Ovulation induction with human menopausal gonadotropins--a changing scene

The aim of human menopausal gonadotropin treatment (hMG), to simulate normal follicular development by injecting FSH and LH and induce follicular rupture with hCG, is rarely met. Multiple follicular development occurs because hypothalamic-pituitary feedback is bypassed. This, exacerbated by the long half-life of hCG, causes the principal complications of hMG therapy--multiple pregnancy and hyperstimulation. The initial use of hMG in pituitary deficiency has been widened to include failure to respond to clomiphene, polycystic ovaries, 'unexplained infertility' and in vitro fertilization. Reported pregnancy rates, incidence of hyperstimulation and of multiple pregnancy vary widely. We reviewed the results of hMG therapy from 1977 to 1989 in 260 consecutive women with clomiphene-resistant infertility. Conception and live birth rates after six treatment cycles were 45.7% and 43.3%, respectively and were influenced by the cause of infertility, age, weight and sperm parameters. The miscarriage rate was 18.6% and multiple pregnancy rate 19.3%. The conception rate fell during the 12-year period in all groups except those with regular anovulatory cycles. Over this period, age, weight and male subfertility increased in patients referred to us. hMG is an effective and safe treatment for women with clomiphene-resistant infertility and patent tubes.     

Are estrogen assays essential for monitoring gonadotropin stimulant therapy?

Ovarian responses to human menopausal gonadotropin (hMG) are conventionally monitored by urinary estrogen or serum estradiol (E2) concentration. E2 can also be measured in saliva but this is rarely used. With ultrasound (USS) however, follicular development is assessed directly and we have previously shown that USS is superior to urinary estrogens for monitoring. We have now compared salivary and serum E2 with USS during hMG therapy in 48 women over 101 cycles. Salivary and serum E2 correlated significantly with each other and with the number of mature follicles. The manufacturers of hMG state that hCG should be given only when E2 is between 100 and 3000 pmol/l. However, there were no mature follicles in 40% of the cycles where E2 lay within this range. USS is the most accurate method of monitoring responses to hMG and, where this is available, estrogen assay provides no additional useful information.     

Polycystic ovary syndrome, diabetes and cardiovascular disease: risks and risk factors.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.     

Book reviews

Irish Journal of Medical Science (1971 -) -     

Longitudinal predictors of caregiver burden in amyotrophic lateral sclerosis: a population-based cohort of patient–caregiver dyads

Objective

Caregiver burden is a recognised consequence of caring for a patient with neurodegeneration. Amyotrophic lateral sclerosis (ALS) differs from other neurodegenerations by its rapid progression and impairment of motor, cognitive, and behavioural function, which contribute to caregiver burden. However, longitudinal factors that determine the extent of caregiver burden, and in particular the impact of psychological distress among caregivers, have not been fully established.

Methods

Patients with ALS (n = 85) and their primary caregivers (n = 85) completed three serial evaluations. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). The Edinburgh Cognitive-Behavioural ALS Screen (ECAS) was used to determine cognitive function in patients. The ALS Functional Rating Scale (ALSFRS-R) measured disease progression.

Results

Using the ZBI, caregivers were categorised as high or low burden. In the low burden group, anxiety scores from the HADS predicted caregiver burden (r = 0.410, F = 3.73, p = 0.033), whereas the depression sub-score from the HADS was predictive of caregiver burden in the high burden group (r = 0.501, F = 5.87, p = 0.006) for cross-sectional analyses. Longitudinally, an elevated score on the HADS at Time 1 was the largest predictor of caregiver burden across serial assessments.

Conclusion

In a patient cohort with relatively preserved cognitive function (65%), anxiety and depression at Time 1, as measured by the HADS, were the best predictors of caregiver burden at Time 3. This observation provides a mechanism by which caregiver burden can be identified by health-care professionals and a stepped care programme of intervention initiated.

     

Hormone changes during ovulation in the rainbow trout (Salmo gairdneri Richardson)

Plasma levels of 17 beta-oestradiol, testosterone, 17 alpha-hydroxy-20 beta-dihydroprogesterone, 17 alpha-hydroxyprogesterone, and gonadotrophin were measured in 14 female rainbow trout during the course of their first ovulation period. Gonadotrophin levels were rising at the beginning of the experiment (12-16 days prior to ovulation) and kept rising to reach a peak (65 ng ml-1) at 20 days after ovulation. 17 alpha-Hydroxy-20 beta-dihydroprogesterone levels rose rapidly to reach a peak (317 ng ml-1) 4 days prior to ovulation and fell gradually over a further 32 days. 17 beta-Oestradiol fell 15-17 ng ml-1 12 days prior to ovulation to basal levels (2-3 ng ml-1) at 4 days prior to ovulation, and remained low. Testosterone fell more slowly, however, from a peak value (276 ng ml-1) 8 days prior to ovulation to basal levels 28 days postovulation. 17 alpha-Hydroxyprogesterone appeared in plasma at the same time as 17 alpha-hydroxy-20 beta-dihydroprogesterone. The level of 17 alpha-hydroxyprogesterone rose more slowly, however, and stayed at a fairly constant level (about 100 ng ml-1) for 16-20 days. These results give the first clear picture of the interrelationships between some of the major hormones known to be involved in salmonid reproduction. They support the existence of feedback inhibition between the sex steroids and gonadotrophin, and provide further evidence for the important role of 17 alpha-hydroxy-20 beta-dihydroprogesterone in the processes of oocyte maturation and ovulation. It is suggested that the rapid rise in 17 alpha-hydroxy-20 beta-dihydroprogesterone prior to ovulation is due to the switching of already highly active steroid cells from C19 (androgen) to C21 (progestagen) production.