Geeta Nargund

Mild ovarian stimulation for IVF.

BACKGROUND Mild ovarian stimulation for in vitro fertilization (IVF) aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment. METHODS Pubmed and Medline were searched up to end of January 2008 for papers on ovarian stimulation protocols for IVF. Additionally, references to related studies were selected wherever possible. RESULTS Studies show that mild interference with the decrease in follicle-stimulating hormone levels in the mid-follicular phase was sufficient to override the selection of a single dominant follicle. Gonadotrophin-releasing hormone antagonists compared with agonists reduce length and dosage of gonadotrophin treatment without a significant reduction in the probability of live birth (OR 0.86, 95% CI 0.72-1.02). Mild ovarian stimulation may be achieved with limited gonadotrophins or with alternatives such as anti-estrogens or aromatase inhibitors. Another option is luteinizing hormone or human chorionic gonadotrophin administration during the late follicular phase. Studies regarding these approaches are discussed individually; small sample size of single studies along with heterogeneity in patient inclusion criteria as well as outcomes analysed does not allow a meta-analysis to be performed. Additionally, the implications of mild ovarian stimulation for embryo quality, endometrial receptivity, cost and the psychological impact of IVF treatment are discussed. CONCLUSIONS Evidence in favour of mild ovarian stimulation for IVF is accumulating in recent literature. However, further, sufficiently powered prospective studies applying novel mild treatment regimens are required and structured reporting of the incidence and severity of complications, the number of treatment days, medication used, cost, patient discomfort and number of patient drop-outs in studies on IVF is encouraged.

Intraobserver and interobserver variability of ovarian volume, gray-scale and color flow indices obtained using transvaginal three-dimensional power Doppler ultrasonography

To assess intraobserver and interobserver variability in ovarian volume and gray‐scale and color flow index measurements using transvaginal, three‐dimensional, power Doppler ultrasonography.

Mild ovarian stimulation for IVF: 10 years later

Ovarian stimulation to achieve multiple follicle development has been an integral part of IVF treatment. In the context of improved laboratory performance, the need for a large number of oocytes as an integral part of a successful IVF programme may be questioned. The aim of the current debate is to summarize the studies performed during the last decade to develop the concept of mild stimulation aiming to obtain fewer than eight oocytes. Here we examine the balance between IVF success and patient discomfort, and complications and cost, and how these might improve by simpler ovarian stimulation protocols aimed at retrieving fewer oocytes. We intend to analyse why progress has been rather slow and why there is much resistance to mild stimulation. Finally, presumed useful directions for future research will be discussed.

Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta.

Abstract Maternally imprinted PEG10 and SGCE, separated by ∼2.15 Mb from Syncytin (HERV-W) gene at 7q21.3, are implicated in choriocarcinoma and Silver-Russell syndrome. Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11–12 wk of gestation. In contrast, transcription from SGCE remained unchanged throughout pregnancy, suggesting two neighboring imprinted genes are differentially regulated at very early pregnancy. Additionally, accumulation of two major species of mRNA (8 kb and 3.1 kb) encoded by HERV-W in placenta is regulated: 3.1 kb mRNA level remained unchanged throughout pregnancy, whereas the production of 8 kb species was highest in term placenta. Western blot and immunohistochemical staining of placental tissues with monoclonal antibodies revealed a marked reduction of syncytin glycoprotein synthesis in late pregnancy. Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus.

Evaluation of endometrial receptivity during in-vitro fertilization using three-dimensional power Doppler ultrasound

To compare sonographic endometrial characteristics in in‐vitro fertilization (IVF) cycles between women who conceive and those who do not.

Low-dose HCG is useful in preventing OHSS in high-risk women without adversely affecting the outcome of IVF cycles

Severe ovarian hyperstimulation syndrome (OHSS) is a rare but potentially fatal condition associated with conventional IVF treatment. It is found predominantly in women with polycystic ovaries who have an exaggerated response to exogenous FSH, leading to a large number of follicles and an overproduction of vascular endothelial growth factor with resultant excessive increases in vascular permeability. There is evidence to suggest that OHSS is also linked to the use of human chorionic gonadotrophin (HCG) to induce ovulation. Therefore, while HCG is essential for corpus luteum function, high amounts of HCG can lead to OHSS in high responders. In a pilot study, infertile patients at high risk of developing OHSS were given half the current minimum dose of HCG (i.e. 2500 IU). No woman developed moderate or severe OHSS; 13 women (61.9%) conceived and there were three twin pregnancies. In women at high risk of OHSS, a low dose of HCG appears to prevent the development of OHSS without compromising success rates.

Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization

OBJECTIVE To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS Forty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate. RESULTS The number of oocytes retrieved correlated with the antral follicle count (R =.458, P =.004) and ovarian volume (R =.388, P <.016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P <.017), flow index (P <.001), and vascularization flow index (P <.007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group. CONCLUSION According to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression.

Towards a more physiological approach to IVF.

The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) is founded to promote a more physiological, less drug-oriented, lower risk, less expensive and more patient friendly approach to Assisted Reproduction embracing not only natural cycle treatment but also gentle stimulation protocols and in-vitro maturation of oocytes. Recent research suggests that IVF in modified natural cycle/mild stimulation with antagonist is likely to replace the current conventional approach in down-regulated cycles. The Society will focus both on the basic science and clinical aspects of assisted reproduction. It will be committed to promoting international multi-centre scientific research, regular practical workshops for training and also seminars for educating assisted reproduction technology professionals. ISMAAR aims to establish a direct dialogue with the voluntary sector and politicians to campaign for IVF to be a safer, softer and affordable treatment globally.

The effect of in vitro fertilization on birth rates in western countries

BACKGROUND We will assess to what extent in vitro fertilization (IVF) is effective in increasing the number of births overall and whether earlier application of IVF will increase this number. METHODS We simulate 100 000 women trying for their first and second child. Natural and IVF pregnancy rates and infertility rates are age-dependent and based on published data. The age at which women start trying for their first child is based on the Netherlands 2002 data. Three cycles of IVF are given during a 12-month period after 1 or 3 years of trying to conceive unsuccessfully. Main outcome measures are live born deliveries and children, both naturally conceived or after IVF, as well as numbers of singletons, twins and triplets, the total fertility rate (TFR) and the number of IVF cycles performed. RESULTS Full access to IVF after 3 years increases the TFR by 0.08 children. Applying IVF after 1 year leads to an additional TFR increase of 0.04, with double the number of IVF cycles and twin and triplet children, and a shift from naturally conceived children to IVF children. CONCLUSIONS Full access to IVF after 3 years is important. It does increase the TFR. Early availability of IVF would further increase the TFR, but with side-effects and high costs.

Characterization of Normal and Polycystic Ovaries Using Three-Dimensional Power Doppler Ultrasonography

AbstractPurpose: To evaluate the characteristics of polycystic compared to normal ovaries using three-dimensional (3-D) power Doppler ultrasonography. Methods: We recruited 42 volunteers, all of whom were commencing IVF treatment. Each patient was examined in the cycle preceeding the start of drug therapy during the late follicular phase. If eight or more subcapsular follicles of 2–8 mm in diameter in one two-dimensional (2-D) plane were detected in either of the ovaries, the patient was categorized as having polycystic ovaries (PCO); otherwise the ovaries were considered normal. The parameters examined were volume of the ovary, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean greyness (MG). In addition, the ovary was arbitrarily divided into cortex and stroma, and thereafter volume, VI, FI, VFI, and MG were calculated for these two regions. Results: Twenty-eight women had normal ovaries and 14 had PCO. The comparison between normal and PCO showed that as a group the PCO were larger, without any differences in VI, FI, VFI, or MG. In patients with PCO, the right ovary was larger than the left one. In patients with normal ovaries, FI was higher on the left side. Division into cortex and stroma revealed that there were no differences in cortical or stromal VI, FI, VFI, or MG between normal and PCO on either side. Conclusions: The ovaries defined as polycystic were larger than normal ovaries, but there was no difference in the echogenicity of the stroma between polycystic and normal ovaries. We were also unable to demonstrate that the polycystic ovarian stroma was more vascularized than the stroma in the normal ovaries.