englert Y, Puissant F, Lejeune B, Delvigne A, Van Rysselberge M, et al. Fertilization failure in IVF: why and what next? Hum Reprod 1990;5:451-6. Hughes EG, King C, Wood EC. A prospective study ofprognostic factors in in vitro fertilization and embryo transfer. Fertil Steril 1989;51:838-44. Jones HW Jr, Acosta AA, Andrews MC, Garcia JE, Jones GS, Mayer J, et al. Three years of in vitro fertilization at Norfolk. Fertil Steril 1984;42:826-34. Lipitz S, Rabinovici J, Ben-Shlomo I, Bider D, Ben-Rafael Z, Mashiach S, et al. Complete failure of fertilization in couples with unexplained infertility: implications for subsequent in vitro fertilization cycles. Fertil Steril 1993;59:34852. Ben-Shlomo I, Bider D, Dor J, Levran D, Mashiach S, BenRafael Z. Failure to fertilize in vitro in couples with male infertility: what next? Fertil Steril 1992;58:187-9. World Health Organization. WHO Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed. Cambridge: The Press Syndicate of the University of Cambridge, 1987:3-6. Rudak E, Dor J, Mashiach S, Nebel L, Goldman B. Chromosome analysis of multipronuclear human oocytes fertilized in vitro. Fertil Steril 1984;41:538-45. Dor J, Rudak E, Nebel L, Serr DM, Goldman B, Mashiach S. Successful in vitro fertilization and embryo transfer in a group of patients with tubal infertility. Isr J Med Sci 1984;20:41-5. Dor J, Shulman A, Levran D, Ben-Rafael Z, Rudak E, Mashiach S. The treatment of patients with polycystic ovarian syndrome by in-vitro fertilization and embryo transfer: a comparison of results with those of patients with tubal infertility. Hum Reprod 1990;5:816-8.
Fertility and Sterility
Vol. 61, No.5. May 1994
Printed on acid-free paper in U. S. A.
Copyright Il:! 1994 The American Fertility Society
Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles
Shlomo Lipitz, M.D.* Jaron Rabinovici, M.D. Mordechai Goldenberg, M.D.
David Bider, M.D. Jehoshua Dor, M.D. Shlomo Mashiach, M.D.
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, and The Sackler School of Medicine, Tel-Aviv, Israel
Objective: To determine whether complete failure of fertilization of oocytes in couples with mechanical infertility during the first IVF cycle indicates a poor prognosis for subsequent IVF cycles. Design: A retrospective study of 172 cycles of IVF in 50 couples with mechanical infertility and complete failure of fertilization during their first IVF trial. Setting: In vitro fertilization unit of the Sheba Medical Center. Patients: Fifty couples undergoing one to eight cycles of IVF for mechanical infertility. Main Outcome Measure(s): Fertilization rate of retrieved oocytes and pregnancy rate. Results: Of the initial 50 couples, 44 underwent additional IVF cycles, and 43 (97.7%) achieved fertilization during the second or third cycle. Twenty-four patients conceived during the study period as a result ofIVF. Conclusions: Complete failure of fertilization in couples with mechanical infertility does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. Complete failure of fertilization during the first cycle of IVF in couples with mechanical infertility is accompanied by a good prognosis for subsequent cycles. Fertil Steril 1994;61:863-6 Key Words: IVF, mechanical infertility, failure of fertilization
Complete failure of fertilization is a frustrating experience for couples undergoing IVF. After successful oocyte retrieval, failure to achieve fertilization of any of the retrieved oocytes can occur in approximately 10% to 20% of all IVF cycles (1-3). Failure of fertilization occurs approximately twice as often in couples with male infertility diagnosed by classic criteria than in couples with normal sperm parameters (3). In addition, the lower rate of fertilization in couples with abnormal sperm parameters often implies a poor prognosis for future IVF cycles (4, 5).
Received August 2, 1993; revised and accepted January 7, 1994. * Reprint requests: Shlomo Lipitz, M.D., Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer 52621, Israel (FAX: 972-3-535-2081). Vol. 61, No.5, May 1994
In our IVF program at the Sheba Medical Center, complete fertilization failure occurs in 8%, 48%, and 22% of all treatment cycles of couples with tubal infertility, male infertility, and unexplained infertility, respectively (6). We showed previously that complete failure of fertilization during the initial IVF attempt in couples with male infertility or with unexplained infertility is associated with decreased oocyte fertilization rates and repeated complete failures of fertilization in subsequent IVF cycles (6, 7). These findings indicate that initial complete failure of fertilization in some couples with male infertility or with unexplained infertility may result from a chronic pathology of sperm-oocyte interaction. Little is known about the clinical significance of fertilization failure during the first IVF cycle in coupIes with mechanical infertility and normal semen Lipitz et al.
Complete failure of fertilization in IVF
863
parameters and whether this initial failure of fertilization signifies a previously undiagnosed pathology. Therefore, the aim of this retrospective study was to examine the results of 172 IVF cycles in 50 couples with mechanical infertility after complete failure of fertilization in their first IVF trial. Specifically, we wanted to examine whether complete failure of fertilization in these couples recurred during subsequent IVF cycles and if not, whether the oocyte fertilization rate during these subsequent cycles was different from that observed with other causes of infertility.
MATERIALS AND METHODS
We carried out a retrospective file search of our computerized data base that contains all clinical and laboratory records of patients who underwent IVF between 1984 and 1990. The search algorithm aimed to identify those couples in whom mechanical infertility was diagnosed either by hysterosalpingography and/or by laparoscopy before IVF. Only those couples were included in this study in whom no retrieved oocytes were fertilized during the first IVF -ET treatment cycle. In all treatment cycles, only the husband's semen was used. In all cases, semen analysis before and during any IVFET treatment cycle was found to be normal according to the criteria of the World Health Organization (8). In each case, the diagnosis of mechanical infertility had been reached after the following tests were found to be within the normal range. Female tests: regular menses; biphasic body temperature; luteal phase serum P; PRL; LH; FSH; and thyroid hormones. Male tests: repeated sperm analyses; bacteriological cultures; testicular volume; LH; FSH; T; repeated postcoital tests. The diagnosis of mechanical infertility was based on a pathologic hysterosalpingography verified by a subsequent laparoscopy. The treatment and monitoring protocols used for IVF-ET were described previously (9, 10). The term "first IVF cycle" refers to the initial IVF cycle with complete failure of fertilization. The subsequent cycles are numbered consecutively, for example, second IVF cycle refers to the cycle after the initial, unsuccessful cycle. The patients were neither specifically encouraged nor discouraged to repeat cycles. Repetition of the cycle depended on the expressed desire of the patients. Micromanipulation or chemical treatments were not used in subsequent cycles. The stimulation protocols were simi864
Lipitz et al.
Complete failure of fertilization in IVF
lar. Pregnancy was defined as fetal heart rate motion on ultrasound. Data were analyzed by nonparametric methods. Correlation between the number of fertilized 00cytes during the different IVF cycles was determined by Kendall's rank correlation coefficient test. Results are expressed as mean ± SEM. Significance was assumed at P s 0.05.
RESULTS
Fifty couples with mechanical infertility failed to fertilize 397 oocytes during the first IVF cycle (Tables 1, 2). Forty-four couples (88%) underwent one cycle, 30 underwent two cycles, 19 underwent three cycles, 14 underwent four cycles, 8 underwent five cycles, 4 underwent six cycles and 3 underwent eight additional cycles of IVF-ET (Table 1). The pregnancies that occurred during the study period and the combined cumulative pregnancy rate (PR) for the study population are shown in Table l. Twenty-four of the initial 44 couples conceived as a result of IVF during the study period after their first failed IVF cycle, that is, the IVF-related PR per couple was 54.5%, and the PR per cycle was 14%. Thirteen pregnancies resulted in deliveries, that is, the take home baby rate per cycle was 7.6%. Number of IVF Cycles Needed to Overcome Complete Failure of Fertilization
All 43 couples who elected to undergo at least two more IVF cycles achieved fertilization in at least one subsequent cycle. One couple did not retry after two initial failures. Most of the "first-time" fertilizations (79.5%) occurred during the second IVF cycle and the rest during the third IVF cycle. Among the 35 couples who achieved fertilization
Table 1 In Vitro Fertilization Cycles, Pregnancies, and Cumulative PR After Failure of Fertilization During the First IVF Cycle*
Cycle
No. of IVF cycles
IVF -related pregnancies
Cumulative IVF-related PR
1 2 3 4 5 6 7 8
50 44 30 19 14 8 4 3
0 7 4 4 6 2 0 1
0 0.16 0.27 0.43 0.67 0.75 0.75 0.84
* This table includes all IVF cycles during the study period.
Fertility and Sterility
Table 2
Estradiol Levels and Number of Oocytes Retrieved and Fertilized During 1VF Cycles
Oocytes retrieved
Fertilization rate
Oocytes fertilized
%
First cycle (n = 50) Second cycle (n = 44) Third cycle (n = 30) Fourth cycle (n = 19) Fifth cycle (n = 14) Sixth cycle (n = 8) Seventh cycle (n = 4) Eight cycle (n = 3)
397 340 234 144 91 55 26 19
(7.9 (7.7 (7.8 (7.5 (6.5 (6.8 (6.5 (6.3
± ± ± ± ± ± ± ±
1.1) [1 to 22]t
0.9) [1 to 25] 0.6) [2 to 18] 0.7) [2 to 15] 0.7) [2 to 13] 0.6) [2 to 14] 0.8) [3 to 10] 1) [2 to 7]
* Conversion factor to S1 unit, 3.671.
during the second cycle, seven pregnancies that resulted in seven singleton deliveries at term were recorded (Table 1). Of the nine couples who again failed to achieve fertilization during the second IVF cycle, eight underwent a third trial. During this third cycle all eight women achieved fertilization, and one woman conceived and delivered at term. It is noteworthy that complete failure of fertilization did not recur in any of the 30 couples who underwent three or more cycles of IVF. Failure of Fertilization in the First Cycle Is Not a Predictor of Decreased Fertilization During Subsequent IVF Cycles in Couples with Mechanical Infertility
The 44 couples underwent 122 subsequent IVF cycles after the initial failed cycle. The overall rate of oocyte fertilization during the IVF cycles that followed the unsuccessful first cycle was 70.5% compared with 67.6% in all couples with mechanical infertility (11). The fertilization rates were similar for the individual cycles, that is, 71.7%, 67.5%, and 75% for the second, third, and fourth cycles, respectively (Table 2). Further, mean E 2 levels were similar in all cycles (Table 2).
DISCUSSION
The results of our study indicate that complete failure of fertilization in couples with mechanical infertility does not persist during subsequent IVF cycles. All 43 couples who elected to undergo at least two more IVF cycle achieved fertilization in at least one subsequent cycle. One couple did not retry after two initial failures. Because all of the firsttime fertilizations occurred during the second and Vol. 61, No.5, May 1994
244 158 108 63 38 17 13
(5.5 (5.2 (5.6 (4.5 (4.7 (4.2 (4.3
± ± ± ± ± ± ±
0 1.8) [0 to 14] 1.2) [0 to 11] 1.5) [1 to 10] 0.9) [1 to 9] 1) [2 to 8] 1.1) [2 to 8] 0.7) [1 to 6]
0 71.7 67.5 75 69.2 69 65.3 68.4
E2 levels on day ofhCG pg/mL*
1,112 1,085 1,099 1,153 1,170 1,200 1,095 1,132
± ± ± ± ± ± ± ±
496 462 399 452 394 512 405 408
t Values are total number with means ± SE oocytes per couple in parentheses and ranges in brackets.
third IVF cycle, at least two additional IVF cycles should be performed after primary failure of fertilization in these couples before considering other diagnoses or other treatment options. Our data indicate that initial complete failure of fertilization during the first IVF cycle in couples with mechanical infertility is not associated with decreased oocyte fertilization rates in subsequent cycles (Table 2). In this study, after the first failed IVF cycle complete failure of fertilization recurred only in 9 of the 122 subsequent IVF cycles. Complete failure of fertilization did not recur in any of the 78 cycles ofthe 30 couples who underwent three or more cycles of IVF. Further, the overall oocyte fertilization rate during the subsequent cycles was 70.5%, and this rate compares favorably with our experience and with the experience of others. The results of this study and of previous studies (6, 7) seem to indicate that initial complete failure of fertilization carries a different prognosis in couples with mechanical infertility than in those with male or unexplained infertility. We reported previously on the fertilization rates of couples with male infertility after at least one previous IVF cycle resulted in complete failure of fertilization (7). Of all couples with male infertility, 81.2% achieved fertilization in a subsequent cycle, but the mean oocyte fertilization rate during these subsequent cycles was decreased (47.7%) and complete failure of fertilization recurred in subsequent cycles (7). In another study on initial complete failure of fertilization in couples with unexplained infertility, we showed that most couples (81.1%) achieved fertilization during the two subsequent treatment cycles (6). However, in these couples with unexplained infertility, initial failure of fertilization also was accompanied by decreased oocyte fertilization rate in subsequent cycles. Thus, we concluded that in these Lipitz et al.
Complete failure of fertilization in IVF
865
cases initial complete failure of fertilization may serve as an indicator of an underlying undiagnosed pathology of oocyte and sperm interaction (6). The results ofthe present study indicate that in contrast to couples with either male or unexplained infertility, initial complete failure of fertilization in couples with mechanical infertility is associated with an excellent prognosis for subsequent IVF cycles. This suggests that complete failure of fertilization in most couples with mechanical infertility occurs due to acute, nonrepetitive reasons such as, inadequate ovarian stimulation and laboratory techniques. In conclusion, the results of this study indicate that complete failure of fertilization during the first IVF cycle in couples with mechanical infertility does not necessarily recur during subsequent IVF cycles. Nearly all couples (97.7%) will achieve fertilization during the first two subsequent treatment cycles. In these subsequent IVF cycles, a normal oocyte fertilization rate and a normal PR can be expected.
REFERENCES 1. Trounson A, Wood C. In vitro fertilization results, 1979-82 at Monash University, Queen Victoria and Epworth Medical Centers. J In Vitro Fert Embryo Transf 1984;1:42-7. 2. Molloy D, Harrison K, Breen T, Hennessey J. The predic-
866
Lipitz et al.
Complete failure of fertilization in IVF
3.
4.
5.
6.
7.
8.
9.
10.
11.
tive value of idiopathic failure to fertilize on the first in vitro fertilization attempt. Fertil Steril 1991;56:285-9. Barlow P, Englert Y, Puissant F, Lejeune B, Delvigne A, Van Rysselberge M, et al. Fertilization failure in IVF: why and what next? Hum Reprod 1990;5:451-6. Hughes EG, King C, Wood EC. A prospective study ofprognostic factors in in vitro fertilization and embryo transfer. Fertil Steril 1989;51:838-44. Jones HW Jr, Acosta AA, Andrews MC, Garcia JE, Jones GS, Mayer J, et al. Three years of in vitro fertilization at Norfolk. Fertil Steril 1984;42:826-34. Lipitz S, Rabinovici J, Ben-Shlomo I, Bider D, Ben-Rafael Z, Mashiach S, et al. Complete failure of fertilization in couples with unexplained infertility: implications for subsequent in vitro fertilization cycles. Fertil Steril 1993;59:34852. Ben-Shlomo I, Bider D, Dor J, Levran D, Mashiach S, BenRafael Z. Failure to fertilize in vitro in couples with male infertility: what next? Fertil Steril 1992;58:187-9. World Health Organization. WHO Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed. Cambridge: The Press Syndicate of the University of Cambridge, 1987:3-6. Rudak E, Dor J, Mashiach S, Nebel L, Goldman B. Chromosome analysis of multipronuclear human oocytes fertilized in vitro. Fertil Steril 1984;41:538-45. Dor J, Rudak E, Nebel L, Serr DM, Goldman B, Mashiach S. Successful in vitro fertilization and embryo transfer in a group of patients with tubal infertility. Isr J Med Sci 1984;20:41-5. Dor J, Shulman A, Levran D, Ben-Rafael Z, Rudak E, Mashiach S. The treatment of patients with polycystic ovarian syndrome by in-vitro fertilization and embryo transfer: a comparison of results with those of patients with tubal infertility. Hum Reprod 1990;5:816-8.
Fertility and Sterility