One Thousand Cases of Infertility

One Thousand Cases of Infertility Clinical Review of a Five-Year Series Robert B. Wilson, M.D. THE RECORDS of 1032 women who complained of infertility have been reviewed. These patients were seen by various physicians in the Section of Obstetrics and Gynecology at the Mayo Clinic during the years 1940 to 1944 inclusive; most of these patients had a primary complaint of infertility. Many patients who had severe menstrual disorders or pelvic disease were not included, although infertility was part of their problem. Since sufficient time now has elapsed and since a sufficient number of cases has been accumulated to allow the data to be of statistical significance, the first portion of this study is being reported at the present time. This work is to be continued and brought up to date in order to provide the necessary data for adequate evaluation of the diagnostic and therapeutic procedures utilized at the clinic. METHODS The diagnostic procedures used in the years covered by this study were those generally employed at the time. They included the customary history and physical and pelvic examinations, determination of the presence or absence of tubal patency by transuterine tubal insufflation with carbon dioxide or examination utilizing iodized oil and, when possible, a premenstrual endometrial biopsy. Examinations of semen were done when the husband was available. Basal metabolic rates were obtained in practically all cases. When menstrual dysfunction was present, pertinent studies, From the Section of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota. Presented at the First World Congress on Fertility and Sterility, New York City, May 30, 1953. 292 ---- ~------~

Vol. 4, No. 4, 1953] INFERTILITY 293 such as roentgenologic examination of the sella turcica and hormonal assays, were conducted. RESULTS Of the 1032 patients, 794 ( 77 per cent) had primary infertility and 238 ( 23 per cent) had secondary infertility. The ages of the patients who had primary infertility, together with its duration, are shown in Table 1, which TABLE 1. Duration of Primary Infertility Age (yr.) Total <25 25-30 31-35 >35 Years Cases % Cases %a Cases %a Cases %a Cases %a 1-2 145 18 64 42 52 15 23 10 6 9 3-4 200 25 52 34 102 30 36 15 10 16 5-6 181 23 27 18 96 28 50 21 8 13 7-10 196 25 10 6 87 25 79 34 20 32 10+ 72 9 7 2 46 20 19 30 TOTALS 794 100 153 100 344 100 234 100 63 100 Age per cent 100 19 43 30 8 a Per cent of the particular age group. reveals that 62 per cent of these patients were less than 31 years of age. Of this group of women, 57 per cent had been infertile for five years or more. In Table 2 are presented data relating to the ages of the patients and duration of secondary infertility, which is that type occurring in women who have conceived previously. Approximately half of these patients were TABLE 2. Duration of Secondary Infertility Age(yr.) Total <25 25-30 31-35 >35 Years Cases % Cases %a Cases %a Cases %a Cases %a 1-2 49 20.5 7 37 26 27 11 12 5 14 3-4 64 27 8 42 21 22 26 30 9 26 5-6 49 20.5 4 21 24 25 17 19 4 11 7-10 64 27 25 26 22 25 17 49 10+ 12 5 12 14 TOTALS 238 100 19 100 96 100 88 100 35 100 Age per cent 100 8 40 37 15 a Per cent of the particular age group.

,J 294 WILSON [Fertility & Sterility less than 31 yea~s of age and half had been secondarily infertile for five years or more. Table 3 lists the results of diagnostic studies in the 794 cases of primary infertility. Definite causes of infertility in the women included nonpatent fallopian tubes, prolonged amenorrheic menstrual dysfunctions, and extensive pathologic changes in the pelvis. Definite causes in the man included,, I I.!! TABLE 3. Cause of Primary Infertility Man and Total Man only Woman only woman Per Per Per Per Cause Cases cent Cases centa Cases centa Cases centa Definite 218 28 107 50.5 95 45 16 46 Presumptive 239 30 105 49.5 115 55 19 54 Not found 337 42 TOTALS 794 100 212 100 210 100 35 100 Sex, per cent 27 27 4 a Per cent of sex. aspermia or severe oligospermia of such degree that quantitative counts were not made, sperm counts less than 20,000,000 per cubic centimeter, and impotence. A definite cause of primary infertility could be found in 218 of these 794 cases; the cause was in the man in 107 ( 49 per cent) and in the woman in 95 ( 44 per cent). Positive causes were found in both partners in 16 ( 7 per cent) of the cases. Among presumptive causes of infertility in women were certain menstrual disorders, evidence of tubal disease in which the tubes remained patent, certain congenital anomalies, and certain types of pathologic changes in the pelvis. A presumptive cause in men was considered present when the spermatozoa numbered between 20,000,000 and 60,000,000 per cubic centimeter, or in instances of greater counts when the spermatozoa displayed extensive abnormal morphologic changes or motility. No ascertainable cause of the primary infertility was found in 337 ( 42 per cent) of these 794 women. However, in 227 ( 28 per cent) of this group, the husbands were not available for examination. Therefore, in only 110 cases ( 14 per cent) of the group of 794 classed as primary infertility were both the man and the woman thought to be normally fertile. Obviously more couples considered to be normally fertile would have been found if all of the husbands had been available for examination.

Vol. 4, No. 4, 1953] INFERTILITY 295 A similar summary of the ascertainable causes in secondary infertility is presented in Table 4. In this group, no cause was found in 92 ( 39 per cent) of the women. However, in 73 ( 31 per cent) of the entire group, the husbands were not available for examination. A striking difference is noted when a comparison is made of positive and presumptive causes in each of TABlE 4. Cause of Secondary Infertility Man and Total Man only Woman only woman Cause Cases % Cases %a Cases %a Cases %a Definite 63 26 12 48 41 41 10 50 Presumptive 83 35 13 52 60 59 10 50 Not found 92 39 TOTALS 238 100 25 100 101 100 20 100 Sex, per cent 11 43 8 a Per cent of sex. the two sexes in secondary and primary infertility. In secondary infertility, definite or presumptive causes were found in 101 ( 43 per cent) of the women and in only 25 ( 11 per cent) of the men. As in the primarily infertile group, an absolute or presumptive cause was found in approximately 60 per cent of those examined. TABlE 5. Sperm Counts Infertility Sperm Primary Secondary (millions) Cases % Cases % oa 63 15 6 7 <20 60 14 16 20 20-40 74 18 15 19 40+-60 50 12 8 10 > 60 174 41 35 44 TOTALS 42P 100 soc 100 a Aspermia or extensive oligospermia. b Among the 794 cases of primary infertility, 373 men were not available for study. Of these 373 cases, the woman was not fertile in 146 ( 39 per cent). c Among the 238 cases of secondary infertility, 158 men were not available for study. Of these 158 cases, the woman was not fertile in 85 (54 per cent). In Table 5 are listed the results of sperm counts. About 60 per cent of the men in the primarily infertile group had counts of 60,000,000 or less per cubic centimeter; approximately 30 per cent of this entire group had counts

296 WILSON [Fertility & Sterility of less than 20,000,000. The findings in the secondarily infertile group were not greatly different. I,, I COMMENT It must be pointed out that the work in gynecology at the clinic is primarily diagnostic and advisory. Many patients included in this study had intensive and extensive investigation elsewhere and came only for an opinion. Examination in others has been incomplete because the patient did not have sufficient time or the husband was not here. Menses may have been present or an adequate investigation may already have been done. Therefore, the present status of this study does not allow proper evaluation of the results of various therapeutic measures. It is hoped that the follow-up study now in progress will disclose a sufficient number of pregnancies in the inadequately studied and treated group of patients to furnish an interesting comparison to the number of pregnancies in those who have had complete care. Of further interest will be the outcome ten or fifteen years hence in those who were thought to be normally fertile at the time of their original examination. Diagnostic procedures for determination of tubal patency and the performance of endometrial biopsy are almost completely innocuous, judging from this study. No instance of pelvic infection occurred after the examinations in this particular series. The iodized oil ( Lipoiodine or Lipiodol) used has given good roentgenograms and has produced no discernible local reactions or deleterious sequelae. Nearly all properly timed endometrial biopsies done in regularly menstruating women have shown a normal secretory endometrium. My associates and I are of the opinion that the best time to obtain maximal information concerning the endometrium is on the twenty-first or twenty-second day of a twenty-eight-day cycle, or approximately six to eight days after ovulation. The incidence of anovulation, as revealed by this examination, has been so infrequent that reasonable doubt exists that an endometrial biopsy must be done invariably in patients who have a menstrual history of the usual regularly cyclic variety. Data relating the age of the patients and the duration of their infertility may appear insignificant to many investigators; however, to me such data are of great importance. As previously noted, almost 4 of 10 patients were more than 30 years of age and slightly more than 5 of 10 had been infertile ------

Vol. 4, No. 4, 1953] INFERTILITY 297 for more than five years. This means that the physician must often deal with a patient who is past her years of optimal fertility and who has been subjected to the mental trauma so characteristically seen in the woman who does not conceive readily. The reason for this delay in the investigation may be the responsibility of patient or physician or both. Strange as it may appear to the physician interested in this problem, a great number of patients are completely unaware of the diagnostic and therapeutic help that is available. It is only after a great amount of valuable time has been lost that such patients learn of the assistance they may obtain. It should be obvious that physicians can do much to correct this particular difficulty by asking every nulliparous patient if pregnancy is desired and, if so, by offering her proper advice. All too often, however, a woman who has been married a relatively short time and who has not conceived will consult her physician. Mter a few superficial questions and an investigation often limited to an examination of the pelvis, she is told that everything is all right and that more time should elapse before she becomes concerned. Conversely, a patient may forego adequate investigation and treatment because, after such an incomplete analysis, she has been told that pregnancy is unlikely or impossible because of the size or position of the uterus. Some gynecologists hold the opinion that a woman should not be considered infertile until three years of marriage have elapsed; such physicians may procrastinate during this length of time before instituting definitive measures. Such practices appear to me to be unjustifiable. Any man and wife who ask should have the benefit of a positive opinion, when such is possible. Only in this way can those who are actually infertile become aware of their status and plan their lives accordingly. In those who have a remediable defect, treatment can be instituted at the earliest possible time. It should be kept in mind that in patients more than 30 years of age, and certainly in those more than 35, a mounting incidence is present of waning ovarian function, endometriosis, and uterine myomas. A particularly pernicious error on the part of the patient is prolonged use of contraception. Not uncommonly contraception is employed for many years by husbands and wives who are actually or relatively infertile. Again important time is lost for those in whom conception is physiologically slow or who have correctible defects. The phvsician can do much to circumvent this problem by reminding those to whom he gives contraceptive advice

298 WILSON [Fertility & Sterility that they are not necessarily fertile. Couples should be warned that it should be reasonably certain that they are normally fertile if contraceptive practices are contemplated for periods longer than approximately one year. Such advice is of particular importance for women who marry when they are more than 25 to 30 years of age. Basically all that has been said about those who have never conceived applies to those who have achieved at least one pregnancy. This group, however, presents to the physician another problem, that of prevention of infertility. For instance, the only pregnancies that had occurred in many patients of this group had been interrupted illegally. Pelvic sepsis, with resultant tubal closure, after such induced abortions was commonly noted. However, many patients in this series who had a history of one or more induced abortions had no demonstrable pathologic changes and yet remained infertile. Why this should be so is entirely speculative. All ethical physicians will, by their counsel, do their utmost to discourage this deplorable adjunct of our times and thus prevent many cases of secondary infertility. Other occasional causes of secondary infertility are traumatic deliveries, postpartum sepsis, and unnecessary pelvic operations. The methods by which these causes can be minimized require no comment. From this study it is possible to state that a reasonable explanation for absolute or relative infertility can be discovered in approximately 60 per cent of patients who are primarily infertile and that these causes will be divided about equally between the two sexes. Thus, a complete examination for infertility must include study of both husband and wife. SUMMARY AND CONCLUSIONS Data concerning 1032 cases of infertility encountered at the Mayo Clinic have been presented relative to the age of the patients, the duration of the infertility, and the diagnostic results. The infertility was primary in 794 cases and secondary in 238. Definite causes of infertility in women included nonpatent fallopian tubes, prolonged amenorrheic menstrual dysfunction, and extensive pathologic changes in the pelvis. Presumptive causes in women included certain menstrual disorders, evidence of tubal disease with maintenance of patency, and certain pathologic changes in the pelvis. Definite or presumptive causes in men were considered to be disturbances

Vol. 4, No. 4, 1953] INFERTILITY 299 in the number of spermatozoa, extensive changes in their morphology and motility, or impotence. A reasonable explanation for absolute or relative infertility can be found in about 60 per cent of patients who are primarily infertile; the causes will be divided about equally between the two sexes. Therefore, a complete study of infertility should include examination of both husband and wife.