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The Duration of Infertility: An Important Datum for The Fertility Prognosis of Men with Semen Abnormalities
Vol. 30, No.4, October 1978 Printed in U.S A.
FERTILITY AND STERILITY Copyright' 1978 The American Fertility Society
THE DURATION OF INFERTILITY: AN IMPORTANT DATUM FOR THE FERTILITY PROGNOSIS OF MEN WITH SEMEN ABNORMALITIES JACOB H. AAFJES, M.D., PH.D.* JAN C. M. v. D. VIJVER, M.D., PH.D.t PETER E. SCHENCK, M.Sc.
Department of Endocrinology, Growth and Reproduction, and Division of Clinical Endocrinology, Department of Medicine III, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands
In a group of 584 men with semen abnormalities the relationship between conception and the duration of infertility was studied. "Spontaneous" pregnancies were reported significantly more frequently for men with an infertility duration of less than 2 years than for men with an infertility duration of more than 2 years. Seventy-three conceptions occurred "spontaneously" and sixty-six occurred while the men were undergoing different forms of therapy. When all pregnancies were considered together it appeared that the "chance" of fathering a child after 2 years of infertility was still about 20% during the ensuing 3 years. Fertil Steril30:423, 1978
In a group of 354 men referred for infertility and semen abnormalities, 83 were azoospermic.! In this group of azoospermic patients fertility was achieved only after appropriate therapeutic measures had been taken, suggesting that extramarital pregnancies are uncommon. In the other patients, "spontaneous pregnancies," i.e., pregnancies which occurred before some form of therapy was instituted, were more numerous than were pregnancies which occurred during the course of therapy. Of the patients who impregnated their wives, the mean duration of infertility was significantly lower than that ofthe patients who did not fertilize during therapy. This finding seems to indicate that the chance of fertility diminishes with the duration of the infertility. That this is the case was suggested in 1953 by MacLeod and Gold. 2 They studied semen quality in relation to the time elapsed before conception occurred. For patients with sperm counts below 20 million/ml or with low sperm motility, more
time was required for pregnancy to occur. For infertile couples the effect of the duration of infertility on prognosis has been reported by Southam. 3 She studied 1568 couples, and decreased male fertility or sterility with no abnormality in the wife was observed in 11% of these couples. Unfortunately, no information was provided about the duration of infertility in these male patients. In the present paper, information concerning the duration of infertility and the occurrence of conception is shown to be useful in counseling infertile men. PATIENTS AND METHODS
Male patients were referred by their wives' gynecologists or by their physicians because semen abnormalities were suspected to be the cause oftheir infertility. Only those patients who were not azoospermic were included in the study. All patients underwent the usual investigations for infertility.4 To calculate the duration of infertility, during his first visit to the clinic, each man was asked when the decision to have a child (with secondary infertility, an additional child) was made or when contraception was stopped. At the end of this interview he was instructed as to the optimal time and methods of coitus.
Received March 6, 1978; revised May 17, 1978; accepted May 22, 1978. *Reprint requests: J. H. Aafjes, M.D., Department of Endocrinology, Growth and Reproduction, Erasmus University, P.O. Box 1738, Rotterdam, The Netherlands. t Division of Clinical Endocrinology, Department of Medicine TIL
423
Vol. 30, No.4
AAFJES ET AL.
424
After the results of the laboratory investigations were obtained a decision was made about whether a testicular biopsy was desirable. Biopsies were thought to be advisable whenever oligospermia existed without signs of testicular atrophy: small, soft testes and/or very high serum levels of follicle-stimulating hormone. As a rule, a decision about therapy was made 3 to 6 months after the patient was seen for the first time. The following forms of therapy were instituted: (1) Varicoceles were operated upon. (2) Oligospermia was treated with mesterolone (10:methyl-50:-dihydrotestosterone), 25 mg three times daily. (3) Low sperm motility was treated with Halotestin (fluoxymesterone).5 (4) When leukospermia was present antibiotics were administered. (5) Patients with low gonadotropin levels were treated with clomiphene citrate, 50 mg twice daily, or occasionally with gonadotropins. Pregnancy was generally diagnosed by the wife's gynecologist or by the physician who had first evaluated the patient and referred him to the authors. RESULTS
Five hundred and eighty-four patients were studied, including fifty-five men who had secondary infertility. For the group as a whole 139 pregnancies were observed. Seventy-three of these pregnancies occurred before therapy had been instituted.The distribution of these "spontaneous" pregnancies in relation to the duration of infertility is given in Table 1, which shows that with an infertility duration of less than 2 years the chance of "spontaneous" fertilization is· approximately 2 times as great as with an infertility duration of2 to 6 years and about 10 times as great as with an infertility duration of more than 6 years. Of the remaining 511 patients, 325 were treated. The patients who were not treated were TABLE 1. Relationship Between Duration oflnfertility and "Spontaneous" Pregnancies Duration of infertility
No. of patients
Spontaneous pregnancies
No.
TABLE 2. Relationship between Duration of Infertility and Pregnancies under Therapy Receiving therapy
Occurrence of pregnancy
No_ of patients
No.
%
No.
%
A: 0-2 B: 2-4 C: 4-6 D: ->6
132 201 89 89
103" 127 55 40
78.0 63.2 61.8 44.9
25 27 10 4
24.3 21.3 18.2 10.0
Total
511
325
63.6
66
20.3
Duration of infertility
yr
"Over-all X' test: X' = 25.39; df = 3; P < 0.01. All individual differences (with correction for continuity) are significant except the one between Band C.
in most instances diagnosed as having unremediable abnormalities; however, 10% withdrew from the study. Table 2 shows the numbers ofpatients treated in the different categories ofinfertilty duration and the occurrence of pregnancies in the wives of these men. Treatment was stopped as soon as pregnancy was diagnosed; however, when pregnancy did not occur, the men were treated or followed for at least 1 year. The percentages of treated patients in the groups with the longer durations of infertility were significantly lower than those in the group with an infertility duration of less than 2 years. There were no significant differences among the groups of treated patients in the percentages of conceptions which occurred. Table 3 shows the distribution of all of the pregnancies which occurred in our sample in relation to the duration of infertility (in years). In Table 3 the figures given by Southam 3 for 1568 infertile couples (as opposed to infertile men) are included for comparison. TABLE 3. Percentage of Conceptions in Relation to Duration of Infertility Duration of infertility
584 Men (this study) 1568 Couples (Southam3 )
1 yr
2yr
3yr
4yr
5 yr
45
34
21
24
22
8
24
63
46
35
37
26
22
37
>5 yr
Total
DISCUSSION
%
yr
A: 0-2 B: 2-4 C: 4-6 D: ->6
171 224 98 91
3~
23 9 2
22.8 10.3 9.2 2.2
Total
584
73
12.5
"Over-all X' test: X' = 27.44; df = 3; P < 0.001. Significant differences (with correction for continuity): A vs. B, C, and D, P < 0.01; B vs. D, P < 0.05.
Tables 1 and 3 show a decrease in the chance of fertility the longer the duration of the infertility. This is conceivably the result of an accumulation of cases with more severe disturbances in the categories with longer durations of infertility, which is also reflected in smaller percentages of patients treated (Table 2). That the duration of infertility is important has been insufficiently appreciated. In a recent book
Vol. 30, No.4
FERTILITY PROGNOSIS OF MEN WITH SEMEN ABNORMALITIES
on male infertility,6 under the heading "History and Workup of the Infertile Male," it is stated only that "a chronology of the patient's marital history is helpful." We would like to stress, however, that for the evaluation of particular types of therapy, the duration of the patient's infertility should be taken into account. Compared with the figures of Southam 3 (Table 3) the incidence of pregnancy in our series is smaller. This finding suggests that the treatment of female partners in infertile marriages more often results in pregnancy than does treatment of the male. This conclusion was also reached by Southam,3 who found that in couples in which only the wife showed abnormalities, 38.6% conceived; of couples in which only the male showed abnormalities, 24.7% conceived. If it is assumed that Southam's sample 3 of infertile males had an average duration of infertility comparable to that of the present sample, then comparison of the over-all conception rates in the two studies suggests that there has been no improvement in the treatment of male infertility
425
during the past 17 years. The remarkable thing, however, is that after 2 years of infertility men with semen abnormalities still have a 20% chance of fathering a child during the ensuing 3 years, provided that they are examined and treated. Acknowledgments. We thank Mrs. Y. G. Bron and Mrs. A. W. Douw for collecting the data. REFERENCES 1. Aafjes JH, van der Vijver JCM: 354 Mannen met verminderde vruchtbaarheid. Ned Tijdschr Geneeskd 120:865, 1976 2. MacLeon J, Gold RZ: The male factor in fertility and infertility. Fertil Steril 4:10, 1953 3. Southam AL: What to do with the "normal" infertile couple. Fertil Steril 11:543, 1960 4. Aafjes JH, van der VijverJCM, Docter R, Schenck PE: Serum gonadotropins, testosterone and spermatogenesis in subfertile men. Acta Endocrinol (Kbh) 86:651, 1977 5. Brown JS: The effect of orally administered androgens on sperm motility. Fertil Steril 26:305, 1975 6. Cockett ATK, Urry RL: Male Infertility: Workup, Treatment and Research. New York, Grune & Stratton, 1977, p 165
FERTILITY AND STERILITY Copyright' 1978 The American Fertility Society
THE DURATION OF INFERTILITY: AN IMPORTANT DATUM FOR THE FERTILITY PROGNOSIS OF MEN WITH SEMEN ABNORMALITIES JACOB H. AAFJES, M.D., PH.D.* JAN C. M. v. D. VIJVER, M.D., PH.D.t PETER E. SCHENCK, M.Sc.
Department of Endocrinology, Growth and Reproduction, and Division of Clinical Endocrinology, Department of Medicine III, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands
In a group of 584 men with semen abnormalities the relationship between conception and the duration of infertility was studied. "Spontaneous" pregnancies were reported significantly more frequently for men with an infertility duration of less than 2 years than for men with an infertility duration of more than 2 years. Seventy-three conceptions occurred "spontaneously" and sixty-six occurred while the men were undergoing different forms of therapy. When all pregnancies were considered together it appeared that the "chance" of fathering a child after 2 years of infertility was still about 20% during the ensuing 3 years. Fertil Steril30:423, 1978
In a group of 354 men referred for infertility and semen abnormalities, 83 were azoospermic.! In this group of azoospermic patients fertility was achieved only after appropriate therapeutic measures had been taken, suggesting that extramarital pregnancies are uncommon. In the other patients, "spontaneous pregnancies," i.e., pregnancies which occurred before some form of therapy was instituted, were more numerous than were pregnancies which occurred during the course of therapy. Of the patients who impregnated their wives, the mean duration of infertility was significantly lower than that ofthe patients who did not fertilize during therapy. This finding seems to indicate that the chance of fertility diminishes with the duration of the infertility. That this is the case was suggested in 1953 by MacLeod and Gold. 2 They studied semen quality in relation to the time elapsed before conception occurred. For patients with sperm counts below 20 million/ml or with low sperm motility, more
time was required for pregnancy to occur. For infertile couples the effect of the duration of infertility on prognosis has been reported by Southam. 3 She studied 1568 couples, and decreased male fertility or sterility with no abnormality in the wife was observed in 11% of these couples. Unfortunately, no information was provided about the duration of infertility in these male patients. In the present paper, information concerning the duration of infertility and the occurrence of conception is shown to be useful in counseling infertile men. PATIENTS AND METHODS
Male patients were referred by their wives' gynecologists or by their physicians because semen abnormalities were suspected to be the cause oftheir infertility. Only those patients who were not azoospermic were included in the study. All patients underwent the usual investigations for infertility.4 To calculate the duration of infertility, during his first visit to the clinic, each man was asked when the decision to have a child (with secondary infertility, an additional child) was made or when contraception was stopped. At the end of this interview he was instructed as to the optimal time and methods of coitus.
Received March 6, 1978; revised May 17, 1978; accepted May 22, 1978. *Reprint requests: J. H. Aafjes, M.D., Department of Endocrinology, Growth and Reproduction, Erasmus University, P.O. Box 1738, Rotterdam, The Netherlands. t Division of Clinical Endocrinology, Department of Medicine TIL
423
Vol. 30, No.4
AAFJES ET AL.
424
After the results of the laboratory investigations were obtained a decision was made about whether a testicular biopsy was desirable. Biopsies were thought to be advisable whenever oligospermia existed without signs of testicular atrophy: small, soft testes and/or very high serum levels of follicle-stimulating hormone. As a rule, a decision about therapy was made 3 to 6 months after the patient was seen for the first time. The following forms of therapy were instituted: (1) Varicoceles were operated upon. (2) Oligospermia was treated with mesterolone (10:methyl-50:-dihydrotestosterone), 25 mg three times daily. (3) Low sperm motility was treated with Halotestin (fluoxymesterone).5 (4) When leukospermia was present antibiotics were administered. (5) Patients with low gonadotropin levels were treated with clomiphene citrate, 50 mg twice daily, or occasionally with gonadotropins. Pregnancy was generally diagnosed by the wife's gynecologist or by the physician who had first evaluated the patient and referred him to the authors. RESULTS
Five hundred and eighty-four patients were studied, including fifty-five men who had secondary infertility. For the group as a whole 139 pregnancies were observed. Seventy-three of these pregnancies occurred before therapy had been instituted.The distribution of these "spontaneous" pregnancies in relation to the duration of infertility is given in Table 1, which shows that with an infertility duration of less than 2 years the chance of "spontaneous" fertilization is· approximately 2 times as great as with an infertility duration of2 to 6 years and about 10 times as great as with an infertility duration of more than 6 years. Of the remaining 511 patients, 325 were treated. The patients who were not treated were TABLE 1. Relationship Between Duration oflnfertility and "Spontaneous" Pregnancies Duration of infertility
No. of patients
Spontaneous pregnancies
No.
TABLE 2. Relationship between Duration of Infertility and Pregnancies under Therapy Receiving therapy
Occurrence of pregnancy
No_ of patients
No.
%
No.
%
A: 0-2 B: 2-4 C: 4-6 D: ->6
132 201 89 89
103" 127 55 40
78.0 63.2 61.8 44.9
25 27 10 4
24.3 21.3 18.2 10.0
Total
511
325
63.6
66
20.3
Duration of infertility
yr
"Over-all X' test: X' = 25.39; df = 3; P < 0.01. All individual differences (with correction for continuity) are significant except the one between Band C.
in most instances diagnosed as having unremediable abnormalities; however, 10% withdrew from the study. Table 2 shows the numbers ofpatients treated in the different categories ofinfertilty duration and the occurrence of pregnancies in the wives of these men. Treatment was stopped as soon as pregnancy was diagnosed; however, when pregnancy did not occur, the men were treated or followed for at least 1 year. The percentages of treated patients in the groups with the longer durations of infertility were significantly lower than those in the group with an infertility duration of less than 2 years. There were no significant differences among the groups of treated patients in the percentages of conceptions which occurred. Table 3 shows the distribution of all of the pregnancies which occurred in our sample in relation to the duration of infertility (in years). In Table 3 the figures given by Southam 3 for 1568 infertile couples (as opposed to infertile men) are included for comparison. TABLE 3. Percentage of Conceptions in Relation to Duration of Infertility Duration of infertility
584 Men (this study) 1568 Couples (Southam3 )
1 yr
2yr
3yr
4yr
5 yr
45
34
21
24
22
8
24
63
46
35
37
26
22
37
>5 yr
Total
DISCUSSION
%
yr
A: 0-2 B: 2-4 C: 4-6 D: ->6
171 224 98 91
3~
23 9 2
22.8 10.3 9.2 2.2
Total
584
73
12.5
"Over-all X' test: X' = 27.44; df = 3; P < 0.001. Significant differences (with correction for continuity): A vs. B, C, and D, P < 0.01; B vs. D, P < 0.05.
Tables 1 and 3 show a decrease in the chance of fertility the longer the duration of the infertility. This is conceivably the result of an accumulation of cases with more severe disturbances in the categories with longer durations of infertility, which is also reflected in smaller percentages of patients treated (Table 2). That the duration of infertility is important has been insufficiently appreciated. In a recent book
Vol. 30, No.4
FERTILITY PROGNOSIS OF MEN WITH SEMEN ABNORMALITIES
on male infertility,6 under the heading "History and Workup of the Infertile Male," it is stated only that "a chronology of the patient's marital history is helpful." We would like to stress, however, that for the evaluation of particular types of therapy, the duration of the patient's infertility should be taken into account. Compared with the figures of Southam 3 (Table 3) the incidence of pregnancy in our series is smaller. This finding suggests that the treatment of female partners in infertile marriages more often results in pregnancy than does treatment of the male. This conclusion was also reached by Southam,3 who found that in couples in which only the wife showed abnormalities, 38.6% conceived; of couples in which only the male showed abnormalities, 24.7% conceived. If it is assumed that Southam's sample 3 of infertile males had an average duration of infertility comparable to that of the present sample, then comparison of the over-all conception rates in the two studies suggests that there has been no improvement in the treatment of male infertility
425
during the past 17 years. The remarkable thing, however, is that after 2 years of infertility men with semen abnormalities still have a 20% chance of fathering a child during the ensuing 3 years, provided that they are examined and treated. Acknowledgments. We thank Mrs. Y. G. Bron and Mrs. A. W. Douw for collecting the data. REFERENCES 1. Aafjes JH, van der Vijver JCM: 354 Mannen met verminderde vruchtbaarheid. Ned Tijdschr Geneeskd 120:865, 1976 2. MacLeon J, Gold RZ: The male factor in fertility and infertility. Fertil Steril 4:10, 1953 3. Southam AL: What to do with the "normal" infertile couple. Fertil Steril 11:543, 1960 4. Aafjes JH, van der VijverJCM, Docter R, Schenck PE: Serum gonadotropins, testosterone and spermatogenesis in subfertile men. Acta Endocrinol (Kbh) 86:651, 1977 5. Brown JS: The effect of orally administered androgens on sperm motility. Fertil Steril 26:305, 1975 6. Cockett ATK, Urry RL: Male Infertility: Workup, Treatment and Research. New York, Grune & Stratton, 1977, p 165