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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.

High serum follicle stimulating hormone (FSH) values are consistent with ovarian failure. We studied the progress of 67 women aged under 35 years with oligomenorrhoea or secondary amenorrhoea in whom the serum FSH value was greater than 20 U/1. Twenty-four patients remained amenorrhoeic, but 17 ovulated and six conceived, two on two occasions. Coincident mean serum luteinising hormone (LH) concentrations were significantly lower and mean total urinary oestrogen concentrations were significantly higher in patients who subsequently ovulated, but the degree of increase in FSH did not correlate well with later ovarian function. Treatment with oestrogens, clomiphene citrate, human pituitary gonadotrophin, and bromocriptine was of no benefit in inducing an ovarian response while FSH concentrations remained raised. Our results suggest that a considerable proportion of younger women with ovulatory disorders associated with FSH values in the menopausal range will spontaneously resume ovulation and some will conceive.

The perinatal mortality associated with breech presentation at the Royal Women's Hospital, Melbourne, between 1974 and 1976 was 10.4%, or almost 5 times the overall hospital figure. Nine of 487 infants (1.8%) weighing greater than or equal to 2500 g died in the perinatal period, but 7 were already dead at the onset of labor or had congenital abnormalities incompatible with life. Sixty of 177 infants (33.9%) weighing 1000-2499 g died in the perinatal period, but 28 of these died due to prematurity alone or from complications of intrauterine hypoxia or birth trauma. Although elective cesarean section for breech presentation could not be justified for infants weighing greater than or equal to 2500 g, this procedure may well reduce the perinatal loss of premature infants by reducing the incidence of intrauterine hypoxia and preventing birth trauma.

Thirty anovulatory patients, previously unresponsive to clomiphene citrate in standard dosage, were treated with a new incremental method of clomiphene therapy. Clomiphene was given continuously with dosage increments every 5 days, up to a maximum dose of 3750 mg, and ovarian response was monitored with urinary estrogen estimation and with ultrasound. Twenty-one patients (70%) ovulated on this regimen and 8 (27%) conceived; 6 patients who ovulated but did not conceive had other infertility factors. Clomiphene response was associated with a progressive rise in follicle-stimulating hormone, luteinizing hormone, and estrogen excretion; these parameters were unchanged in nonresponders. Side effects of treatment were minimal and only 1 case of hyperstimulation occurred. Preliminary testing with estrogen-amplified gonadotropin-releasing hormone did not differentiate responders from nonresponders. Incremental clomiphene treatment appears to be a less complicated alternative for patients who would otherwise require exogenous gonadotropin therapy.

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.

The perinatal mortality associated with breech presentation at the Royal Women's Hospital, Melbourne, between 1974 and 1976 was 10.4%, or almost 5 times the overall hospital figure. Nine of 487 infants (1.8%) weighing greater than or equal to 2500 g died in the perinatal period, but 7 were already dead at the onset of labor or had congenital abnormalities incompatible with life. Sixty of 177 infants (33.9%) weighing 1000-2499 g died in the perinatal period, but 28 of these died due to prematurity alone or from complications of intrauterine hypoxia or birth trauma. Although elective cesarean section for breech presentation could not be justified for infants weighing greater than or equal to 2500 g, this procedure may well reduce the perinatal loss of premature infants by reducing the incidence of intrauterine hypoxia and preventing birth trauma.

Intravenously administered salbutamol inhibited premature labour for at least 48 hours in 49 of 76 patients (64%), but was more effective (89%) when the cervical dilatation was less than 2 cm, and no apparent cause for the premature labour was evident. Even when premature labour complicated multiple pregnancy, hydramnios, or followed a small antepartum haemorrhage, suppression of labour could often be achieved for at least 48 hours, thus following the administration of betamethasone or the transfer of the patient to a hospital with intensive care facilities for both mother and child. Treatment with betamethasone, in addition to salbutamol, was associated with a less severe form of respiratory distress syndrome, and did not increase the risk of maternal or fetal infection, except in patients with cervical incompetence when 46.2% of such patients were infected.

Motor-car accidents in the State of Victoria in the years 1973 to 1975 inclusive resulted in five maternal and 27 fetal deaths. Severe maternal injury only occurred in women not wearing seat belts; however, fetal death may well have been due to seat belt injury in 14 subjects. The commonest genital tract injury was placental abruption. However, uterine rupture was observed on three occasions and these cases are described in detail. /TRRL/

The metabolic clearance rate (MCR) of human luteinizing hormone (hLH) has been determined in 10 normal men, 3 normal women, and in 12 women with ovulatory disorders resulting in oligomenorrhea or amenorrhea. The MCR was determined by the constant infusion technique using either iodinated or unlabeled highly purified hLH, and these results were compared to MCR determined by using crude pituitary preparations containing both follicle-stimulating hormone and hLH. Both preparations produced essentially similar results for the MCR of hLH and virtually identical results were obtained when complete or incomplete immunoprecipitation of the infused material was achieved. The MCR/body surface area of hLH was significantly greater in normal men (25.6 plus or minus 3.6 ml/min-m-2) than in normal premenopausal (19.2 plus or minus 0.9 ml/min-m-2) or postmenopausal women (17.4 plus or minus 1.9 ml/min-m-2). No difference was noted in the MCR of hLH in women with oligomenorrhea or amenorrhea. Production rates (PRs) were calculated by using a pituitary standard, the values being 85.1 plus or minus 21.5 IU/24 h in normal men, 39.9 plus or minus 12.6 IU/24 h in normal premenopausal women, and 294.6 plus or minus 61.9 IU/24 h in normal postmenopausal women. The initial half-times of disappearance of the alpha- and beta-subunits of hLH were measured in two normal men and found to be 15-18 min, respectively. The half-time of intact hLH was twice as great.

Seventeen patients treated with clomiphene citrate were examined using real-time ultrasound timing 28 ovulatory cycles to determine the pattern of follicular development under clomiphene stimulation. The rate of growth was faster, but the follicular diameter range at ovulation was similar to that during spontaneous cycles. This information was used to time midcycle human chorionic gonadotropin (hCG) administration in over 97 cycles in 21 patients responsive to clomiphene who had not conceived. When hCG was given when the mean follicular diameter reached 18 mm, 92% of these cycles were ovulatory. Fourteen patients (67%) conceived within 6 ovulatory treatment cycles. Five of 7 patients (71%) who did not conceive were found to have endometriosis at laparoscopy. Midcycle cervical scores were significantly lower in clomiphene-treated as compared with spontaneous ovulatory cycles, and additional treatment with ethinyl estradiol did not effect a significant improvement. Timing of midcycle hCG using ultrasound is an effective method of inducing ovulation in patients in whom an estrogenic follicular response without ovulation is obtained with clomiphene treatment.

In order to determine whether infertility of unexplained aetiology would respond to therapy with bromocriptine, 50 regularly ovulating infertile patients were studied in a double-blind placebo controlled trial. Following an observation cycle in which midluteal urinary oestrogen and pregnanediol excretion and late luteal serum PRL and hCG levels were determined, patients were randomly allocated to treatment with either bromocriptine or placebo for three cycles. Patients who did not conceive were then treated for three cycles with the alternative therapy. Eighteen women (36%) conceived, five during the observation cycle, four during treatment with bromocriptine, four whilst receiving placebo and five during the 12 month follow-up period. The pregnancy rate achieved in patients treated with bromocriptine was thus no better than that for the group as a whole.

One or more semen analysis results were available for 195 men whose wives responded to ovulation induction with gonadotrophins performed at The Royal Women's Hospital since 1963. Fifty-three men (27%) has subnormal semen analyses by conventional criteria: sperm concentration less than or equal to 20 X 10(6)/ml, motility less than or equal to 40% or normal morphology less than or equal to 50%. The lifetable pregnancy rates were not significantly different for those with subnormal and normal semen (chi 2 = 0.169), by six cycles 64% (s.e.m. = 7) with subnormal semen had conceived compared with 59% (s.e.m. = 5) with normal semen. It appears that lower limits of semen quality could be relaxed for women needing ovulation induction with gonadotrophins.

This report details the outcome of pregnancy in 469 patients admitted before 34 weeks' gestation with premature labor with intact membranes (253 patients) or premature rupture of the membranes (PROM) but no labor (216 patients). Betamethasone significantly reduced the incidence of severe respiratory distress syndrome (RDS) both in patients with intact membranes and in those with PROM. PROM had a significant beneficial effect on the incidence of RDS in both groups of patients, those who had received betamethasone and those who had not. Fetal sex did not significantly influence the respiratory response to either PROM or betamethasone administration, except that betamethasone treated female fetuses showed a significantly better response to PROM than similarly treated males. Except in patients with PROM associated with a cervical suture, betamethasone administration did not increase the risk of perinatal or maternal infection.

A large cohort of consecutive live births with gestational ages assessed antenatally from 24 to 28 weeks from one tertiary center was studied to determine the association between mode of delivery and in-hospital mortality and morbidity and morbidity at two years of age. Between 1 January 1977 and 31 March 1982, 52.8% (172 of 326) of such infants survived their primary hospitalization. Obstetric factors independently associated with improved survival were increasing gestational age (P less than .0001), the absence of maternal hypertension (P = .007), singleton pregnancy (P = .007), and antenatal steroid therapy (P = .018). Although 62.7% (32 of 51) of infants delivered by cesarean section survived compared with 50.9% (140 of 275) of infants delivered vaginally, the increased survival was not statistically significant (X 2 = 1.97). Moreover, the trend favoring cesarean section disappeared after adjustment for confounding obstetric factors. In univariate analyses cesarean births more frequently required ventilatory support and there was a trend toward a lower incidence of cerebroventricular hemorrhage; again, however, when adjusted for extraneous factors these associations disappeared. Of the 172 in-hospital survivors, five died at home unexpectedly; 162 of the remaining 167 were traced; 18 (11.1%) had cerebral palsy and two (1.2%) were deaf. Of the 111 children who were fully assessed, 13.5% had major handicaps, 23.4% were suspect, and 63.1% were free of handicap at two years' corrected age. There was no association between mode of delivery and frequency of handicap. Little evidence was found from mortality or morbidity data to support routine delivery of infants of borderline viability by cesarean section.

Hydrohaematometrocolpos may occur secondary to isolated imperforate hymen, genital tract duplications, and complex urogenital sinus or cloacal abnormalities. The presenting symptoms and relation to menarche provide clues to the diagnosis. Examination of the abdomen, introitus, and vagina may confirm the diagnosis and assist in clarification of the anatomy. In genital duplications ultrasonography further delineates the pelvic anatomy and demonstrates unilateral renal agenesis. We have reviewed our 10-year experience and present an approach for the diagnosis and investigation of these patients.

One hundred and nineteen women with sustained hyperprolactinaemia were followed for a mean duration of 5.5 years. Where pregnancy was desired, treatment with bromocriptine (+/- clomiphene) was effective in 86% of subjects. Following cessation of bromocriptine therapy one third of subjects whose initial serum prolactin (PRL) level was less than 4 times normal had a 'spontaneous' resolution of their hyperprolactinaemia and resumed cyclical menstrual activity and fertility. Subjects with higher PRL levels or those not treated with bromocriptine, did not show this beneficial effect. Pituitary or hypothalamic tumours were identified in 11% of subjects at the time of presentation and developed in a further 15.1% during follow-up. Most of these tumours were small, occurred more commonly when the PRL level was greater than 4 times normal, and were less likely to develop when treatment with bromocriptine had been administered. Bromocriptine therapy can thus be justified in hyperprolactinaemic subjects to reduce troublesome galactorrhoea, achieve pregnancy, improve the chance of a 'spontaneous' return of menstruation and fertility, control or reduce tumour growth where a pituitary tumour has been identified, and reduce the risk of tumour development in patients with normal plain X-rays of the pituitary fossa at the time of presentation.

Positive sperm immobilization tests were found in the sera of 6.3% of 491 infertile men. There was a higher frequency of family histories of autoimmune diseases than for other subfertile men. Prognosis for fertility was related to results of sperm-mucus penetration tests: progressively motile sperm indicated a fair outlook--8 of 15 couples conceived within 7 months either spontaneously or with artificial insemination with husband's semen. Absence of progressively motile sperm indicated severe infertility - only 6 of 72 couples produced pregnancies. Treatment of the latter group by temporary suppression of spermatogenesis with testosterone or with Artificial Insemination by Husband (AIH) appeared to be ineffective. However, sperm immobilization titres fell and sperm concentrations, motility and mucus penetration increased during treatment of 14 of the men with prednisolone (0.5-0.75 mg/kg per day) for 4-7 months and there were three pregnancies. It is concluded that sperm autoimmunity in men causing failure of sperm to penetrate cervical mucus produces severe but not absolute infertility. Immunosuppression with continuous high dose glucocorticoid reduces antibody levels and improves semen quality. A controlled trial is needed to determine if this treatment is a practical method for improving fertility in men with sperm autoimmunity.

Motor-car accidents in the State of Victoria in the years 1973 to 1975 inclusive resulted in five maternal and 27 fetal deaths. Severe maternal injury only occurred in women not wearing seat belts; however, fetal death may well have been due to seat belt injury in 14 subjects. The commonest genital tract injury was placental abruption. However, uterine rupture was observed on three occasions and these cases are described in detail. /TRRL/