Does it really matter how far from the fundus embryos are transferred?

OBJECTIVE: Embryo transfer (ET) is an important last step during the process of IVF. Over the years much has been learned about the importance of the details of this procedure including the potential impact of transfer depth on outcome. The objective of our study was to evaluate whether transfer depth assessed by air bubble location after ET is associated with clinical outcome. STUDY DESIGN: Retrospective analysis of the association between transfer distance from the fundus (assessed by air bubble location after ET) and IVF outcome based on cycles (N=409) of patients with good prognosis undergoing infertility treatment for various indications. Treatments followed standard stimulation, IVF-ICSI and ET procedures. The distance of the air bubble as a surrogate marker of embryo location after transfer was measured and was correlated with implantation (IR) and pregnancy rates (PR) after day 3 and day 5 ET. Univariate comparisons were performed by nonparametric methods and multiple logistic regression was used to further evaluate the association between pregnancy rate and those factors that might influence outcome. RESULTS: The distance of the bubble was similar in those cycles that led to a pregnancy and those that did not (6.7 vs 6.5mm; p=0.48) and PR were comparable when the transfer was in the upper or middle third of the cavity. The IR did not differ when embryos were transferred into the upper, middle or lower third of the uterine cavity. Outcome was analyzed separately based on the day of transfer (cleavage vs blastocyst stage) and the IR did not differ based on the location of the transfer. CONCLUSIONS: Transfer depth does not affect implantation and pregnancy rates when the ET is in the middle or upper third of the uterus.

Detrimental effects of high-dose gonadotropin on outcome of IVF: making a case for gentle ovarian stimulation strategies.

OBJECTIVE: Limited data identify detrimental influences of aggressive use of gonadotropins (G) for controlled ovarian hyperstimulation (COH); the underlying mechanisms however remain unclear. We report on the relationship between G dose and in vitro fertilization (IVF) cycle parameters (ovarian response, endometrial thickness [EMT]) and cycle outcome (implantation rate [IR] and clinical pregnancy [CP] rate) in a cohort of women undergoing IVF. METHODS: Retrospective analysis of fresh embryo transfer (ET) cycles. Univariate and multivariable regression analyses assessed relationship between G dose and outcomes of interest. RESULTS: Higher G dose related positively with advancing age (P < .001) and inversely with EMT (P < .001). The overall CP rate was 30%. Significantly lower IR (.003) and CP rate (.002) were observed across increasing tertiles of G dose. Increasing G dose was identified as an independent negative predictor of EMT after adjusting for age, COH protocol and duration, infertility diagnosis, and ovarian response (P = .016). Adjusting for age, suppression protocol (gonadotropin-releasing hormone agonist vs antagonist), infertility diagnoses, EMT, quality, and cleavage of ET, lower G dose was an independent positive predictor of CP rate (odds ratio for CP rate was 1.57 for G dose in middle compared to the highest G dose quartile (95% confidence interval 1.09-2.24). Stratified analyses identified detrimental associations of higher G dose with CP rate to be relevant in women aged 35 years and younger. CONCLUSIONS: Our analyses suggest detrimental influences of higher G dose on the endometrium and confirm the previously reported adverse association between higher G dose and IVF outcome. Gentler COH regimens may be of particular benefit in women aged ≤35 years.

The role of hyaluronic acid binding assay in choosing the fertilization method for patients undergoing IVF for unexplained infertility.

PURPOSE: Patients with unexplained infertility may have fertilization problems. Split fertilization (ICSI and conventional IVF on sibling oocytes) is often used to avoid poor fertilization. Our aim was to assess the ability of hyaluronic acid binding (HA-binding) assay to predict spontaneous fertilization during IVF. METHODS: Prospective, blinded, controlled trial. Patients undergoing their first IVF cycle for unexplained infertility were eligible. Split fertilization was used. IVF and ICSI fertilization rates and embryo development based on 3 HA-binding cut-offs (< 60%; 60-80%; >80%) were compared. RESULTS: ICSI fertilization was higher than IVF, but none of the HA-binding cut-off levels predicted those cases where IVF was less effective, therefore ICSI only would have lead to improved outcome. Embryo development and morphology were similar in all cut-off groups. CONCLUSIONS: HA-binding did not predict spontaneous fertilization in patients with unexplained infertility undergoing IVF treatment. When it was used for "screening" it did not help to select the method of fertilization.

Embryo selection or uterine environment: which plays the greater role in blastocyst transfer cycles?

AIM: Blastocyst stage embryo transfer (BET) leads to higher pregnancy rates when compared to cleavage stage transfer. Better embryo selection and a more physiologic stage of transfer are possible explanations. We assessed the significance of embryo selection in achieving an improved outcome. METHODS: Retrospective analysis of all BETs from our 2007 IVF database was performed. The BET cycles were grouped based on the number of top-quality cleavage stage embryos (≤3 or >3). A cut-off of ≤3 embryos was chosen, because with ≤3 embryos those that will likely make it to the blastocyst stage have already been identified, therefore embryo selection becomes less important. Baseline characteristics, stimulation and embryology parameters, as well as treatment outcome, were compared. The T-test and χ(2)-test were used where appropriate. P < 0.05 was considered significant. RESULTS: A total of 251 cycles where at least one blastocyst was transferred on day 5 were identified and included in the analysis (≤3 top-quality cleavage embryos, n = 32; >3 top-quality cleavage embryos, n = 219). The number of follicles >14 mm and the number of eggs/mature eggs were higher in the group with >3 good quality day 3 embryos. Slightly more embryos were transferred in the ≤3 embryo group. Pregnancy rates (14/32 [43.8%] vs 96/219 [43.8%]; P = NS) and ongoing pregnancy rates (10/32 [31.2%] vs 80/219 [36.5%]; P = NS) were comparable. CONCLUSION: Based on the analysis of our data, the number of top-quality cleavage stage embryos did not significantly influence BET outcome. Besides embryo selection, other factors such as improved embryo-endometrium synchrony probably play an important role in the higher implantation and pregnancy rates.

Results with early follicular phase recombinant luteinizing hormone supplementation during stimulation for in vitro fertilization.

OBJECTIVE: To study the effect of early follicular phase recombinant LH supplementation on stimulation outcome among women undergoing IVF using the GnRHa long protocol and recombinant FSH. DESIGN: Randomized, controlled trial. SETTING: Private IVF unit. PATIENT(S): Women under the age of 40 with normal ovarian function undergoing their first or second IVF cycle. INTERVENTION(S): All stimulations followed the standard luteal long GnRHa down-regulation protocol. At suppression, patients in the experimental group received 75 IU of rLH daily for 4 days, and recombinant FSH at a fixed starting dose of 150 IU for the first 5 days was started a day later, on day 2 of rLH. In the control group, patients started rFSH at a fixed dose of 150 IU for the first 5 days at suppression. MAIN OUTCOME MEASURE(S): Baseline, stimulation, embryology parameters, and treatment outcome were compared. Of primary interest, recombinant FSH need during stimulation was assessed. RESULT(S): Stimulation, embryology parameters, and treatment outcome were comparable. The amount of gonadotropins used and medication expense were similar in the two groups. CONCLUSION(S): Early follicular phase recombinant LH supplementation at a daily dose of 75 IU does not improve response to stimulation among normal responder women undergoing IVF.

Comparison of serum and follicular fluid hormone levels with recombinant and urinary human chorionic gonadotropin during in vitro fertilization.

OBJECTIVE: To study serum and follicular fluid (FF) hormone levels after the administration of urinary or recombinant hCG to initiate the final stages of oocyte maturation during IVF. DESIGN: Prospective randomized study between 250 microg of recombinant hCG and 7,500 IU of urinary hCG as the final trigger of ovulation during IVF. SETTING: Private IVF center. PATIENT(S): Infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) using the long protocol and recombinant FSH. INTERVENTION(S): IVF treatment. Serum and FF hormone measurements on the day of oocyte collection. MAIN OUTCOME MEASURE(S): Serum and FF E(2), P, hCG, and T levels. RESULT(S): Stimulation parameters, serum and follicular E(2), P, T, and hCG levels were similar in the recombinant and urinary hCG groups. The number of oocytes retrieved from follicles >14 mm, the proportion of mature oocytes, fertilization rate, and pregnancy rate (PR) were also comparable. CONCLUSION(S): Recombinant and urinary hCG provided similar serum and follicular hormonal environments during the final stages of oocyte maturation. The IVF outcome parameters were also comparable. The two medications appear to be equally effective.

Effect of coasting on cycle outcome during in vitro fertilization/intracytoplasmic sperm injection cycles in hyper-responders.

OBJECTIVE: To investigate the effect of coasting on IVF outcome in GnRH agonist cycles. DESIGN: Retrospective analysis. SETTING: Private IVF center. PATIENT(S): Infertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment (normal responders [control], hyper-responders [coasting] groups). INTERVENTION(S): Coasting to reduce the risk of ovarian hyperstimulation syndrome (OHSS) among hyper-responders. MAIN OUTCOME MEASURE(S): Stimulation, embryology parameters, and pregnancy rate (PR). RESULT(S): The average length of coasting was 2.2 days. Age and baseline FSH were comparable to control cycles. There were more follicles and oocytes in the coasting group, but the number of fertilized oocytes and embryos transferred were similar. Implantation rate (22.4% vs. 13.9%) was higher in the control group but the PRs were comparable (45.1% vs. 38.5%). Within the coasting group, baseline, stimulation, and embryology parameters were comparable between successful and unsuccessful cycles. Pregnancy rates were comparable after 1, 2, and 3 or more days of coasting (36.3% vs. 38.4% vs. 40%). Pregnancy rates were also comparable (28.5% vs. 35.7% vs. 44.4%) when groups were compared based on change in E2 (<25%, 25%-50%, >50%). CONCLUSION(S): Coasting for 3 days can be used successfully in the management of the hyper-responding patients during IVF.

Comparison of clinical outcome and costs with CC + gonadotropins and gnrha + gonadotropins during Ivf/ICSI cycles.

OBJECTIVE: To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles. MATERIALS AND METHODS: Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates. RESULTS: Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p < 0.001). More ampoules of gonadotropins were used in the GnRHa group (24.0 +/- 0.3 vs 20.0 +/- 0.5, p < 0.001). Medication costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol. CONCLUSIONS: Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.

Do lunar cycles influence in vitro fertilization results?

PURPOSE: Our objective was to investigate the lunar influence on IVF-ET outcomes. METHODS: Between 1992 and 1999 we have completed 7572 preprogrammed IVF-ET treatment cycles with the same stimulation protocol in two outpatient units. (Vienna, Austria and Budapest, Hungary) Multiple regression (SAS; proc Logistic) and two separate analyses were performed on pregnancy rates using a harmonic sinoidal trend based on the synodic and anomalistic lunar cycles respectively. RESULTS: The overall pregnancy rate was 30.9%. The amplitude of harmonic sinoidal, trend for the synodic lunar cycles was chi2 = 1.63,2d.f., p = 0.44 and chi2 = 6.27,2d.f., p = 0.044 for the anomalistic moon periods. For the anomalistic lunar months the amplitude of harmonic sinoidal trend was borderline in terms of higher pregnancy rates with the moon in Perigee. CONCLUSION: The cause of seasonal changes in IVF-ET outcomes is probably very complex. Our results indicate that lunar influence may only be one of the contributing factors. Further studies are needed to clarify unexplained fluctuations of pregnancy outcomes.

Ascorbic acid supplement during luteal phase in IVF.

PURPOSE: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study. METHODS: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private outpatient infertility clinics. All women were stimulated by the same protocol. The mean age was 31.73 (+/- 4.4 SD) years. RESULTS: No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups. CONCLUSIONS: There was no clinical evidence of any beneficial effect, as defined by main outcome measures, of ascorbic acid on IVF-ET. Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment.