Edward T. Tyler

The Clinical Use of Frozen Semen Banks

In humans, use of frozen semen is still limited to the activities of a few centers. Procedure for freezing semen involves adding .1 ml of glycerol for each milliliter of semen to be frozen. The specimen is then transferred into sterilized ampules in 1 ml quantities and sealed. The ampules are then suspended in liquid nitrogen vapor at a temperature of -99 degrees C for 1/2 hour. Following this, ampules are maintained at -198 degrees C for storage, after appropriate coding. The major application is for donor inseminations. An experimental use is for pooling of a husbands specimens which are deficient in sperm numbers. Another clinical application is the storage of semen prior to sterility-inducing procedures in the husband, e.g., therapeutic irradiation. A similar application is for men contemplating vasectomy. Less than 1% of vasectomy patients have been interested in this procedure. There is no guarantee that the specimen will be usable at a later date. The longest successful utilization has been after 2 1/2 years. Results of insemination have been comparable with reports from elsewhere. Of a group of 92 pregnancies, 68 had delivered at term, 4 had spontaneous abortions, and 20 had not as yet delivered. Only 1 fetal abnormality was found, that of a child who had a missing digit. There were 1986 inseminations. Some required several inseminations. In this study, the total number of pregnancies through the use of frozen semen has been 137. The success rate is comparable to that obtained with nonfrozen specimens.

Immunologic Aspects of Human Infertility

Blood sera of 148 infertile patients from the Tyler Clinic was sent to the Bombay laboratory for examination. The macroscopic agglutination technique by Kibrick et al was used for examination of sperm agglutinin. 16 of these samples contained autoagglutinins and 14 isoagglutinins. 220 samples of sera were collected from infertile patients of the Family Welfare Bureau in Bombay. Of these 20 contained autoagglutinins and 17 had isoagglutinins. 3 of the 50 female fertile sera examined with the semen of Donor 1 were +. No + reactions were observed when these sera were tested with semen of other donors. 17 (11.6%) of 146 infertile female specimens tested had + reactions with semen specimens from Donor 1 as compared to 3 with sperm from Donor 2. The results were negative in another group of 132 infertile female sera similarly tested. 18 + reactions among the infertile male specimens (12.2%) were observed with Donor 1; 6 (4.0%) with Donor 2 and 3 (2.3%) with Donor 3. 4+ reactions were noted in the prenatal sera examined but when retested with semen from another donor the results were negative. Autoagglutinins or isoagglutinins were found in 18% of 368 infertile sera when the hemagglutination technique was used to detect sperm agglutinins in blood sera. Sera of unmarried females did not exhibit detectable levels of agglutinins nor did those of married couples whose blood were obtained just before or soon after conception.

Present Status of Injectable Contraceptives: Results of Seven-Years Study

2 experimental contraceptive injection programs are reported. 1 method provides for administration of a combined long-acting estrogen-progestogen product once a month, the other uses a long acting progestogen alone once every 90 days. In the once-a-month injection program in Los Angeles 615 patients representing 871 admissions were studied; treatment data are for both 1st and all admissions. Age distribution was 21-25 years. Patients received 150 mg of progestogen/10 mg estrogen injection. 88.1% reported cycles of 22-30 days/on admission. Some results are: For 1st and all admissions average duration of flow was 6.6 days; for 1st admission group complaints consisted of breast tenderness, 46% dysmenorrhea, 61.8%, weakness or dizziness, 42.8%, local reaction to injection, 37.4%. For all admissions, complaints were: breast tenderness, 43.3%, dysmenorrhea, 59.6%, weakness, 40.2%, local reaction, 33%. Reasons for dropout for both groups included rigidity of protocol, about 52%, moved away, 4.5%, extraneous illness, 1.5%; 64.4% of all admissions discontinued treatment due to unrelated reasons. No pregnancies were reported. The once every 90 day injection of medroxyprogesterone acetate given in doses of 150 mg were given to 243 women, of whom 57% were aged 20-29. Some results are: 1) number of days of bleeding ranged from 6-20 days, 2) 4.6% reported nervousness, 3.4% nausea, 2.1% headaches, 3) main reasons for dropouts were moving away, 11.8%, bleeding, 4.6%, and 4) 1/3 resumed ovulation within 1/2 year. Both methods are found to be extremely effective.

Ophthalmologic Findings in Patients Using Oral Contraception

A detailed study was initiated to investigate thoroughly the possibility that any significant ophthalmologic changes might have occurred in patients using oral contraceptives (OCs) for varying periods. There were 212 patients and 50 control patients who were selected at random, 1/2 from private ophthalmology practice and 1/2 from Planned Parenthood Centers in Los Angeles. During eye examinations, the visual acuity and tonometric measurements were recorded. After pupillary dilation, slit-lamp and funduscopic examinations were performed. Among the compounds being taken by patients in this program were norethynodrel-mestranol combinations, norethindrone-mestranol preparations, medroxyprogesterone acetate with ethinyl estradiol, norethindrone acetate-ethinyl estradiol, and norethindrone-mestranol sequential. None of the control patients were using any medication similar to that of the patients under study, and all were given the same examination by the same opthalmologist. A substantial percentage of patients using OCs had some degree of ocular pathology. Much of this was of an insignificant variety and could in no way be related to OC use. In 212 patients (424 eyes) there were 6 instances in which there were potentially progressive lens conditions of unknown cause. None was of the classic complicated or toxic types of cataract. In the small group of control patients, 4% of the eyes had subcapsular vacuoles of the lens. In the contraceptive-treated group, there were only approximately 1.5% showing similar potentially progressive lens pathology. There was 1 case of potential galucoma in the control group and 1 in the contraceptive-treated group. No papilledema was observed in this series.

Biochemical findings in long-term oral contraceptive usage. I. Liver function studies.

A long-term wide-range biochemical screening study of patients taking oral contraceptive pills at the Los Angeles Planned Parenthood Center is described. The study was designed to assess what if any alterations are produced in body systems other than the reproductive system by the steroids in the contraceptive pills investigated. Results on a total of 213 control patients new on the pill and 711 treated patients who had taken the pill for up to 8-9 years were analyzed. The majority of the patients were Negroes generally obese and most had had at least 1 and usually several pregnancies. Of the controls 2.3% showed abnormal bromosulphalein (BSP) retention. In the treatment group 6.8% showed abnormal retention a significant difference (p less than .05). The weight of the patient governs the dose of BSP and should be modified in the obese patient as the standard 5 mg/kg dose classifies too many normal patients as abnormal in the presence of obesity. The administration of contraceptive steroids caused a statistically significant increase in the number of abnormal BSP tests and the number of abnormalities in BSP excretion increases as the steroid dosage increases. At the 1 mg level there is no statistical difference between treated patients and controls when norethindrone is employed. In the controls there appears to be a cyclic variation in BSP excretion abnormalities being more frequent during the luteal phase of the menstrual cycle. In the treated patients there is a statistically significant menstrual cycle effect with more abnormalities in the luteal phase. This seems to indicate that each patient may go through a normal and abnormal BSP excretion phase resulting partially from her own cyclic steroidal environment. However this may represent merely a cumulative effect of endogenous cycling and accumulated exogenous steroids seems more likely. There is strong indication that the percentage of abnormal BSP tests decreases as the length of time of steroid administration increases. This appears to represent the now familiar adaptation phenomenon.

A clinical evaluation of long-term continuous use of norethynodrel-mestranol for contraception.

To assess the effect of long-term usage of norethynodrel-mestranol oral contraceptives upon human health 176 women who had used this type of agent for periods of 4-10 years were given a physical examination plus a battery of laboratory studies. Laboratory tests for white blood count differential white blood count hemoglobin hematocrit fasting blood sugar serum alkaline phosphatase and serum glutamic pyruvic acid transaminase all fell within the normal ranges for all 176 (with the exception of 1 woman who had a white blood count of 3000/cu mm). Women who were underweight before beginning therapy tended to gain weight while those who were overweight before tended to gain and lose in equal numbers. Hypertension was recorded for 22 of the 176 women 12 of whom had prior history of hypertension. Overall 19 of the 22 hypertensive women were overweight. Uterine fibromyomas was found in 39 of the 176 women (22%). Of these 39 2 had a previous history of fibroids. Cervical erosion was reported in 82 of the 176 women but with an expected relationship to age and parity. Fundoscopic examinations revealed narrowing of the retinal arteries in 4 women (all hypertensive) and slight arterial-venous nicking in 1 woman (also hypertensive). The general health of 168 of the 176 women was stated to be unchanged while 4 were considered worse. 172 of the women wished to continue using the contraceptive while 2 were undecided. No unplanned pregnancies occurred.

Infertility: SEQUENTIAL MESTRANOL-CHLORMADINONE ACETATE AS AN ORAL CONTRACEPTIVE

In a study of sequential mestranol-chlormadinone acetate as an oral contraceptive 491 patients were followed for a total of 7704 cycles. Of the group of patients who started taking medication 295 dropped out: 9 because of pregnancy 37 by their own decisions for reasons unrelated to side effects 19 because of side effects (of the 19 4 left by their own decisions and 15 by the physicians decision) 66 patients moved or could not be located 1 was dropped for noncooperation 1 was hospitalized 6 left for unknown reasons and 156 were due to termination of the study upon the sponsors decision. Of the 9 pregnancies 8 were attributed to patient failure. In general the side effects for the chlormadinone-mestranol sequential contraceptive method were quite low in incidence and the patients tolerated the medication extremely well.(AUTHORS MODIFIED)