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The relationships of certain variables to conceptions in treated infertility patients
The relationships
of certain variables to
conceptions in treated infertility FRANCES
V.
ROBERT Syracuse,
E. New
DE
L.
GEORGE,
patients
M.A.
NESBITT,
JR.,
M.D.
York
Data were analyzed from a sample of 73 patients (33 nulligravidas and 40 prior gravidas) who presented with infertility problems. Only patients who accepted investigation and therapy, apparently maintained interest in conceiving, and were not immediately lost to follow-up were included in the sample. The onset of follow-up was post investigation for all patients. The incidence of viable births, with the use of the life-table procedure, was found to be 50 per cent at 72 months of follow-up in nulligravidas and 64 per cent at 92 months of follow-up in prior gravidas. The results indicate that the magnitude of the disturbance(s) is associated with treatment outcome, i.e., the frequency of viable births was significantly higher in patients with single disturbances compared to patients with multiple disturbances. To the extent that the magnitude of disturbance(s) is related to age in nulligravidas and in prior gravidas, and duration of infertility is not independent of age in nulligravidas, there is a tendency for the latter two variables to be associated with treatment results.
investigation of patients with reproductive failure. Data were analyzed to test the associations between variables and the relationship of each variable to the follow-up result. The findings in nulligravidas and in prior gravidas are given separately. The incidences of conception during follow-up are expressed in life-table form.
THE FREQUENCY Of COnCeptiOn in patients presenting as infertility cases has been reported to vary in relation to the age of the patient, duration of infertility, and nature of the disturbance.lf 2 However, conclusions usually have been based on deviations between mean values or on distributions which were not subjected to statistical tests of significance21 3 ; therefore, the likelihood of obtaining the differences observed has not been considered. It is also of interest that the variables are not entirely independent, and it may be of value to attempt to define their relationships. The present report gives the results of an
Materials
for publication
February
for publication
May
methods
There were 116 patients with infertility problems seen in private practice during the period of 1962 through 1971, excluding patients who became pregnant prior to evaluation or who are currently being evaluated (Table I). All patients were physician referrals, and many had been subjected to various t.ypes of work-up and therapies over extended periods of time before consultation was sought. So that the results may be indicative of the degree of success of therapeutic efforts, only the 73 patients who accepted investigation, apparently maintained interest in conceiving, and were not immediately lost to follow-up constitute the
From the Department of Obstetrics and Gynecology, State University of New York, Upstate Medical Center. Received 1972. Accepted
and
28,
13, 1972.
Reprint requests: Dr. F. V. De George, Dept. of Ob.JGyn., The University Hospital of the Upstate Medical Center, 750 E. Adams St., Syracuse, New York 13210. 175
176
De
George
and
Table I. Patients relation
with infertility problems and follow-up
to work-up
No. of patients
Status of work-up
10
No problem husband’s subnormal
26
Refused satisfactory treatment
7
No follow-up, physician, pregnancy
73
Husband: screen, Routine tries
and
evident semen sperm
in
fo~fow-up
in patient, but analysis indicated characteristics work-up
or
e.g., returned to referring or patients not desirous of after work-up
Received work-up of follow-up
116
Table
September Am. J. Obstet.
Nesbitt
and
varying
lengths
Basic work-up general, endocrine,
laboratory
in infertility
genitourinary-sperm metabolism tests,
electrolyte
analysis panel
Papanicolaou smear (colpocytogram) survey (ascorbic acid) Study of mucus: description; barkheit; cultures, etc.
fern
chemis-
: dietary test;
spinn-
Postcoital test Basal body temperature record, coital pattern Rubin’s test (7 days postmenstrual) Hysterosalpingogram (7th to 10th days of cycle) Premenstrual extrauterine arteriography, dilatation and curettage, laparoscopy (or culdoscopy) Date of endometrium Glycogen stains Alkaline phosphatase Tubal perfusion under
endoscopy
study sample of this report. There were 33 nulligravidas and 40 prior gravidas, i.e., patients who had experienced at least one pregnancy before work-up. The clinical evaluation of every patient followed a broadbased investigation according to standard protocol. The aspects of the investigation are outlined in Tables II and III. The sample was not restricted to patients with a minimal period of one year of apparent infertility because in some instances this requirement is unjustified. For example,
endocrine-metabolic
screen Pituitary Skull x-ray Crude visual fields, Follicle-stimulating Other
funduscopic hormone
Thyroid Free T, Td by column Murphy-Pattee Protein-bound iodine thyroxine) 1 (total T3 uptake ?, ? basal metabolic Thyroid-binding globulin I rate Cholesterol, ? photomotorgram Other (radioactive iodine test) (hyperthyroid) Genetics Buccal Other
Total
II.
Table III. General
15, 1972 Gynecol.
smear (all (karyotype)
amenorrheic
Adrenal 17-Ketosteroids, testosterone l7-Ketogenic steroids 17-OH Pregnanetriol Other (intravenous pyelography, Metabolism 2 hr. postprandial Glucose tolerance Other Ovary Pregnanediol Estrogens Other
blood test
patients)
electrolytes)
sugar
(total)
Special tests Sperm antibody test (if above is negative) Psychiatric consultation as required Adrenocorticotropic hormone stimulation/ cortisone suppression with > 17-ketosteroids Perirenal air studies as required Acid-fast studies, biopsies Rubin’s test after tranquilizers or hydrotubation
patients presenting as infertility cases with primary or secondary amenorrhea, or with anomalous development of the genital sysvagina, are very tem, e.g., a rudimentary unlikely to be successful by time alone. Regarding the data referred to as “duration of recognition should be made of infertility,” the fact that this point of information, insofar as it can be assumed to denote the length of time that a couple has actually concentrated on reproducing, is subject to a considerable degree of inaccuracy not only
Volume Number
114 2
Conceptions
Table IV. Mean
age in relation
to follow-up
in treated
Follow-up result
No.
Mean
Conceived No conception
16 17 33
Total Viable
births
13
patients
Prior
gravidas Age (YT.1
S.D.
No.
Mean
S.D.
27.19 27.94
4.71 2.95
25 15
27.96 29.40
2.91 5.44
27.58
3.86
40
28.50
4.04
21
27.90
2.81
27.23
on the part of the patient, but also on the part of the interviewer. (Undoubtedly, this pertains, at least to some degree, to all infertility studies.) Therefore, for the most part, the data concerning this variable more accurately represent a period of time in which there was no evidence that a (successful) pregnancy occurred, and, since the patient presents with the desire to reproduce, presumably efforts have been directed toward this end during at least a fraction of the time period. The beginning of the follow-up period varied among the patients. The earliest was immediately post investigation, which pertained to the two patients with negative findings and to some patients with positive findings who required hormone therapy, whereas, in patients with conditions associated with anovulation, the follow-up period began at the earliest indication that the patient might be ovulating, e.g., at the time of the first menstrual period after a wedge resection in cases of polycystic ovarian disease. The data on nulligravidas and prior gravidas have been analyzed separately because the nature of the disturbances would be expected to vary between the two samples. It is clear that all cases in the nulligravida sample represent primary sterility. However, the prior-gravida sample consists of patients with secondary sterility, patients unable to maintain a pregnancy successfully, and patients who have both problems. Consequently, the results of treatment in the samples may not be the same. Due to the limited size of the prior-gravida sample, it
177
result
Nulligravidas Age (YT.) 1
infertility
4.80
was considered impractical to attempt to analyze such groups separately. Data concerning the following variables have been analyzed: age of patient at first visit, duration of infertility, extent of disturbances (to be defined later), and result of follow-up, i.e., whether or not conception occurred and its outcome. The incidence of conceptions, as well as of abortion and of viable births, was calculated by the life-table procedure for monthly intervals of follow-up. There was one patient in each sample who had not completed her pregnancy to date. Therefore, in each instance, the contribution of the patient to the “incidence of conception” (see Table VI) has been divided between the “abortion” and “viable birth” categories. The following formula was used to obtain the proportion to be accredited to “viable births,” and the remainder was accredited to the “abortion” incidence: V is the sum of the incidence of “viable births,” and A is the sum of the incidence of “abortions” up to the month of follow-up that the incompleted pregnancy occurred : months of
y. to “viable births incidence”
category
Results The mean ages of patients in the two samples are quite similar (Table IV) . Although the prior gravidas are a year older than the nulligravidas, this difference is not unusual for the samples involved. This is also true when comparisons are made of the
178
De
George
and
Nesbitt Am.
ages within and between samples for patients conceiving, or with viable births, and patients who did not conceive during follow-up. In spite of the similarity in age between the two samples, they are quite dissimilar for the site of the disturbances apparently associated with reproductive failure (Table V). The most prevalent problem was polycystic ovaries (45.45 per cent) among nulligravida patients; progestational defects in 7 patients and acquired adrenogenital syndrome in 6 patients account for the predominance of endocrine disturbances in the prior-gravida patients. Furthermore, in many there was more than one dispatients, turbance to be corrected. Although multiple problems in a given patient cannot be considered to be independent events always, they may be indicative of the severity of the problem. In order to examine the possible relationships between the general magnitude of disturbances and other variables, patients were divided into the following two groups. A patient was considered to have more than one disturbance when two or more conditions were present that are not generally known to be part of a syndrome or associated; otherwise, the patient was classified as having a single disturbance. For example, a patient with Stein-Leventhal syndrome would be classified as having a single disturbance; a patient with polycystic ovaries, endometriosis, and a uterine myoma would be classified as having more than one disturbance. Accordingly, 33 of the 73 patients in the total sample, or 45.21 per cent, were classified as having more than one disturbance. The extensive protocol which is designed to detect multiple disturbances appears to be quite well justified. The mean ages of patients in the two categories of disturbances are presented in Table VI, A. In view of the established association between gynecologic disease and age, it should be possible to predict the direction of age differences between the two categories, provided that the criterion for assigning patients to the categories sufficientmean
September J. Obstet.
15, 1972 Gynecol.
Table V. Distribution of predominant* of reproductive disturbances NUlliSite of disturbance
Uterine Tubal
Ovarian Endocrine Other, e.g., vaginal, cervical Negative work-up Total “Patients with more than different sites have been entered considered to be most severe.
grauidas (No.) 4 3 15
8 2 1
site
Prior gravidas (No.) 9 6 3
19 ‘2 1
33
40
one disturbance according to the
involving disturbance
ly makes the distinction intended. As expected, the mean age was observed to be elevated in patients with more than one disturbance, and, in each sample, the age difference between the two categories is significant. To test the relationship of age to duration of infertility, patients were divided into two categories: patients with a duration of infertility of 24 months or less and those with infertility of more than 24 months; this division is based on the median duration of infertility observed in the 73 patients. It may be noted in Table VI, B that the trend is the same in the two samples, viz., the mean age is higher in patients with a longer duration of infertility. Nevertheless, only the difference between the means in nulligravidas is statistically significant. In fact, the most striking differences between the two samples were observed in reference to the duration of infertility. The mean duration of infertility was 44.15 months in nulligravidas compared to 25.10 months in prior gravidas, and the difference between these values is statistically significant (Table VII, A), and the variability in nulligravidas is also greater (P = 0.005). Moreover, in nulligravidas, a very marked deviation in the mean duration of infertility was observed between patients with single and with multiple disturbances; the mean as well as the variance is significantly greater in patients with multiple disturbances (P < 0.001). Actually, the means for patients with single disturbances are very simiIar in two samples,
Volume Number
1 I4 2
Conceptions
Table VI. Mean of infertility
age in relation
to single and multiple
in treated
disturbances
infertility
gravidas
Prior
Age (~7.1 Mean
S.D.
16 17
26.25 28.82
3.56 3.80
13 20
25.92 28.65
4.21 3.28
Age
t
1
179
and to duration
Nulligravidas
NO.
patients
Mean
( S.D.
(~7.)
P
NO.
)
t
1
P
2.00
< 0.05”
f;
27.58 29.88
2.87 5.14
1.81
< 0.05*
2.09
< 0.05
;;
27.54 29.94
3.59 4.36
1.90
> 0.05
A. Disturbances
Single Multiple B. Duration
of infertility
24 months months >< 24 “One-tail
test.
Table VII. disturbances
Mean duration of infertility and to follow-up result
in relation
to single
and multiple
Prior
Nulligravidas Duration No.
S.D.
of infertility (months) /
t
1
gravidas
Duration P
No.
Mean
of infertility (months)
1 S.D.
/
t
1
P
A. Disturbances
Single Multiple
16 17
22.25 62.18
15.15 37.85
4.02
< 0.001
24 16
19.83 27.88
20.06 23.98
Total
33
44.15
34.44
x75*
< 0.02
40
25.10
22.09
16 17
37.38 50.53
34.90 33.80
1.10
> 0.20
25 15
20.28 33.13
14.85 29.51
nulligravida
and
B. Follow-up
> 0.20
1.57
> 0.10
result
Conceived No conception *Test
1.15
of difference
between
means
of total
and, although in prior gravidas the larger mean is also associated with multiple disturbance, it does not vary appreciably from the mean observed in patients with singIe disturbances. When the duration of infertility is viewed in relation to the results of follow-up, the findings are consistent in both samples (Table VII, B) . The mean duration of infertility was lower in patients who conceived than in those who did not conceive, and in neither sample does the difference between means deviate significantly from zero (P > 0.10). Generally, it would be expected that treatment would be more successful in patients with single disturbances than in those with multiple disturbances and that this would be reflected in the results of follow-up. Such is the case. The numbers of patients conceiv-
prior-gravida
samples.
ing during follow-up and the outcome of the conceptions in the two categories of disturbances are shown in Table VIII. In nulligravidas, relatively more of the patients with single disturbances conceived and were delivered of viable infants than the patients with multiple disturbances. While conceptions resulting in abortions may represent some progress in treating nulligravidas because they are all characterized by primary sterility, this is not true for prior gravidas. The prior-gravida sample includes some patients who presented with the problem of early abortions in preceding pregnancies, i.e., they did not necessarily have difficulty conceiving; therefore, the number of viable births in this sample is more appropriate than the number of conceptions. As in nulligravidas, the proportion of viable births is higher in patients with
180
De
George
and
Nesbitt Am.
Table VIII. to follow-up
Numbers results
of patients
Follow-up
Disturbances
Abortions* (No.)
Single MultipIe
tFinures in counts, mobility,
4(l)
3 of
first
parentheses and/or
single
13 conception indicate morphology.
following numbers
and multiple
disturbances
in nulligravidas Without conception <(No.)
Follow-up
15, 1972 Gynecol.
in relation
result Viable births (No.1
Abortions (No.)
Total
Q(2)?
1 2
Totals *Termination
result Viable births* (No.)
with
September J. Obstet.
l!(3)
16 17
2 ‘)
15~2) 6
17
33
4
21
in firior
gravidas
No conception (No.)
Total 24 16
7(l)
8(l) 15
40
treatment. of Datients
within
single disturbances, although the association is not significant in either sample. However, when the two samples are combined, the distribution of patients with conceptions terminating in viable births and without conceptions during follow-up deviates significantly in the two categories of disturbances (P < 0.03); there is an excess of patients with single disturbances with viable births. Among viable births, there were 4 infants with birth weights of less than 5yz pounds (11.76 per cent): 1 in a nulligravida and 3 in prior gravidas; two of the latter infants were delivered prematurely; all other deliveries were at term. All infants are known to have survived the neonatal period. As specified in Table VIII, several cases were complicated by subnormal sperm characteristics in the husbands of the patients. This was observed in 13.70 per cent of the cases, and, in 5 of the 10 cases involved, the patients per se had more than one disturbance. Understandably, such cases contribute to the number of failures following treatment and to the difficulties in determining the effectiveness of treatment of such patients. In accordance with the life-table procedure, the incidence of conceptions for monthly intervals of follow-up are presented in Table IX. The final incidences of conceptions observed were 61 per cent in nulligravidas and 82 per cent in prior gravida. The more meaningful figure, in every respect, is the incidence of conceptions that terminated in viable births. As can be seen
the
category
who
also
have
husbands
with
subnormal
sperm
in Table IX, throughout the period of follow-up, the incidence of viable births is consistently higher in prior gravidas, but the difference between the two distributions is not statistically significant (z = 0.6061, P + 0.27). The incidences of conceptions terminating in abortions of the respective samples involve 3 nulligravida and 4 priorgravida patients. An undelivered patient makes a slight contribution to the incidence in each sample. Comment In surveys of infertility patients, the proportion of conceptions attributable to medical care has been open to question.4, 5 Furthermore, the extent to which the conceptions reported represent a measure of successful management of patients varies with the characteristics of the survey, e.g., composition of study sample+ 4, 5 and methods of ana1yses.l’ 2~ 5~6 Thus, comparisons between different investigations can be misleading. For example, the characteristics of the study of Buxton and Southam are quite different from those of the investigation of the present report. Buxton and Southam included in their sample all patients interviewed for sterility, clinic and private, regardless of findings or status of investigation; the first visit marked the onset of follow-up. Consequently, their results contain 38 patients who were pregnant and 57 patients who were in the preovulatory phase of the conception cycle at their initial visit. These 95 pregnancies amount to 16.21 per cent of the 586 conceptions reported;
Volume Number
114 2
they affect the pregnancy rate and the clinical interpretation of the result. Moreover, the data entered into the calculation of the conception rate were modified. Evidently, the following formula was employed: No. of patients pregnant from date of first visit to end of follow-up time No. of patients pregnant during first year plus No. of patients followed one year or more Hence, the numerator contains the total number of patients pregnant. The majority of pregnancies occurred during the first year of follow-up, which amounted to 63 per cent of the pregnancies they observed. In the light of having included the latter pregnancies, the denominator should also include the 485 patients followed less than one year who did not become pregnant. In other words, the denominator should include the total sample who were at risk of becoming pregnant. With the appropriate denominator, their figure of 37.4 per cent becomes 28.5 per cent for the proportion of patients known to have had a pregnancy. The same problem arises in their calculation of “conception rate according to years of follow-up since first consultation.” Briefly, all patients lost to follow-up within each year who were not known to have become pregnant within the given year were disregarded, When the conception rate is computed for their data by the life-table procedure, whereby the latter patients enter into the calculations, their “cumulative pregnancy rate” of 60.0 per cent is found to be 44.0 per cent, which is the ten-year incidence of pregnancies. The extent that this rate may vary in specific segments of their sample, e.g., private and clinic, or white and black patients, is not known. That outcome might vary between the two racial groups is suggested by observation of a higher frequency of certain diseases, e.g., pelvic inflammatory disease or fibromyomas of the uterus, in blacks. Hence, the results and conclusions of this study are in reference to a sample with varied features which may not be inherent in other samples. Conse-
Conceptions
in treated
infertility
patients
181
meaningful comparisons between quently, different surveys are frequently not feasible; this is apparent when the characteristics of the current report are considered. The study sample of the current report was confined to patients who presented with reproductive failure who were not pregnant prior to investigation, and with the follow-up period commencing post investigation, as defined earlier. All patients were from a private practice which undoubtedly differs markedly from a clinic clientele. This is the consequence of the factors inherent in the referral of patients to a specialist, e.g., cases resistant to previous therapy or requiring particular therapeutic measures. That these influences pertain to our sample is evidenced by the fact that 45 per cent of the patients with primary sterility were found to have polycystic ovaries and that approximately 55 per cent of the cases had been significantly investigated previously. Recognition of the concentration of such patients in the sample is necessary to interpretation of the results.s Nevertheless, it is impossible to know of patients termed “successes” how many would have conceived without investigation and therapy, and of those termed “failures” how many may not have exerted the proper effort to conceive, especially among patients who were only followed a few months. McElin and associate? noted that intercourse was more frequent for patients who conceived, and there are a variety of factors related to coital frequency.‘j Moreover, a change in motivation7 may occur, unknown to the physician. If the change of attitude involves one member of the couple, the patient may continue to be followed for some time as a failure. This was known to be true for two patients in the original series of subjects (Table I), and they were excluded from the study sample; one patient abstained from coitus after her evaluation was completed, during the period of follow-up. Aside from these influences on the results which cannot be controlled, considering the sample studied, it is reasonable to infer that the patients who conceived, and had viable births, are treatment successes, and those who did not
182
De George
Table
IX.
and
September Am. J. Obstet.
Nesbitt
Incidence
of conceptions
during
15, 19X? Gynecol.
follow-up Nulliaravidas
Months
No.
of
follow-up
Followed
1 2 3 4 5 6 7 8 9 10 11 19 13 14 16 17 18 19 PO 'I? -23 79 92 “One
patient
) Pregnant
33 “7 “6 24 “3 ‘0 19 18 16
3 1 2
14
1”
13 12
1 2
9 8 7
1
1
currently
of patients
2
Incidence )
Lost 3
1 1
1
1 1
1 1 1
1
Conceptions 0.0909 0.1246 0.1919 0.2622 0.2991
Abortions
of 1 Viable
births
0.0909 0.0337 0.0674 0.1025
0.1245 0.1597 0.1966
0.3380 0.3794
0.23X 0.2769
0.4237
0 . 31”8-
0.4681 0.5567
0.3571 0.4458
0.6121
0.5012
0.6121
0.501:!
1 1
1
pregnant.
conceive are treatment failures during the time followed. Although a conception per se in a patient with primary or secondary sterility may represent an accomplishment, if the pregnancy terminates as a spontaneous abortion, the patient continues as a case of reproductive failure. Therefore, it is preferable to consider results in terms of the conceptions that produced viable births. What the anticipated probability of viable births might be in the study sample of this report is unknown. However, almost half of the patients had multiple disturbances, and the majority of patients classified as having single disturbances had serious problems, i.e., there were several patients with polycystic ovarian disease, acquired adrenogenital syndrome, and anomalous uterine development. In view of the composition of the sample, we consider the incidence of viable births of 50 per cent at 72
months of follow-up in nulligravidas and of 63 per cent at 92 months of follow-up in prior gravidas to be “respectable.” These results justify the individual attention and meticulous investigation rendered to these patients. Of further clinical interest are the relative probabilities of viable births for 6 month intervals. In both samples, the highest incidence is realized during the first 6 months, i.e., 19.66 per cent in nulligravidas and 31.32 per cent in prior gravidas, which were approximately twice as large as the respective incidences observed during the next interval. However, from 12 to 18 months, the probability of a viable birth in nulligravidas was essentially as good as that for the first 6 months, whereas in prior gravidas it was half of the incidence seen for the 6 to 12 month interval. In general, the ranges of incidences for the three intervals were approximately 10 to 20 per cent in nulligravidas and 10 to 30 per
Volume Number
114 2
Conceptions
in treated
infertility
patients
183
Table IX-Cont’d Prior No.
of
Months
follow-up
Followed
1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 17 18 19 20 22 23
grauidas
of patients 1 Pregnant
Incidence 1
Lost
Conceptions
Abortions
of Viable
births
40
3
1
0.0750
0.0750
36 32 29 27 24 19
3 3 1 3* 3 1
1
0.1521 0.2316 0.2581 0.3405 0.4229 0.4533
0.1521 0.2316
17 14 12 11
1 1
2 1 1 1
1 2 1
0.0265 0.0273
0.4855 0.5222
0.3132 0.3956 0.4260 0.4582 0.4950
10 9 7
0.5700 0.6656 0.7133
0.0751 0.1229
6 4
0.7611 0.8208
0.1826
0.5428 0.5905
0.6383
72 1
9; *One
patient
currently
1
0.1826
0.6383
pregnant.
cent in prior gravidas; the likelihood of a successful result decreases with the increase in the time post investigation. A speculation is that patients with multiple disturbances may require more time to succeed and that they may be well represented in the relatively later intervals. The data of this survey are too limited to permit a fair test of this supposition. The incidences of abortions observed, 11 per cent in nulligravidas and 18 per cent in prior gravidas, are within the ranges quoted of early pregnancy wastage in the general population of pregnancies. In these data, which we recognize to be limited in size, this result implies that the probability of an early pregnancy loss is apparently not unduly increased among conceptions in treated infertility patients. This may, in part, be explained by the more knowledgeable management of the pregnancy, due to in-
sights gained in treating the infertility problem. In any event, of the variables examined in this report, differences in the magnitude of reproductive disturbances were found to be most closely associated with outcome of treatment. Patients with single disturbances had a higher frequency of conceptions which terminated in viable births than patients with multiple disturbances. Furthermore, the age trend in the disturbance groups conforms with the known association of age with gynecologic disease, i.e., the mean age was found to be higher in patients with multiple disturbances. These findings were consistent in nulligravidas and prior gravidas. However, it is not surprising that the duration of infertility is significantly related to age, and, therefore, also to the disturbance categories only in nulligravidas, i.e., the mean age was lower in patients with the relatively
184
De
George
and
shorter period of infertility, and the mean duration of infertility was markedly less in patients with single disturbances. These differences between the two samples seem to be logical. In contrast to the situation in prior gravidas, in nulligravidas, the duration of infertility more closely reflects age because the relationship has not been interrupted by pregnancies at various ages and intentional intervals between pregnancies. Consequently, the mean and variance for the duration of infertility is significantly larger in nulligravidas compared to the values in prior gravidas. The shorter duration of infertility in prior gravidas may also indicate a tendency for them to seek medical attention sooner. Thus, the foregoing evidence indicates that success in treating infertility cases, nulli-
REFERENCES
1. Jones, G. S., and Pourmand, K.: Fertil. Steril. 13: 398, 196’2. 2. Turner, V. H., Davis, C. D., Zanartu, J., and 3. 4.
September Am. J. Obstet.
Nesbitt
Hamblen, E. Cl.: South. Med. J. 44: 628, 1951. McElin, T. W., Danforth, D. N., and Young, I. J.: Fertil. Steril. 11: 135, 1960. Keettel, W. C., Bunge, R. G., Bradbury, J. T.,
15, 1972 Gynecol.
gravidas and prior gravidas, which shows a trend with age, relates to the fact that the younger patient is more likely to have a single disturbance than multiple problems. Insofar as duration of infertility reflects age and single or multiple disturbances in nulligravidas, it is a variable related to treatment results. Hence, we conclude that, of the variables tested, the magnitude of disturbance( s) is the best predicator of treatment outcome in infertility patients. By the same token, insights into these problems may be influential in obtaining optimal results during pregnancy. We are most grateful to Professor Paul R. Sheehe, Department of Preventive Medicine, Upstate Medical Center, State University of New York, for valuable discussions and statistical assistance.
and Nelson, W. 0.: J. A. M. A. 160: 102, 1956. 5. Buxton, C. L., and Southam, A. L.: Human
6. 7.
Infertility, New York, 1958, Paul B. Hoeber, Inc., Medical Book Division of Harper & Row, Publishers. Rocker, I.: Fertil. Steril. 16: 531, 1965. Gray, L. A.: Obstet. Gynecol. 4: 177, 1954.
of certain variables to
conceptions in treated infertility FRANCES
V.
ROBERT Syracuse,
E. New
DE
L.
GEORGE,
patients
M.A.
NESBITT,
JR.,
M.D.
York
Data were analyzed from a sample of 73 patients (33 nulligravidas and 40 prior gravidas) who presented with infertility problems. Only patients who accepted investigation and therapy, apparently maintained interest in conceiving, and were not immediately lost to follow-up were included in the sample. The onset of follow-up was post investigation for all patients. The incidence of viable births, with the use of the life-table procedure, was found to be 50 per cent at 72 months of follow-up in nulligravidas and 64 per cent at 92 months of follow-up in prior gravidas. The results indicate that the magnitude of the disturbance(s) is associated with treatment outcome, i.e., the frequency of viable births was significantly higher in patients with single disturbances compared to patients with multiple disturbances. To the extent that the magnitude of disturbance(s) is related to age in nulligravidas and in prior gravidas, and duration of infertility is not independent of age in nulligravidas, there is a tendency for the latter two variables to be associated with treatment results.
investigation of patients with reproductive failure. Data were analyzed to test the associations between variables and the relationship of each variable to the follow-up result. The findings in nulligravidas and in prior gravidas are given separately. The incidences of conception during follow-up are expressed in life-table form.
THE FREQUENCY Of COnCeptiOn in patients presenting as infertility cases has been reported to vary in relation to the age of the patient, duration of infertility, and nature of the disturbance.lf 2 However, conclusions usually have been based on deviations between mean values or on distributions which were not subjected to statistical tests of significance21 3 ; therefore, the likelihood of obtaining the differences observed has not been considered. It is also of interest that the variables are not entirely independent, and it may be of value to attempt to define their relationships. The present report gives the results of an
Materials
for publication
February
for publication
May
methods
There were 116 patients with infertility problems seen in private practice during the period of 1962 through 1971, excluding patients who became pregnant prior to evaluation or who are currently being evaluated (Table I). All patients were physician referrals, and many had been subjected to various t.ypes of work-up and therapies over extended periods of time before consultation was sought. So that the results may be indicative of the degree of success of therapeutic efforts, only the 73 patients who accepted investigation, apparently maintained interest in conceiving, and were not immediately lost to follow-up constitute the
From the Department of Obstetrics and Gynecology, State University of New York, Upstate Medical Center. Received 1972. Accepted
and
28,
13, 1972.
Reprint requests: Dr. F. V. De George, Dept. of Ob.JGyn., The University Hospital of the Upstate Medical Center, 750 E. Adams St., Syracuse, New York 13210. 175
176
De
George
and
Table I. Patients relation
with infertility problems and follow-up
to work-up
No. of patients
Status of work-up
10
No problem husband’s subnormal
26
Refused satisfactory treatment
7
No follow-up, physician, pregnancy
73
Husband: screen, Routine tries
and
evident semen sperm
in
fo~fow-up
in patient, but analysis indicated characteristics work-up
or
e.g., returned to referring or patients not desirous of after work-up
Received work-up of follow-up
116
Table
September Am. J. Obstet.
Nesbitt
and
varying
lengths
Basic work-up general, endocrine,
laboratory
in infertility
genitourinary-sperm metabolism tests,
electrolyte
analysis panel
Papanicolaou smear (colpocytogram) survey (ascorbic acid) Study of mucus: description; barkheit; cultures, etc.
fern
chemis-
: dietary test;
spinn-
Postcoital test Basal body temperature record, coital pattern Rubin’s test (7 days postmenstrual) Hysterosalpingogram (7th to 10th days of cycle) Premenstrual extrauterine arteriography, dilatation and curettage, laparoscopy (or culdoscopy) Date of endometrium Glycogen stains Alkaline phosphatase Tubal perfusion under
endoscopy
study sample of this report. There were 33 nulligravidas and 40 prior gravidas, i.e., patients who had experienced at least one pregnancy before work-up. The clinical evaluation of every patient followed a broadbased investigation according to standard protocol. The aspects of the investigation are outlined in Tables II and III. The sample was not restricted to patients with a minimal period of one year of apparent infertility because in some instances this requirement is unjustified. For example,
endocrine-metabolic
screen Pituitary Skull x-ray Crude visual fields, Follicle-stimulating Other
funduscopic hormone
Thyroid Free T, Td by column Murphy-Pattee Protein-bound iodine thyroxine) 1 (total T3 uptake ?, ? basal metabolic Thyroid-binding globulin I rate Cholesterol, ? photomotorgram Other (radioactive iodine test) (hyperthyroid) Genetics Buccal Other
Total
II.
Table III. General
15, 1972 Gynecol.
smear (all (karyotype)
amenorrheic
Adrenal 17-Ketosteroids, testosterone l7-Ketogenic steroids 17-OH Pregnanetriol Other (intravenous pyelography, Metabolism 2 hr. postprandial Glucose tolerance Other Ovary Pregnanediol Estrogens Other
blood test
patients)
electrolytes)
sugar
(total)
Special tests Sperm antibody test (if above is negative) Psychiatric consultation as required Adrenocorticotropic hormone stimulation/ cortisone suppression with > 17-ketosteroids Perirenal air studies as required Acid-fast studies, biopsies Rubin’s test after tranquilizers or hydrotubation
patients presenting as infertility cases with primary or secondary amenorrhea, or with anomalous development of the genital sysvagina, are very tem, e.g., a rudimentary unlikely to be successful by time alone. Regarding the data referred to as “duration of recognition should be made of infertility,” the fact that this point of information, insofar as it can be assumed to denote the length of time that a couple has actually concentrated on reproducing, is subject to a considerable degree of inaccuracy not only
Volume Number
114 2
Conceptions
Table IV. Mean
age in relation
to follow-up
in treated
Follow-up result
No.
Mean
Conceived No conception
16 17 33
Total Viable
births
13
patients
Prior
gravidas Age (YT.1
S.D.
No.
Mean
S.D.
27.19 27.94
4.71 2.95
25 15
27.96 29.40
2.91 5.44
27.58
3.86
40
28.50
4.04
21
27.90
2.81
27.23
on the part of the patient, but also on the part of the interviewer. (Undoubtedly, this pertains, at least to some degree, to all infertility studies.) Therefore, for the most part, the data concerning this variable more accurately represent a period of time in which there was no evidence that a (successful) pregnancy occurred, and, since the patient presents with the desire to reproduce, presumably efforts have been directed toward this end during at least a fraction of the time period. The beginning of the follow-up period varied among the patients. The earliest was immediately post investigation, which pertained to the two patients with negative findings and to some patients with positive findings who required hormone therapy, whereas, in patients with conditions associated with anovulation, the follow-up period began at the earliest indication that the patient might be ovulating, e.g., at the time of the first menstrual period after a wedge resection in cases of polycystic ovarian disease. The data on nulligravidas and prior gravidas have been analyzed separately because the nature of the disturbances would be expected to vary between the two samples. It is clear that all cases in the nulligravida sample represent primary sterility. However, the prior-gravida sample consists of patients with secondary sterility, patients unable to maintain a pregnancy successfully, and patients who have both problems. Consequently, the results of treatment in the samples may not be the same. Due to the limited size of the prior-gravida sample, it
177
result
Nulligravidas Age (YT.) 1
infertility
4.80
was considered impractical to attempt to analyze such groups separately. Data concerning the following variables have been analyzed: age of patient at first visit, duration of infertility, extent of disturbances (to be defined later), and result of follow-up, i.e., whether or not conception occurred and its outcome. The incidence of conceptions, as well as of abortion and of viable births, was calculated by the life-table procedure for monthly intervals of follow-up. There was one patient in each sample who had not completed her pregnancy to date. Therefore, in each instance, the contribution of the patient to the “incidence of conception” (see Table VI) has been divided between the “abortion” and “viable birth” categories. The following formula was used to obtain the proportion to be accredited to “viable births,” and the remainder was accredited to the “abortion” incidence: V is the sum of the incidence of “viable births,” and A is the sum of the incidence of “abortions” up to the month of follow-up that the incompleted pregnancy occurred : months of
y. to “viable births incidence”
category
Results The mean ages of patients in the two samples are quite similar (Table IV) . Although the prior gravidas are a year older than the nulligravidas, this difference is not unusual for the samples involved. This is also true when comparisons are made of the
178
De
George
and
Nesbitt Am.
ages within and between samples for patients conceiving, or with viable births, and patients who did not conceive during follow-up. In spite of the similarity in age between the two samples, they are quite dissimilar for the site of the disturbances apparently associated with reproductive failure (Table V). The most prevalent problem was polycystic ovaries (45.45 per cent) among nulligravida patients; progestational defects in 7 patients and acquired adrenogenital syndrome in 6 patients account for the predominance of endocrine disturbances in the prior-gravida patients. Furthermore, in many there was more than one dispatients, turbance to be corrected. Although multiple problems in a given patient cannot be considered to be independent events always, they may be indicative of the severity of the problem. In order to examine the possible relationships between the general magnitude of disturbances and other variables, patients were divided into the following two groups. A patient was considered to have more than one disturbance when two or more conditions were present that are not generally known to be part of a syndrome or associated; otherwise, the patient was classified as having a single disturbance. For example, a patient with Stein-Leventhal syndrome would be classified as having a single disturbance; a patient with polycystic ovaries, endometriosis, and a uterine myoma would be classified as having more than one disturbance. Accordingly, 33 of the 73 patients in the total sample, or 45.21 per cent, were classified as having more than one disturbance. The extensive protocol which is designed to detect multiple disturbances appears to be quite well justified. The mean ages of patients in the two categories of disturbances are presented in Table VI, A. In view of the established association between gynecologic disease and age, it should be possible to predict the direction of age differences between the two categories, provided that the criterion for assigning patients to the categories sufficientmean
September J. Obstet.
15, 1972 Gynecol.
Table V. Distribution of predominant* of reproductive disturbances NUlliSite of disturbance
Uterine Tubal
Ovarian Endocrine Other, e.g., vaginal, cervical Negative work-up Total “Patients with more than different sites have been entered considered to be most severe.
grauidas (No.) 4 3 15
8 2 1
site
Prior gravidas (No.) 9 6 3
19 ‘2 1
33
40
one disturbance according to the
involving disturbance
ly makes the distinction intended. As expected, the mean age was observed to be elevated in patients with more than one disturbance, and, in each sample, the age difference between the two categories is significant. To test the relationship of age to duration of infertility, patients were divided into two categories: patients with a duration of infertility of 24 months or less and those with infertility of more than 24 months; this division is based on the median duration of infertility observed in the 73 patients. It may be noted in Table VI, B that the trend is the same in the two samples, viz., the mean age is higher in patients with a longer duration of infertility. Nevertheless, only the difference between the means in nulligravidas is statistically significant. In fact, the most striking differences between the two samples were observed in reference to the duration of infertility. The mean duration of infertility was 44.15 months in nulligravidas compared to 25.10 months in prior gravidas, and the difference between these values is statistically significant (Table VII, A), and the variability in nulligravidas is also greater (P = 0.005). Moreover, in nulligravidas, a very marked deviation in the mean duration of infertility was observed between patients with single and with multiple disturbances; the mean as well as the variance is significantly greater in patients with multiple disturbances (P < 0.001). Actually, the means for patients with single disturbances are very simiIar in two samples,
Volume Number
1 I4 2
Conceptions
Table VI. Mean of infertility
age in relation
to single and multiple
in treated
disturbances
infertility
gravidas
Prior
Age (~7.1 Mean
S.D.
16 17
26.25 28.82
3.56 3.80
13 20
25.92 28.65
4.21 3.28
Age
t
1
179
and to duration
Nulligravidas
NO.
patients
Mean
( S.D.
(~7.)
P
NO.
)
t
1
P
2.00
< 0.05”
f;
27.58 29.88
2.87 5.14
1.81
< 0.05*
2.09
< 0.05
;;
27.54 29.94
3.59 4.36
1.90
> 0.05
A. Disturbances
Single Multiple B. Duration
of infertility
24 months months >< 24 “One-tail
test.
Table VII. disturbances
Mean duration of infertility and to follow-up result
in relation
to single
and multiple
Prior
Nulligravidas Duration No.
S.D.
of infertility (months) /
t
1
gravidas
Duration P
No.
Mean
of infertility (months)
1 S.D.
/
t
1
P
A. Disturbances
Single Multiple
16 17
22.25 62.18
15.15 37.85
4.02
< 0.001
24 16
19.83 27.88
20.06 23.98
Total
33
44.15
34.44
x75*
< 0.02
40
25.10
22.09
16 17
37.38 50.53
34.90 33.80
1.10
> 0.20
25 15
20.28 33.13
14.85 29.51
nulligravida
and
B. Follow-up
> 0.20
1.57
> 0.10
result
Conceived No conception *Test
1.15
of difference
between
means
of total
and, although in prior gravidas the larger mean is also associated with multiple disturbance, it does not vary appreciably from the mean observed in patients with singIe disturbances. When the duration of infertility is viewed in relation to the results of follow-up, the findings are consistent in both samples (Table VII, B) . The mean duration of infertility was lower in patients who conceived than in those who did not conceive, and in neither sample does the difference between means deviate significantly from zero (P > 0.10). Generally, it would be expected that treatment would be more successful in patients with single disturbances than in those with multiple disturbances and that this would be reflected in the results of follow-up. Such is the case. The numbers of patients conceiv-
prior-gravida
samples.
ing during follow-up and the outcome of the conceptions in the two categories of disturbances are shown in Table VIII. In nulligravidas, relatively more of the patients with single disturbances conceived and were delivered of viable infants than the patients with multiple disturbances. While conceptions resulting in abortions may represent some progress in treating nulligravidas because they are all characterized by primary sterility, this is not true for prior gravidas. The prior-gravida sample includes some patients who presented with the problem of early abortions in preceding pregnancies, i.e., they did not necessarily have difficulty conceiving; therefore, the number of viable births in this sample is more appropriate than the number of conceptions. As in nulligravidas, the proportion of viable births is higher in patients with
180
De
George
and
Nesbitt Am.
Table VIII. to follow-up
Numbers results
of patients
Follow-up
Disturbances
Abortions* (No.)
Single MultipIe
tFinures in counts, mobility,
4(l)
3 of
first
parentheses and/or
single
13 conception indicate morphology.
following numbers
and multiple
disturbances
in nulligravidas Without conception <(No.)
Follow-up
15, 1972 Gynecol.
in relation
result Viable births (No.1
Abortions (No.)
Total
Q(2)?
1 2
Totals *Termination
result Viable births* (No.)
with
September J. Obstet.
l!(3)
16 17
2 ‘)
15~2) 6
17
33
4
21
in firior
gravidas
No conception (No.)
Total 24 16
7(l)
8(l) 15
40
treatment. of Datients
within
single disturbances, although the association is not significant in either sample. However, when the two samples are combined, the distribution of patients with conceptions terminating in viable births and without conceptions during follow-up deviates significantly in the two categories of disturbances (P < 0.03); there is an excess of patients with single disturbances with viable births. Among viable births, there were 4 infants with birth weights of less than 5yz pounds (11.76 per cent): 1 in a nulligravida and 3 in prior gravidas; two of the latter infants were delivered prematurely; all other deliveries were at term. All infants are known to have survived the neonatal period. As specified in Table VIII, several cases were complicated by subnormal sperm characteristics in the husbands of the patients. This was observed in 13.70 per cent of the cases, and, in 5 of the 10 cases involved, the patients per se had more than one disturbance. Understandably, such cases contribute to the number of failures following treatment and to the difficulties in determining the effectiveness of treatment of such patients. In accordance with the life-table procedure, the incidence of conceptions for monthly intervals of follow-up are presented in Table IX. The final incidences of conceptions observed were 61 per cent in nulligravidas and 82 per cent in prior gravida. The more meaningful figure, in every respect, is the incidence of conceptions that terminated in viable births. As can be seen
the
category
who
also
have
husbands
with
subnormal
sperm
in Table IX, throughout the period of follow-up, the incidence of viable births is consistently higher in prior gravidas, but the difference between the two distributions is not statistically significant (z = 0.6061, P + 0.27). The incidences of conceptions terminating in abortions of the respective samples involve 3 nulligravida and 4 priorgravida patients. An undelivered patient makes a slight contribution to the incidence in each sample. Comment In surveys of infertility patients, the proportion of conceptions attributable to medical care has been open to question.4, 5 Furthermore, the extent to which the conceptions reported represent a measure of successful management of patients varies with the characteristics of the survey, e.g., composition of study sample+ 4, 5 and methods of ana1yses.l’ 2~ 5~6 Thus, comparisons between different investigations can be misleading. For example, the characteristics of the study of Buxton and Southam are quite different from those of the investigation of the present report. Buxton and Southam included in their sample all patients interviewed for sterility, clinic and private, regardless of findings or status of investigation; the first visit marked the onset of follow-up. Consequently, their results contain 38 patients who were pregnant and 57 patients who were in the preovulatory phase of the conception cycle at their initial visit. These 95 pregnancies amount to 16.21 per cent of the 586 conceptions reported;
Volume Number
114 2
they affect the pregnancy rate and the clinical interpretation of the result. Moreover, the data entered into the calculation of the conception rate were modified. Evidently, the following formula was employed: No. of patients pregnant from date of first visit to end of follow-up time No. of patients pregnant during first year plus No. of patients followed one year or more Hence, the numerator contains the total number of patients pregnant. The majority of pregnancies occurred during the first year of follow-up, which amounted to 63 per cent of the pregnancies they observed. In the light of having included the latter pregnancies, the denominator should also include the 485 patients followed less than one year who did not become pregnant. In other words, the denominator should include the total sample who were at risk of becoming pregnant. With the appropriate denominator, their figure of 37.4 per cent becomes 28.5 per cent for the proportion of patients known to have had a pregnancy. The same problem arises in their calculation of “conception rate according to years of follow-up since first consultation.” Briefly, all patients lost to follow-up within each year who were not known to have become pregnant within the given year were disregarded, When the conception rate is computed for their data by the life-table procedure, whereby the latter patients enter into the calculations, their “cumulative pregnancy rate” of 60.0 per cent is found to be 44.0 per cent, which is the ten-year incidence of pregnancies. The extent that this rate may vary in specific segments of their sample, e.g., private and clinic, or white and black patients, is not known. That outcome might vary between the two racial groups is suggested by observation of a higher frequency of certain diseases, e.g., pelvic inflammatory disease or fibromyomas of the uterus, in blacks. Hence, the results and conclusions of this study are in reference to a sample with varied features which may not be inherent in other samples. Conse-
Conceptions
in treated
infertility
patients
181
meaningful comparisons between quently, different surveys are frequently not feasible; this is apparent when the characteristics of the current report are considered. The study sample of the current report was confined to patients who presented with reproductive failure who were not pregnant prior to investigation, and with the follow-up period commencing post investigation, as defined earlier. All patients were from a private practice which undoubtedly differs markedly from a clinic clientele. This is the consequence of the factors inherent in the referral of patients to a specialist, e.g., cases resistant to previous therapy or requiring particular therapeutic measures. That these influences pertain to our sample is evidenced by the fact that 45 per cent of the patients with primary sterility were found to have polycystic ovaries and that approximately 55 per cent of the cases had been significantly investigated previously. Recognition of the concentration of such patients in the sample is necessary to interpretation of the results.s Nevertheless, it is impossible to know of patients termed “successes” how many would have conceived without investigation and therapy, and of those termed “failures” how many may not have exerted the proper effort to conceive, especially among patients who were only followed a few months. McElin and associate? noted that intercourse was more frequent for patients who conceived, and there are a variety of factors related to coital frequency.‘j Moreover, a change in motivation7 may occur, unknown to the physician. If the change of attitude involves one member of the couple, the patient may continue to be followed for some time as a failure. This was known to be true for two patients in the original series of subjects (Table I), and they were excluded from the study sample; one patient abstained from coitus after her evaluation was completed, during the period of follow-up. Aside from these influences on the results which cannot be controlled, considering the sample studied, it is reasonable to infer that the patients who conceived, and had viable births, are treatment successes, and those who did not
182
De George
Table
IX.
and
September Am. J. Obstet.
Nesbitt
Incidence
of conceptions
during
15, 19X? Gynecol.
follow-up Nulliaravidas
Months
No.
of
follow-up
Followed
1 2 3 4 5 6 7 8 9 10 11 19 13 14 16 17 18 19 PO 'I? -23 79 92 “One
patient
) Pregnant
33 “7 “6 24 “3 ‘0 19 18 16
3 1 2
14
1”
13 12
1 2
9 8 7
1
1
currently
of patients
2
Incidence )
Lost 3
1 1
1
1 1
1 1 1
1
Conceptions 0.0909 0.1246 0.1919 0.2622 0.2991
Abortions
of 1 Viable
births
0.0909 0.0337 0.0674 0.1025
0.1245 0.1597 0.1966
0.3380 0.3794
0.23X 0.2769
0.4237
0 . 31”8-
0.4681 0.5567
0.3571 0.4458
0.6121
0.5012
0.6121
0.501:!
1 1
1
pregnant.
conceive are treatment failures during the time followed. Although a conception per se in a patient with primary or secondary sterility may represent an accomplishment, if the pregnancy terminates as a spontaneous abortion, the patient continues as a case of reproductive failure. Therefore, it is preferable to consider results in terms of the conceptions that produced viable births. What the anticipated probability of viable births might be in the study sample of this report is unknown. However, almost half of the patients had multiple disturbances, and the majority of patients classified as having single disturbances had serious problems, i.e., there were several patients with polycystic ovarian disease, acquired adrenogenital syndrome, and anomalous uterine development. In view of the composition of the sample, we consider the incidence of viable births of 50 per cent at 72
months of follow-up in nulligravidas and of 63 per cent at 92 months of follow-up in prior gravidas to be “respectable.” These results justify the individual attention and meticulous investigation rendered to these patients. Of further clinical interest are the relative probabilities of viable births for 6 month intervals. In both samples, the highest incidence is realized during the first 6 months, i.e., 19.66 per cent in nulligravidas and 31.32 per cent in prior gravidas, which were approximately twice as large as the respective incidences observed during the next interval. However, from 12 to 18 months, the probability of a viable birth in nulligravidas was essentially as good as that for the first 6 months, whereas in prior gravidas it was half of the incidence seen for the 6 to 12 month interval. In general, the ranges of incidences for the three intervals were approximately 10 to 20 per cent in nulligravidas and 10 to 30 per
Volume Number
114 2
Conceptions
in treated
infertility
patients
183
Table IX-Cont’d Prior No.
of
Months
follow-up
Followed
1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 17 18 19 20 22 23
grauidas
of patients 1 Pregnant
Incidence 1
Lost
Conceptions
Abortions
of Viable
births
40
3
1
0.0750
0.0750
36 32 29 27 24 19
3 3 1 3* 3 1
1
0.1521 0.2316 0.2581 0.3405 0.4229 0.4533
0.1521 0.2316
17 14 12 11
1 1
2 1 1 1
1 2 1
0.0265 0.0273
0.4855 0.5222
0.3132 0.3956 0.4260 0.4582 0.4950
10 9 7
0.5700 0.6656 0.7133
0.0751 0.1229
6 4
0.7611 0.8208
0.1826
0.5428 0.5905
0.6383
72 1
9; *One
patient
currently
1
0.1826
0.6383
pregnant.
cent in prior gravidas; the likelihood of a successful result decreases with the increase in the time post investigation. A speculation is that patients with multiple disturbances may require more time to succeed and that they may be well represented in the relatively later intervals. The data of this survey are too limited to permit a fair test of this supposition. The incidences of abortions observed, 11 per cent in nulligravidas and 18 per cent in prior gravidas, are within the ranges quoted of early pregnancy wastage in the general population of pregnancies. In these data, which we recognize to be limited in size, this result implies that the probability of an early pregnancy loss is apparently not unduly increased among conceptions in treated infertility patients. This may, in part, be explained by the more knowledgeable management of the pregnancy, due to in-
sights gained in treating the infertility problem. In any event, of the variables examined in this report, differences in the magnitude of reproductive disturbances were found to be most closely associated with outcome of treatment. Patients with single disturbances had a higher frequency of conceptions which terminated in viable births than patients with multiple disturbances. Furthermore, the age trend in the disturbance groups conforms with the known association of age with gynecologic disease, i.e., the mean age was found to be higher in patients with multiple disturbances. These findings were consistent in nulligravidas and prior gravidas. However, it is not surprising that the duration of infertility is significantly related to age, and, therefore, also to the disturbance categories only in nulligravidas, i.e., the mean age was lower in patients with the relatively
184
De
George
and
shorter period of infertility, and the mean duration of infertility was markedly less in patients with single disturbances. These differences between the two samples seem to be logical. In contrast to the situation in prior gravidas, in nulligravidas, the duration of infertility more closely reflects age because the relationship has not been interrupted by pregnancies at various ages and intentional intervals between pregnancies. Consequently, the mean and variance for the duration of infertility is significantly larger in nulligravidas compared to the values in prior gravidas. The shorter duration of infertility in prior gravidas may also indicate a tendency for them to seek medical attention sooner. Thus, the foregoing evidence indicates that success in treating infertility cases, nulli-
REFERENCES
1. Jones, G. S., and Pourmand, K.: Fertil. Steril. 13: 398, 196’2. 2. Turner, V. H., Davis, C. D., Zanartu, J., and 3. 4.
September Am. J. Obstet.
Nesbitt
Hamblen, E. Cl.: South. Med. J. 44: 628, 1951. McElin, T. W., Danforth, D. N., and Young, I. J.: Fertil. Steril. 11: 135, 1960. Keettel, W. C., Bunge, R. G., Bradbury, J. T.,
15, 1972 Gynecol.
gravidas and prior gravidas, which shows a trend with age, relates to the fact that the younger patient is more likely to have a single disturbance than multiple problems. Insofar as duration of infertility reflects age and single or multiple disturbances in nulligravidas, it is a variable related to treatment results. Hence, we conclude that, of the variables tested, the magnitude of disturbance( s) is the best predicator of treatment outcome in infertility patients. By the same token, insights into these problems may be influential in obtaining optimal results during pregnancy. We are most grateful to Professor Paul R. Sheehe, Department of Preventive Medicine, Upstate Medical Center, State University of New York, for valuable discussions and statistical assistance.
and Nelson, W. 0.: J. A. M. A. 160: 102, 1956. 5. Buxton, C. L., and Southam, A. L.: Human
6. 7.
Infertility, New York, 1958, Paul B. Hoeber, Inc., Medical Book Division of Harper & Row, Publishers. Rocker, I.: Fertil. Steril. 16: 531, 1965. Gray, L. A.: Obstet. Gynecol. 4: 177, 1954.