Glasgow Medical Journal 7th Series March, 1945 Vol. XXV. No. III. SOME ASPECTS OF HUMAN INFERTILITY* By ALBERT SHARMAN, B.Sc., M.D., Ph.D., M.R.C.O.G., Assistant Surgeon, Royal Samaritan Hospital for Women, Glasgow. The title of our paper indicates both its scope and its limitations. Its limitations are determined by the time at our disposal, which makes it quite impossible to give an exhaustive account of the subject or to make any reference to the enormous literature which has now accumulated; we are compelled to confine our attention to certain major aspects of the problem. Although infertility is one of the oldest human problems, it is only within the present century that real progress has been made in its study. The social significance of the problem is illustrated by the fact that, according to various estimates by English and American investigators, the proportion of childless marriages is about ten per cent, of the total. As there are almost one million barren marriages (as far as can be estimated) in Britain, the seriousness of the position is obvious: the last precise figure was given in the census of 1931 as 1,092,399. Moreover, in the year 1890, 869,937 babies were born in England and Wales; in the year 1940 this figure fell to 590,120. In Scotland, the figures are comparable: in 1890, 121,526 babies were born, in 1940 the figure fell to 86,403. The successful treatment of sterility must therefore be one of the more important tasks of medical science. * Based on a communication read to the Royal Medico-Chirurgical Society of Glasgow on 1st December, 1944. VOL. CXLIII. NO. III. 77 E Albert Sharman It is unnecessary to postulate a period of years of married life as a criterion of sterility, because in normal relations, in the large majority of cases, pregnancy follows within one year of marriage. Indeed, one authority states that 84 per- cent. of first children are born within 2 years of marriage and that after another year only 4*5 per cent, of marriages prove fertile. Moreover there is good cause for investigating the couple who complain of their barren marriage even if it is only of as little as one year's standing, for at this stage it is possible to treat with success a number of lesions which, if neglected, tend to become incurable. Thanks to modern research, notably of the American gynaecologist, Meaker, it is now recognized that while sterility is sometimes due to a single cause in one or other partner, " it is more often due to several infertility factors." A search for the causal factors involves a complete examination of both parties. "There is more to the problem of sterility than potent males and patent tubes." A minimal diagnostic survey should include the systematic investigation of the following 5 major factors: 1. Grossly recognizable pelvic conditions. 2. The condition of the Fallopian tubes. 3. The endocrine balance. 4. The cervical secretion. 5. The investigationo 0f the male. Grossly recognizable pelvic conditions. The first condition to be considered is that of tumour or neoplasm. It may involve any portion of the genital tract and, when it arises in the vulva or vagina, operates mainly in the direction of producing dyspareunia, i.e. as a mechanical or obstructing agent. Much more commonly, however, the tumour involves the uterus or ovaries. In the former case it is most frequently a fibroid (single or multiple) and in the ovaries one variety or another of cyst. The association of fibroids with sterility is well known ; their mode of action, however, has been the source of much discussion. The fibroid may act in a mechanical way, or its frequently associated cystic ovarian changes may be the main factor. The present tendency, 78 Some Aspects of Human Infertility however, is to regard both the fibroid and the infertility as being due to a common extragenital factor, probably pituitary dysfunction, which is responsible for both conditions. The mere presence of a fibroid or fibroids is not in itself a major infertility factor, since the association of fibroids and preg- nancy is common. Cysts of the ovaries may act in two ways : (a) by pressure upon or blockage of a tube, or (b) by inter- ference with or complete inhibition of ovulation. Infections of the genital tract may act inimically to fertilisation wherever they may be, but particularly when they involve the tubes and ovaries. Cervical and vaginal infections are not in themselves, in normally fertile women, barriers to conception. Gross inflammatory infection of the tubes, however, is responsible for tubal blockage and is obviously a major infertility factor. Uterine hypoplasia has for long been blamed for infertility. Recent investigations have produced evidence which would seem to show that minor degrees of hypoplasia have but little relationship to it and are purely an incidental finding. " As Meaker expresses it: The infantile womb is a favourite diagnosis of many practitioners." It is quite different, how- ever, with major degrees, which are uncommon, but which very definitely afford a poor fertility prognosis. Severe genital hypoplasia, involving the external genitalia in addition, and especially when associated with a narrow vaginal canal or introitus, is a serious infertility factor. The relative inci- dence of these conditions is seen in the following figures, obtained in a survey of 810 consecutive cases of sterility in the Royal Samaritan Hospital for Women: 388 (48 per cent.) showed a minor degree of uterine hypoplasia, 10 a major degree and 160 had a narrow vaginal introitus or canal or both. Any conditions which render normal coitus impossible or very infrequent are obviously definite factors in infertility. It is not uncommon to find that, even after a relatively long period of marriage, there is present a more or less unruptured hymen. The Fallopian tubes. ? The tubo-ovarian apparatus is not a static entity, but is subject to continuous changes in the interrelationship of its parts. In all animals (including the monkey) which have been 79 Albert Sharman investigated, it has been found that the muscular equipment of the adnexa effects periodic changes in the relative position of the fimbriae and the ovary. In some animals the ovary appears to be cupped by the tube at certain stages of the cycle, and this approximation, which seems to facilitate the reception of the ovum by the tube, coincides with the ovula- tory phase. When, as in the monkey, the infundibulum reaches and embraces the ovary, the latter plays more than a purely passive part. There is evidence that a similar mechanism operates in woman. The tube itself is subject to cyclical changes, the fibres of the muscular coat of the tube increasing and decreasing in length with the phases of the cycle. Changes in the nature and function of the epithelial lining also occur; in the first phase of the cycle the epithelium is mainly ciliary in character, whereas after ovulation secretory activity becomes manifest. Since the functional condition of the tube and the associated muscular apparatus determines to a large extent the chances of fertilisation, it is obviously desirable to investigate this aspect of the reproductive mechanism. Although the available methods are relatively unphysiological, they have the advantage of being easy to apply and of yielding sufficiently accurate information for clinical purposes. They should be adopted as part of the routine examination of the wife, for impairment of tubal function cannot be excluded by the ordinary gynaeco- logical examination, however carefully conducted. The methods in general use fall into two main groups? those designed to investigate the passage of a gas through the genital tract (Utero-tubal insufflation) and those in which the condition of the tubes is revealed by their radiographic appearances after the injection of a suitable opaque substance (Hysterosalpingography). Utero-tubal insufflation. In 1920 Rubin first described his methods of investigating tubal patency by means of intra-uterine inflation with oxygen.* *The following quotation from the Aphorisms of Hippocrates, vol. IX, is of interest: 4'If a woman does not conceive and you wish to know if she will, cover her head with wraps and burn perfume underneath. If the smell seems to pass through the body to the mouth and nostrils, be assured that the woman is not barren through her own physical fault." 80 Some Aspects of Human Infertility Since that date, the principle of Rubin's method has been universally adopted and variations and modifications of apparatus and technique have been developed. Oxygen was abandoned at an early stage and carbon dioxide substituted. It is now well established that the tubes may be occluded and the patient rendered sterile without physical signs or symptoms. It is 4not proposed to discuss the various types of apparatus for testing tubal patency, but merely to refer briefly to the one introduced by the writer in 1943 to the Royal Society of Medicine, London. This apparatus, the most recent in the kymograph class, is a modification of that of Bonnet of Paris and has given excellent results. It contains a regulating and measuring system whereby the pressure of gas is kept constant and its rate of flow is accurately regulated by moving a tap indicator on a dial till it faces the figure corresponding to the desired rate. A metal manometer measures the pressure of gas, whose variations are recorded on a revolving drum, oper- ated by an electric motor. [The apparatus was shown.] Whereas most methods serve only to distinguish between " " " " the blocked and the open tube, the use of the kymograph makes possible the registration of tubal contractions and thus takes into consideration the actual behaviour of the tubes during the test.