Artificial Insemination Using Homologous Semen: A Review of 158 Cases

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VoL 27, No, 6, June 1976 Printed in U,S,A,

FERTILITY AND STERILITY Copyright < 1976 The American Fertility Society

ARTIFICIAL INSEMINATION USING HOMOLOGOUS SEMEN: A REVIEW OF 158 CASES RICHARD E, DIXON, M.D.,* VEASY C. BUTTRAM,

JR.,

M.D.,t

AND

CAROLYN W. SCHUM, M.A.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77025

One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 15 (9.5%) were successful. Women with anatomical abnormalities were not excluded from the study and they were less successful than the normal women, but results were disappointing in both groups. The most frequently recorded indication for AIH was decreased density or motility of the husband's sperm, but pregnancy occurred in only 2 of the 48 cases in which sperm count was consistently <50 x 10 6/ml and in only 3 of the 63 cases in which sperm motility was consistently <60%. When several semen analyses revealed considerable fluctuation in semen quality, the chances for impregnation by natural means appeared to be greater than the likelihood of success with AIH. The procedure does not seem to compensate for diminished count or motility, does not seem to be of particular value in cases of unexplained infertility, and appears to be indicated only in very special cases, if at all.

Over the years that artificial insemination with the husband's semen (AIR) has been a method of treating infertility, the reported rates of success have ranged from barely above zero to nearly 100%.1-11 This disparity arises for many reasons. The multiple factors related to the female's reproductive system and male's semen quality as well as the interaction of the two are unique in each couple. Moreover, in the studies done, indications for therapy, duration of therapy, and techniques of semen analysis and insemination have differed. In the face of such variability, comparing results from study to study has not been particularly hel pful. Nevertheless, the amount of Accepted February 20, 1976. *Endocrine-Infertility Fellow, Department of Obstetrics and Gynecology. t Associate Professor, Department of Obstetrics and Gynecology.

available data is increasing, and a pooling of carefully defined and controlled data might substantiate what are now, necessarily, only speculations. The following is a retrospective report of 158 cases of artificial insemination using homologous semen. The results are analyzed in terms of possible influences of male and female abnormalities and of techniques of insem ination. EXPERUMENTALPROCEDURE

Patients. The medical records of 158 consecutive private patients who underwent AIH from January 1970 through December 1973 were examined for the following: indication for insemination, age of patients, length of infertility, pelvic disease, previous gravidity, pregnancy rate, and outcome of pregnancy. Inpatient records on 131 of the females hospitalized

647

DIXON ETAL.

648

for evaluation were also reviewed. At the close of the study, 14 candidates were continuing therapy, having completed two to eight unsuccessful cycles. Semen Collection and Evaluation. Semen, collected by masturbation after 3 days of continence, was evaluated within 2 hours of ejaculation, always in the same laboratory and generally by the same person. Total volume, density, motility, and percentage of abnormal spermatozoa were recorded. In addition, immunologic screening according to the procedure of Franklin and Dukes 12 was performed on all initial samples and repeated at least once on all positive specimens. In the final 2 years, sperm testing was modified to include the procedures developed by Kibrick et al. 13 and Isojima et al. 14 Split ejaculates were obtained from 38 males and analyzed in a fashion similar to that described above. Multiple specimens frequently were obtained when analysis indicated some abnormality. Six or more analyses were recorded in 13 cases and three to five analyses in 64 cases. However, in 35 cases two analyses were done,

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and in 46 cases a single analysis was performed. Indications for Insemination. Indication for insemination was not always stated in the records and, in some 32 cases in which volume, density, and motility were normal, the therapy evidently was initiated because of unexplained infertility. Table 1 shows what were judged to be the primary indications. Insemination Procedure. Inseminations were performed daily or on alternate days one to four times per cycle beginning 1 or 2 days prior to expected ovulation and terminating upon the shift in basal body temperature. Semen was collected by masturbation. In two cases, because of retrograde ejaculation, the technique for semen recovery was basically the same as that described by Hotchkiss et al. 15 In every case insemination took place within 2 hours of the time semen was collected. Two methods of insemination were used. The cervical cap technique was employed in 42 patients, and that technique in combination with intracervical

TABLE 1. Indications {or Insemination Indication

Decreased volume « 1 mD + normal count and motility + decreased count + decreased motility Fluctuating volume + normal count and motility Decreased count and motility « 50 x 10o/ml; <60%) + decreased volume Fluctuating count and motility + fluctuating volume Fluctuating count and normal motility Fluctuating motility and normal count Decreased count + normal motility + fluctuating motility Decreased motility + normal count + fluctuating count Hypospadias Retrograde ejaculation Psychogenic impotence Immune reaction Unexplained infertility Total

No. of cases

4 1

No. pregnant

with AIR

1

1 1

22

No. of spontanteous pregnancies

1

1 3

4

5

3

22 2 9

2

8 14

2 2

7 18 2 2

3 6

o

1

2

o o

32

1 6

158

15

9

o o o o 5

29

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HOMOLOGOUS ARTIFICIAL INSEMINATION

TABLE 2. Influence ofAge, Length ofInfertility, and Gravidity on Success of AIH No. of No. % pregpatients pregnant nant attempting AIR

Age (yr) <25 25-29 :330 Duration of infertility (yr) <2 2-4 >4 Gravidity 1 infertile ~ infertile 0

20 110 36

3 10 2

15.0 9.1 5.6

37 90 39

4 9 2

10.8 10.0 5.1

120 46

10 5

8.3 10.9

649

exercise and instructed to remove the cap in 6 to 8 hours. An attempt to conceive was considered terminated when pregnancy occurred or when the patient desired no further insemination. Over the 4-year study period, 1309 inseminations during a total of 560 cycles were performed on 158 patients. On a per-patient basis this represented an average of 3.54 cycles or 8.3 exposures to homologous semen. Those who became pregnant were treated an average of 3.1 cycles with 7.7 inseminations. Patients who failed to conceive were exposed an average of 8.3 times during 3.6 cycles.

infusion of 0.2 ml o(semen was used in the remainder. In 38 cases, split ejaculates were obtained and the portion of highest quality was introduced by the RESULTS latter method. In two cases, hypospadiac males, who were instructed in use of Number and Pattern of C(M1,ceptions. the cervical cap, performed the insemina- Fifteen pregnancies were achieved by tion at home. the 158 couples, for an over-all success After insemination, the reclining pa- rate of 9.5%. More than one-half of the tient was given several minutes to adjust pregnancies occurred within two cycles, to the presence of the cap and then and 14 of the patients had conceived encouraged to resume her routine ac- within 5 months of treatment. However, tivity. She was advised against strenuous almost half of the original 158 women TABLE 3. Presence of Female Abnormalities and Results of AIH and Natural Insemination in 158 Patients Diagnosis

Complete evaluation Anatomical abnormality Endometriosis Endometriosis + adhesions Endometriosis + uterine abnormality Tubo-ovarian adhesions Tubal occlusion Uterine abnormality One of the above + anovulation One of the above + immune reaction Anovulation alone Immune reaction alone Normal Total Incomplete evaluation Anovulation Immune reaction alone Normal Total

No. of patientsfl

No. pregnant with AIR

96 42 (2) 14 8 (1) 7 (2) 5 5 (2) 11 (2) 4

No. of spontaneous pregnancies

21

5 3

8 5

1 1

3 5

14 6 15

3

2

3

3

131

11

26

1 3 23

1 3

2

27

4

3

1

aThe numbers in parentheses indicate the number of patients who did not undergo surgery but are included in the accompanying figure.

DIXONETAL.

650

had dropped out by the end of the 3rd month and 113 of the 158 had discontinued therapy by the end of the 5th month. Influence of Age, Length of Infertility, and Gravidity on Success ofAIH. Records were examined for influence of age, length of infertility, and gravidity on results (Table 2). The data reflect trends reported elsewhere,16 but the limited number of pregnancies precludes any meaningful conclusions. Influence of Female Abnormalities on Success of AIH (Table 3). Prior to or during the early course of therapy, 131 patients underwent a complete examination which included endoscopy or laparotomy. Significant abnormalities were found in 96 women. Eighty-seven of them were treated with conservative surgery prior to AIH therapy, which continued for 1 to 18 cycles. (Thirty-two women underwent a single cycle of treatment following surgery.) Of the 87 patients, 5 became pregnant after surgery. The nine patients who decided against surgery did not conceive. Fifteen patients were found to be anovulatory, and after proper treatment three conceived with AIH. Thirteen women had a positive reaction to the Franklin-Dukes

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test; of the thirteen, three also had a positive reaction to the Kibrick test, and two had a negative reaction. Nine of the women with an immune reaction appeared to be normal otherwise; one conceived. Of the 38 women who were considered normal (15 after evaluation which included endoscopy), 6 became pregnant. Influence of Semen Quality on Success of AIH. Various indications for AIH have been suggested,17. 18 but, as Table 1 shows, the most common in the present study was diminished quantity or quality of semen. In five cases deposition of sperm in the vagina was impossible because of hypospadias, impotence, or retrograde ejaculation. The two hypospadiac males, both of whom performed the inseminations themselves, were successful. In one instance the wife was normal and semen was optimal; in the other, the wife had undergone surgery, and semen analysis showed a count of 34 x 106/ml and motility of38%. The impotent male, with a count of 150 x 10 6/ml, motility of 60%, and a wife with no apparent abnormality, was unsuccessful in 13 inseminations. Although pregnancies have been reported after recovery of semen from the bladder,15. 19 semen

TABLE 4. Joint Frequency of Sperm Count and Percentage of Motility Recorded for 156 a Males, with Indication of Condition of Females and Number of AIH Pregnancies Sperm motility

<40% Sperm count

40-59% Pregnancies

Males

Femalesb

Males

AIH

Sp"

"'60% Pregnancies

Pregnancies Females

Males

AIR

Sp

Females

AIR

Sp

millionlml

<20

1

Ab 1

0

0

5

N 4, Ab 1

0

0

20-39

7

1

3

N 1, Ab 2

0

1

12 (2)

40-59

2

N 2, Ab 4, 2 1m 1 N 1, Ab 1 0

1

10

N 3, Ab 7

0

1

16 (6)

N 3, Ab 7

4

25 (12) N9,AbI5, 1 1m 1

4

;;.60

10 (6)

0

4

N 1, Ab 2, 0 1m 1 N I,Ab 11 0

N3,Ab11, 3 1m2 61 (27) N 23, Ab 9 34, 1m 4

1 2 1 13

aln two cases of retrograde ejaculation, quantity was not sufficient to be measured. Numbers in parentheses indicate number of males with erratic count or motility. b Ab, Abnormal; N, normal; 1m, immune. "Sp, Spontaneous.

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HOMOLOGOUS ARTIFICIAL INSEMINATION

recovered in the two cases of retrograde ejaculation was not of sufficient quantity to offer any reasonable chance of success. Normal Forms. The percentage of normal forms was recorded for 131 patients. Fewer than 80% normal forms appeared in 48 cases; AIH was successful in 3 of these. (Spontaneous pregnancies subsequently occurred in 13 others.) Table 4, which includes the one impotent and the two hypospadiac patients, indicates the joint frequency of specified levels of sperm count and motility. It also shows the condition of wives of the men in each category and the number of pregnancies that occurred. It is based on the highest sperm count and motility recorded for each patient, a level which in 65 cases was not reached consistently, as semen quality fluctuated from subnormal to normal. In 53 cases, count fluctuated from <60 to >60 x 106/ml by a difference of 40 to 50 x 106/ml. In 41 patients motility fluctuated from < 60% to > 60% by a difference of at least 20%. Of the 65 men whose semen quality was erratic along at least one dimension, 4 achieved conception with AIH and 18 reported spontaneous pregnancies.

Influence of Techniques of Insemination upon Success of AIH. In 42 cases the cervical cap alone was used; 4 pregnancies were achieved (9.5%). In 116 cases a combination of the cervical cap and intracervical infusion of semen was used, and a total of 11 conceptions occurred (9.5%). Although some studies have reported encouraging results with the use of split ejaculates to improve semen quality,2o.21 only 2 pregnancies occurred in the 38 cases in which split ejaculates were introduced by the combination of techniques. Pregnancy Outcome. The 15 pregnancies resulted in 11 live births (6 males and 5 females). Three pregnancies terminated in either the first trimester or early second trimester. One patient

651

was lost to follow-up after an uneventful second trimester. Spontaneous Pregnancies. Spontaneous pregnancies following failure with AIH have been reported by others.2. 5. 16 In the present study the number subsequently reporting impregnation by natural means is almost twice the number successful with artificial insemination. (N 0 spontaneous pregnancies were reported for 171 patients who underwent artificial insemination with donor semen during the same time period. 22) Female Factors. Of the 143 women for whom AIR was unsuccessful, 29 became pregnant 3 months to 2 years after therapy. Initial evaluation of the 29 had shown 3 to be anovulatory and 5 to be normal. Pelvic abnormalities were recorded for 21, 13 of whom had undergone conservative corrective surgery prior to AIH therapy. None of the 13 women in whom an immune interaction had been identified reported spontaneous pregnancies. The average age for this group was 27.5 years, length of infertility 2.5 years, and exposure cycles 3.2, for 8.3 inseminations per patient. Sixteen were nulligravidas prior to conception. Along dimensions such as age, length of infertility, abnormalities of the reproductive organs, and number of inseminations received, the women with spontaneous pregnancies did not differ demonstrably from the group as a whole. Male Factors. An interesting characteristic of the men who ultimately achieved impregnation by natural means was that, in 18 of the 29, semen quality and/or quantity fluctuated significantly from analysis to analysis. In seven cases the highest recorded count and percentage of motility were what we have called optimal (;:: 60 x 106/ml and ;::60%), but either count or motility had appeared subnormal as often as it had appeared normal.

DIXON ET AL.

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In 13 cases there was a wide disparity between count and motility in terms of normalcy or quality, one being optimal when the other was subnormal (i.e., count 201 x 106/ml, motility 35%). This disparity was recorded consistently in six cases. In seven others, while semen was consistently suboptimal on one dimension, it was normal in at least one analysis on the other dimension. In three cases both count and motility were consistently low; in two of those volume fluctuated from < 1 ml to > 1 ml. Five males were judged normal (on the basis of a single analysis), and a sixth showed optimal count and motility with fluctuating volume. The maximum number of semen analyses recorded for any of the 29 patients was 5; there were 2 of those. As many as 13 had had only one or two analyses. DISCUSSION

So many factors are known to be invol ved in the process of conception and so many more are still the subject of speculation that evaluation of a procedure such as AIR is at best frustrating and at worst futile. In this study, as in any of which we are aware, the number of variables is so great in proportion to the number of patients treated that true statistical analysis of data is impossible. Although some of the data are drawn from possibly incomplete records and some must, of necessity, be based on subjective evaluation, the results are perfectly clear: AIR was successful in only 15 of the 158 cases reviewed. Indications for AIR, the nature of disorders diagnosed and treated, and techniques of insemination were reviewed in an effort to explain the discouraging results. Evaluation of patients, analysis of semen, and actual insemination had followed frequently used and accepted procedures. We found, as have others,2. 3, 17 that results did not differ

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significantly whether the means of insemination was a cervical cap or intracervical infusion in combination with the cap. Of those couples who were successful, three achieved impregnation in a single AIR cycle of 2 inseminations, and one couple was successful only after 9 cycles and a total of 21 inseminations. Although persistence is encouraged,23, 24 it seems unlikely that extension of therapy would have affected results in any couples except, perhaps, those who later reported spontaneous pregnancies. The group treated was not unusual in terms of age, length of infertility, or previous gravidity when compared with patients described in other studies. 16, 25 A factor undoubtedly important to the results of AIR in this group, however, was the physical condition of the women presenting for therapy (Table 3). Admittedly, the number of normal females was only 53. Nine became pregnant with AIR and eight reported subsequent spontaneous pregnancies. There is no way of knowing how many of the 87 women treated with conservative surgery were actually capable of conception after treatment, although 5 became pregnant with AIR and 21 later achieved pregnancy by natural means. Four of the women whose only apparent difficulty was an immune reaction indicated by a positive response to the Franklin-Dukes test (and, in two instances, to the Kibrick test as well) were paired with normal males; one was successful. (As Behrman and Menge 26 suggest, immune interaction may be multifocal and not reserved solely to the cervical mucus.) In as many as 28 cases semen quality was consistently optimal and the wives were either normal (15 cases) or considered normal after minor treatment (13 cases). Seven were successful with AIR; three had subsequent spontaneous

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HOMOLOGOUS ARTIFICIAL INSEMINATION

pregnancies. Moreover, it should be noted that, in practically every case reviewed, one or the other partner received some treatment, medical or surgical, which might have eliminated or ameliorated factors contributing to infertility even before AIH therapy was initiated. Various indications for AIR have been discussed elsewhere.17, 18,23 As Table 1 shows, the greatest number of patients in the present study turned to AIR because of diminished quantity or quality of semen. Of some interest, however, was the degree of fluctuation in sperm density and percentage of motility in 65 cases. That there were 4 AIR pregnancies and 18 spontaneous pregnancies in this group suggests the need for at least three and possibly as many as six analyses before a program of artificial insemination is initiated. The success of AIR when semen quality is so erratic may be only a matter of chance, perhaps enhanced by the physicians aiding in regulation and prediction of the time of ovulation. 27 AIR does not seem to compensate for diminished count or motility, and when several analyses reveal considerable fluctuation in semen quality the chances of natural impregnation may be as great as, or greater than, chances of success with AIR. The results of AIR therapy in these 158 patients suggest that AIH is of dubious value except in a few unusual circumstances, and, within the limits of this study, even in the special situations in which AIR was successful, the numbers were too limited to be significant. If AIR increased fertility at all when either sperm density or motility was consistently suboptimal, it did not do so sufficiently to warrant the inconvenience, expense, or emotional tension that can accompany the procedure. The only time AIR might be indicated, in our opinion, is when, for reasons physical or psychologic, normal coitus is not possible for a male with semen of optimal count and

653

motility, or when volume of semen of optimal count and motility is so low that vaginal dilution prevents sperm from reaching the os. REFERENCES 1. Behrman SJ: Techniques of artificial insemination. In Progress in Infertility, Edited by SJ Behrman, RW Kistner. Boston, Little, Brown and Co, 1968, p 717 2. Mastroianni L Jr, Laberge JL, Rock J: Appraisal of efficacy of artificial insemination with husband's sperm and evaluation of insemination techniques. Fertil Steril 8:260, 1957 3. Hanson FM, Rock J: Artificial insemination with husband's sperm. Fertil Steril 2:162, 1951 4. Kaskarelis D, Comninos A: A critical evaluation of homologous artificial insemination. Int J Fertil 4:38, 1959 5. Payne S, Skeels RF: Fertility as evaluated by artificial insemination. Fertil Steril 5:32, 1954 6. Swyer GIM: Results of artificial insemination. J Reprod Fertil 2:11, 1961 7. Shields F: Artificial insemination as related to the female. Fertil Steril 1:271, 1950 8. Rubin A: Studies in human reproduction. V. The relationship of type of seminal deficiency to difficulty of conception, based on experience in five hundred inseminations. Fertil Steril 12:581, 1961 9. Ulstein M: Fertility of husbands at homologous insemination. Acta Obstet Gynecol Scand 52:5, 1973 10. Barwin BN: Intrauterine insemination of husband's semen. J Reprod Fertil 36:101, 1974 11. Schellen A: Artificial Insemination in the Human. Amsterdam, Elsevier Publishing Co, 1957 12. Franklin RR, Dukes CD: Antispermatozoal antibody and unexplained infertility. Am J Obstet Gynecol 89:6, 1964 13. Kibrick S, Belding DL, Merrill B: Methods for the detection of antibodies against mammalian spermatozoa. II. A gelatin agglutination test. Fertil Steril 3:430, 1952 14. Isojima S, Ki TS, Ashitaka Y: Immunologic analysis of serum sperm-immobilizing factor in women with unexplained sterility. Am J Obstet Gynecol 101:677,1968 15. Hotchkiss RS, Pinto AB, Kleegman S: Artificial insemination with semen recovered from the bladder. Fertil Steril 6:37, 1955 16. Gregoire AT, Moran MJ, Quintero R, O'Connell K: The pregnancy rate, duration of infertility, months of treatment, and semen character-

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18. 19.

20.

21.

DIXON ET AL.

istics expressed in age specific groups of couples attending a fertility service. Fertil Steril 23:894,1972 Guttmacher AF: The role of artificial insemination in the treatment of sterility. Obstet Gynecol Survey 15:767, 1960 Finegold WJ: Artificial Insemination. Springfield Ill, Charles C Thomas, 1964 Bourne RB, Kretzschmar WA, Esser JH: Successful artificial insemination in a diabetic with retrograde ejaculation. Fertil Steril 22:275, 1971 Amelar RD, Hotchkiss RS: The split ejaculate, its use in the management of male infertility. Fertil SteriI16:46, 1965 Perez-Pelaez M, Cohen MR: The split ejaculate in homologous insemination. Int J Fertil 10:25,1965

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22. Dixon RE, Buttram VC Jr: Artificial insemination using donor semen: a review of 171 cases. Fertil Steril 27:130, 1976 23. Warner MP: Artificial insemination: review after thirty-two years' experience. NY State J Med 13:2358, 1974 24. Hill AM: Experience with artificial insemination. Aust NZ J Obstet Gynaecol 10:112, 1970 25. Warner MP: Results of a twenty-five-year study of 1,553 infertile couples. NY State J Med 62:2663, 1962 26. Behrman SJ, Menge AC: In Human Reproductive Conception and Contraception, Edited by ESE Hafez, TN Evans. New York, Harper and Row, 1973, p 237 27. Foldes JJ: Artificial insemination: induced ovulation with intravenous estrogens. Int J Fertil17:104,1972