J.R.T. Coutts

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.

Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders

Objective To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. Design A prospective study with comparison of control and GH-treated cycles. Patients Poor responder patients (n=10) required >44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n=10) required Main Outcome Measures Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E 2 ) response and hCG criteria. Total doses and duration of hMG, follicular development and E 2 concentrations on day 0, and embryology were also assessed. Results Growth hormone showed no effect on any of the parameters studied in either patient group. Conclusion Follicular recruitment, E 2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment.

Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids

Objective To investigate the effect of the gonadotrophin releasing hormone (GnRH)‐agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre‐operative symptoms, difficulty of operation and operative blood loss.

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.

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.

A detailed study of the effect of videoframe rates of 25, 30 and 60 Hertz on human sperm movement characteristics

A comparison was made of the movement characteristics of human spermatozoa analysed at three videoframe rates (25, 30 and 60 Hz) using two computerized motility analysers from Hamilton-Thorn Research (the HTM-2030 and the IVOS) operating at 25 and 30 Hz respectively. Analysis at 30 and 60 Hz was performed on the IVOS. The use of uncapacitated, capacitated and pentoxifylline-stimulated spermatozoa ensured a full range of movement characteristics was analysed. The velocity parameters curvilinear velocity and average path velocity were highly frame-rate dependent, and mean values increased with videoframe rate. An interaction of framing rate and time of data collection resulted in an increase in straight-line velocity with framing rate. Mean lateral head displacement and linearity were similar at 25 or 30 Hz but significantly depressed at 60 Hz. Beat-cross frequency increased by 74% when analysed at 60 rather than 30 Hz. The following criteria: curvilinear velocity > 100 microns/s, linearity < 65% and lateral head displacement > 7.5 microns, were used to define hyperactivated spermatozoa. Significantly more hyperactivated cells were identified at 30 Hz than 25 Hz (1-10%) but not at 60 Hz. A different population of cells is likely to have been identified as hyperactivated at 60 Hz due to alterations in component movement parameters from which the definition of hyperactivation was derived. In conclusion, direct comparisons should not be drawn between data analysed at 25 and 30 Hz. Analysis at 60 Hz introduced complex alterations which made simple comparisons with 30 Hz data invalid.

11 LHRH analogues for ovulation induction, with particular reference to polycystic ovary syndrome

Summary Infertile women with PCO have been treated with exogenous gonadotrophins (hMG/hCG) for ovulation induction either with or without LHRH-agonist treatment. Those treated without LHRH-agonist-induced LH suppression showed PL in >30% of the cycles and this problem was eliminated by LHRH-agonist therapy. The pregnancy rate (approximately 80% of patients) during the combined therapy was approximately twice that of the group treated with hMG/hCG alone. The suppression of endogenous LH by the LHRH-agonist appeared to have no effect upon the profiles of follicular development in response to hMG, and a high rate of follicle recruitment characterized all PCO treatment cycles irrespective of circulating LH concentrations. These results suggest that LH suppression improves the efficacy of ovulation induction but has no influence on the primary metabolic disturbance in the PCO syndrome.

AN ASSESSMENT OF URINARY AND PLASMA STEROID ESTIMATIONS FOR MONITORING TREATMENT OF ANOVULATION WITH GONADOTROPHINS

Total urinary oestrogens (UE), plasma oestradiol‐17β (PE2), plasma progesterone and urinary pregnanediol values were estimated during 28 cycles of treatment with human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) in seven patients with primary or secondary amenorrhoea who complained of infertility. Ovulation occurred in 23 courses of treatment and three patients became pregnant. PE2 estimations gave a more accurate day to day assessment of the response of patients to treatment than UE values. Monitoring of treatment with PE2 values should reduce any tendency to overstimulation with HMG and allow more accurate timing of the first HCG injection which is critical for a successful ovulatory response. The first HCG dose is an effective stimulus to ovulation when administered on the day of the UE peak which is the day after the PE2 peak. The first HCG dose appeared to be an ineffective stimulus to ovulation if given subsequent to this time or more than two days after the last HMG stimulation.

Spontaneous follicular and luteal function in infertile women with oligomenorrhoea: role of luteinizing hormone.

OBJECTIVE There is a paucity of longitudinal endocrine studies of infertile patients with oligomenorrhoea. We have assessed the frequency and quality of spontaneous follicular development and Meal function in patients with ollgomenorrhoea and infertility (PCOS), and have related the observed criteria to circulating LH activity.

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.