M. C. Macnaughton

A new systematic treatment for infertile women with abnormal hormone profiles

Summary. Five infertile women, with normal menstrual rhythm who had been investigated previously by daily hormone analyses throughout at least one complete menstrual cycle and had shown poor luteal‐phase steroid‐hormone profiles were treated by a new approach. They were rendered hypogonadotrophic with large doses of a luteinizing hormone releasing‐hormone analogue (Hoe 766) and were then treated with exogenous gonadotrophins to induce follicular growth and ovulation. Progesterone production after ovulation in all cases was superior to that observed in the individual patients’ without treatment. One patient conceived in her first conception cycle and another in her fourth. This regimen offers a systematic approach to the treatment of unexplained infertility in women with deficient luteal‐phase steroid‐hormone profiles.

The Scottish perinatal mortality survey.

Perinatal deaths in single births that occurred in Scotland during 1977 were investigated by case-record analysis. Causes of death were divided into nine categories, an extended version of the Aberdeen classification being used. Out of 1012 single perinatal deaths, 265 were due to fetal abnormality, which in 140 cases was malformation of the central nervous system. Of the 747 normally formed infants, 446 weighed 1500 g or more, of whom 82 died intra partum and 154 were born alive. The largest single cause of death was low birth weight in normally formed babies whose mothers had no complications of pregnancy (302 cases). Of these babies, 103 (34%) were growth-retarded. Rhesus incompatibility (16 deaths) and maternal diabetes (seven deaths) were not major causes of perinatal loss. These results were thought to be valuable in illustrating the main causes of perinatal mortality and directing attention to important issues. Hence a modified version of the study is being continued to see whether yearly audit by regional assessors is a feasible and practical way of monitoring trends in perinatal mortality.

HORMONES IN RECURRENT ABORTION

THE GESTAGEN With the explosive growth of synthetic progestational compounds there is an embarrassment de riches in the drugs available but critical consideration can eliminate many of them for use in the treatment of abortion. Many of them are related, not to progesterone, but to testosterone (e.g. ethisterone and dimethylethisterone), or to nortestosterone (e.g. norethynodrel and norethisterone). Such compounds have marked effects on the endometrium and on the functional relationships between the ovary and the pituitary in the menstrual cycle, but there is little reason, either experimental or theoretical, to expect that they will substitute for progesterone in the maintenance of pregnancy. Gestagens which are derivatives of 17 a-hydroxyprogesterone seem in this respect to be more promising, but one of them (1 7 a-hydroxyprogesterone caproate), has already been shown to be ineffective in an excellent trial by Shearman and Garrett (1963). A very few orally active derivatives of true progesterone itself have been prepared. The most notable are retroprogesterone (Duphaston, Crookes) and the cyclopentyl enol ether of progesterone (Enol Luteovis, Vister). The latter is of particular interest as it is the only artificial gestagen which is, like progesterone, metabolized to pregnanediol in the body (Caie and Klopper, 1964). If the pregnancy maintaining action of progesterone is at all bound up with its metabolism this would seem to be the compound of choice. The patients in our trial were given 100 mg. of Enol Luteovis per day in two doses. The drug was dissolved in sesame oil and given in gelatin capsules. The placebo consisted of similar capsules containing solvent only.

INFERTILITY IN WOMEN WITH APPARENTLY OVULATORY CYCLES

Six infertile patients had been studied previously (Dodson et al., 1975b) and were shown to produce inefficient corpora lutea which appeared to be predetermined by ovulation of “poorly grown” follicles. In a second cycle these infertile patients were treated with 50 mg of clomiphene per day for five days. The resulting plasma sex steroid and gonadotrophin profiles were compared with those found before treatment and with the profiles in normal patients (Dodson et al., 1975a). Treatment with clomiphene appeared to produce increased follicular growth and more active corpora lutea.

A routine system for monitoring perinatal deaths in Scotland

Summary. Since 1983 the monitoring of perinatal deaths in Scotland has been incorporated into the established data collection system which monitors maternal and child health in Scotland. This paper describes the transition from a research project to the routine system and the extension of the data collection to include paediatric and pathological findings. This information is provided by local co‐ordinators in active clinical practice. Baseline data are obtained from the routine maternity discharge document (SMR 2). A summary of the findings for the first 4 years of the study, 1977, 1979, 1980 and 1981 is presented, including information about birthweight and gestation‐specific perinatal mortality rates; perinatal mortality rates by time of death in relation to labour and singleton and multiple perinatal mortality rates by the obstetric complication preceding the death.

Perinatal deaths: analysis by clinical cause to assess value of induction of labour.

Over the 10 years 1966-75 the rate of induction of labour in the Glasgow Royal Maternity Hospital has increased from 16-3% of all births. During the same period perinatal mortality fell from 33 to 22 per 1000, mainly because of significantly fewer deaths due to antepartum haemorrhage; trauma; maternal diseases; and unknown causes in mature babies. The reduction in the number of deaths of unknown causes in mature fetuses was achieved by preventing deaths occurring after 40 weeks and was recorded in all age and parity groups. The results suggested that increased use of induction of labour has contributed to the improved perinatal mortality rate.

PLASMA SEX STEROID AND GONADOTROPHIN PATTERNS IN HUMAN MENSTRUAL CYCLES

Sensitive and specific displacement analysis methods for the assay of steroid hormones in small volumes of plasma are described. Plasma sex steroid and gonadotrophin hormone patterns were determined throughout a number of normal menstrual cycles. The mean cycles showed patterns which were similar to those described by other workers. However, examination of individual cycles provided information which may contribute to our understanding of menstrual cycle regulation with particular reference to the pattern of 17a‐hydroxyprogesterone and steroid‐gonadotrophin interactions.

Luteal cysts and unexplained infertility: biochemical and ultrasonic evaluation

A prospective, controlled study of ovarian function using ovarian ultrasound and daily plasma hormone estimations (estradiol, progesterone [P], follicle-stimulating hormone [FSH], luteinizing hormone [LH]) was carried out on 175 spontaneously cycling patients with unexplained infertility. Forty-one (23.4%) demonstrated luteal phase cyst formation. In 21 cycles the dominant follicle reduced in size after the LH peak (cystic corpus luteum cycles), and in 20 no shrinkage was seen (luteinized unruptured follicles). Progesterone concentrations in the early luteal phase were significantly reduced in the luteinized unruptured follicle cycles. Elevation in plasma FSH was seen in the early follicular and luteal phases of both cyst forming groups and may be due to disturbances in ovarian metabolism. Follicular rupture is important for efficient P release by the corpus luteum.

Ethical aspects of termination of pregnancy following prenatal diagnosis

Prenatal diagnosis provides information on both the normal and the pathological characteristics of the fetus. Increasingly, prenatal screening will confront women in countries where termination is permissible, with the choice between abortion and continuation of the pregnancy. Most parents do not wish to bring suffering into the world and medical advances have contributed to the expectation that at least physical suffering can be prevented. When prenatal diagnosis shows that there is a serious abnormality which will occur early and result in a life of suffering, many would choose termination of pregnancy. At the other end of the scale, some parents, either on religious grounds or from conscientious objection, may feel that the only permissible justification for termination is risk to the life of the mother. A similar range of attitudes may be found among their medical advisors. Women who agree to prenatal screening experience considerable stress and the pressures, dilemmas and anxieties should be recognized. These are likely to become more severe as prenatal screening expands, due to more and more abnormalities becoming capable of antenatal detection. Individuals must have the choice to participate or decline from participation in screening programs and the choice must be based on appropriate information. It will be particularly important to monitor the effect of screening, as it expands, on the women and their families. Prenatal screening will eventually be capable of detecting thousands of single gene defects as well as providing data of aesthetic concern, such a sex, hair color and body build. As human genome mapping proceeds, information will become available in early pregnancy, not only of defects and diseases present at birth, but also of others of late onset in adult life. This new knowledge will give rise to very complex choices about the future quality of life of an individual and whether that life is worth living; and decisions will need to be made without the possibility of consulting the individual involved. Such decisions raise serious ethical concerns, especially when selective abortion is considered for trivial or only moderately serious genetic indications, or for indications that will result in late onset disease. A good example would be Turner’s syndrome, which results in

Ethics and reproduction

In Western culture, the ethical principles of respect for persons can be further divided into 2 categories - a) autonomy and b) protection of the vulnerable; beneficence; and justice. The principles of ethics can be directed towards 2 levels: microethics - concerned with the individual and macroethics - concerned with the greater community. In the case of obstetrical procedures such as in vitro fertilization, prenatal diagnosis, and fetal sex selection, the principles of microethics and macroethics conflict. The exact number and/or kind of babies may benefit the parents by they may not benefit a society that is expected to accommodate these new members. This aspect can also be addressed when dealing with abortion. Support for and against has led to a questioning and reexamining of present abortion laws; the aim is to either restrict abortion or reduce the abortion time limit from 28 to 24 weeks. Policies of the United States have an effect on other policies, worldwide. Abortions are needed as a form of birth control in developing countries; 500,000 women/year die from birthing complications and 100,000 die from complications of illegal abortions. There has also been some questioning of in vitro fertilization. Why fertilize a certain number of eggs which may never be allowed to grow and mature? There has also been some questioning of whether or not an embryo in vitro fertilization is a person or not. Deciding the status of the embryo has opened up research possibilities in the United State and the United Kingdom. Discussion on in vitro fertilization has opened up discussion on surrogacy. There seems to be more support for surrogacy in the United States than in the United Kingdom - where there is a restrictive ban on commercial surrogacy.