https://www.cell.com/cell/pdf/S0092-8674(05)80085-6.pdf

Role of Insulin-like Growth Factors in Embryonic and Postnatal Growth

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 

The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

Polycystic ovary syndrome.

We studied the risk of early loss of pregnancy by collecting daily urine specimens from 221 healthy women who were attempting to conceive. Urinary concentrations of human chorionic gonadotropin (hCG) were measured for a total of 707 menstrual cycles with use of an immunoradiometric assay that is able to detect hCG levels as low as 0.01 ng per milliliter, with virtually 100 percent specificity for hCG in the presence of luteinizing hormone. Our criterion for early pregnancy--an hCG level above 0.025 ng per milliliter on three consecutive days--was determined after we compared the hCG levels in the study group with the levels in a comparable group of 28 women who had undergone sterilization by tubal ligation. We identified 198 pregnancies by an increase in the hCG level near the expected time of implantation. Of these, 22 percent ended before pregnancy was detected clinically. Most of these early pregnancy losses would not have been detectable by the less sensitive assays for hCG used in earlier studies. The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent. Most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.

https://www.nejm.org/doi/pdf/10.1056/NEJM198807283190401

Incidence of Early Loss of Pregnancy

Parental imprinting of the mouse insulin-like growth factor II gene

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(97)11280-6.pdf

UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

https://www.bmj.com/content/bmj/297/6653/883.full.pdf

Maternal serum screening for Down's syndrome in early pregnancy.

Maternal Serum Screening for Down Syndrome in Early Pregnancy

Pregnancy-specific beta-glycoprotein in complications of early pregnancy.

OBJECTIVES--To assess the implementation of antenatal screening for Down9s syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN--Demonstration project of Down9s syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING--Hospital and community antenatal clinics in four health districts in London. SUBJECTS--12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES--Uptake of screening, detection rate for Down9s syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS--The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down9s syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION--Antenatal maternal serum screening for Down9s syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.

https://www.bmj.com/content/bmj/305/6850/391.full.pdf

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

Evidence is accumulating that a non-GH dependent insulin-like growth factor-binding protein (IGF-BP) is not only a carrier protein but also has an active role in the growth process. We have measured levels of this IGF-BP, using a specific RIA, over 12 or 24-h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normal the IGF-BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 micrograms/l. The levels of IGF-BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 micrograms/l if a long-acting insulin preparation was administered in the evening but were 400-500 micrograms/l if the long-acting preparation was administered in the morning. The IGF-BP was strongly correlated with plasma glucose in this latter group. In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF-BP and free insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Tim Chard

Papers

Maternal serum screening for Down's syndrome in early pregnancy.

Maternal Serum Screening for Down Syndrome in Early Pregnancy

Pregnancy-specific beta-glycoprotein in complications of early pregnancy.

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin. A new role for insulin?