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Home , Artificial insemination, Insemination

Artificial in the Human*

JOHN A BOARD, M.D.

Professor of and Gynecology, Medical College of Virginia, Richmond, Virginia

The idea that impregnation might occur with­ tion using the husband's has not resulted out coitus has aroused interest since ancient times. in . In the second century AD., there was recorded When Rh incompatibility has already resulted a hypothetical discussion concerning a who in the birth of an erythroblastotic infant, and partic­ had been inseminated by semen previously de­ ularly when the husband is homozygous Rh posi­ posited in the bath water in which she bathed. In tive, insemination of the wife with semen from an 1322, an Arab used with Rh negative donor will prevent the recurrence of horses. A wad of wool was introduced into the erythroblastosis. Fortunately, the availability of of a and left overnight. It was then Rho (D) immune globulin (human) has dramati­ held over the nostrils of a , and with this cally reduced the number of Rh negative women stimulus the stallion ejaculated on a cloth held who have been sensitized, and this is becoming in readiness. The ejaculated material was then a less common indication for artificial insemination. introduced into the vagina of a mare, which foaled When the husband has a family history of after the appropriate length of time. genetic disease which makes fatherhood inadvis­ During the 1700's, isolated instances of hu­ able or when the couple has had affected offspring man artificial insemination were reported, almost indicating abnormal recessive genes with the likeli­ always using the husband's semen. In the United hood of producing serious congenital defects in States, human artificial insemination using donor's subsequent , artificial insemination with semen was first practiced by Dr. Robert L Dick­ donor's semen may be used. Examples of this are inson in 1890. His work was initially done in Tay-Sachs disease, and cases where both husband secrecy, although subsequently he did much to and wife have AS hemoglobin. train others in the technique and to gain public The presence of agglutinating antibodies acceptance of the procedure. against the husband's but not against donor sperm may occur in a woman with prolonged and Artificial Insemination Using Donor's Sperm. otherwise unexplained · (Dukes and The most common indication for artificial insemina­ Franklin, 1968). The test for this is not an absolute tion using donor's semen is sterility of the hus­ one, as some women who agglutinate their husband's band. This may be manifest as total azoospermia sperm have been of high . In a situation or severe , demonstrated on repeated where antibodies are present, in some cases the examinations. The husband should, of course, have use of for a time to protect against repeated a thorough medical and urologic examination to be exposure to antigen will result in disappearance of certain that his sterility is not secondary to a treat­ agglutinating antibodies followed by pregnancy. able condition. Considerable judgment is required Where condom therapy fails, artificial insemination to decide when to treat cases of oligospermia this using donor's sperm which are not agglutinated way. In most instances, this is done when ap­ by the wife's antibodies may be used. The ABO propriate medical therapy has failed to improve relationship to infertility is even more unclear, the quality of the ejaculate and artificial insemina- although there seems to be a statistically significant effect when an ABO incompatibility exists and the husband is a "secretor," in which case donor * Presented at the 43rd Annual McGuire Lecture Series, December 2, 1971, at the Medical College of Vir­ semen from a male of appropriate blood type may ginia, Richmond. result in pregnancy.

MCV QUARTERLY .8(1): 13-18, 1972 13 14 BOARD: ARTIFICIAL INSEMINATION IN THE HUMAN

Donor insemination has special emotional hyperemia test to predict the time of ovula­ connotations, and both husband and wife should tion. This test is said to be capable of determining be aware of the possible emotional effect of the the time of within six to twelve hours procedure on their future relationship. Both hus­ (Farris, 1948). More recently, the use of rapid band and wife should be reasonably well-adjusted radio immunoassay procedures for LH, in order to individuals, and they should feel that they have a detect the pre-ovulatory LH peak, has been sug­ stable . It is extremely important not to do gested as an aid in timing the deposition of sperm, this procedure to "save the marriage" as this is whether it be by natural or artificial means. far too big a job to place upon the shoulders of an Kleegman has found there is a differentia­ individual who weighs only seven pounds or so. tion in infants related to the time of artificial in­ Both husband and wife should have a desire for semination and ovulation (Kleegman, 1967). She children, and the man should not feel that he is utilized basal temperatures somewhat to determine being coerced into this procedure in order to pro­ the time of ovulation, but put more emphasis on vide fulfillment of his wife's maternal instincts. mittelschmerz (sometimes elicited with a "bounce In most cases, it is advisable to wait for a while test") and mucorrhea. Using this as evidence of after the husband has found out about his sterility ovulation, she has noted that exposure 2-24 hours problem before carrying out artificial insemination before ovulation was more likely to result in a because he will need time to recover from the male infant and that exposure 36 or more hours shock that such news is to every man. When it has before ovulation or 2-8 hours after ovulation was been decided to use insemination with donor's se­ more likely to result in a female infant. She was men, both husband and wife should sign a consent able to predict sex in 77% of cases utilizing this form. method. She also noted that men who have severe In the past when there was no shortage of oligospermia but whose wives have still become babies for adoption, we did not encourage artificial pregnant, have a preponderance of female chil­ insemination, but did it only when the couple dren and that rhythm failures with conception oc­ specifically requested it, feeling that adoption curring on cycle days 4 to 7 usually result in solved two social problems, that is, providing a fam­ female infants. Certain other investigators have been ily to the child and a child to the family. With the unable to reduplicate this accuracy in prediction recent increase in therapeutic , the supply (Cohen, 1966), but in fairness to Kleegman, it of infants for possible adoption has so dwindled should be noted that most have used only basal that artificial insemination is more often mentioned temperature as an index of ovulation and have not to the couple as a solution to their infertility or relied on mittelschmerz or cervical changes. genetic problems. Aside from suggesting the avail­ Most of the donors which we use are either ability of donor's semen to such couples, we do medical students or house officers, who are married not try to encourage this where either partner and are already of normal children. These expresses any hesitancy. men report no knowledge of hereditary disease A fertility investigation is done for each couple and are of above average intelligence, If the wife seeking artificial insemination, if this has not been has Rh negative blood, an Rh negative donor is previously accomplished. As a minimum, patency also chosen. We do not make any effort to match of the wife's fallopian tubes is established by a blood types otherwise, because any good laboratory Rubin's test using carbon dioxide, and an endo­ could readily establish the fact that the woman's metrial biopsy is done to confirm ovulation. The husband is not the of the child by utilizing patient is also instructed to begin keeping basal other blood groups such as the MN, Kidd, Duffy, temperature charts, in order that the most optimal and Kell which establish a "fingerprint." We make time for insemination may be selected. After re­ an effort to match donor to husband by somatic viewing temperature charts for several months, a type, skin, hair, and eye coloration, but this is not day is selected. This day will likely be one or two always possible. We would not, however, use a days prior to the basal temperature rise. It has short, black-haired donor of Mediterranean origin been our practice to perform insemination once a for a couple where both husband and wife were tall, month for the first three months, and if pregnancy blonde, and fair-skinned. has not occurred in this time, then to perform sev­ Our experience has been entirely with fresh eral at two-day intervals until the temperature rise semen, and the donor is instructed to obtain a has definitely occurred. Some physicians use a rat specimen by into a clean glass con- BOARD: ARTIFICIAL INSEMINATION IN THE HUMAN 15

tainer shortly before the couple's appointment. The By this time, active sperm should be well on their donor then delivers the semen to a designated way up the female reproductive tract and any lethal point, and it is then transferred to the patient area activity in the seminal plasma would be of no con­ by other personnel. It is important that the donor sequence. not deliver the specimen himself to this office, in When a woman has somewhat irregular ovula­ order to exclude the possibility that he and the tion, she is given an injection of 5000 international recipients might meet. In order to preserye ano­ units of human chorionic gonadotrophin to act as nymity, the couple always pays the donor in cash. µn LH surge, hopefully to cause an impending Our practice is to keep no record of which donor ovulation to occur while viable sperm are still is used for insemination, and this precludes using present (Fuchs, et al, 1966). ·· the sarne donor for subsequent pregnancies. It is The effectiveness of insemination using donor of note that some physicians do not even record semen has been shown in many studies. In an anal­ in the patient's chart the fact that insemination ysis of seven reported series which included 630 was done. couples who had used artificial insemination with On the selected day, the patient lies on an donor semen, the proportion becoming pregnant examining table, and an unlubricated vaginal varied from 55-78 % . Of the women who' eventually speculum is inserted. The donor's semen is drawn became pregnant, between 31 and 46% became into a syringe which has a small length of poly­ pregnant during the first month of inseminµtion. The ethylene tubing attached to it. The husband then number of inseminations per menstrual 1"cycle ap­ comes to the examining room. The husband holds peared to be more significant in obtaining an early the syringe and deposits 0.1 to 0.5 ml. of semen pregnancy than the method of semen deposit about 1 cm. within the endocervical canal. The (Potter, 1958). About 90% of the women who polyethylene tubing and speculum are then re­ became pregnant did so in 6 months, and if a moved, and a plastic cap with an attached · tubing pregnancy has not resulted within 12 months, the is placed over the . The remainder of the chances of success are very remote. · donor's semen is then inserted into the cervical Artificial Insemination Using Husband's Semen. cap by the husband. We feel that this active par­ Indications for insemination using husband's semen ticipation in the insemination of the wife by the include failure to deposit the serrien in the posterior husband is very important for him psychologically. , inadequate cervical invasion, and a The cervical cap is sometimes difficult for the patient moderate but irreversible degree of . to remove, so while the husband is in the examining The failure to deposit the semen may be due room, we instruct both him and his wife on the to penile or vaginal malformations, impotence, or removal of the cervical cap, and to date, between retrograde . Penile hypospadias was one the two of them, this has always been accomplished of the first-recorded indications for artificial at home. inseminations, and this is still valid. The cases of We do not advocate the mixing of husband's impotence are best individualized,. and decisions ejaculate with donor's semen or that the couple should be made ·only after consultation with the have intercourse immedfately prior to coming to husband's psychiatrist. The the~apy for male the office for insemination. A cervical mucus­ impotence · is psychiatric, · and in some instances a spermatozoa incompatibility is not alway due to a pregnancy in the wife and impending ·fatherhood cervical factor, and one case was reported where will exert a beneficial psychiatric effect, while in the donor's sperm but not the husband's sperm others this is best postponed until psychotherapy readily entered the wife's cervical mucus (Kuni­ has progressed further. may take and Davajan, 1970). When the husband's follow injury to the internal bladder sphincter due sperm was separated from the seminal plasma and to surgery such as transurethral resection. However, resuspended in seminal plasma from a donor retrograde ejaculation may also be due to con­ who had had a , good penetration of genital anatomical abnormalities or neurologic the wife's cervical mucus was obtained. Unless problems, including diabetes and chemical sym­ this seminal plasma factor is checked for, it would pathectomy achieved with guanethidine. Typically, be inadvisable to mix husband's semen with donor's there is not. only azoospermia but also markedly semen. After the cervical cap has been · in place reduced semen volume, although an ejaculatory for six hours or so, the couple is advised to remove sensation is experienced with . To corroborate it, and it is suggested that they ~hen have intercourse. the diagnosis, the patient empties his bladder and 16 BOARD: ARTIFICIAL INSEMINATION IN THE HUMAN

then ejaculates in one glass, after which he collects indicated that the first half contains the main bulk in a separate glass whatever urine is in the bladder. of acid phosphatase, which comes from the pro­ Artificial insemination using husband's semen state, along with the products of the testes, epi­ is also sometimes used in an attempt to bypass the didymis, and vas deferens. Since lactic acid ac­ cervical mucus when it is found that normal sperm cumulates as an end product of the metabolism cannot migrate through this or when postcoital tests of spermatozoa, it is also found in greater con­ reveal no living sperm In the presence of ap­ centration here. In the second half of the split parently normal mucus and a good sperm count. The ejaculate, the higher · concentration of fructose is achievement of pregnancy in these last two instances found, a substance specific to the seminal vesicles is quite rare in our hands, although Kleegman (Amelar and Hotchkiss, 1965; MacLeod and Hotch­ reported a success rate of around 85 % in the small kiss, 1942). group where the only abnormal factor was a cer­ Centrifugation of the full specimen concen­ vical secretion impenetrable to sperm (Kleegman trates the sperm, but frequently depresses the and Kaufman, 1966). She stated that most cases of motility and also concentrates the debris and mucus. cervical impenetrability are due to endocrine dys­ Concentration of the sperm can be obtained using function rather than cervicitis, and the results of the split ejaculate without injuring the cells and husband insemination in this group are poor. Others without concentrating debris also. have found consistently poor results in all attempts Kleegman reports that with 100 consecutive to bypass the cervix (Balin, 1967). women who had intrauterine insemination of the When intrauterine insemination is done, the split ejaculate in cases where there was subnormal cannula is placed in the endometrial cavity and husband's sperm quality, 17 women )Jecame preg­ only 0.5 ml. or less of semen is instilled. This is nant (Kleegman and Kaufman, 1966). Other re­ done very slowly with practically no pressuq:~. The ports include 15 % pregnancies in 86 women with physician must be careful not to inject the insemination of husband's semen (Kaskarelis and semen through the fallopian tubes into the perito­ Comninos, 1959). A number of women who failed neal cavity where it will cause a peritonitis, and he with insemination conceived subsequently with must be ready to stop the installation if the patient normal intercourse. complains of any cramping. Insemination with husband's sperm suspended · Insemination with husband's semen may be in donor's seminal plasma may be considered in the tried when the wife is of apparently good fertility rare cases where the husband's own seminal and the husband's sperm consistently has a low plasma contributes to cervical mucus-spermatozoa count with the postcoital test showing only a few incompatibility or where there is excessively low sperm in the . This may also be fructose in the husband's seminal plasma (Moon utilized when the husband's sperm count is within and Bunge, 1968). normal limits, but the motility of the sperm is less Frozen Semen. Much has been written about than normal. The split ejaculate offers a concentrated the practical applications of frozen human semen, number of better sperm, and is often employed with the establishment of human semen banks. when husband's semen is to be inseminated. For example, by utilizing such a bank, couples Split ejaculates are obtained simply by using could be suitably matched according to many phy­ one clean container for the first part of the ejacu­ sical characteristics and by blood type, regardless late and another for the remainder. It is most useful of the time and place. Another possible use of when the volume of the ejaculate is over 2 ml. froien semen entails its use in insemination with In one study of 86 husband donors, the count was husband's semen where the husband is oligosper­ significantly higher in the first portion than in the matic. Several split ejaculates could be pooled, and second portion of the total specimen in 88%, tl:len delivered to the wife at the calculated fertile equally distributed in both in about 8 % , and titne. It has been proposed that men might deposit significantly higher in the second portion than in semen in a bank for possible fvture use prior to the first in 6 % . Sperm motility was greater in the having a vas ·ligation. Other possible uses of semen first portion in 77%. In · 25 cases of increased banks sound like science fiction stories. They in­ viscosity of the total ejaculate, the second portion clude ( 1) having a supply safely stored behind was consistently the most viscous ( Amelar and thick walls in case of nuclear attack which might Hotchkiss, 1965). sterilize the entire male population of the country, Biochemical studies of the split ejaculate have (2) making it possible for a man to sire offspring BOARD: ARTIFICIAL INSEMINATION IN THE HUMAN 17 many years after he had died; and ( 3) complete tration, it seems probable that morphologic chqnges population control where all pregnancies are from in this region result in enzyme changes. It is possi­ bank sperm and only those sperm known to trans­ ble that the changes reported here were influenced mit characteristics thought to be useful to the state by the protective substance in which the sperma­ are dispensed, thus enabling the development of tozoa were mixed rather than by the freezing either a "super race" or a "leader-slave culture." itself, nevertheless, the structural changes did fol­ In any event, various techniques have been low an accepted method of sperm preservation. used to freeze sperm. Most employ glycerol as a Because of the lowered conception rate and protecting medium. One study from the University the ultrastructure changes associated with frozen of Michigan used a protective medium of yolk, semen, we do not think that t.his technique is ready glycerol, glucose plus sodium citrate solution, and for routine clinical use, but believe that its present glycine, which was buffered at pH 7.3. The semen usefulness is in an investigational setting. sample was mixed with the protective medium, cooled Artificial insemination in appropriate cases, us­ slowly to -80°C and then stored at -196.5°C. ing fresh human semen from either husband or Thawing was performed in a 37°C. water bath, donor, will result in a high and will and inseminations were then done within 30 min­ successfully treat infertility. utes of thawing the samples (Behrman and Sawada, 1966). A conception rate of 40-50 % may be expected REFERENCES when frozen semen is used, and this compares un­ ACKERMAN, D. R. The effect of cooling and freezing on the favorably with the 75% which may be achieved by aerobic and anaerobic lactic acid production of human using fresh specimens for donor insemination. semen. Fertil. Steril. 19·: 123-128, 1968. This would be an indication that the fertilizing AMELAR, R. D. AND HOTCHKISS, R.S. The split ejaculate. Its capacity of the frozen-preserved sperm is relatively use in the management of male infertility. Ferti/. Steril. low. In the experience which was reported from 16:46-60, 1965. the University of Michigan in 1968, conception had never been achieved when a frozen-preserved spe­ BALIN, H. A rtificia/ lnseminati9n, Diagnosis and Treatment cimen had been administered more than 24 hours of Menstrual Disorders and Steriiity, 5th Ed. S. L. Israel prior to ovulation as determined by basal tempera­ (ed.). New York: Harper & Row, 1967, pp. 570-579. ture records. This was thought .to indicate a rela­ tively short term of viability. Human sperm have BEHRMAN, s. J. AND SAWADA, Y. Hetrologous and homolog­ ous inseminations with human semen frozen and stored in . an apparently good motility after thawing, but de­ a liquid-nitrogen refrigerator. F ertil. Steril. 17 :457-466, spite this, fertility potential is reduced. Ackerman 1966. was able to demonstrate a pronounced effect upon sperm metabolism by cold-shock and believes that COHEN, M. R. Differentiation of sex a.s determined by the metabolic changes occurring in frozen­ ovulating timing. International Congress Series No 133 . preserved human sperm may account for its low­ Proceedings of the Fifth World Congress on Fertility and ered fertility capacity (Ackerman, 1968). Sterility, Stockholm, June 1966. Edited by B. Westin and N. Wiqvist. Amsterdam. Exerpta Medica Foundation, 1967, Pedersen and Lebech found that most cells pp. 1196-1202. showed varying and often pronounced ultrastructure changes after a routine method of freezing for se­ DUKES, c. D. AND FRANKLIN, R. R. Sperm agglutinins and men storage (Pedersen and Lebech, 1971). The human infertility: Female. Fertil. Steril. 19 :263-267, 1968. most conspicuous changes were found in the acro­ some region, the anterior segment of the acrosome FARRIS, E. J. The prediction of the day of human ovulation becoming increasingly swollen, the content thinned by the rat test as confirmed by fifty conceptions. Am. / . out, and the outer acrosome membrane becoming Obstet. Gynec. 56:347-352, 1948. tortuous and discontinuous. As a result, the anterior end of the spermatozoa loses the cell membrane FUCHS, K., BRANDES, J. M., AND PALDi, E. Enhancement of and the anterior segment of the acrosome. Changes ovulation by Chorigon for successful artificial insemination. Int. /. Fertil. 11 :211-214, 1966. in the mitochondrial matrix and in the endpiece were also noted. As the acrosome has previously KASKARELIS, D. AND COMNINOS, A. A critical evaluation of been shown to contain enzymes which probably homologous artificial insemination. Int. / . Fertil. 4:38-41 , play a role in lysing the zona pellucida during pene- 1959. 18 BOARD: ARTIFICIAL INSEMINATION IN THE HUMAN

KLEEGMAN, S. J. Can sex be planned by the physician? MACLEOD, J. AND HOTCHKISS, R. s. The distribution of International Congress Series No 133. Proceedings of the spermatozoa and of certain chemical constituents in the hu­ Fifth World Congress on Fertility and Sterility, Stockholm, man ejaculate. J. Ural. 48:225-229, 1942. June 1966. Edited .by B. Westin and N. Wiqvist. Amster­ dam. Exerpta Medica Foundation, 1%7, pp. 1185-1195. MooN, K. H. AND BUNGE, R. G. Observations on the bio­ chemistry of human semen. Fertil. Steril. 19: 186-191, 1968. KLEEGMAN, s. J . AND KAUFMAN, s. A. Infertility in Women. PEDERSEN, H. AND LEBECH, P. E. Ultrastructural changes in Philadelphia: F. A. Davis Company, 1966, pp. 160-178. the human after freezing for artificial insemi­ nation. Fertil. Steril. 22: 125-133, 1971. KUNITAKE, G. AND DAVAJAN, v. A new method of evaluat­ ing infertility due to cervical mucus-spermatozoa incompat­ POTTER, R. G. JR. Artificial insemination by donors. Fertil. ability. Fertil. Steril. 21:706-714, 1970. Steril. 9:37-53, 1958.