Coasting, embryo development and outcomes of blastocyst transfer: a case-control study.

This study compared the effect on blastocyst development and clinical outcome of coasting in women at increased risk of moderate-severe ovarian hyperstimulation syndrome (OHSS; n=389) with a control group matched for age and basal FSH that did not undergo coasting (n=386) in IVF/intracytoplasmic sperm injection (ICSI) cycles. The main outcome measures were rate of blastocyst development and live birth. More cycles progressed to the blastocyst stage in the coasted group (n=169) compared with the control group (n=83; 43.4% versus 21.5%; P<0.001). The biochemical pregnancy, clinical pregnancy and live birth rates were similar (46.5% versus 42.0%; 40.6% versus 37.8%; 31.6% versus 30.1%). The duration of coasting up to 4 days did not affect progression to blastocyst stage. The multivariate model showed that coasting (OR 1.73, P=0.004) and the number of oocytes retrieved (OR 1.17, P=0.001) were positively correlated with blastocyst formation. Coasting, a measure to reduce the risk of OHSS, does not impair blastocyst development or clinical outcome. Coasting should remain an effective measure to prevent OHSS.

Serum FSH Levels in Coasting Programmes on the hCG Day and Their Clinical Outcomes in IVF ± ICSI Cycles.

Introduction. Coasting is the most commonly used strategy in prevention of severe OHSS. Serum FSH levels measurements during coasting may aid in optimizing the duration of coasting. Objective(s). To study live birth rates (LBRs), clinical pregnancy rates (CPRs), and optimal duration of coasting based on serum FSH levels on the hCG day. Materials and Methods. It is a retrospective study performed between 2005 and 2008 at Barts and The London Centre for Reproductive Medicine, NHS Trust, London, UK, on 349-coasted women undergoing controlled ovarian stimulation (COS) for IVF ± ICSI. The serum FSH level measurements on the hCG day during coasting programme were analysed to predict the LBR and CPR. Result(s). LBR and CPR were significantly higher when the FSH levels on the hCG day were >2.5 IU/L (LBR: 32.5%, P = 0.045 and CPR: 36.9%, P = 0.027) compared to FSH <2.5 IU/L. The optimal FSH cut-off level for LBR and CPR is 5.6 IU/L on the hCG day. The optimal cutoff for coasting is 4 days. Conclusion(s). Coasting may be continued as long as either serum FSH level is > 2.5 IU/L on the hCG day without compromising the LBR and CPR or to maximum of 4 days.

Can the fall in serum FSH during coasting in IVF/ICSI predict clinical outcomes?

This retrospective cohort study determined whether the total falls in serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection could predict clinical outcomes. Ninety-nine cycles, with gonadotrophin-releasing hormone-agonist down-regulation where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of severe ovarian hyperstimulation syndrome, were consecutively included. The primary clinical outcome was live-birth rate (LBR); other outcomes measured were number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates. LBR for FSH fall>10 IU/l compared with 5-10 and<5 IU/l were 45.4% versus 22.0% and 25.0%, respectively. Mean serum FSH fall was similar with and without live birth (8.4 ± 6.2 versus 7.3 ± 5.0 IU/l) as were mean oestradiol and FSH concentrations on HCG administration, oestradiol fall, percentage fall in FSH/oestradiol and duration of coasting. None of the variables efficiently predicted live birth on regression analysis. The AUC of FSH fall was 0.53 at 11.0 IU/l. Basal FSH, starting and total gonadotrophin dose and duration of coasting were positively correlated with FSH fall. A potentially clinically important association between live birth and FSH fall during coasting was apparent, which requires further evaluation. The purpose of this retrospective cohort study was to determine whether the magnitude of fall in the serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection cycles could predict the clinical outcomes. Gonadotrophin-releasing hormone-agonist down-regulated cycles (n=99), where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of ovarian hyperstimulation, were consecutively included. Live birth was the primary clinical outcome measured; number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates were the other outcomes examined. Live-birth rate tended to be high when FSH fall was >10 IU/l, compared with 5-10 IU/l and <5 IU/l, although not statistically significantly. Mean serum FSH fall were similar in live-birth and no-live-birth cycles (8.4 ± 6.2 versus 7.3 ± 5.0) as were mean oestradiol and FSH concentrations on hCG administration, oestradiol fall, percentage fall in FSH and oestradiol and duration of coasting. None of the variables efficiently predicted live birth. The area under the curve of FSH fall was 0.53. FSH fall of <11.0 IU/l was found to be more likely to predict negative outcome (specificity 84.72%) than predicting positive outcome when FSH fall was >11 IU/l (sensitivity 34.48%). Women's basal FSH, starting and total gonadotrophin dose of ovarian stimulation and duration of coasting had direct positive correlation with the magnitude of FSH fall. A potentially clinically important rise in live birth in association with greater FSH fall during coasting was apparent, which requires further evaluation.

Controlled ovarian hyperstimulation for low responders in in vitro fertilization/intracytoplasmic sperm injection: a low-dose flare protocol.

In this retrospective study of 652 anticipated low response women, the overall clinical outcomes (live birth rate and clinical pregnancy rate [PR]) of low-dose flare (LDF) protocol appeared lower than those of conventional down-regulation (DR) (LDF: 15.1% vs. DR: 20.6% and LDF: 10.3% vs. DR: 17.4%, respectively). The findings that LDF protocol improved the clinical outcome in older women, or when LDF followed an unsuccessful IVF/intracytoplasmic sperm injection (ICSI) cycle with DR (LDF: 19.4% vs. DR: 9.76% and LDF: 13.9% vs. DR: 4.2% respectively), need further evaluation through randomized trials.

The correlation between basal serum follicle-stimulating hormone levels before embryo cryopreservation and the clinical outcome of frozen embryo transfers.

OBJECTIVE: To evaluate the correlation between basal serum FSH level before the fresh IVF/intracytoplasmic sperm injection (ICSI) cycle and the clinical outcome of the subsequent frozen embryo replacement cycles. DESIGN: Retrospective observational study. SETTING: University tertiary referral center, London, United Kingdom. PATIENT(S): Five hundred four consecutive frozen embryo transfer (FET) cycles where serum FSH levels were obtained, on days 1-4 of the cycle before the fresh IVF +/- ICSI cycles. INTERVENTION(S): Frozen-thawed embryo transfer. MAIN OUTCOME MEASURE(S): Clinical pregnancy (CP) and live birth (LB). RESULT(S): Basal serum FSH in 127 women (25.2%) who had a CP was significantly lower compared with that in women who did not have a CP. Multivariate regression analysis showed significant correlation between basal serum FSH levels and clinical pregnancy and a low significance to LB, but there was no statistical significant differences between women who had a CP and those who did not with regard to age, treatment protocol (natural or hormone treatment cycle), or the freeze-thaw interval. The LB rate was higher in natural cycles (n = 71; 21.2%) than in hormone treatment cycles (n = 28; 16.7%). Conceiving in the fresh cycle had a positive influence on the FET outcome. CONCLUSION(S): Basal serum FSH level before fresh IVF/ICSI cycle is inversely correlated to a CP outcome in FET cycles. A trend was present between FSH levels and LB, but this failed to reach statistical significance.

Does measuring early basal serum follicular luteinising [correction of lutinising] hormone assist in predicting in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome?

BACKGROUND: The aim was to examine the correlation of early follicular serum lutinising hormone (LH) and the clinical outcome of assisted reproduction technique (ART). METHODS: An observational study included 1333 consecutive women undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). 964 women were having their first cycle of ART. Data were entered prospectively. All women had serum LH measured in the 6 months before the index cycle studied. No repeat cycles were included. The main outcomes measured were clinical pregnancy (CP) and live birth (LB) correlation to serum LH. Forward multivariate stepwise regression analysis was applied, and other statistical tests were used as appropriate. RESULTS: There was non significant correlation between basal serum LH and CP and LB in the polycystic ovary syndrome group (R2 = 0.02, F = 1.7 and P = 0.76) (R2 = 0.01, F = 2.6 and P = 0.77) respectively after adjusting for age, BMI, day of oocyte retrieval, starting dose, total dose of stimulation, type of gonadotrophin used, number of oocytes retrieved, fertilization rate and number of embryos transferred. Other aetiological causes group there was similarly non significant correlation between basal serum LH and CP (R2 = 0.05, F = 13.1 and P = 0.66), nor for LB (R2 = 0.007, F = 4.5 and P = 0.9). CONCLUSION: Early follicular serum LH measurements in the 6 months before IVF/ICSI treatment cycle did not correlate with the clinical pregnancy or the live birth rate.

Safety of drugs used in assisted reproduction techniques.

Infertility may affect one in six couples; however, the development of the assisted reproduction technique (ART) created the opportunity for a large proportion of the infertile population to bear children. Pharmacological agents are routinely used in ART, and new ones are introduced regularly, with the aim of retrieving multiple oocytes to increase the prospect of pregnancy. The combinations of drugs that are used have specific adverse effects, but it is mostly the combined action of more than one agent that causes the greatest concern. The matter is complicated by the suspicion that some techniques in ART, for example intracytoplasmic sperm injection for severe male infertility problems (including azoospermia), may also contribute to the increase in adverse effects, especially congenital malformation. Gonadotropin releasing hormone (GnRH) agonists are widely used in controlled ovarian hyperstimulation. It may give rise to a short period of estradiol withdrawal symptoms and it may also lead to luteal phase deficiency. Similarly GnRHa antagonists, which have been recently introduced to control ovarian hyperstimulation, can lead to luteal phase deficiency and may cause some local injection site reactions. The more pure form of gonadotropin leads to less local injection site reactions and their main adverse effects are associated with the consequences of multiple ovulations. It has been proposed that gonadotropins may be a factor in the increasing risk of ovarian cancer and possibly breast cancer, but this has not been substantiated. Prion infection is another potential hazard, although no cases have been reported. Ovarian hyperstimulation syndrome is a well recognised complication of controlled ovarian hyperstimulation in ART. It is usually a result of recruitment of a large number of ovarian follicles. Efforts to minimise the incidence of this syndrome and its severity are now well developed. Congenital malformations are another possible adverse effect of fertility drugs, but it is more probable that the increase in congenital abnormality that is reported in ART is because of the population studied, i.e. patients already at high risk of congenital malformation, rather than the fertility drugs used or the technique employed. High order multiple pregnancy and its sequela is a well established complication of controlled ovarian hyperstimulation. This could be a result of multiple ovulations or more than one embryo replacement. Reducing the number of embryos transferred can reduce this more serious adverse effect for expectant mothers and for children conceived from ART.