Graeme J. Hughes

The Influence of Advanced Age on the Outcome of Assisted Reproduction

Purpose:Our purpose was to determine the influence of age on the outcome of assisted reproduction, with particular interest in women aged 40 years or older.Methods:A retrospective review of the 779 patients enrolled in the Royal Hospital for Women Fertility Group fertility program between 1987 and 1994 was performed. The results for women aged 40 years or older were compared with those for women between 36 and 39 years and those younger than 36 years. The main outcome measures were pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response.Results:Compared with those in younger women, pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response to controlled ovarian stimulation were significantly worse in women aged 40 years or older.Conclusions:The outcome of assisted reproduction in women of 40 years of age or older was extremely poor. Compared with those in younger women, pregnancy outcome and ovarian response to controlled ovarian stimulation were significantly worse in women of 40 years or more.

STUDIES ON PREGNANCY‐ASSOCIATED PLASMA PROTEIN A IN THE THIRD TRIMESTER OF PREGNANCY

The plasma concentration of pregnancy‐associated plasma protein A (PAPP‐A) was measured in 34 women during the last 10 weeks of pregnancy. From 30 to 36 weeks the concentration of this protein increased steadily. Thereafter the concentration of PAPP‐A rose more steeply, the highest amounts being found in early labour. The concentration of PAPP‐A in peripheral venous blood and in the uterine vein was much the same. It was less in the retroplacental blood and a great deal less in the peritoneal fluid. The day‐to‐day variation was small; the coefficient of variation at 38 weeks was only 7.3 per cent. After delivery, the concentration of PAPP‐A fell more slowly than other placental proteins and steroids, the average half‐life being 51 hours. Although there is no doubt that PAPP‐A is a product of the syncytiotrophoblast, our findings suggest that it is not simply secreted by the chorionic villi directly into the intervillous space but makes its way into the maternal circulation by a more circuitous route.

TESTS OF FETAL WELLBEING IN THE THIRD TRIMESTER OF PREGNANCY

Five different products secreted by the fetoplacental unit into the maternal circulation were measured in 272 patients when they were 34 weeks pregnant. The most useful indicator of present pathology or future complications of pregnancy was a placental protein, pregnancy associated plasma protein A which was raised in pre‐eclamptic toxaemia, antepartum haemorrhage and premature labour. The highest values were recorded in pre‐eclampsia before any signs of the disease were evident. Schwangerschafts protein 1 was also raised in pre‐eclampsia and antepartum haemorrhage but only after the disease had presented. Placental lactogen was also raised in pre‐eclampsia and its measurement may have some predictive value. Total oestriol was lowered in fetal growth retardation and the unconjugated steroid raised in pre‐eclampsia and lowered in retarded fetal growth.

Power doppler ultrasound assessment of the relationship between age and ovarian perifollicular blood flow in women undergoing in vitro fertilization treatment

Purpose: To examine the relationship between age and ovarian perifollicular blood flow (PFBF) in women undergoing IVF.Methods: Serial transvaginal power Doppler ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively throughout the follicular phase of ovarian stimulation in women undergoing IVF. The ultrasound assessment days were categorized according to day of hCG trigger.Results: A total of 1050 ovarian follicles from 34 women undergoing one IVF treatment cycle were used for data analysis. The median age of the women was 38.5 years, ranging from 28 years to 44 years. There was a significant negative correlation between age and ovarian PFBF on the day of hCG trigger or trigger day minus 1, but not beforehand during the follicular phase.Conclusions: There was a significant negative correlation between age and ovarian PFBF in women undergoing IVF which was only observed very late in the follicular phase of ovarian stimulation.

RECOMBINANT HUMAN LUTEINIZING HORMONE, LUTROPIN ALFA, FOR THE INDUCTION OF FOLLICULAR DEVELOPMENT AND PREGNANCY IN PROFOUNDLY GONADOTROPHIN-DEFICIENT WOMEN

Objective  To provide evidence of efficacy and safety for use of lutropin alfa in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency.

THE COMPARTMENTAL DISTRIBUTION OF OESTROGENS AND PREGNANCY SPECIFIC β1 GLYCOPROTEIN.

Pregnancy specific β1 glycoprotein (PSβ1, G), unconjugated oestriol, total oestriol and oestradiol were measured in the peripheral venous blood of 25 pregnant women. The results were compared with similar measurements in maternal tissue fluid, cerebrospinal fluid, and uterine vein blood; or with retroplacental blood, umbilical cord blood, and amniotic fluid. The highest mean concentration of PSβ1G occurred in maternal venous blood and was 17.37 (SD 7.07) mg/dl. The mean peritoneal value was 21 per cent of the mean peripheral vein value. Two tissue fluid values were 32 per cent and 5 per cent of the corresponding peripheral vein values. No measurable amount of PSβ1G was found in maternal cerebrospinal fluid and cord artery. Unconjugated oestriol was found in highest concentration in retroplacental blood. The concentration fell from here to contiguous compartments. An exchange between these compartments was suggested by significant correlations in their oestriol content. Conjugated forms of oestriol, as represented by the measurement of total oestriol, were present in highest concentration on the fetal side in cord arterial blood, but could be found in all other compartments. Oestradiol appeared in highest concentrations in retroplacental blood. Low values of oestradiol were found in the fetal compartment. Correlations between maternal compartments were few and this was considered evidence of impeded transmission between these compartments.

Placental secretion of oestrogens and protein hormones.

SummaryIn order to trace the passage of steroids and proteins from the placenta to the maternal peripheral blood, samples of retroplacental blood, uterine vein blood and peripheral blood were taken from women undergoing Caesarean section at term. The concentration of unconjugated oestriol, total oestriol, human placental lactogen and pregnancy specificβ1 glycoprotein was measured. The oestrogen concentration in the uterine vein was higher than the peripheral blood, the placental lactogen was slightly higher and the pregnancy specificβ1 glycoprotein was the same in the uterine vein and the peripheral veins. In keeping with this, the retroplacental blood had a high concentration of oestrogen, moderately raised placental lactogen and a low pregnancy specific glycoprotein concentration. It is concluded that there is a rapid secretion of oestriol from placenta to the mother; a slower secretion of placental lactogen and no clear evidence of a flow of pregnancy specific glycoprotein from the placenta.

Longitudinal assessment of ovarian perifollicular and endometrial vascularity by power Doppler ultrasound in pregnant and non-pregnant cycles in the IVF setting.

Purpose: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles.Methods: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0–4 for PFBF and grades 1–3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into ‘Pregnant’ and ‘Non-pregnant’ cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups.Results: In pregnant cycles, the proportion of large (⩾15 mm) follicles with high (2–4) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0–1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups.Conclusion: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.

Predictive value of mid luteal progesterone concentration before luteal support in controlled ovarian hyperstimulation with intrauterine insemination.

Background:  There is no published data assessing whether higher mid luteal serum progesterone (P4) levels are associated with a higher cycle pregnancy rate (CPR) in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI).

Relationship of obstetric parameters to the concentration of pregnancy-associated plasma protein A

Pregnancy-associated plasma protein A (PAPP-A) was measured by rocket immunoelectrophoresis in 272 patients at 34 weeks of pregnancy and within 48 hours before delivery. The values obtained have been compared to maternal parameters (age, weight, weight gain, blood group, rhesus factor, and parity) and to fetal parameters (sex, weight, Apgar score, rhesus factor, blood group, and placental weight). Maternal age, increased parity, and increased body weight are related to decreased PAPP-A levels. On the other hand, mothers carrying male fetuses, rhesus-negative children, and babies with Apgar scores higher than 7 at 1 minute have increased PAPP-A concentrations. These findings are discussed in relation to PAPP-As involvement in the maternal immunologic system.