https://gynecology.gr/userfiles/file/scientific-studies/eshr_asrm_pcos.pdf

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. Hypoxia has been shown to be a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality. VEGF is critical also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. In situ hybridization studies demonstrate expression of VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with various VEGF inhibitors in a variety of malignancies are ongoing. Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.

/pdf/vascular-endothelial-growth-factor-basic-science-and-17gyy6h97s.pdf

Vascular endothelial growth factor: basic science and clinical progress.

https://www.fertstert.org/article/S0015-0282(00)00518-5/pdf

Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer

Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Ge...

Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications

Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.

In vitro fertilization and the ovarian hyperstimulation syndrome

The aim of this study was to determine basal serum vascular endothelial growth factor (VEGF) concentrations and Doppler blood flow changes within the ovarian stroma of women with polycystic ovaries (PCO) and women with normal ovaries. Pulsed and colour Doppler blood flows within the ovarian stroma were recorded, and serum VEGF concentrations measured, in the early follicular phase (days 2-3 of a menstrual cycle) in 60 women undergoing ovarian stimulation for in-vitro fertilization. 36 women had normal ovaries, 14 women had PCO as seen on pelvic ultrasound examination and 10 had polycystic ovarian syndrome (PCOS). Mean ± SD serum VEGF concentrations were significantly higher (P < 0.001) in women with PCO and PCOS (3.4 ± 0.7 and 3.2 ± 0.66 ng/ml respectively) compared with women with normal ovaries (2.3 ± 0.5 ng/ml). Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were significantly higher (P < 0.001) in women with PCO and PCOS compared with women with normal ovaries. The mean PSV were 15 ± 4 and 16 ± 4 cm/s in women with PCO and PCOS respectively, compared with 9 ± 2 cm/s in women with normal ovaries. The TAMXV were 9 ± 3 and 11 ± 3 cm/s in women with PCO and PCOS respectively compared with women with normal ovaries (5.8 ± 1.5 cm/s). Serum VEGF concentrations were positively correlated with PSV (r = 0.44, P = 0.001) and TAMXV (r = 0.45, P < 0.000) in all three groups of women. Higher serum concentrations of VEGF in women with PCO and PCOS may relate to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow velocity measurements in these women. The results may explain the higher risk of ovarian hyperstimulation syndrome in programmes of ovarian stimulation in patients with PCO compared with those with normal ovaries.

/pdf/serum-vascular-endothelial-growth-factor-concentrations-and-3fnasddp00.pdf

Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries.

Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides: relationships with motility and fertilization in vitro.

The perinatal outcome and congenital malformations in children born between 1978 and 1987 in Great Britain after in-vitro fertilization (IVF) at Bourn Hall Clinic and the Hallam Medical Centre are presented. The average maternal age was 34.2 years. Multiple births were frequent, constituting 23% of all deliveries; 19% were twins and 4% triplets. There were no quadruplet or higher order multiple births during that period. Twenty-five per cent of all deliveries were preterm. The mean birth weight was 2793 g and was strongly related to multiplicity of pregnancy and gestational age. Overall, 32% of babies had a low birthweight (less than 2500 g) with 6% having a very low birthweight (less than 1500 g). The overall stillbirth and infant mortality rates were two to three times higher than those of infants born after natural conception in England and Wales; this is attributed to the high incidence of multiple births. The stillbirth rates were 5.07, 20.8 and 24.7 per thousand total births in singletons, twins and triplets respectively. The corresponding figures for perinatal mortality were 13.5, 38.2 and 37 per thousand. Overall, 2.5% of the babies had one or more major congenital malformations diagnosed within one week of life. This was within the range of expected values in the United Kingdom and there was no significant increase in any specific malformation.

S.L. Tan

Papers

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In vitro fertilization and the ovarian hyperstimulation syndrome

Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries.

Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides: relationships with motility and fertilization in vitro.

Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group