Twenty-one year experience with intrauterine inseminations after controlled ovarian stimulation with gonadotropins: maternal age is the only prognostic factor for success.

PURPOSE: To report our experience on homologous intrauterine insemination (IUI) with gonadotropin controlled ovarian stimulation (COS) cycles and to examine different variables which could predict IUI success. MATERIALS AND METHODS: This is a retrospective analysis of IUIs performed between January 1997 and December 2017. A total of 7359 COS IUI's procedures (2901 couples) were reviewed. Clinical pregnancy, live birth rate and age, body mass index (BMI), smoking habit, duration of infertility, sperm characteristics before and after treatment (total motile count, morphology, and vitality), day 3 FSH, total gonadotropin dose, and number of follicles were assessed by multivariate logistic regression analysis, and data were expressed as odds ratio (OR). RESULTS: The mean female age at the time of COS was 35.10 ± 3.93 years. The most common single infertility diagnoses were unexplained infertility (53.55%), mild male factor (19.69%), and anovulation (10.95%). The total progressive motile sperm count (TPMC) was > 1 × 106/ml (mean 1.34 ± 1.08 × 106/ml). The clinical pregnancy rate was 9.38%, and the live birth rate was 7.19% per cycle. Twin pregnancies were 12.17%. Cumulative pregnancy was 21.89% and cumulative live birth rate was 17.58% per couple. Clinical pregnancy and live birth rates were significantly associated with female age [OR 0.97 (95% CI 0.95-0.99) and 0.95 (95% CI 0.93-0.97), respectively] and day 3 FSH [OR 0.91 (95% CI 0.87-0.94) e 0.90 (95% CI 0.87-0.94), respectively]. CONCLUSIONS: Clinical pregnancy rate and live birth rates after COS-IUIs were significantly influenced by female age and FSH levels. TRIAL REGISTRATION: Clinical trial registration number: NCT03836118.

Vascular endothelial growth factor and its soluble receptor in patients with polycystic ovary syndrome undergoing IVF.

We aimed to examine the behaviour of the angiogenetic factor vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in polycystic ovary patients undergoing In vitro fertilisation (IVF) compared with respect to normally ovulating controls. Levels of VEGF and sVEGFR-1 were compared in follicular fluid and serum, both on the day of human choriogonadotropin (hCG) administration and on the day of oocyte retrieval (OR), in controls and polycystic ovarian syndrome (PCOS) patients undergoing IVF cycles. The bioactivity of VEGF (VEGF/sVEGFR-1 ratio) in the two groups was calculated. Thirty PCOS patients and 20 controls referring to the IVF Centre of the University of Pisa (Italy) were enrolled. In each patient, blood samples were collected on the day of hCG and on the day of OR administration, and follicular fluid samples. VEGF and sVEGFR-1 were measured by Enzyme Linked Immuno Sorbant Assay (ELISA). Serum VEGF bioactivity markedly increased in both groups after hCG administration. Serum and follicular fluid VEGF bioactivity was greater in PCOS patients than in controls on the day of OR. The increase in VEGF bioactivity in PCOS patients undergoing IVF was not only because of increasing levels of VEGF but also to decreasing levels of its soluble receptor. We believe that additional studies will clarify their role in the pathogenesis of ovarian hyperstimulation syndrome, which most often occurs in patients with PCOS.

Vascular endothelial growth factor level changes during human embryo development in culture medium.

OBJECTIVE: Implantation is a complex phenomenon consisting of the first strong contact between embryo and endometrium. Recent studies have demonstrated that this process is dependent not only on the 'readiness' of the endometrium, but also on complex interactions between endometrial and embryonic tissues that cross-talk by means of different molecules (growth factors, cytokines, vasoactive factors). Investigations performed on human blastocysts indicate a role for vascular endothelial growth factor (VEGF) in these processes. The aim of the present study was to investigate VEGF levels at different stages in human embryo culture medium. STUDY DESIGN: We selected 20 women among patients undergoing assisted reproduction with the in vitro fertilization-blastocyst transfer protocol. The oocytes were inseminated by intracytoplasmic sperm injection. For each patient, approximately two cultures of four microinjected oocytes (and then of four embryos) were performed. Each culture of four oocytes/embryos was placed in one dish to increase the probability to detect small VEGF concentrations. RESULTS: Results showed significantly higher VEGF levels in the medium at blastocyst stage (12.16 +/- 2.80 pg/ml) compared with embryos at pronuclear stage (13.58 +/- 2.32 pg/ml) and microinjected oocytes (12.80 +/- 3.45 pg/ml). CONCLUSIONS: An important VEGF synthesis by blastocysts occurs during human embryo development.

Growth factors and folliculogenesis in polycystic ovary patients.

Ovarian folliculogenesis is regulated by a fine balance between endocrine and intraovarian factors. In this review, we focus on the role of growth factors in physiological folliculogenesis and in polycystic ovaries. Recent evidence shows that the main systems implicated in polycystic ovary folliculogenesis are the growth hormone and insulin-like growth factor system, vascular endothelial growth factor, and the transforming growth factor-ß family. Growth hormone and the insulin-like growth factor system could affect follicular development and oocyte maturation if their balance was altered, while vascular endothelial growth factor is implied in follicular dominance by providing an increasing vascular supply. The transforming growth factor-ß family is composed of various molecules, which have different roles in cellular proliferation. Finally, a series of different factors seem to be involved in altered polycystic ovary follicular growth.