L. W. Cox

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±0.4 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.

Predicting me Luteinizing Hormone Surge: Relationship Between me Duration of me Follicular and Luteal Phases and the Length of the Human Menstrual Cycle

Determination of blood serum levels of luteinizing hormone (LH) are used to detect the day of the midcycle surge. This information, collected over several menstrual cycles of numerous women, is used to derive mathematical expressions relating the day of the surge to the length of the cycle. The equations are subsequently employed to predict the most likely day of the LH surge, and hence the time of ovulation, solely from knowledge of the average length and variability of a womans cycles, without the need for determinations of LH. A convenient table is provided for making this prediction.

Human luteal phase function following oocyte aspiration from the immediately preovular graafian follicle of spontaneous ovular cycles.

Human luteal phase function as evaluated by peripheral venous blood steroid levels does not appear to be impaired following the aspiration of follicular fluid together with a cumulus enclosed oocyte and a number of granulosal cells from the immediate preovular follicle in women having otherwise spontaneous ovular cycles. The day to day levels of luteinising hormone, oestradiol‐17β, 17α‐hydroxyprogesterone, progesterone and basal temperatures in 14 women who had their preovular follicle aspirated were compared with a control group of 28 spontaneously ovulating women. It was concluded that a carefully performed single aspiration of the contents of a preovular follicle, for the purpose of extra‐corporeal fertilisation of the mature oocyte, did not lead to impaired steroid function of the subsequent corpus luteum, although the prolactin levels were increased due to the effects of the relaxant anaesthetic and/or the laparoscopic procedure. A safe and simple laparoscopic procedure is also described, which is particularly suitable for women with a likelihood of extensive pelvic adhesions.

Experience with in Vitro Sperm Penetration Testing in Infertile and Fertile Couples

The ability of spermatozoa to penetrate periovulatory cervical mucus was investigated in 132 infertile couples using an in vitro test system. Particular emphasis was placed upon the accurate endocrinologic localization of ovulation time, on the complete testing during this period, and on repeated testing for couples who demonstrated abnormal results. By comparison, the results of similarly performed tests in the conceptional or immediately preconceptional cycle of 63 couples provided the control data. In addition, when penetration was deficient, crossover testing was instituted using optimal semen or cervical mucus. Absent penetration was found in 17 (13%) of the initial cycles tested of the infertile group. However, with the exception of 2 couples who could not be retested, and 3 couples for whom a semen factor was clearly the explanation, all of the remaining 12 couples demonstrated normal migration when tested during subsequent cycles. The results suggested that defective sperm penetration as delineated by this study is an unlikely contributor to the explanation of the long-term infertility of couples. The results also demonstrated how misjudgments of the importance of this area could have arisen, as 61 % of couples tested showed some periovulatory days when penetration was absent. Over-all, 24% of the days tested showed absent migration, even though closely allied days showed normal penetration. Since a spectrum of normal and subnormal semen was used for testing, the influence of semen on optimal mucus conditions could be evaluated. Such testing was not found to be particularly discriminatory between different semen abnormalities, since satisfactory migration could be seen using semen with gross defects. However, severe motility defects of semen appeared to have the most adverse influence. Deficient penetration due to a semen factor explained only 2.3% of the infertility of the 132 couples investigated.

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.

Neonatal body water turnover: A putative index of perinatal morbidity

The water metabolism of 46 newborn babies was determined during a 10 day period by means of an isotope dilution technique, and correlations were sought with the clinical assessment of the babies by multiple obstetric and pediatric clinical criteria. The babies, 48 to 72 hours of age, were given a single oral dose (2 ml/kg) of deuterated water (D2O), a nonradioactive tracer, and the urinary excretion rate was followed by means of infrared spectrophotometry. After a period of equilibration of the D2O with body water (20 hours), the rate of D2O clearance was found to be a single exponential decay process, thus allowing the fraction of total body water lost each hour (the rate constant) to be calculated for each baby. The median values of the rate constants X 10(4)(h-1) for 14 growth-retarded babies ws 104 (98% confidence limits, 97.8 to 122) compared with 76.3 (67.0 to 80.2) for 16 normal mature babies and 82.1 (73.4 to 90.6) for 16 normal premature babies. These data indicate that, compared with normal mature or normal premature babies, growth-retarded infants have a significantly (P less than 0.05) faster turnover of water during the first 10 days of postnatal life. Since there was little overlap in results between the normally grown and the retarded infants, the measurement of water turnover may provide a useful index of perinatal morbidity.

Endocrine profiles and fertility status of human menstrual cycles of varying follicular phase length

Assessment of the relationship between ovarian endocrine function and follicular phase length was made in 48 patients (51 cycles) with spontaneous ovular cycles of varying length. On the basis of follicular phase length when measured from the first day of menstruation to, and including, the day of the luteinizing hormone (LH) peak, cycles were grouped into short (less than 21 days), medium (12 to 16 days), and long (more than 6 days). Daily serum LH, androstenedione, 17 beta-estradiol, progesterone, and 17 alpha-hydroxyprogesterone concentrations were determined in the periovular period. The overall pattern of serum steroid concentrations in medium and long cycles was similar to that previously described for normal women. However, cycles with a short follicular phase had lower mean concentrations of androstenedione and estradiol. In order to assess the fertility potential of cycles with follicular phases of varying length, the prior 265 cycles of 92 consecutive patients who conceived with artificial insemination by donor (AID) were studied. In all cases, insemination occurred on day 0 and day + 1 with respect to the LH peak, and all cycles were assumed to have equal fertility potential. Statistical analysis revealed no significant difference in fertility potential among cycles with follicular phases of differing length.

Endocrinology of Ovarian Stimulation for In Vitro Fertilization

Summary: 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.

Melatonin in Man

Considerable advances in the understanding of melatonin in man are now possible. The advent of melatonin measurement has allowed previous conjectural possibilities for melatonin and pineal gland function in man to be tested. The impressive feature of melatonin physiology in the human is the stability of secretion, which fits with an enviromental sensing function of the pineal gland and with melatonin as having some coordinating role in human endocrinological function. The possibilities for the use of melatonin in human and veterinary clinical medicine is raised.

Induction of ovulation. An attempt to avoid complications.

Abstract Attempts to induce ovulation in a series of 66 infertile women with human gonadotropins, clomiphene citrate, or both were successful in 91 per cent of cases, and pregnancy resulted in 50 per cent. Daily monitoring of estrogen excretion at critical phases of the cycle is believed to be an important factor in avoiding complications such as multiple pregnancy and ovarian cyst formation. Some patients who failed to respond to clomiphene or to gonadotropin were treated with combinations which were followed by ovulation, and in one case pregnancy occurred.