Hilus cell tumour of the ovary in a virilized, premenopausal woman. Case report and review of hyperandrogenism of ovarian origin.

A 35 year-old woman presented with virilization and was found to have elevated serum testosterone levels. Investigation revealed an 11 mm hilus cell tumour in the left ovary. After unilateral oophorectomy, serum testosterone levels rapidly returned to normal levels. The various ovarian tumours and conditions causing virilization are described and a clinical approach to the investigation of virilization is outlined.

Profile and recruitment in Australasia.

There are 12 medical schools in Australia and New Zealand producing a total of 1600 graduates per year. Academic recruitment is poor as a result of lack of career paths, poor financial remuneration, problems with lack of research funding and the small size of departments. Increased demands from the clinical service and lack of 'start-up' research funds act as a deterrent to recruitment of junior academics. Clinical academics need to convince governments that, without strong and continuing academic leadership, there will be a deterioration in patient care, teaching and research in obstetrics and gynaecology.

Management of vaginal agenesis with a functioning uterus. Is hysterectomy advisable?

Cryptomenorrhoea associated with vaginal agenesis is uncommon. However, when laparoscopy or ultrasound reveal the uterus to be present early laparotomy is mandatory unless there is clear evidence of haematocolpos, in order to define the cervix and undertake reconstructive surgery. Once a uterovaginal tract has been established prolonged use of a mould is necessary to maintain patency of the neovagina. If the cervix is absent or atretic then immediate hysterectomy is required.

Folliculogenesis--the stimulated way.

The initial techniques of stimulating follicular development in the anovulatory woman involved the use of human pituitary gonadotrophin (hPG) and thus replaced the function of the pituitary gland. Despite extreme care with administration of hPG and extensive monitoring to assess the ovarian response, ovarian hyperstimulation and multiple pregnancy were common. Less expensive and easier methods of treatment soon followed with oral clomiphene citrate (early 1960s), oral bromocriptine (early 1970s) and pulsatile gonadotrophin-releasing hormone (late 1970s) being used. Currently all of these methods, alone or in combination, are employed and successful ovulation induction (except in women with elevated FSH levels) can now virtually be guaranteed. Controlled ovarian hyperstimulation, just the outcome one was attempting to avoid in the treatment of anovulatory women, has become the treatment of choice for women having in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). The extra oocytes produced by this treatment results in more embryos being available for transfer and/or freezing and improves the overall pregnancy rate. The concurrent use of gonadotrophin-releasing hormone agonists (GnRH-a) has resulted in more mature oocytes being developed, less cancelled cycles for a spontaneous midcycle LH surge, and allowed even more embryos to be produced thereby increasing the pregnancy rate further to the current expected 20% per cycle commenced. As techniques are further modified, adverse effects of elevated LH levels on pregnancy and take home baby rates should be able to be overcome, and oocyte freezing and long-term storage should become a possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrapartum cardiotocography and the expert witness.

Fetal heart rate changes occur in the majority of labours and correlate poorly with perinatal outcome and subsequent neurological development. Obstetricians giving expert evidence related to the interpretation of intrapartum cardiotocographs are advised to exercise caution when expressing their opinions.

Can ultrasonography reliably predict the occurrence of multiple pregnancies in gonadotrophin ovulation induction?

A retrospective study of 78 patients with 106 stimulated conception cycles after successful gonadotrophin ovulation induction was made to analyze the relationship between the sizes and numbers of ovarian follicles seen on ultrasound and the eventual number of conceptions that resulted in each cycle. Fifteen cycles (14.2%) resulted in spontaneous abortions. There were 58 singleton pregnancies (54.8%), 26 sets of twins (24.5%), 6 sets of triplets (5.6%) and 1 set of quadruplets (0.9%). In 86 cycles with the last scans performed shortly before the ovulating dose of HCG, 3 or more mature follicles were found in 50 (58%). These cycles resulted in 31 (62%) singletons, 16 (32%) twin pregnancies and 3 (6%) triplet pregnancies. Pregnancies resulted even when there were no 'mature' follicles seen on scan. No statistical correlation was found between plurality of pregnancy and size or number of follicles, or oestradiol excretion on the day the ovulating dose of HCG was given, although high-order multiple pregnancies were more likely if the oestrogen excretion was more than 200 ug/24 hours (p = 0.001). The dosage of HCG correlated inversely with the occurrence of multiple pregnancies (p = 0.02). In conclusion, neither oestrogens nor ultrasonography could accurately predict multiple conceptions in gonadotrophin stimulated cycles.

Treatment of recurrent aborters by immunization with paternal cells--controlled trial.

A paired sequential trial was undertaken to establish whether paternal mononuclear cells improved the prognosis in couples with recurrent abortions. For this purpose, 10(7)-10(8) cells obtained from the blood of partners were injected intravenously, subcutaneously, and intra-dermally into women who had had three or more consecutive miscarriages with the same partner. Control women were given normal saline, injected in the same manner. The result of the sequential analysis showed that there was no significant beneficial effect of the cells compared to control. The overall success rate was 70% (32/46 couples). The success rate in patients given cells was 62% (13/21), while in those given saline it was 76% (19/25). While the overall success rate in this study compares with a number of other studies, we find an equally high success rate with non-immunized patients. We conclude that the value of immunization for the prevention of recurrent miscarriage has not been established.

Home monitoring of gonadotropin ovulation induction using the Ovarian Monitor.

The safe use of gonadotropins relies on close hormonal and/or ultrasound monitoring to assess the response to treatment, requiring multiple hospital visits. Home monitoring with the Ovarian Monitor (St. Michael Research Foundation, Macleod, Victoria, Australia) minimizes hospital visits and overcomes many of the logistic difficulties associated with gonadotropin use. It utilizes a system of homogenous enzyme immunoassay using lysozyme conjugates to measure quantitatively either urinary estrone-3 or pregnanediol-3-glucuronide. Results obtained by 24 patients in 57 cycles using the Ovarian Monitor at home correlate closely with results obtained in the laboratory (estrone-3-glucuronide r = 0.955; pregnanediol-3-glucuronide r = 0.958). Cycle outcomes (ovulation, 74%/cycle; clinical pregnancy, 30%/cycle; multiple pregnancy, 13%/pregnancy; hyperstimulation, 11%/cycle) are no different from those achieved in laboratory-monitored patients. Home monitoring can be as safe and effective as laboratory monitoring, offers significant social benefits, and improves access to this form of therapy.

Hirsutism in a gynaecological context.

Investigation of patients presenting with hirsutism to a gynaecological endocrine clinic revealed a high incidence of anovulation, obesity and elevated androgen levels. The underlying abnormality was polycystic ovarian syndrome (PCOS) in the majority of patients. Low levels of sex hormone binding globulin were common; these increased with oestrogen treatment. Treatment with a combined oral contraceptive pill and low dose spironolactone was often effective in reducing symptoms.

Factors affecting fetal loss in induction of ovulation with gonadotropins: increased abortion rates related to hormonal profiles in conceptual cycles.

Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to-estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome.

Anti-oestrogens: their clinical physiology and use in reproductive medicine.

The anti-oestrogens are important both as therapeutic agents in reproductive medicine and as tools to investigate the physiology of the oestrogen receptor and hormonal control mechanisms. Clomiphene occupies the oestradiol receptor and, although initially stimulatory, has a net antagonistic effect as oestrogen receptors are not replenished. The major fertility-enhancing effect is to cause an increase in LH and FSH output by increasing the frequency of pulsatile output of these hormones. Many effects due to an anti-oestrogenic effect have been postulated; some, such as an adverse effect on cervical mucus, have been proven. The clinical use of the anti-oestrogens is outlined in Table 1. In well chosen patients a rewarding pregnancy rate is obtained with minimal intervention and few important side-effects. The challenge for the reproductive biologist is successfully to manage the patient who is clomiphene-resistant, either because of failure to ovulate or failure to conceive once ovulation is induced.