Factors affecting the success of donor insemination

Transcription

1 FERTIUTY AND 8TERIUTY Copyright c 98 The American Fertility Society Vol. 37, No., January 98 Printed in U.S A. Factors affecting the success of donor insemination James Aiman, M.D. The Cecil H. and Ida Green Center for Reproductive Biology Sciences, and The University of Texas Southwestern Medical School, Dallas, Texas 7535 Of 8 women who completed six ovulatory of properly timed donor insemination using freshly ejaculated semen, 65 (80%) conceived. The mean sperm concentration and motility in of conception were 79.5 millionlml and 69%. In where conception did not occur, the mean sperm concentration and motility were 78.4 million/ml and 67%, values similar to those in of conception. There was also no significant difference between conception and nonconception in the following: number of inseminations per cycle (.43 versus.34), percentage of with a preovulatory fall in basal temperature (35.% versus 45.4%), maximum spinnbarkeit (5.6 versus 5 em), and the interval between basal temperature nadir and maximum spinnbarkeit (0 versus 0. days). The distribution of inseminations in relation to the basal temperature nadir was similar in conception to that of nonconception. Sixteen women (0%) did not conceive, and there was an apparent explanation in 3 of these: was occasionally anovulatory during several ; had no intraperitoneal passage of C0 ; and of 3 women who underwent laparoscopy had peritubal adhesions. Fertil Steril37:94, 98 Pregnancy occurs in 60% to 80% of women inseminated with freshly ejaculated semen from a donor. 3 Conception rates are lower than this when women are inseminated with donor semen that has been cryopreserved. 4 5 A 30% to 40% reduction in sperm motility, 5 6 microscopic changes in sperm morphology, 7 and biochemical changes 8 have been reported for frozen semen. The reduced conception rate associated with these changes is suggestive that semen quality is an important determinant of success with donor insemination. Strickler et al. 9 performed occasional semen analyses as a means of quality control, but apparently no one has systematically examined Received July, 98; revised and accepted September, 98. Present address and reprint requests: James Aiman, M.D., Department of Gynecology and Obstetrics, The Medical College of Wisconsin, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin the effect of sperm concentration and motility on conception rates resulting from donor insemination. The purpose of this report is to assess the importance of semen quality and certain other factors in relation to the outcome of artificial insemination with fresh donor semen. MATERIALS AND METHODS One hundred seventy-seven couples have consented to donor insemination (AID) since April 975 (Table ). Fifty-six of these couples are now waiting to begin or chose not to start. Eighteen women are now being inseminated. The data from the remaining 03 women are analyzed in this study. Before each of these 03 women started insemination, they recorded their basal temperatures for 3 to 4 months to document the presence of ovulation and to compute the average day of the menstrual cycle on which the basal temperature nadir occurred. The nadir was defined as the last day before the basal temperature rose at least 0.5 F for to 4 days.

2 Vol. 37, No. SUCCESS OF AID 95 Table. Couples Consenting to AID April to April8, 98 ' Couples consenting Couples on a waiting list Couples choosing not to start Women stopping Women now being inseminated Women failing to conceive Women conceiving Conceptions Before these 03 women began AID, tubal patency was assessed by tubal insufflation. A hysterosalpingogram was done in lieu of tubal insufflation in any woman with a history of tubal disease and also in any woman in whom tubal insufflation was suggestive of occlusion. Women with evidence of tubal occlusion were not offered donor insemination. Indications for donor insemination are listed in Table. Cou~les choosing not to start (n = 4), women stoppmg (n = ), women conceiving (n = 65), and women failing to conceive (n = 6) are included. Each woman was offered insemination for six. Since conception will not occur in anovulatory or in where insemination was not performed at the time of ovulation, such were not considered as one of the six offered to each woman. However, data from these are included for analysis. Twenty-two women discontinued insemination before completing six properly timed of donor insemination. The reasons offered by these women and the 4 women who did not begin donor insemination are listed in Table 3. None of the 45 medical student donors had a congenital or genetic disease, and all denied chronic illness or the regular use of any drugs. Few of the donors had been married, and only one had knowingly fathered a child. However, no donor was accepted unless he produced semen with a sperm concentration and motility of more than 40 million/ml and 60%, respectively. No donor was tested for venereal disease or hepatitis, but no woman developed either of these. The karyotype of the donors was not determined, but no offspring has inherited a genetic disease. No donor had a family member with a genetic disease due to a single gene abnormality, nor were there more than occasional family members with multifactorial diseases, such as diabetes, cancer, or hy ~ertensio~. M~ltifactorial diseases were sought m the family history because they may occur with greater than expected frequency in offspring of donors with affected family members. By 8:00 A.M. of the morning of insemination, the donor collected his sample by masturbation in a glass jar provided for that purpose. Within 60 minutes, the sperm concentration was determined with a hemocytometer and the percentage of sperm that were motile was estimated by viewing a drop of the ejaculate at 400 x magnification. Intracervical insemination with a glass pipette was done within hours of semen collection. Insemination was begun to days before the basal temperature nadir usually occurred. The quality of cervical mucus was assessed by inserting a cotton swab into the cervical canal and measuring the centimeters of spinnbarkeit after touching the swab to a microscope slide. Following insemination, each woman was kept in the Trendelenburg position for 0 to 5 minutes, then asked to return in days if a rise in her basal temperature had not occurred and if her cervical mucus reflected preovulatory estrogen effects. Changes in basal temperature and cervical mucus were the only methods used to detect ovula ~ion. Serum concentrations of estrogen, luteinizmg hormone, or progesterone were not performed. All inseminations were done on Mondays, Wednesdays, and Fridays, and each woman returned until changes in basal temperature and cervical mucus were suggestive of ovulation. The Table. Indications for Donor Insemination Oligospermia Idiopathic Cryptorchidism Varicocele Mumps Alcoholism Diethylstilbestrol exposure Vasectomy Not reversed Failed reversal Azoospermia Idiopathic Androgen-resistanta Cryptorchidism Traumatic Mumps Genital ambiguity Absent vasa deferentia Chemotherapy Klinefelter's syndrome Cystic fibrosis Hypo~onadotropic hypogonadism Genetic Impotence areduced androgen binding capacity in cultured genital skin fibroblasts. bvon Hippel-Lindau disease (n = ) and Carpenter's syndrome (n = ). No

3 96 AlMAN January, 98 Table 3. Couples Not Starting or Stopping Dooor Insemination Reason Moved Chose to adopt Psychologic problem Ethical concern Marital problems Financial problems Pregnancy No basal temperatures Other infertility factor Unknown No. not starting No. stopping number of inseminations varied from one to seven per cycle, depending on how erratically ovulation occurred. Because several inseminations were usually done in each cycle, it is impossible to be certain which insemination resulted in conception. Therefore, the mean sperm count and motility of all ejaculates in conception were compared with mean values of all ejaculates inseminated in nonconception. The fraction of with a preovulatory drop of0.3 F in one day or 0.5 F in days was also computed. This was done to determine whether the presence of such a fall improved prediction of impending ovulation and was associated with a difference in pregnancy rate. The observed maximum spinnbarkeit and the relationship of the day of maximum spinnbarkeit to the day on which the basal temperature nadir occurred during of conception were compared with these characteristics in nonconception. This was done as one means of describing a possible cervical factor affecting the success of donor insemination. RESULTS The mean elapsed time for conception to occur was.3 months, but the number of women who conceived decreased with the increasing number of months of AID (Fig. ). The apparent decline in the success of artificial insemination with months of AID suggests that the probability of conception declines with time. A second method to describe the outcome of these women is by life table analysis (Table 4). Since the women were counted each time they conceived, the 6 who began AID includes the second conception of 3 women. Twenty-one percent to 9% of the women who began donor insemination conceived in each of the first 3 months. In the 4th month and thereafter, conception rates were lower, but this may be a statistical quirk reflecting the small number of women remaining and not a true decline in success rates. Six variables that may account for success or failure are listed in Table 5. The number of inseminations per cycle was similar in conception to that in nonconception. There was also no significant difference in the percentage of with a preovulatory fall in basal temperature, maximum spinnbarkeit, or the interval between the day of maximum spinnbarkeit and the day of basal temperature nadir. The principal purpose of this study was to determine whether semen quality was a factor in the success of donor insemination. The mean sperm concentration in conception, 79.5 million/ml, was similar to that in nonconception, 78.4 million/mi. Also, sperm motility was nearly identical in conception and nonconception (Table 5). The timing of donor insemination in relation to the basal temperature nadir (day 0) was similar in conception to that in nonconception (Table 6). By x analysis, the differences were not significant (P = 0.). Sixty-five of 8 women (80%) conceived. These 65 women conceived a total of 78 times, and 0 of these pregnancies (.8%) have aborted. These 0 spontaneous abortions occurred in 8 of the 65 women (.3%). Fifty-four infants have been delivered: 3 boys (43%) and 3 girls (57%). Five of the 54 infants weighed less than 500 gm (9.3%), but of these weighed more than 300 gm. Two of the remaining three premature infants were twins born at 30 weeks to a mother who required clomiphene to ovulate. The last premature infant weighed 00 gm when delivered at 5 weeks of a mother with a bicornuate uterus. The mean age of the 6 women who did not conceive was 8.7 years (range to 35 years). 3 c CD i E :s z Number of Months Figure Conception with donor insemination.

4 Vol. 37, No. SUCCESS OF AID 97 Table 4. Outcome of Women Beginning Donor Insemination Months of insemi- No. women start- No. women conceiv- Conception rate No. women stopping" No. women failing" nation ing ing (.7%) (3.8%) (0.0%) (4.6%) (.9%) (3%) (9.%) 6 (55%) (5%) (50%) (00%) an umber (percent) of women who started insemination that month. Six of these women had conceived previously, and all but one ovulated monthly, as judged by a sustained rise in basal temperature. One woman was considered to be anovulatory in two of seven insemination. Patency of the fallopian tubes was assessed in 5 of the 6 women who did not conceive. Nine women had a hysterosalpingogram, and the findings were normal in each of them. Tubal insufflation was normal in four women but suggested tubal occlusion in one. Peritubal adhesions were found at laparoscopy in one woman who had no other evaluation of her fallopian tubes. Two other women in this group who did not conceive underwent laparoscopy, and findings were normal in both. Since 3 of these 6 women did not undergo laparoscopy, the findings of tubal disease in of these women may be an underestimate of the frequency of tubal abnormalities in the women who did not conceive during donor insemination. DISCUSSION Sixty percent to 80% of women who are inseminated with sperm from a donor should conceive, " 3 and the failure to conceive in the remaining women has been attributed to a variety of causes. Anovulation has been found in 0% to 64% of women who did not conceive during donor insemination performed for a reasonable period of time. 0 In the present series, 6 women failed to conceive after 6 months of insemination, but only woman had a basal temperature record suggestive of occasional anovulatory. Other than changes in the characteristics of cervical mucus, a sustained rise in the basal temperature was the only method used to detect ovulation. If a biphasic basal temperature pattern does not correlate with other evidence for ovulation, then the number of anovulatory women in this group would have been underestimated. This is unlikely, since additional evidence of ovulation has been reported for more than 90% of women with biphasic basal temperatures. 3 Although 0% of women with monophasic basal temperatures may have hormonal evidence of ovulation, 4 women in the present report who had a monophasic temperature pattern during the three to four before starting donor insemination were considered anovulatory and received clomiphene. Three of the four women who received clomiphene delivered a single child at term, and the 4th woman delivered twins prematurely. None of the 6 women who did not conceive received clomiphene. Pelvic pathology has been found in % to 7% of women who did not conceive during donor insemination, but conception has occurred in only 0% of such women who underwent corrective surgery. 5 6 Based on these figures, only 3 more women of 00 who begin donor insemination would conceive as a result of diagnostic laparoscopy and subsequent corrective surgery. If pel- Table 5. Factors Affecting the Success of Donor Insemination Conception Nonconception No. inseminations/.43 ± o.o8a.34 ± 0.08 cycle Sperm count (mil ± ± 3. lion/ml) Sperm motility(%) 69 ±.4 67 ±.4 Cycles with drop in basal ternperature (%)c Maximum spinn- 5.6 ± ± 0.3 barkeit (em) Days between 0 0. maximum spinnbarkeit and basal temperature nadir amean ± standard error of the mean. bnot statistically significant (i.e., P > 0.05). c A preovulatory drop of 0.3 F in day and/or of 0.5 F over days. p b

5 98 AlMAN January, 98 Table 6. Timing of Donor Insemination in Relation to the Basal Temperature Nadir (Day 0) Day No. in- ---: semina.;;; ' ;;;. + tions Nonconception 4.8% 0.6% 0.8%.3% 3.5% 6 Conception 6.8% 8.% 5.% 9.3% 30.6% 83 vic abnormalities are found in only 33% or 3% 9 of women, then the pregnancy rate by donor insemination would increase by less than women in 00 as a result of laparoscopy and corrective pelvic surgery. Nonetheless, it is possible that more than women in this group of 6 who did not conceive failed to do so because of undiagnosed tubal pathology. The quality of cervical mucus 9 7 and the number of inseminations per cycle 7 have been suggested as additional factors affecting the success of donor insemination. Neither of these was a factor in the present group of women, since observed differences between conception and nonconception were insignificant. The mean elapsed time for pregnancy to occur,.3 months in the present report, was similar to the time reported by others, 3 despite differences in technique and number of inseminations per cycle. Schwartz and co-workers did note a significant increase in the pregnancy rate when the cervical canal was dilated, cervical mucus was abundant ' or spinnbarkeit was greater than 0 cm. 7 In the present report, midcycle dilatation of the cervix and the quantity of cervical mucus were not recorded. Schwartz et alp performed insemination once in a maximum of two of 59 women and achieved a pregnancy rate of 3%. In their study, there was no single day in relation to the basal temperature nadir that was clearly more successful than other cycle days. Five women in the present series conceived in with one insemination, which were done either on day + (n = 3) or + (n = ). All other women conceived during with two or more inseminations. Since the distribution of inseminations was similar in conception and nonconception, timing of donor insemination was not a factor in determining conception in these women. Pregnancy with donor insemination has been reported to occur less often in women over 30 years and in women with a history of abdominal surgery! 5 Only of the 6 women of the present report had had previous abdominal surgery (a cesarean section), and 8 women were older than 30 years. However, six of these eight women had been pregnant at least once. Age and parity in these women were similar to those of the 65 women who conceived. The apparent preponderance of female infants (3 of 54) in this report is probably misleading due to small numbers. If the number of female and male infants reported by three other groups 3 are added to the numbers of the present series, then a normal sex ratio of 40 female and 4 male infants resulted from donor insemination. Finally, the mean sperm concentration and motility of conception were nearly identical to these values in nonconception. The range of sperm concentrations in the women who conceived was million/ml to 70 million/mi. Other aspects of semen quality, such as sperm penetration assays or biochemical measurements, were not done. In summary, all the inseminations were performed in an identical fashion by the author or one of two nurses. The number of inseminations per cycle, the sperm concentration and motility, characteristics of the temperature charts, the quality of cervical mucus, and the timing of insemination were similar in conception to those factors in nonconception. No one of these appears to have determined the success or failure of donor insemination. Differences in the selection of women who will be inseminated may be the primary reason for the variable success rates reported for donor insemination. Acknowledgments. The valuable assistance of Barbara Grun, R.N. and Mary Ann Fitzgerald, R.N. is acknowledged and appreciated. In addition to helping with the inseminations, they encouraged and counseled the women who participated. REFERENCES. Goss DA: Current status of artificial insemination with donor semen. Am J Obstet Gynecol:46, 975. Dixon RE, Buttram VC: Artificial insemination using donor semen: a review of 7 cases. Fertil Steril 7:30, Chong AP, Taymor ML: Sixteen years' experience with therapeutic donor insemination. Fertil Steril 6:79, Behrman SJ, Sawada Y: Heterologous and homologous insemination with human semen frozen and stored in a liquid nitrogen freezer. Fertil Steril7:457, Steinberger E, Smith KD: Artificial insemination with fresh or frozen semen: a comparative study. JAMA 3: 778, 973

6 Vol. 37, No. SUCCESS OF AID Smith KD, Steinberger E: Survival of spermatozoa in a human sperm bank: effects of long term storage in liquid nitrogen. JAMA 3:774, Escalier D, Bisson JP: Quantitative ultrastructural modifications in human spermatozoa after freezing. In Human Artificial Insemination and Semen Preservation, Edited by G David, WS Price. New York, Plenum Press, 979, p Guerin JR, Menezo Y, Czyba JC: Biochemical modifications of frozen semen. In Human Artificial Insemination and Semen Preservation, Edited by G David, WS Price. New York, Plenum Press, 979, p Strickler RC, Keller DW, WarrenJC: Artificial insemination with fresh donor semen. N Engl J Med 93:848, Beck WW: A critical look at the legal, ethical, and technical aspects of artificial insemination. Fertil Steril7:, 976. Corson SL: Factors affecting donor artificial insemination success rates. Fertil Steril 33:45, 980. Hilgers TW, Bailey AJ: Natural family planning. II. Basal body temperature and estimated time of ovulation. Obstet G)'necol 55:333, Magyar DM, Boyers SP, Marshall JR, Abraham GE: Regular menstrual and premenstrual molimina as indications of ovulation. Obstet Gynecol 53:4, Moghissi K: Accuracy of basal body temperature for ovulation detection. Fertil Steril 7:45, Sulewski JM, Eisenberg F, Stenger VG: A longitudinal analysis of artificial insemination with donor semen. Fertil Steril 9:57, Broekhuizen FK, Haning RV, Shapiro SS: Laparoscopic findings in twenty-five failures of artificial insemination. Fertil Steril 34:35, Schwartz D, Mayaux M, Boyce A, Deyaglik F, David G: Donor insemination conception rate according to cycle day in a series of 8 with a single insemination. Fertil Steril 3:6, 979