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Biomedical subjects

L W Cox

Publications and source records attributed to L W Cox.

At least 19 recordsLinked to original sources

The development of infertility treatment in Australia.

The development of fertility clinics in Australia began in Sydney at the Women's Hospital, Crown Street, in 1938 with Alan Grant. Clinics in other cities followed: Melbourne (1940), Adelaide (1946), Brisbane (1948), Perth (1949) and Hobart (1967). At first, the work was confined to clinical investigation and tubal surgery. In the early 1960's the university departments of Obstetrics and Gynaecology appointed scientists and developed endocrinology enabling investigation of anovulation and leading to ovarian stimulation with gonadotrophin and clomiphene. Male infertility had been investigated, but although there was occasional use of fresh semen donations, it was not until 1972 that sperm banks were set up, the first being in Adelaide. In 1979 the first IVF baby was born in Melbourne, and clinics in other cities had success over the next 3 years. Microsurgery had by then been introduced for tubal reconstruction. The high standing of Australian clinics has been due to the pioneers who were careful investigators, considerate doctors, and enthusiastic teachers; and later, to the close cooperation between clinicians and scientists and the sharing of new advances both informally and at scientific meetings.

Australia

Deuterium labelled steroid hormones: tracers for the measurement of androgen plasma clearance rates in women.

A method employing stable isotope-labelled tracers and gas chromatograph-mass spectrometry (GC-MS) analysis has been used to measure the plasma clearance rates (PCR's) of androstenedione (A) and testosterone (T) in normal women and women with androgen abnormalities including hirsutism and polycystic ovary syndrome. A solution of deuterium-labelled A and T is infused at a constant rate and blood samples taken at 2 and 2.25 h. Solvent extracts of the derived plasma samples, to which an internal standard has been added, are derivatized with pentafluoropropionic anhydride and the endogenous steroid and deuterated steroid are quantitated after an injection of the derivatization mixture into a capillary column GC-MS. The concentration of the deuterated steroid in the infusion mixture is measured and the PCR is calculated. In premenopausal normal women the PCRA is 1950 +/- 184 1/24 h (n = 5) and the PCRT is 484 +/- 82 1/24 h (n = 7).

Androgens

The effect of porcine relaxin vaginally applied at human embryo transfer in an in vitro fertilization programme.

It has been suggested that the polypeptide hormone relaxin is an early pregnancy factor which facilitates implantation and pregnancy maintenance. To test this hypothesis a double blind randomized placebo controlled trial was conducted where 2 mg purified porcine relaxin or distilled water was given in a vaginal gel on the day of embryo transfer and again 3 days later in a human in vitro fertilization (IVF) programme. There were 96 patients in the randomized trial and 73 patients who were treated concurrently in the same IVF programme acted as a further control group. Of the 51 patients who received relaxin, 10 pregnancies were confirmed and 8 continued successfully. In the 45 patients treated with placebo 10 pregnancies were also confirmed and 6 continued successfully. Amongst the 73 patients concurrently treated outside the trial 14 achieved a pregnancy and 10 continued to term. Thus, porcine relaxin given in these circumstances in a human IVF programme did not appear to improve or interfere with the pregnancy rate. Possible factors that affected the implantation rates in this trial are discussed.

Animals

Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen.

The efficacy of high intrauterine insemination of a washed motile fraction of spermatozoa from men with poor quality semen on the day after the luteinising hormone (LH) surge was compared with that of natural intercourse based on symptothermal methods and a single act of intercourse timed on the day after the LH surge in the same 35 couples in a controlled and randomised trial of the three types of cycle. Each couple had been trying to conceive for at least 3 years, the woman being potentially fertile and the only detectable defect related to poor semen quality. After 39 intrauterine insemination cycles, 8 women conceived (all in their first insemination cycle); this procedure was significantly more successful than LH-timed intercourse (0/38; p less than 0.05) and natural intercourse timed by symptothermal methods (1/34; p = 0.022). The technique of intrauterine AIH, with a 'Tomcat' catheter, was simple, painless, and uncomplicated.

Clinical Trials as Topic

In vitro fertilization and embryo transfer program, Department of Obstetrics and Gynecology, University of Adelaide at the Queen Elizabeth Hospital, Woodville, South Australia.

A review is presented summarizing the in vitro fertilization experience at the University of Adelaide, Australia. Initial attempts utilizing the normal cycle were unsuccessful in obtaining a pregnancy. Since 1982 the overall ongoing pregnancy rate has been 21% per embryo transfer, 16% per laparoscopy, and 12% per treatment cycle. A detailed description of presently utilized methodology is presented.

Adult

Endocrinology of ovarian stimulation for in vitro fertilization.

Understanding of the endocrinology of in vitro fertilization has advanced rapidly in the past 5 years. Despite a multitude of ovarian stimulation regimens a particular regimen has not demonstrated a marked superiority. In principle the achievement of high FSH levels during the early follicular phase to recruit a maximum number of follicles with a tolerable degree of asynchrony for final maturation is confined to a limited time span or 'FSH window' of about 3 to 4 days before negative E2 feedback induces below-threshold FSH levels, thereby condemning all subsequent follicles in that cycle to atresia. It appears that one can widen and/or amplify the 'FSH window' too far from gross hyperstimulation resulting in the recruitment of many follicles with an intolerable degree of asynchrony. This may lead to a defective endocrine environment for the oocytes contained within these follicles or an abnormal luteal environment and an increased frequency of fertilization, cleavage and implantation failure. Whichever regimen is used, the stimulation should ideally be sufficient to promote the development of at least 3 follicles beyond 18mm diameter at the time of OPU. This can be expected to result in at least 2 embryos to be available for transfer. Monitoring of follicular response by a combination of E2 and ultrasonic parameters is recommended so that the administration of HCG is given close to the anticipated endogenous rise of LH. This can be achieved by detecting a reduction in the rate of E2 rise (to plateau).(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin

Incidence of multiple pregnancy after in-vitro fertilisation and embryo transfer.

7 multiple pregnancies occurred in a series of 20 pregnancies after oocyte recovery for in-vitro fertilisation and embryo transfer. After ovarian stimulation with clomiphene alone or with human menopausal gonadotropin, 102 laparoscopies were carried out in 62 women and the ongoing pregnancy rate beyond the first trimester was 17/102 laparoscopies (17%), including 5 sets of twins. 1 triplet and 1 twin pregnancy showed evidence of regression of two sacs and one sac, and both are progressing as singleton pregnancies at 16 and 34 weeks, respectively. 3 abortions occurred at 7, 8, and 9 weeks--a spontaneous abortion rate of 15%. The pregnancy and multiple pregnancy rates after stimulation with clomiphene alone or with human menopausal gonadotropin were comparable, but oocyte pickup based on a knowledge of the duration of the endogenous rise in luteinising hormone, rather than 36 h after administration of human chorionic gonadotropin, increased the pregnancy rate. As the quality and number of embryos transferred to the uterus increased, the risk of multiple pregnancy also rose. Consideration should therefore be given to restricting the number of embryos transferred to limit multiple pregnancies to twins.

Adult

Incidence of the luteinized unruptured follicle phenomenon in cycling women.

A prospective study is presented in order to determine the frequency of the luteinized unruptured follicle (LUF) in a population of 66 regularly cycling women. They were monitored by daily ultrasound for a total of 183 cycles, and the LUF was detected in 9 cycles, giving an incidence of 4.9%. The results of daily changes of luteinizing hormone, estradiol, and progesterone provide support for the thesis that the LUF behaves steroidogenically as a corpus luteum and that the luteal phase duration is normal. Continued monitoring in 35 cycles revealed a recurrence in only one case during a fourth subsequent cycle. Thus, the findings indicate that the LUF is a sporadic and infrequent phenomenon. It is therefore an uncommon cause of infertile cycles in potentially fertile women and represents a biologic variable rather than a syndrome. Based on ultrasonic and endocrine observations, a mechanism is proposed for the resolution of the LUF.

Adult

The effect of clomid induced superovulation on human follicular and luteal function for extracorporeal fertilization and embryo transfer.

The administration of clomiphene citrate (Clomid) 150 mg/day from days 5-9 of the menstrual cycle to spontaneously ovulatory women in order to induce adequate multiple follicular development followed by timed laparoscopic aspiration of mature oocytes does not appear to impair luteal phase length or the steroid pattern of oestradiol-17 beta (E2) or progesterone (P) production as reflected by their peripheral blood concentrations. In Clomid stimulated cycles where preovular oocyte pickup (OPU) and embryo transfer (ET) occurred but no recognizable pregnancy resulted, the cycle length was 30.0 (s.e.m. = 0.3) days, the follicular phase length was 15.6 (s.e.m. = 0.3) days and the luteal phase length was 14.4 (s.e.m. = 0.3) days, which did not differ from a group of women having spontaneous ovular cycles. Following Clomid stimulation the dominant follicle was similar in size to the pre-ovulatory follicle in spontaneous uniovular cycles, but the second, third, fourth and fifth order follicles were significantly larger (P less than 0.0001). The ultimate test of luteal competence was the successful implantation of 11 concepti in 7 women (4 sets of twins) from 49 laparoscopies (14%) or 33 embryo transfers (21%). Comparisons between conceptual and non-conceptual embryo transfers following identical Clomid regimes showed no difference between plasma E2 concentrations at the time of hCG administration or the start of an endogenous LH rise; follicle volume, follicular fluid E2, P and testosterone concentrations were also not different. However, there was a trend for follicular P to be higher in the non-conceptual group indicating that advanced luteinization may hinder successful implantation. The follicular fluid androstenedione (A4) concentration was significantly lower in the conceptual group and the total androgen concentration (A4 + T) was also lower which was indicative of active aromatase activity in these follicles. It was concluded from this study that there was no indication to give exogenous hormonal support to the luteal phase, provided there was both optimal follicular growth and steroidogenic function following Clomid stimulation and that exogenous hCG was administered very close to the expected rise of LH. This observation was supported by the finding that timing of OPU based on a knowledge of the start of the LH surge was associated with a higher pregnancy rate than when hCG was administered and indicates that the endogenous mid-cycle events may permit superior maturation of the oocyte and/or permit better synchronization of endometrial maturation for implantation.

Adult

Use of imported cryopreserved hamster oocytes in the diagnosis of male infertility.

Frozen hamster oocytes have been imported from England to Australia to establish a test for human sperm fertilizing capacity based on penetration of zona-free hamster oocytes. When examined under similar conditions used for human in vitro fertilization (IVF), high and consistent rates of penetration by human spermatozoa were obtained which were similar whether the spermatozoa had been stored frozen or freshly collected. The availability of a validated test of the capacity of human spermatozoa to fuse with a receptive vitelline membrane should prove useful in combination with other clinical parameters in the evaluation of male infertility.

Animals

Morphological and functional relations of Graafian follicle growth to ovulation in women using ultrasonic, laparoscopic and biochemical measurements.

The daily growth rates of ovarian follicles were recorded ultrasonically for five days until ovulation in 56 spontaneously ovulating women and related to endocrine and clinical parameters. Over the 5-day period, the average diameter of the follicle destined to ovulate increased from 12 to 23 mm, the second largest follicle from 6 to 12 mm, the third largest follicle from 5 to 9 mm and the fourth largest follicle from 4 to 8 mm. Similar but lesser growth rates occurred in the follicles in the contralateral ovary. Ovulation occurred within 24 hours of the luteinizing hormone (LH) peak, and the mean peak diameter of the ovulating follicle was 23.2 +/- 0.3 (SEM) mm, (range 18-29 mm) before ovulation, and subsequent luteal function was judged to be normal. Follicular growth was most closely correlated with increasing peripheral blood oestrogen levels. In 16 women who had a laparoscopy within 12 hours of the last ultrasound and following the LH peak, the mean diameter of the largest follicle as measured by ultrasound (23.6 +/- 0.4 mm) was similar to that measured at laparoscopy (22.8 +/- 0.04 mm) and estimated from the volume of follicular fluid aspirated (average 5.8 +/- 0.2 ml), 22.5 mm. The follicular fluid levels of progesterone were high on the day of the LH peak and blood progesterone levels had risen significantly indicating that luteinization of the dominant Graafian follicles had already occurred prior to ovulation. This study confirms that ultrasonic monitoring provides a reliable measure of follicular growth and allows studies correlating morphological changes with both normal and abnormal endocrine function of the human ovary.

Adult

Tubal patency testing in a programme of artificial insemination with donor semen.

The value of investigating tubal patency by hysterosalpingography, before artificial insemination with donor semen (AID), was studied retrospectively in 167 patients. The results suggest that unless there is a history of pelvic inflammatory disease preliminary hysterosalpinography is unnecessary. Conception rates were similar in women who had a normal hysterosalpingogram (44%), in those who had an abnormal hysterosalpingogram (46%), and in those who had no preliminary tubal investigation (39%) before AID. Life table analysis of expectancy of conception suggests that tubal patency testing should be delayed until after AID has been unsuccessful for four cycles. Laparoscopy is then the most worthwhile investigation.

Fallopian Tube Patency Tests