The Endometrium in Infertile Women: Prognostic Significance of the Initial Study Biopsy

Transcription

1 The Endometrium in Infertile Women: Prognostic Significance of the Initial Study Biopsy Findings in a Series of 97 Selected Couples CHARLES S. STEVENSON, M.D. 0 NE OF THE GREAT NEEDS of the physician who studies and treats infertile women is a means through which he can state to the patient, after 3-4 weeks of study, some generally meaningful word regarding her ultimate chances of being able to deliver a baby of her own. Five years ago we published a study on the prognostic value of the initial findings in the midcycle cervical mucus, 25 and we are herewith reporting a study of the endometrium made in this same regard. The study of endometrial tissue biopsied from a woman at various phases of her menstrual cycle has revealed that it usually reflects dependably the functional status of her ovaries It has also been recognized that the finding of normal, healthy, and "fulsome" progestational endomeb ium from day 17 through day 27 of the normal 28-day cycle indicates that the general ovulation process has occurred and that a corpus luteum, either small and weak or healthy and strong, has formed (it does not guarantee, however, that a "normal, healthy, fertilizable ovum" has been extruded from the ovary into the peritoneal cavity or ostium of the tube) Similarly, when studies of infertile women have produced endome trial specimens in which the progestational picture has seemed to be "weak and inadequate" it has only occasionally been found that the fault lay in the endometrium itself, which is to say that the endometrium has failed to respond adequately to normal blood levels of estrogen and From the Department of Obstetrics and Gynecology, Wayne State University School of Medicine, and from the Obstetrics and Gynecology Services of The Grace Hospital and Detroit Memorial Hospital, Detroit, Mich. We express gratitude to the following good friends and pathologists in whose laboratories the pathology slides were made of the endometrial specimens used in the study reported here: John J. Swihart, M.D., Frank J. Eurs, M.D., Clarence I. Owen, M.D., Dorr Stobbe, M.D., Richard J. Pollard, M.D., John D. Langston, M.D., and the late Osborne A. Brines, M.D. Their generous interest and help are much appreciated. 208

2 VoL. 16,No. 2,1965 ENDOMETRIUM IN INFERTILITY 209 progesterone Thus it is that normal endometrium in the second half of the menstrual cycle has been studied, its day-to-day changes noted and confirmed, and endometrial biopsy performed at selected times during the second half of an infertile woman's menstrual cycle (or, hopefully, within days of the onset of her next menses if she is having periodic amenorrhea) has come to be a basic procedure in her initial study. Biopsy of the endometrium repeated at about the same time in several consecutive cycles has also produced information regarding the consistency or inconsistency of a given woman's ovarian functioning when she is not receiving any endocrine therapy. Indeed, when a few women in our studies have had a series of endometrial biopsies every other month or so, they have been found, for instance, to have a weak secretory endometrium on day of their cycle one month, a good healthy secretory endometrium at the same time in their next cycle, and a poor secretory endometrium in the third cycle. Despite the fact that these variations can and do occur in many fertile and infertile women, month by month, we believed that it would be of interest to make a study of the initial, pretreatment biopsies taken from a series of such women with the view of determining if any prognostic significance could be derived from them, and thus this series of cases is presented. MATERIALS AND METHODS During the past 14 years we have been able to follow adequately 107 women upon whom initial endometrial biopsy was obtained. We discarded 10 from this group because their infertility was due primarily to infertile husbands, to hopeless blockage of their fallopian tubes, or to other irreparable factors. This left 97 couples in which the husbands apparently were fertile, the wife's tubes were patent, and no other nonfunctional cause for infertility was discernible. Our study thus deals primarily with cases involving endocrine disturbances, which is fortuitous because in them there is the greatest likelihood that the initially biopsied endometrial tissues may have some significant bearing on the cause of their infertility. The endometrial slides from each of the 97 women were studied, diagnosed, and "dated" (where possible) by the senior author according to the criteria of Noyes et al., 21 2!l with only a number assigned to each slide so that the patient's identity, history, physical findings, and the cycle day on which the biopsy was taken were all unknown to him. Then these endometriums were sorted into three major groups, the first of which was designated "those which are definitely abnormal and would seem to preclude the possibility of future pregnancy," the second, "those which, although abnor-

3 210 STEVENSON FERTILITY & STERILITY mal, do not seem to preclude eventual pregnancy," and the third "those which are normal and seem to indicate normal fertility." The slides in each of these groups were then identified as to the individual patients they represented, and data were taken from the patients' records regarding their previous pregnancy performance, if any, their pregnancy performance subsequent to the biopsy taking, and then the cycle day on which the biopsy was taken-determined by counting backward from the first day of the next subsequent menses, a method found to be dependable by Noyes and Haman. We had no difficulty in determining the day of onset of the menses which followed the taking of the biopsy in our patients; we instructed them to mark on their calendars the first day upon which their scant, brownish, vaginal flow (which may persist for a few days following biopsy) was superseded by regular menstrual flow, and only rarely did any confusion seem to arise over this determination. Into the first major group, in which subsequent pregnancy seemed to be precluded, we put all cases of endometrial atrophy, of "resting" or inactive endometrium, and of endometrial hyperplasia in which all fragments on the slide were completely hyperplastic. The second group, which contained patients having abnormal endometriums that did not seem to preclude eventual pregnancies following therapy, was comprised of those showing normal proliferative endometrium, weak and inadequate secretory endometrium, and normal secretory endometrium 3 or more days out of phase with the actual cycle day on which the biopsies were taken. The third group was composed of patients having normal secretory endometriums which were in phase or not more than 1-2 days out of phase with the cycle day. It is of interest that most of the endometriums were lagging behind the cycle day when they were out of phase with it, which duplicates the experiences of Gillam, Noyes, and Noyes and Haman. In dating the endometriums we based our decisions on the most advanced areas we could find after studying all fragments in each slide: the importance of this policy has heen shown hy Noyes/ 9 and confirmed by us in this study. The biopsies in our series were taken from the twentieth through the twenty-fourth days in nearly all cases, a few having been taken during the last 4 days of the cycle or on the day of menstrual onset because of difficulties in office scheduling. All endometrial biopsy procedures were done in the author's office without anesthesia, using the Novak curet hut without suction. Our method consisted of cleaning the cervix with aqueous Zephiran" solution, 1:750 strength, picking up its anterior lip with a sharp two-pronged tenaculum, inserting the curet all the way to the fundus, and withdrawing *Winthrop Laboratories, New York, N.Y.

4 VoL. 16, No.2, 1965 ENDOMETRIUM IN INFERTILITY 211 it-so that it would scrape up some endometrium-as far as the internal os before reinserting it to the fundus in preparation for the next withdrawal stroke. About six such withdrawal strokes were taken in every case before the curet was removed from the uterus. The tissue was then blown out of the curet tube into 10% formalin fixative solution, and was processed in the pathology laboratory in the usual manner, hematoxylin-eosin stains being done. Through following this careful technic for obtaining endometrial tissue for study, we were able to avoid the usually misleading information which results when the endometrium is obtained only from the lower part of the uterine cavity, where it may be somewhat hypoplastic and where it may not fully respond to the ovarian hormones in the woman's bloodstream. PRESENTATION OF DATA In Table 1 we see that 35% of the 97 women in the study produced living infants following the initial biopsy, and we also note that the pregnancy rates in the second and third groups, those in which pregnancy seemed likely to occur, were about the same ( 38 and 35%), and were fairly low, being only about twice that of the small first group ( 20%), in which pregnancy would seem unlikely. It should here be pointed out that nearly all of these 97 infertile women had been studied and treated by one or more physicians before they consulted the author, and that they thus represent, in greater part, a residue of cases which are not easy to cure. TABLE 1. Pregnancy Performance Following Therapy of Patients Grouped According to General Endometrial Category General category of endometrium No. of women pregnant before biopsy No. of women pregnant after bioprji Living infants delivered after biopsy o/o of women No. of 11Iis- Term 11Iis- Term No. of producing women carriage.~ deliv. carria,qes deliv. infants infants Types generally precluding pregnancy 10 Abnormal types not definitely precluding pregnancy 47 Normal types generally indicative of normal fertility 40 TOTALS " *These 2 women had periodic amenorrhoea when the first biopsies were taken, and they respon<led well to protracted hormone therapy and eventually delivered babies.

5 212 STEVENSON FERTILITY & STERILITY In Table 2 are summarized data on women whose endometrial specimens seemed to preclude further pregnancy and to explain the patients' infertility. The woman whose endometrium was atrophic (Fig. 1 ) had a very small uterus, of about prepubertal size, and it did not grow under estrogen therapy. Two of the 4 women having inactive endometriums were in periods of amenorrhea when their initial biopsies were taken; they subsequently responded to oral cortisone therapy, and to estrogen therapy given cyclically for 3 months at a time, off and on for several years, evenhmlly became pregnant, and delivered infants. Had it not been for these 2 women, there would have been no pregnancies among the 10 women described in Table 2. The 39-year-old woman who was found to have "adenoma malignum" had just remarried, after having been unable to become pregnant by her first husband, and we regretted the necessity of removal of her uterus, but its endometrium was involved throughout in a nearly anaplastic proc- TABLE 2. Pregnancy Performance after Therapy of Patients Whose Endometrial Status Seemed to Preclude the Possibility of Pregnancy Living infants de- No. of women No. of women livered after biopsy pre,qnant be- pregnant after fore biopsy biopsy %of women Types of No. of Mia- Term Mia- Term No. of producing endometrium women carriages deliv. carriages deliv.* infant,q infanf,q Atrophic Inactive-"resting" or 0 "aplastic" 4t "Endometrial hyperplasia" in all fragmentsi Mild Moderate Marked TOTAL "Adenoma malignum" TOTALS *Deliveries during the thirty-fifth week or later. ttwo of these women were having periodic amenorrhea when the first biopsy was taken, and following successful hormone therapy they eventually became pregnant. The other 2 were having very irregular and scant menses and never did respond to hormone therapy or become pregnant. :t;five other women {included in Tables 3 and 4) had endometriums showing areas of hyperplasia; 3 of them had predominantly weak secretory endometrium, while 1 had mainly normal secretory and 1 normal proliferative endometriums. Thirty-nine-year-old patient, who underwent hysterectomy.

6 VoL. 16,No.2,1965 ENDOMETRIUM IN INFERTILITY 213 ess. The prognosis for subsequent pregnancy for the women in this group, which is too small for valid statistical analysis of the results, is truly poor, despite the 20% pregnancy rate achieved. (Figures 2 and 3 represent endometrial hyperplasia.) Fig. 1. Initial endometrium from J. H., a 32-year-old nulligravida who menstruated for about 1 day 2-3 times a year, flow being so scant as not to require use of perineal pad. This is all the endometrium that could be obtained with the curet from extremely small uterus (it sounded to a depth of 4.5 em.). This fragment was judged to be "atrophic." Patient did not respond to therapy, has never become pregnant. Fig. 2 (left). First endometrial specimen from B. S., a 28-year-old nulligravida whose menses were irregular and occurred 4-5 times a year, with prolonged periods of scant vaginal bleeding preceding or following them. Her uterus and ovaries were definitely smaller than normal; she has not responded to several prolonged periods of oral hormonal therapy during the past 8 years and has not become pregnant. All fragments of her endometrium showed mild "endometrial hyperplasia" seen above. Fig. 3 (right). Initial endometrial specimen from E. P., a 28-year-old nulligravida whose menses were occasionally irregular, with intervals up to 38- days. She did not respond to oral hormone therapy and has never been pregnant. This tissue showed moderate to marked hyperplasia in all fragments, even though it was obtained on day 22 of her cycle.

7 214 STEVENSON FERTILITY & STERILITY Table 3 shows that 18 of 47 women, or 38%, bore infants despite the fact that 12 of them had proliferative eridometriums when ideally they should have been secretory (Fig. 4 and 5), that 13 of them had "weak" secretory endometriums when they should have been of normal strength and fulsomeness (Fig. 6-10), and that 22 had secretory endometrium which was 3 or more days out of phase with the cycle day on which it was taken for study. In other words, although these 47 women had what are generally considered to be abnormal endometriums in the cycle in which their biopsies were taken, 18 of them eventually developed relatively normal healthy endometriums in at least one cycle because they became pregnant and delivered living infants. It is of interest that of the 12 women who had frankly anovulatory cycles when biopsied, only one third subsequently delivered babies, while of those with "weak" secretory endometriums-in whom corpora lutea of sorts certainly did form, and from whose follicles ova in some condition, however poor, may have been extruded-nearly half gave birth to TABLE 3. Pregnancy Performance after Therapy of Patients Whose Endometrial Status, Although Abnormal, Did Not Seem to Preclude Pregnancy ~ Living infants dtj- No. of women No. of women livered after b-iops,ij pregnant be- pregnant afte-r fore biopsy biopsy %of women Types of No. of Mia- Term Mis- Term No. of producilltf endometrium women carriages deliv. carriages deliv. infants infants Normal proliferative endometrium" (days 8-14) "Weak" and "inadequate" secretory endometrium" t ("dating" also done) Normal secretory en dometrium," 3 or more days "out of phase " TOTALS *In 3 women in the "normal proliferative group" the endometriums were moderately or markedly hypoplastic, and none of these women was ever pregnant; 3 women in the "weak and inadequate" secretory group had hypoplastic endometriums, and 2 were never pregnant, while 1 miscarried a "blighted ovum" at 7 calendar weeks; 3 women in the "normal secretory- 3 or more days out of phase" group had hypoplastic endometriums, and 2 never were pre!!.' nant, while 1 had marked adrenogenital syndrome and responded well to cortisone therapy and had 1 baby. tin 11 cases in this group the endometrium was also lagging behind the cycle day by from I to 10 days; in 2 patients it was 1 and 3 days ahead of the cycle day, respectively.

8 VoL. 16, No.2, 1965 ENDOMETRIUM IN INFERTILITY 215 babies, which seems more than would be expected. In the 22 women who had normally strong endometriums, except that it was 3 or more days out of phase with the cycle day on which it was taken, the pregnancy rate of 36% was about the same as that of the other two groups, which, again, is not quite as one would expect it to be, but then these groups are too small for the results to bear statistical significance. Nine women in the abnormal-endometrium category had marked hypoplasia of the endometrium, and it was usually associated with a very small and frequently hard uterus. In them it was difficult to obtain much endometrium with the curet, and that which was obtained by dint of forceful scraping came away in tiny fragments. Histologically, it showed very little evidence of any growth activity, and its thinness was generally confirmed by microscopic study. In 6 of these 9 cases, however, it did reflect response to the ovarian hormones, and these are in the "weak" and the normal secretory groups in Table 3. Only 1 of these 9 women has given birth to a baby (according to the data obtainable on May 1, 1964, the date of summation of this series); she (Fig. 8) had moderately severe adrenogenital syndrome that responded well to cortisone therapy. Another patient (Fig. 10) became Fig. 4 (left). Endometrial specimen from S. N., a 21-year-old woman who had had periodic amenorrhea (with occasional menses that were profuse and prolonged) since her menarche at age 15. She responded well to oral hormone therapy and had a baby at age 23. Endometrial tissue above was taken on day 22, was mostly "proliferative phase, day 8," but some areas were suggestive of mild hyperplasia. Fig. 5 (right). Endometrial specimen from M. B., a 32-year-old nulligravida whose menses were regular and normal except that flow was scant and of only 2-3 days' duration. She did not respond to oral hormone therapy, has not become pregnant. Endometrial tissue above was obtained on day 23, and was called "proliferative phase, day 12, with occasional glands and some stroma (see gland to the right, above) suggestive of very weak secretory function."

9 216 STEVENSON FERTILITY & STERILITY Fig. 6. Initial endometrial specimen from K. F., a 23-year-old nulligravida whose menses had come at intervals of days and were moderately scant in flow. She had adreno-genital syndrome of moderate degree, responded well to cortisone therapy, and now has 2 children. Surface of endometrium above is in upper right corner. This was judged to be "mixed endometrium, some areas heing frankly hyperplastic, and

10 VoL. 16, No.2, 1965 ENDOMETRIUM IN INFERTILITY 217 pregnant but aborted, very early, a small and degenerated, "blighted," conceptus. Circumscribed small areas of true hyperplasia were present in the endometriums of 5 women, 3 of whom showed the "weak'' secretory effect in most of their endometrial fragments, while the other 2 had principally normal proliferative endometriums. Two of the 3 women in the "weak" secretory group had frank adrenogenital syndrome; one of these is represented in Fig. 6. Both became pregnant after months of cortisone therapy and delivered healthy infants; one now has had a second one. The other woman with "weak" secretory endometrium did not have adrenogenital syndrome and has not responded to treatment or become pregnant. One of the 2 women having principally normal proliferative endometriums delivered a baby after 4 years of endocrine therapy, while the other has been relatively unresponsive to treatment and has not become pregnant. In Table 4 are summarized data for 40 women whose endometriums were about normal, and it might be expected, therefore, that they would have a relatively good rate of cure of their infertility-perhaps in the range of 40-50%. Instead, however, only 14 of them, or 35%, subsequently delivered living infants. The two groups of women, those 1-2 days out of phase and those in phase with the cycle day on which their endometriums were biopsied, had roughly similar pregnancy performances after their initial endometrial biopsy, and it was no better than that of the 12 completely anovulatory women who had proliferative endometriums (Table 3). others showing weak secretory function, of about day 16." Biopsy was taken on day 21. Fig. 7. First endometrial specimen from L. G., a 32-year-old nulligravida whose menses were regular and normal. Despite 18 months of oral hormone therapy she has not become pregnant. This tissue was called "weak secretory endometrium, day 23," and it was lagging 3 days behind. Fig. 8. Initial endometrium from F. A., a 34-year-old nulligravida with moderately severe adrenogenital syndrome ( 24-hr. 17 -ketosteroid excretion, 18 mg.). She responded well to cortisone therapy and delivered a healthy infant 28 months after starting therapy. Tissue above shows "weak and incomplete secretory phase, day 23" and is lagging 3 days behind. Fig. 9. Endometrial specimen from M. C., a 28-year-old nulligravida who had regular menses but never became pregnant over 10 years, during which she had many courses of oral hormone therapy. Biopsy specimen above was called "weak secretory phase, day 22, with excessive edema"; this tissue was lagging 4 days behind. Fig. 10. Endometrial specimen from T. C., a 33-year-old nulligravida who was having fairly regular menses of about 4 days' duration and fairly scant How. Her only pregnancy followed 5 years of intermittent oral hormone therapy; it occurred when she was 38 years of age and consisted of miscarriage at 7 calendar weeks of a very small amount of partly degenerated conceptus tissue. Initial endometrial tissue above was obtained on day 24 and shows mostly day 12 proliferative phase, but there were a few glands showing very weak secretory activity estimated to represent about day 26.

11 218 STEVENSON FERTILITY & STERILITY ~orrnal TABLE 4. Pregnancy Performance after Therapy of Patients of Normal Endometrial Status Seeming to Indicate Normal Fertility Living infants de- No. of women No. of women livered after biopsy pregnant be- pregnant after fore biopsy biopsy %of women Types of No. of Mia- Te~ m Mia- Term No. of producing endometrium women carriages deliv. carriages deliv. infants infants secretory en dornetriurn" 1-2 days out of phase Behind cycle day llt Ahead of cycle day TOTALS secretory endornetriurn" exactly in phase with cycle day TOTALS ~ormal *In 4 of the 29 women in the group that was 1-2 days behind in phase, there was moderate-tomarked hypoplasia of the endometrium, and this was also true of 2 of the 4 women whose endometrium was 1-2 days ahead of phase; none of these 6 women was ever pregnant. In 3 of the 7 women in the "exactly-in-phase" group there was also real hypoplasia of the endometrium, and only I became pregnant subsequent to the biopsy-she had 2 babies, one 4 years and one II years following initial biopsy. tseven of the II women producing infants following biopsy had endometriums lagging 1 day behind, and 4 were 2 days behind the cycle day. DISCUSSION A comparison of the prebiopsy pregnancy performance of the women in Tables 2-4 shows that the 10 in the "unlikely-to-become-pregnant" group (Table 2) had not been pregnant before the biopsy was taken, and that only 2 of them ever became pregnant subsequently, which is an understandably poor pregnancy record for this group. The 47 women in Table 3 were also a truly infertile group, since only 4 had had babies and only 2 had had miscarriages prior to biopsy. The other 41 women, or 87%, had definite primary infertility. Following the initial biopsy, mostly as the result of endocrine therapy, 3 had miscarriages, and 18, or 38%, delivered term infants, which was nearly a fivefold improvement in fertility for the group as a whole. It is important to note, in comparing these women to those in Table 4, that this represents a fairly good cure rate of primary infertility in selected cases of this type. Of the 40 women in Table 4, however, 33% had secondary infertility, while only 67% had primary infertility. Since it has long been recognized that secondary infertility is considerably more difficult to treat successfully than is

12 VoL. 16, No. 2, 1965 ENDOMETRIUM IN JNFERTILITY 219 primary infertility, the lower rate of successful pregnancy following endocrine therapy in the women in Table 4 is probably chiefly explainable on this basis. Was the relatively poor pregnancy performance subsequent to initial biopsy of the 40 women in Table 4 due to causes other than the fact that one third of them had secondary infertility? In superficially going over our material with this question in mind, we found that many of these women had unfavorable midcycle cervical mucus even though their endometriums were normal and healthy. We also found that some had small but definite degrees of emotional disturbance; most of these women were in the secondary-infertility group. We have already mentioned that 9 women in Table 3 had true endometrial hypoplasia, and this was also the case in 9 women of the 40 in the "normal" group in Table 4. Not one of these 9 women in the "normal" group ever became pregnant, and thus, of the 18 women having truly hypoplastic endometriums in Tables 3 and 4, only 1, or 5%, has become pregnant. Three of the 7 women in the group having normal secretory endometrium exactly in phase with the cycle day on which they were taken had this hypoplasia, and so they are principally responsible for the unexpectedly low pregnancy success rate for this group. Did the fact that the secretory endometrium was out of phase with the cycle day on which it was obtained appear to play any role in the production or support of the woman's infertile state? It did not seem to do so in this series. Although the three "out-of-phase" groups (in Tables 3 and 4) are too small for their summation values to carry valid statistical significance, the following figures should be noted: The women who were 3 or more days out of phase had a subsequent pregnancy rate of 36%, those who were 1-2 days out of phase had a rate of 36%, and the rate for those who were in phase was 29%. In view of the small numbers in these three groups, their rates must be considered as being roughly the same. The general significance of this study seems to be that the findings in the initially obtained endometrial tissues may be conclusive, or nearly so, only when actual atrophy, true hypoplasia, or complete hyperplasia (of moderate-to-marked degree) of the endometrium is found. The chances that women having these endometrial conditions will have babies of their own are almost nil. The women having the other endometrial conditions listed in this study (excepting those with dysplastic or anaplastic lesions) fall into a general group in which there are many variable factors that control the actual state of their endometriums in any given cycle, and thus their endometrial states at the time of biopsy, while helpful, can be only generally indicative of their underlying fertility potential,

13 220 STEVENSON FERTILITY & STERILITY CONCLUSIONS Is there any real prognostic value in our findings upon study of the initial endometriums from these 97 infertile women? Yes, we believe that some rough figures can be drawn from our data. If the endometrium is atrophic, or shows real endometrial hyperplasia in all fragments, the woman can be told that her chances of ever having a baby of her own are poor, and that she and her husband should begin to think about adopting a baby. Women found to have inactive or "resting" endometriums, usually with amenorrhea, may be told that they have a zero-to-50% chance of having a baby of their own following study and treatment. To anovulatory women who are found to have normal proliferative endometriums during the last 2 weeks before their next menses, a statement to the effect that they have about 1 chance in 3 of eventually having a baby of their own may not be far from the truth. Finally, infertile women who have "weak" or normal secretory endometriums, whether they are in phase or out of phase, may be told that they have at least a 30-40% chance of eventually giving birth to their own infant following treatment, provided, of course, that their husbands are fertile, that their endometriums are not truly hypoplastic, and that they do not have other bars to successful pregnancy. True hypoplasia of the endometrium has shown itself to be practically unchangeable under endocrine therapy in our hands, and there was only a 5% chance for pregnancy in this group in our series. Women with true and complete endometrial hyperplasia have a similarly low chance of attaining eventual pregnancy, in our experience, unless the woman is under 21 years of age and exhibits other evidences of arrested pubertal development. The presence of a few circumscribed islands of true hyperplasia in endometrium which was otherwise secretory did not decrease the pregnancy production rate below the 30-40% rate for the group as a whole. Finally, we believe it is important to tell an infertile couple, as gently as we can, what their relative chances of successful pregnancy are as soon as we are able to determine them in a general way. If the wife does not become pregnant after 2-3 years of study and observation, and of endocrine and other therapy (her husband likewise being treated the while if need be), she and her husband should be advised to consider adoption of a baby, lest her years of potential good foster-motherhood go by without some parentless infant getting the benefit of them. SUMMARY 1. In a series of 97 selected infertile women the prognostic value of the initial endometrial-biopsy evaluation was studied. All patients in the series had patent tubes, fertile husbands, and were trying to become pregnant.

14 VoL. 16, No. 2, ENDOMETRIUM IN INFERTILITY These cases were divided into three groups: ( 1) those in whom preg~ nancy was unlikely because of atrophic, inactive, or completely hyperplastic endometriums; ( 2) those who, although their endometriums were abnormal, seemed to have a fair chance of successful pregnancy because they had normal proliferative, "weak" secretory, or normal but out-of-phase secretory endometriums; and ( 3) those whose normal secretory endometriums seemed to give them a good chance of successful pregnancies. 3. It was found that 20% of the women in the first group eventually produced living infants, and that 38% of those in the second group did so; in the third group, which was heavily loaded with cases of secondary infertility, only 35% subsequently delivered infants. 4. The fact that secretory endometrium was 1, 2, or 3 or more days out of phase with the cycle day on which it was obtained had no apparent bearing on the subsequent pregnancy performances of these different subgroups, as their pregnancy success rates were about the same. 5. From a prognostic standpoint, it was found that if an infertile woman's initial endometrium is atrophic or shows real endometrial hyperplasia in all fragments, she can be told she has little chance of having a baby of her own. Women who have inactive or resting endometrium, with or without amenorrhea, may be told that they have a zero-to-50% chance of delivering their own infant following proper treatment. Infertile women who have proliferative endometrium in the second half of their cycle may be told that they have about 1 chance in 3 of having their own baby, and those who have secretory endometriums in the last 2 weeks before the onset of their next menses may be told that they have a % chance of successful pregnancy if they receive proper treatment Rivard St. Detroit 7, Mich. REFERENCES 1. ALLEN, E. "The ovarian follicular hormone, theelin; animal reactions," in Sex and Internal Secretions, ed. 1, Williams & Wilkins, Baltimore, 1932, pp BROWN, W. E. Current reviews: The role of the ovary (exclusive of ovulation) in infertility. Fertil. & Steril. 6:416, CoRNER, G. W. Ovulation and menstruation in Macacus Rhesus. Contribs. to Embryol. (Carnegie Inst. Wash.) 15:13, F'RAENKEL, L. Die Function des Corpus Luteum. Archiv. f. Gynak. 91:795, GILLAM, J. S. Study of inadequate secretion phase endometrium. Fertil. & Steril. 6:18, GLASS, S. J., and LAZARUS, M. L. Improved fertility and prevention of abortion after nutritional-hormonal therapy. ].A.M.A. 154:908, GRANT, A. Habitual abortion: Preconceptional investigations and postconceptional treatment. Fertil. & Steril. 4:169, HARTMAN, C. G. Studies in the reproduction of the monkey, Macacus Rhesus,

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