The rate of ovarian and utero-placental blood flow through vessels of less than 25 mum diameter was examined with radioactive microspheres in 5 non-pregnant rats and 19 rats at Day 22 of pregnancy. Total blood flow to the reproductive organs was 0-559 ml/min in the non-pregnant animals and 13-2 ml/min in those near term, a 23-fold difference. The mean ovarian blood flow was high and increased from 0-202 ml/min to 0-845 ml/min. Myometrial and endometrial blood flow increased from 0-156 to 2-24 ml/min. The mean maternal placental blood flow at Day 22 of pregnancy was 0-76 ml/min or 121 ml.,min-1 .100 g-1. Litter size was negatively correlated with mean fetal weight but showed little relationship to mean placental weight or to mean maternal placental blood flow.

This study investigated the association between psychosocial stress and outcome of in-vitro fertilization and gamete intra-Fallopian transfer treatment. Ninety women, enrolled for treatment at a private infertility clinic, completed two self-administered psychometric tests (Bi-polar Profile of Mood States, POMS; and State-Trait Anxiety Inventory, STAI) and a questionnaire to ascertain demographic and lifestyle characteristics before the start of treatment. Approximately 12 months later an outcome measure was determined for each participant in terms of whether she was pregnant or not pregnant and the number of treatment cycles undertaken to achieve clinical pregnancy. The women's scores on the psychological tests were similar to published normative scores. On univariate analysis, history of a previous pregnancy was positively related to the probability of pregnancy and full-time employment, a more 'hostile' mood state and higher trait anxiety were associated with a lower cumulative pregnancy rate. A Cox multiple regression model found previous pregnancy history, trait anxiety, and the POMS agreeable-hostile and elated-depressed scales to be the most important lifestyle and stress variables predictive of pregnancy. The results emphasize the importance of psychosocial stress in treatment outcome but indicate that the relationships are complex. Further studies are required to validate whether these findings can be generalized to other populations.

The radioactive microsphere technique was used to determine the rate of blood flow through vessels of up to 15 mum diameter in the ovaries of 23 anaesthetized sheep in the 72 hr preceding ovulation. The validity of the microsphere technique was established in two preliminary studies. On Days 14, 15 and 16 of the cycle the rate of blood flow (ml.min-1 .100 g-1 tissue) was 1122, 708 and 116 to the CL; 157, 258 and 140 to the stroma; and 627, 742 and 1096 to the follicles, respectively. Blood flow to grossly atretic follicles did not differ significantly from that to non-atretic follicles of an equivalent size. Change in blood flow do not appear to initiate or control the activation, steriodogenic function or atresia of follicles.

The objective of this study was to compare average stress levels during the month of conception to those of previous infertile months. We postulated that stress level during the actual month of conception would be lower than that during previous non-conception cycles. Thirteen normal women from the general community, who were attempting pregnancy, kept daily records of coital activity and basal body temperature, and twice a month completed self-administered questionnaires and provided a 12 h overnight urine sample. On average, women reported significantly more favourable mood states on standard psychometric tests, during the month of conception than during the previous non-conception cycles. In addition, they felt significantly less 'hassled' during the month of conception. However, mean urinary hormone excretion of adrenaline, noradrenaline and cortisol did not significantly differ between conception and non-conception cycles and there was little relationship between the psychological measures of mood state and excretion of adrenaline and cortisol. There was no evidence of increased coital frequency during the month of conception when mood states were improved, suggesting that stress effects on libido were unlikely to account for the findings. The results support the conclusion that psychosocial stress influences fertility in females but as yet mechanisms remain unclear.

High doses of estrogens cause embryonic mortality, and fetal and placental growth retardation in rats. This study addresses the physiological relevance of such findings. Estradiol benzoate (EB), by s.c. injection, or estradiol-17beta (E2), delivered by a miniosmotic pump, raised maternal E2 concentrations from only slightly above control values to 5-fold. EB (1 microgram/day) over Days 6-13, 8-13, and 11-13, and continuous infusion of E2 (15 ng/h; Days 10-13) reduced fetal survival to 0%, 0%, 22%, and 75%, respectively. Single injections of EB showed that its lethal effect declined rapidly over Days 9 (44% survival) to 13 (90% survival). Embryos died within 48 h, but death was not due to luteal failure since progesterone levels were maintained and progesterone administered with EB did not reduce mortality. Administration of EB at 1 microgram/day (Days 14-21) or E2 at 40 ng/h (Days 13-16) retarded fetal and placental growth but did not affect survival. The rat embryo is highly sensitive to elevated maternal estradiol concentrations over much of gestation. The early lethal effect implies that endogenous E2 production is carefully regulated to maintain pregnancy; the latter growth-retarding effect suggests that E2 may have a role in the normal control of fetal growth.

The cellular pattern of corpus luteal (CL) growth was studied in rats a t Days 6, 10, 12, 14, 16, 17 and 22 of pregnancy: term is Day 23. Measurements were taken of the percentage of the CL occupied by luteal cells, connective tissue and vascular space, luteal cell and nuclear volumes, and the number of luteal and endothelial cells in each of three CL in both ovaries of five rats a t each stage of pregnancy. Total CL volume increased from 1.08-3.23 pl over Days 10-17. This was mainly due to an increase in luteal cell volume from 3.72 pl to 9.30 pl. Neither the number of luteal cells per CL (range 212,000-287,000) nor the percentage of the CL occupied by luteal cells (range 85-90%) had much influence on growth. Nuclear volume increased roughly in proportion to cytoplasmic volume but near term it decreased despite little change in cytoplasmic volume. The number of endothelial cells per CL increased steadily from 398,000 a t Day 6 to 1,545,000 at Day 22. There was a strong negative correlation (r = -0.78) between the number of luteal cells per CL and mean luteal cell volume that was evident at all stages of pregnancy. There was a positive, but weaker correlation (r = 0.35) between number of luteal cells and CL volume. Thus, CL volume seems to be partly determined by the number of luteal cells at Day 6 but this effect is moderated by local control of luteal cell volume.The corpora lutea are the major source of progesterone during pregnancy in the rat. The rate of progesterone production assessed from the collection of ovarian venous effluent (Fajer and Barraclough, '67; Hashimoto et al., '68; Uchida et al., '70) and indirectly from peripheral plasma progesterone levels (Wiest et al., '68; Morishige et al., '73; Bartholomeusz et al., '76) rises during the first five days of pregnancy, plateaus, or falls slightly until about Day 10, increases to a peak at about Day 16 then falls to very low levels about 24 hours prior to parturition on Day 23. Although this temporal pattern of secretion has now been well-established, little is known of its control or indeed of the limitation to progesterone production in any one rat.We are interested in morphological factors which may be of significance and whether morphology can be used as an index of function in the corpus luteum. Changes in the total mass of secreting tissue (Uchida et al., '70) and in some ultrastructural features of luteal cells (Long, '73) have already been reported. However, other than some relatively qualitative studies (Bassett, '49; Long, '73) there is little information on changes in the number and size of luteal cells, particularly during mid-gestation when corpus luteal volume and rate of progesterone synthesis reach maximum levels. This forms the major subject of the present study. We also carried out statistical analyses to identify cellular differences between corpora lutea and whether these might be related to the number of corpora lutea per rat. MATERIALS A N D METHODSThirty-five nulliparous Albino Wistar rats with a mean weight at mating of...

Fetal weights, placental weights, myometrial, vaginal and maternal placental blood flows (estimated with radioactive mi cro\x=req-\ spheres) were measured in forty-one rabbits at 16, 20, 24 or 28 days of gestation; term occurs around Day 31. Multiple linear regression analysis indicated that fetal weight and placental weight were positively related at all stages of gestation examined. Fetal weight and placental blood flow were negatively related at Day 16, but positively related at Days 20, 24 and 28. The conceptus adjacent to the ovary had greater placental weight and flow values than the means from all conceptuses in the horn by Day 20 but fetal weight was only greater by Day 28. The relevance of these findings to the determination of fetal weight is discussed.

The synthesis and secretion of progesterone by the corpus luteum (CL) may be limited or controlled by transport mechanisms operating between circulating blood and luteal cell cytoplasm. To examine this possibility, the structural features involved in transport, including membrane surface areas and diffusion distances, were quantitated in the CL of 16-day pregnant rats. One ovary from each of eight rats was fixed by perfusion via a cannula inserted into the parametrial artery, and two CL from each ovary were processed for electron microscopy and examined with standard morphometric techniques. For comparison, one CL from each of a further eight ovaries was diced into small cubes, fixed by immersion, and analyzed similarly. In perfusion-fixed CL, there was a substantial volume of vascular space (20% of the total) and interstitial space (5%) and an extensive surface area of capillaries (441 mm2 per CL). The luteal-cell membrane had numerous projections which increased its surface area by a factor of 3.08. Almost 60% of the luteal-cell surface directly faced a capillary, and a further 37% faced interstitial space which probably extended to a capillary surface. Only 3% was in direct contact with a neighboring luteal cell. Despite the extensive interstitial space the harmonic mean thickness, an estimate of likely effective diffusion distance between luteal cell cytoplasm and blood, was only 0.42 micron. This was less than half of the calculated arithmetic mean thickness owing to the presence of surface projections and an uneven capillary endothelium. Results from immersion-fixed CL were qualitatively similar; but the proportion of interstitial space was only 59% of that in perfusion-fixed CL, and the contribution of surface projections to the total area of luteal-cell membranes was significantly reduced. Collectively, these results suggest that membranes and spaces between blood and luteal-cell cytoplasm are structured so as to minimize transport distances.