ARTIFICIAL INSEMINATION USING HOMOLOGOUS SEMEN: A REVIEW OF 158 CASES

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1 - FERTILITY AND STERILITY Copyright < 976 The American Fertility Society VoL 7, No, 6, June 976 Printed in U,S,A, ARTIFICIAL INSEMINATION USING HOMOLOGOUS SEMEN: A REVIEW OF 58 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 7705 One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 5 (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 of the 48 cases in which sperm count was consistently <50 x 0 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 00%.- 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 0, 976. *Endocrine-Infertility Fellow, Department of Obstetrics and Gynecology. t Associate Professor, Department of Obstetrics and Gynecology. 647 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 58 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 ins em i nation. EXPERUMENTALPROCEDURE Patients. The medical records of 58 consecutive private patients who underwent AIH from January 970 through December 973 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 3 of the females hospitalized

2 648 DIXON ETAL. June 976 for evaluation were also reviewed. At the close of the study, 4 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 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 was performed on all initial samples and repeated at least once on all positive specimens. In the final years, sperm testing was modified to include the procedures developed by Kibrick et al. 3 and Isojima et al. 4 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 3 cases and three to five analyses in 64 cases. However, in 35 cases two analyses were done, 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 3 cases in which volume, density, and motility were normal, the therapy evidently was initiated because of unexplained infertility. Table 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 or 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. 5 In every case insemination took place within hours of the time semen was collected. Two methods of insemination were used. The cervical cap technique was employed in 4 patients, and that technique in combination with intracervical Indication TABLE. Indications {or Insemination Decreased volume «md + normal count and motility + decreased count + decreased motility Fluctuating volume + normal count and motility Decreased count and motility «50 x 0o/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 o No. pregnant with AIR 4 o 6 5 No. of spontanteous pregnancies o o 5 9

3 Vol. 7, No.6 HOMOLOGOUS ARTIFICIAL INSEMINATION 649 TABLE. Influence of Age, Length of Infertility, and Gravidity on Success of AIH No. of No. % pregpatients pregnant nant attempting AIR Age (yr) < : Duration of infertility (yr) < > Gravidity infertile ~ infertile infusion of 0. 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 latter method. In two cases, hypospadiac males, who were instructed in use of the cervical cap, performed the insemination at home. After insemination, the reclining patient was given several minutes to adjust to the presence of the cap and then encouraged to resume her routine activity. She was advised against strenuous 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, 309 inseminations during a total of 560 cycles were performed on 58 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. cycles with 7.7 inseminations. Patients who failed to conceive were exposed an average of 8.3 times during 3.6 cycles. RESULTS Number and Pattern of C(M,ceptions. Fifteen pregnancies were achieved by the 58 couples, for an over-all success rate of 9.5%. More than one-half of the pregnancies occurred within two cycles, and 4 of the patients had conceived within 5 months of treatment. However, almost half of the original 58 women TABLE 3. Presence of Female Abnormalities and Results of AIH and Natural Insemination in 58 Patients Diagnosis No. of No. pregnant No. of spontaneous patientsfl with AIR pregnancies Complete evaluation Anatomical abnormality 96 5 Endometriosis 4 () 3 8 Endometriosis + adhesions 4 5 Endometriosis + uterine abnormality 8 () Tubo-ovarian adhesions 7 () 3 Tubal occlusion 5 Uterine abnormality 5 () One of the above + anovulation () 5 One of the above + immune reaction 4 Anovulation alone 4 3 Immune reaction alone 6 Normal Total 3 6 Incomplete evaluation Anovulation Immune reaction alone 3 Normal 3 3 Total athe numbers in parentheses indicate the number of patients who did not undergo surgery but are included in the accompanying figure.

4 650 DIXONETAL. June 976 had dropped out by the end of the 3rd month and 3 of the 58 had discontinued therapy by the end of the 5th month. Influence of Age, Length of Infertility, and Gravidity on Success of AIH. Records were examined for influence of age, length of infertility, and gravidity on results (Table ). The data reflect trends reported elsewhere,6 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, 3 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 to 8 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 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 (5 after evaluation which included endoscopy), 6 became pregnant. Influence of Semen Quality on Success of AIH. Various indications for AIH have been suggested,7. 8 but, as Table 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 06/ml and motility of38%. The impotent male, with a count of 50 x 06/ml, motility of 60%, and a wife with no apparent abnormality, was unsuccessful in 3 inseminations. Although pregnancies have been reported after recovery of semen from the bladder,5. 9 semen TABLE 4. Joint Frequency of Sperm Count and Percentage of Motility Recorded for 56 a Males, with Indication of Condition of Females and Number of AIH Pregnancies Sperm motility <40% 40-59% "'60% Sperm count Pregnancies Pregnancies Pregnancies Males Females b Males Females Males Females AIH Sp" AIR Sp AIR Sp millionlml <0 Ab N 4, Ab N, Ab, 0 m N, Ab 4, 3 N, Ab 0 () N I,Ab 0 m N, Ab 0 0 N 3, Ab (6) N3,Ab, 3 m ;;.60 0 (6) N 3, Ab () N9,AbI5, 4 6 (7) N 3, Ab 9 3 m 34, m 4 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; m, immune. "Sp, Spontaneous.

5 Vol. 7, No.6 HOMOLOGOUS ARTIFICIAL INSEMINATION 65 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 3 patients. Fewer than 80% normal forms appeared in 48 cases; AIH was successful in 3 of these. (Spontaneous pregnancies subsequently occurred in 3 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 06/ml by a difference of 40 to 50 x 06/ml. In 4 patients motility fluctuated from < 60% to > 60% by a difference of at least 0%. Of the 65 men whose semen quality was erratic along at least one dimension, 4 achieved conception with AIH and 8 reported spontaneous pregnancies. Influence of Techniques of Insemination upon Success of AIH. In 4 cases the cervical cap alone was used; 4 pregnancies were achieved (9.5%). In 6 cases a combination of the cervical cap and intracervical infusion of semen was used, and a total of conceptions occurred (9.5%). Although some studies have reported encouraging results with the use of split ejaculates to improve semen quality,o. only pregnancies occurred in the 38 cases in which split ejaculates were introduced by the combination of techniques. Pregnancy Outcome. The 5 pregnancies resulted in live births (6 males and 5 females). Three pregnancies terminated in either the first trimester or early second trimester. One patient normal. was lost to follow-up after an uneventful second trimester. Spontaneous Pregnancies. Spontaneous pregnancies following failure with AIH have been reported by others 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 7 patients who underwent artificial insemination with donor semen during the same time period. ) Female Factors. Of the 43 women for whom AIR was unsuccessful, 9 became pregnant 3 months to years after therapy. Initial evaluation of the 9 had shown 3 to be anovulatory and 5 to be normal. Pelvic abnormalities were recorded for, 3 of whom had undergone conservative corrective surgery prior to AIH therapy. None of the 3 women in whom an immune interaction had been identified reported spontaneous pregnancies. The average age for this group was 7.5 years, length of infertility.5 years, and exposure cycles 3., 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 8 of the 9, 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 06/ml and ;::60%), but either count or motility had appeared subnormal as often as it had appeared

6 65 DIXON ET AL. June 976 In 3 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 0 x 06/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 < ml to > 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 9 patients was 5; there were of those. As many as 3 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 5 of the 58 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,. 3, 7 that results did not differ 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 inseminations, and one couple was successful only after 9 cycles and a total of inseminations. Although persistence is encouraged,3, 4 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. 6, 5 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 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 Menge6 suggest, immune interaction may be multifocal and not reserved solely to the cervical mucus.) In as many as 8 cases semen quality was consistently optimal and the wives were either normal (5 cases) or considered normal after minor treatment (3 cases). Seven were successful with AIR; three had subsequent spontaneous

7 Vol. 7, No.6 HOMOLOGOUS ARTIFICIAL INSEMINATION 653 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.7, 8,3 As Table 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 8 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. 7 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 58 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 motility, or when volume of semen of optimal count and motility is so low that vaginal dilution prevents sperm from reaching the os. REFERENCES. Behrman SJ: Techniques of artificial insemination. In Progress in Infertility, Edited by SJ Behrman, RW Kistner. Boston, Little, Brown and Co, 968, p 77. Mastroianni L Jr, Laberge JL, Rock J: Appraisal of efficacy of artificial insemination with husband's sperm and evaluation of insemination techniques. Fertil Steril 8:60, Hanson FM, Rock J: Artificial insemination with husband's sperm. Fertil Steril :6, Kaskarelis D, Comninos A: A critical evaluation of homologous artificial insemination. Int J Fertil 4:38, Payne S, Skeels RF: Fertility as evaluated by artificial insemination. Fertil Steril 5:3, Swyer GIM: Results of artificial insemination. J Reprod Fertil :, Shields F: Artificial insemination as related to the female. Fertil Steril :7, 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 :58, Ulstein M: Fertility of husbands at homologous insemination. Acta Obstet Gynecol Scand 5:5, Barwin BN: Intrauterine insemination of husband's semen. J Reprod Fertil 36:0, 974. Schellen A: Artificial Insemination in the Human. Amsterdam, Elsevier Publishing Co, 957. Franklin RR, Dukes CD: Antispermatozoal antibody and unexplained infertility. Am J Obstet Gynecol 89:6, Kibrick S, Belding DL, Merrill B: Methods for the detection of antibodies against mammalian spermatozoa. II. A gelatin agglutination test. Fertil Steril 3:430, Isojima S, Ki TS, Ashitaka Y: Immunologic analysis of serum sperm-immobilizing factor in women with unexplained sterility. Am J Obstet Gynecol 0:677, Hotchkiss RS, Pinto AB, Kleegman S: Artificial insemination with semen recovered from the bladder. Fertil Steril 6:37, Gregoire AT, Moran MJ, Quintero R, O'Connell K: The pregnancy rate, duration of infertility, months of treatment, and semen character-

8 ~-~ ' ~ DIXON ET AL. June 976 istics expressed in age specific groups of couples attending a fertility service. Fertil Steril 3:894,97 7. Guttmacher AF: The role of artificial insemination in the treatment of sterility. Obstet Gynecol Survey 5:767, Finegold WJ: Artificial Insemination. Springfield Ill, Charles C Thomas, Bourne RB, Kretzschmar WA, Esser JH: Successful artificial insemination in a diabetic with retrograde ejaculation. Fertil Steril :75, Amelar RD, Hotchkiss RS: The split ejaculate, its use in the management of male infertility. Fertil SteriI6:46, 965. Perez-Pelaez M, Cohen MR: The split ejaculate in homologous insemination. Int J Fertil 0:5,965. Dixon RE, Buttram VC Jr: Artificial insemination using donor semen: a review of 7 cases. Fertil Steril 7:30, Warner MP: Artificial insemination: review after thirty-two years' experience. NY State J Med 3:358, Hill AM: Experience with artificial insemination. Aust NZ J Obstet Gynaecol 0:, Warner MP: Results of a twenty-five-year study of,553 infertile couples. NY State J Med 6:663, Behrman SJ, Menge AC: In Human Reproductive Conception and Contraception, Edited by ESE Hafez, TN Evans. New York, Harper and Row, 973, p Foldes JJ: Artificial insemination: induced ovulation with intravenous estrogens. Int J Fertil7:04,97