Peak Estradiol Levels Research Articles

Letrozole Reduces Estrogen and Gonadotropin Exposure in Women with Breast Cancer Undergoing Ovarian Stimulation before Chemotherapy

Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/- 278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17-18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery. Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.

Obstetric Outcomes After In Vitro Fertilization in Obese and Morbidly Obese Women

In addition to numerous health detriments caused by obesity, fertility and pregnancy success may also be compromised. The aims of this study were to compare the effects of obesity and morbid obesity on in vitro fertilization (IVF) outcomes. We also investigated the effects of obesity on obstetric outcomes after IVF treatment. Retrospective study of women less than 38 years of age during their first fresh IVF cycle (January 1995 to April 2005). A total of 1,293 women were included in the study, with 236 obese women (body mass index [BMI] = 30-39.9) and 79 morbidly obese women (BMI > or = 40). The morbidly obese group had a 25.3% IVF cycle cancellation rate compared with 10.9% in normal-weight women (odds ratio 2.73, 95% confidence interval 1.49-5.0), P < .001). Morbidly obese women without polycystic ovarian syndrome had an even higher cancellation rate (33%). Women with higher BMI required significantly more days of gonadotropin stimulation but had lower peak estradiol levels (P < .001). There were no significant differences in clinical pregnancy or delivery rates between the four BMI groups. Of the women who delivered, there was a significant linear trend for risk of preeclampsia, gestational diabetes, and cesarean delivery with increasing BMI (P < .03). We report a significantly higher risk for IVF cycle cancellation in morbidly obese patients with no effect of BMI on clinical pregnancy or delivery rate. However, obese and morbidly obese subjects had a significantly higher risk for obstetric complications. This target population should be aggressively counseled regarding their increased obstetric risk and offered treatment options for weight reduction before the initiation of fertility therapy. II-2.

A randomized controlled trial of increasing recombinant follicle-stimulating hormone after initiating a gonadotropin-releasing hormone antagonist for in vitro fertilization-embryo transfer

Pituitary suppression with a GnRH antagonist before IVF may result in a plateau or decrease in estradiol levels. We sought to investigate the effect of increasing recombinant FSH (rFSH) after starting a GnRH antagonist on estradiol levels, implantation rates, and pregnancy rates. Prospective, randomized multicenter study. Military medical center and private practice. Sixty infertile women undergoing IVF who met the appropriate inclusion criteria. Participants were pretreated with combined oral contraceptives (COCs) and received a dose 150-300 IU of rFSH 5 days after taking their last COC. They were randomly assigned to receive their current dose of rFSH (control group) or an additional 75 IU of rFSH (step-up group) after starting a GnRH antagonist. Daily GnRH antagonist injections were started when the lead follicles were 13-14 mm in diameter and continued until hCG was given when two follicles were >or=18 mm. One to three embryos were transferred 3 or 5 days following oocyte retrieval. Women with PCOS, a body mass index >33, a day 3 FSH >14.1 mIU/mL, or prior poor stimulation were excluded. The primary endpoints of this pilot study were embryo implantation, pregnancy, and livebirth rates. Secondary endpoints included the amount and days of rFSH; number of days of GnRH antagonist use; estradiol levels on the day of GnRH antagonist initiation, day 1 and day 2 after initiation, and on the day of hCG; endometrial stripe thickness; number of follicles; and number of oocytes. No differences were reported within the groups with respect to age, BMI, baseline FSH, use of intracytoplasmic sperm injection, vials of rFSH, number of GnRH antagonist injections, changes in estradiol patterns, or peak estradiol level. The control and step-up groups had similar pregnancies (73.3% vs. 63.3%, P=.41), clinical pregnancies (70.0% vs. 60.0%, P=.42), live births (56.7% vs. 60.0%, P=.8), and implantation rates (50.0% and 39.1%, P=.22). The use of rFSH and a GnRH antagonist in good candidates for IVF resulted in outstanding implantation and pregnancy rates. Increasing the dose of rFSH after starting a GnRH antagonist does not alter the estradiol response or improve the implantation and pregnancy rates.

P-23: Peak Follicular Estradiol Levels and Its Significance in Predicting Pregnancy Outcomes

Objectives: To determine the influence of peak follicular estradiol levels on pregnancy outcomesMethods: 80 completed cycles of patients undergoing IVF-ET with controlled ovarian hyperstimulation (COH) were analyzed. Patients underwent standard protocols using gonadotropins and embryo transfer was done on day 3 or day 5 after oocyte retrieval. Estradiol levels were drawn throughout the follicular phase when the patient had sonographic evaluation to evaluate ovarian response. Biochemical pregnancy was confirmed by a serum HCG drawn 14 days after embryo transfer. Clinical pregnancy was confirmed sonographically by evidence of embryonic heartbeat. Chi square analysis was used to assess any difference in pregnancy outcomes based on peak estradiol levels. Paired student t-test was used to compare the difference in peak estradiol levels of pregnant and nonpregnant cycles. Pearson’s correlation was used to correlate peak estradiol levels with the number of eggs retrieved, the number of eggs fertilized, and the fertilization rate.Results:Tabled 1Mean peak estradiol ± Std (pg/ml)PregnantNon-pregnantP valueBiochemical pregnancies2941 ± 12002818 ± 1988.76Clinical pregnancies2884 ± 11952860 ± 1679.96 Open table in a new tab Figure 2View Large Image Figure ViewerDownload (PPT)Tabled 1<1000>1000Pregnant229Nonpregnant1237Chi square = 4.27p-value = .04<2000>2000Pregnant526Nonpregnant1930Chi square = 4.64p-value = .03 Open table in a new tab This difference, however, was not present when comparing peak estradiol levels to clinical pregnancies.Conclusion: 1Higher estradiol levels during the follicular phase of IVF-ET cycles correlate with increased number of eggs retrieved and fertilized.2Fertilization rates, however, are negatively correlated with peak estradiol levels. This may be explained by the possibility of more immature oocytes with increasing estradiol levels.3As a result of the above two conclusions, no difference exists between peak estradiol levels in pregnant and nonpregnant cycles4When stratified by estradiol levels <2000 and >2000, there is a significant difference in the number of biochemical pregnancies achieved. This difference does not continue on to the number of clinical pregnancies. Objectives: To determine the influence of peak follicular estradiol levels on pregnancy outcomes Methods: 80 completed cycles of patients undergoing IVF-ET with controlled ovarian hyperstimulation (COH) were analyzed. Patients underwent standard protocols using gonadotropins and embryo transfer was done on day 3 or day 5 after oocyte retrieval. Estradiol levels were drawn throughout the follicular phase when the patient had sonographic evaluation to evaluate ovarian response. Biochemical pregnancy was confirmed by a serum HCG drawn 14 days after embryo transfer. Clinical pregnancy was confirmed sonographically by evidence of embryonic heartbeat. Chi square analysis was used to assess any difference in pregnancy outcomes based on peak estradiol levels. Paired student t-test was used to compare the difference in peak estradiol levels of pregnant and nonpregnant cycles. Pearson’s correlation was used to correlate peak estradiol levels with the number of eggs retrieved, the number of eggs fertilized, and the fertilization rate. Results: This difference, however, was not present when comparing peak estradiol levels to clinical pregnancies. Conclusion: 1Higher estradiol levels during the follicular phase of IVF-ET cycles correlate with increased number of eggs retrieved and fertilized.2Fertilization rates, however, are negatively correlated with peak estradiol levels. This may be explained by the possibility of more immature oocytes with increasing estradiol levels.3As a result of the above two conclusions, no difference exists between peak estradiol levels in pregnant and nonpregnant cycles4When stratified by estradiol levels <2000 and >2000, there is a significant difference in the number of biochemical pregnancies achieved. This difference does not continue on to the number of clinical pregnancies.

Does gravidity influence the success of in vitro fertilization–embryo transfer cycles?

Objective. To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)–embryo transfer (ET) cycles.Patients and methods. All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed.Results. Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas.Conclusions. Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF–ET cycles.

Aggressive Outpatient Management of Severe Ovarian Hyperstimulation Syndrome Avoids Complications and Prolonged Disease Course

Aggressive Outpatient Management of Severe Ovarian Hyperstimulation Syndrome Avoids Complications and Prolonged Disease Course

IVF Success Rates in Patients With an Elevated Baseline FSH (> 10 mIU/ml): Antagonist vs. Microdose Flare

ObjectiveTo compare IVF success rates between antagonist (ANT) protocols and microdose agonist flare (MCD) protocols among patients with baseline FSH levels >10 mIU/ml.DesignRetrospectiveMaterials and methodsTabled 1ResultsThere was no significant difference in the patient age, cycle number, or BMI between Groups I and II, and Groups III and IV (Table 2). There was also no significant difference in most cycle parameters between the groups (Table 2). Peak estradiol (pE2) levels were significantly lower, for both age groups, among antagonist cycles compared to MCD cycles. The total dose of gonadotropins utilized for COH was statistically higher in Group II compared to Group I. The implantation rate (de.ned as the number of sacs/number of embryos transferred) was significantly higher in Group III vs. Group IV (14% vs. 6%, p < 0.05). Although not statistically significant, a trend towards higher clinical pregnancy rates was observed in antagonist cycles. The results, expressed as mean ± SD or percentages, as appropriate, are summarized in table 2.ConclusionTabled 1 ObjectiveTo compare IVF success rates between antagonist (ANT) protocols and microdose agonist flare (MCD) protocols among patients with baseline FSH levels >10 mIU/ml. To compare IVF success rates between antagonist (ANT) protocols and microdose agonist flare (MCD) protocols among patients with baseline FSH levels >10 mIU/ml. DesignRetrospective Retrospective Materials and methodsTabled 1 ResultsThere was no significant difference in the patient age, cycle number, or BMI between Groups I and II, and Groups III and IV (Table 2). There was also no significant difference in most cycle parameters between the groups (Table 2). Peak estradiol (pE2) levels were significantly lower, for both age groups, among antagonist cycles compared to MCD cycles. The total dose of gonadotropins utilized for COH was statistically higher in Group II compared to Group I. The implantation rate (de.ned as the number of sacs/number of embryos transferred) was significantly higher in Group III vs. Group IV (14% vs. 6%, p < 0.05). Although not statistically significant, a trend towards higher clinical pregnancy rates was observed in antagonist cycles. The results, expressed as mean ± SD or percentages, as appropriate, are summarized in table 2. There was no significant difference in the patient age, cycle number, or BMI between Groups I and II, and Groups III and IV (Table 2). There was also no significant difference in most cycle parameters between the groups (Table 2). Peak estradiol (pE2) levels were significantly lower, for both age groups, among antagonist cycles compared to MCD cycles. The total dose of gonadotropins utilized for COH was statistically higher in Group II compared to Group I. The implantation rate (de.ned as the number of sacs/number of embryos transferred) was significantly higher in Group III vs. Group IV (14% vs. 6%, p < 0.05). Although not statistically significant, a trend towards higher clinical pregnancy rates was observed in antagonist cycles. The results, expressed as mean ± SD or percentages, as appropriate, are summarized in table 2. ConclusionTabled 1

Biochemical Pregnancy Rate in ICSI Cycles: GNrH Agonist Versus Antagonist

Aim of this study was to compare the biochemical pregnany rates between GnRH agonist and antagonist cycles. retrospective analysis Clinical and biochemical pregnancies in ICSI cycles between January 2004 and april 2005 were retrospectively reviewed. The culture systems and supplemented mediums used embryo culture were identical between two groups during this period. Patients with a distorted uterine cavity (history of uterin surgery or any uterine pathology) were excluded from this study. Routine ICSI was applied for all our patients recruited in this study. Embryo tranfers were performed on day 2 or day 3. Serum samples were obtained at 12 days after embryo transfer and were considered to be positive if serum β HCG level measured ≥ 15 mIU/ml. Pregnancies were categorized as clinical or biochemical according to β HCG levels and ultrasound findings. All patients underwent transvaginal ultrasound 10 days after β HCG test. Statistical analysis was performed using Mann - Whitney U test. The two groups were comparable with respect to age, basal hormone characteristics, peak estradiol levels on HCG day, number of metaphase-II oocytes and transferred embryo number and quality. During this period, totally 97 pregnancies were recorded in the GnRH agonist group and 214 pregnancies in the antagonist group. There were 19 biochemical pregnancies in the agonist group and 45 biochemical pregnancies in the antagonist group. Both GnRH agonist and antagonist cycles resulted in similar biochemical pregnancy rates. Tabled 1NS: Non significant (P>0.05) NS: Non significant (P>0.05) There is no trend toward higher biochemical pregnancy rates in GnRH antagonist in comparison with the long GnRH agonist protocol.

Natural Cycle and Timing of Intrauterine Insemination: HCG vs. Spontaneous LH Surge

To determine if there is a difference in fertility outcomes of natural cycles in which human chorionic gonadotropin (HCG) was administered versus allowing a spontaneous leutinizing hormone (LH) surge. This is a retrospective cohort study of 427 patients (HCG 261 patients, LH surge 166 patients) who underwent natural cycles at the Center for Reproductive Medicine and Infertility, (CRMI),between 1/1/03-12/31/04. Development of ovarian follicles was monitored by transvaginal ultrasound measurement of mean follicular diameter and serial assays of estradiol and serum or urine LH. When the mean follicular diameter was ≥ 18mm, 10,000 mIU of HCG was given to trigger ovulation. Intrauterine insemination, (IUI), was performed 24 hours after HCG administration. Alternatively, laboratory serum LH or patient monitoring of urinary LH levels was performed and when an LH surge was detected (from data previously found to be consistent with LH surge, ≥18 mIU/ml), IUI was performed the following day. All insemination cycles were performed with sperm from subfertile partners or frozen donor specimens. Pregnancy was diagnosed by quantitative Beta-Human Chorionic Gonadotropin, (B-HCG), two weeks after IUI. A comparison of groups with HCG administration versus spontateous LH surge was performed with the Student’s t-test and the Chi-square test where appropriate.Statistical analysis was performed using the SPSS software program. The two groups (HCG administration vs LH surge) were similar with respect to age (37.1yrs for HCG, 36.9yrs for LH), BMI (23.2 for HCG, 23.1 for LH) and peak estradiol level (215pg/ml for HCG, 232pg/ml for LH). Significant differences were noted for IUI day (14 for HCG, 15 for LH surge; p<0.001) and peak LH (14.8mIU/ml for HCG, 30.3mIU/ml for LH; p<0.0001). Patients receiving HCG were more likely to have a positive BHCG 8.04% than those patients with LH surge, 5.95%, though this difference was not statistically significant, p=0.4. The percentage of patients using donor sperm was not significantly different between the two groups, 30.3% for HCG and 35.7% for LH, p=0.24. The percentage of patients that had prior attempts of natural cycles or IVF was also not significantly different between the two groups, 48.7% for HCG and 53.0% for LH,p=0.4. View Large Image Figure ViewerDownload (PPT) HCG administration resulted in a greater number of patients with positive BHCG but did not show a statistically significant difference in outcome from those patients who had utilized spontaneous LH surge to time IUI. However, the patients who received HCG did have IUI performed an average of one day earlier than those patients awaiting an LH surge. It is important to note that this sample population has a large number of patients who have prior attempted cycles, almost 50% in both groups.

Office Administration of Single Dose GnRH Antagonist: Minimizing Patient Injections Utilizing a Simple and Highly Effective IVF Protocol

To evaluate the clinical utility and outcome of a novel protocol in which the single dose GnRH antagonist is administered in the office by the clinical team during controlled ovarian hyperstimulation (COH) and IVF-ET. Case control study. During calendar year 2004 seventy-two patients undergoing COH and IVF received the administration of 3 mg of Cetrorelix in the office immediately after the morning ultrasound evaluation for follicular growth. A lead follicle of 14 mm was used as the sole criteria for administering the antagonist. Estradiol levels were concomitantly measured and patients were instructed to add 75 units of HMG on the day the antagonist was given. Oocyte retrieval was performed 35 hours after hCG, followed by ultrasound guided embryo transfer on day 3 or day 5. Our control group consisted of 119 patients during the same time period who self administered either a GnRH agonist or daily dose 0.25 mg GnRH antagonist in the evening. Ultrasounds, retrievals and transfers were performed by a single investigator to ensure uniformtiy of findings and procedures. Statistical analysis was performed by t-test and Fisher’s exact test where applicable. Our study group consisted of 72 patients, of which 70 underwent embryo transfer. The mean age of our study group was 34.9 +5.0 years, with a B.M.I. of 24.0 ± 5.5 kg/m2 and a basal FSH/E2 6.7 ± 2.2 mIU/ml/ 42.4 +15.2 pg/ml. There were no significant differences between the baseline study characteristics in our study group (N= 70) as compared to our control group (N=119). The mean FSH start dose was 224.7 ± 87.2 units and the mean HMG start dose was 105.2 ± 115.1 units. On average, our study group required 8.8 ± 1.5 days of stimulation and 2683.3 ± 1048.5 units of total gonadotropins, which resulted in a mean peak estradiol level of 1931.8 ± 899.8 pg/ml. The mean total number of oocytes were 12.2 ± 5.3 and among patients that underwent ICSI a mean of 9.3 ± 4.3 MII oocytes were noted. The mean total number of embryos from standard insemination and ICSI were 7.7 ± 4.4 and 8.2 ± 3.9 respectively (P > 0.05). The clinical and ongoing pregnancy rates per transfer were as follows; ≤ 34 years of age (N=31) 64.5% (20/31) and 54.8% (17/31), 35-37 (N=17) 58.8% (10/17) and 47.1% (8/17), 38-39 (N=9) 44.4% (4/9) and 33.3% (3/9), 40-43 (N=13) 38.5% (5/13) and 23.1% (3/13). The total ongoing pregnancy rate per transfer in this study group was 44.3% (31/70), compared to 39.5% (47/119) in our control group (P > 0.05). Single dose GnRH antagonist administration in the office provides a convenient and simple approach to minimize compliance issues for patients undergoing COH and IVF. Our data suggests that aside from the advantages of a more injection friendly stimulation, the use of a single dose GnRH antagonist on the morning of the lead follicle reaching 14 mm results in comparable ongoing pregnancy rates in this case control study. Overall, clinical parameters of ovarian stimulation and outcome were consistent with an efficient and effective protocol for patients undergoing COH and IVF.

Continuous Combined Letrozole-FSH Stimulation Requires Less FSH With Similar Outcomes Compared To Standard Ovarian Stimulation Regimens for IVF

We have previously described a combined letrozole-FSH stimulation protocol (letFSH) for breast cancer patients undergoing IVF for embryo cryopreservation. Our current objective was to compare this protocol to standard IVF protocols. Prospective study with age matched controls. Twenty-five breast cancer patients were treated by letFSH protocol in which letrozole 5 mg was started on cycle day 2 and FSH 150 IU was added on cycle day 4. Both medications continued until the day of hCG. GnRH antagonist was administered when E2>250pg/mL. Standard protocol group consisted of leuprolide suppression followed by gonadotropins (n=68) or gonadotropins with GnRH antagonists (n=27). Day-3 FSH levels were similar between the letFSH and the age-matched standard IVF protocol patients (table). Despite the significantly lower peak estradiol levels in the letFSH group, endometrial thickness, percent mature oocytes, fertilization rates and number of 2-pronuclei embryos were similar to standard-IVF patients (table). However, hCG had to be administered at a significantly larger follicle diameter to achieve these results. The loess fit analysis showed that an average diameter of approximately 20 mm of the two leading follicles resulted in the best fertilization rates with letFSH. The length of stimulation was not different between letFSH and standard IVF stimulation cycles (table). While letFSH resulted in higher number of ≥17 follicles, 46 % less FSH was required to achieve these results compared to all standard-IVF cycles. When this was compared to the results of the stimulation with gonadotropins+GnRH antagonist, a protocol more comparable to the stimulation in letFSH, the FSH requirement was reduced further by 65%. Tabled 1 Continuous administration of letrozole with FSH results in similar fertilization rates, number of two pronuclear embryos per cycle, and endometrial thickness while significantly reducing the requirement for gonadotropin administration compared to standard ovarian stimulation protocols. The hCG administration criteria has to be modified but since length of stimulation with letFSH is similar to that of with standard IVF, this is likely to be due to altered antral fluid dynamics. In addition to its use for embryo cryopreservation in breast cancer patients prior to chemotherapy, this combined continous letrozole-FSH protocol may be a cost saving alternative to standard ovarian stimulation protocols.

In Vitro Fertilization may Overcome the Negative Effects of Smoking on Fertility

Cigarette smoking is widely believed to decrease fecundity in naturally conceiving populations. However, the effect of smoking by females undergoing in vitro fertilization (IVF) is less clear. We retrospectively evaluated the effect of smoking on pregnancy rate and other measures of IVF outcome in a large, diverse socioeconomic population located in a state where IVF coverage is mandated by law. Retrospective cohort analysis of a database at an academic medical center. We analyzed cycle data from 404 patients who had undergone either their first attempt at IVF treatment or their first cycle of IVF following a clinical pregnancy. Standard IVF and intracytoplasmic sperm injection (ICSI) cycles followed by embryo transfer were included; cycles using donor eggs were excluded. Outcomes of the stimulation response, egg and embryo number and quality, pregnancy and live birth rates were assessed in patients reported as never smokers, past smokers and current smokers. The sample size was nearly twice that needed to have 80% power to detect a 5% effect of smoking on pregnancy outcome, based on preliminary data indicating a 26% smoking incidence. Potential covariates were evaluated and data was stratified between two groups dependent upon patient age (< 35 and ≥ 35 years old). Categorical variables were compared using a chi-square tests and Fisher’s exact tests were used to compare small sample sizes. Continuous variables were compared using PROC ANOVA. Relative risks for association with positive pregnancy and live birth were estimated using a log-binomial regression model estimated using PROC GENMOD. 9.3% of patients reported current smoking, and 12.1% reported a history of smoking. Two-thirds of currently smoking women (21/30) smoked 10 cigarettes or fewer per day with a range of 1-30. Smoking status did not significantly affect peak estradiol levels, number of oocytes retrieved, egg maturity, log mean ovarian volume, fertilization rate, cleavage rate, embryo quality, percent of 6 cell embryos, pregnancy rate or live birth rate in women < 35 or ≥ 35 years old. Outcomes were then evaluated controlling for day 3 FSH alone, and for FSH, number of oocytes retrieved and embryo quality score together. The relative risk of smoking continued to have no significant impact on pregnancy rate or other fertility outcomes when controlling for these factors. The question of whether smoking affects IVF outcome is significant to patient care given that some insurance companies are considering denying coverage for IVF to women who smoke. 21.4% of IVF patients in this study had past or present exposure to cigarette smoking with no measurable effect on IVF outcome. It is possible that the aggressive controlled ovarian hyperstimulation employed with ART overcomes the negative effects of smoking on fertility, and that the relative paucity of vascular supply to primordial follicles may protect them from the detrimental effects of smoking. Smoking may have served as a surrogate marker for other, more significant lifestyle factors in previous retrospective studies reporting adverse effects of smoking on IVF outcome.

Prognostic Factors Affecting the Outcomes of Oocyte Donation Cycles

Oocyte donation cycle has been a useful model for the assessment of potential factors affecting human pregnancy, such as oocyte quality or uterine receptivity. The purpose of this study was to investigate the variable clinical factors affecting the outcomes of oocyte donation cycles. Retrospective analysis This study analyzed 109 cycles of 85 women who underwent oocyte donation in Seoul National University Hospital infertility clinic from March 1992 to February 2004. Variable clinical characteristics were compared between pregnant and non-pregnant groups. Clinical pregnancy rates were also compared according to the endometrial thickness and pattern. Clinical pregnancy was defined as the presence of fetal heart tone on first trimester transvaginal ultrasound exam. Cryopreserved oocyte donation cycles were excluded in the analysis. Data were evaluated by student’s t-test, oneway ANOVA, and Chi-square test. Clinical pregnancy rate was 38.5% per cycle and 48.2% per recipient. When pregnant and non-pregnant cycles were compared, there was a significant difference in donor age between cycles that resulted in pregnancy and those that did not. (30.2±3.6 vs. 32.1±4.3, p=0.017). On the other hand, there were no significant differences in mean age, BMI, gravidity of recipient, and peak estradiol level of donor. The number of oocytes retrieved, embryos transferred, fertilization rate, and cumulative embryo score were not different between pregnant and non-pregnant cycles. Among the various donor age groups, clinical pregnancy rate was significantly higher in <30years group than ≥35years group (50.0% vs. 18.2%, p=0.015). There was a tendency to increase of pregnancy rate with younger age of donor. The number of retrieved oocytes was also lower in ≥35years group (11.5±7.5 vs. 13.4±7.4 vs. 7.5±5.9, p=0.007). Up to 10 mm of cutoff, there was a higher pregnancy rate with thicker endometrium. But above 10mm, pregnancy rate was not related with endometrial thickness. There was no significant difference in the pregnancy rate between various endometrial patterns. The most reliable predictive factors of the outcome in oocyte donation cycles are the age of oocyte donor and the endometrial thickness of recipient. As the age of oocyte donor is younger, the pregnancy rate is higher. Up to 10 mm, endometrial thickness, but not endometrial pattern, is useful in predicting the outcome of oocyte donation cycle.

Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation

The p.N680S sequence variation of the follicle-stimulating hormone (FSH) receptor gene was previously shown to influence the ovarian response to FSH in normo-ovulatory women undergoing controlled ovarian hyperstimulation. In this prospective, randomized, controlled study, we tested whether the same daily dose of FSH results in lower levels of oestradiol in women homozygous for the p.N680S sequence variation, and whether the difference can be overcome by higher FSH doses. Women undergoing controlled ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection and homozygous for the wild-type or for the p.N680S FSH receptor were randomly assigned to group I (Ser/Ser, n=24), receiving an FSH dose of 150 U/day, or group II (Ser/Ser, n=25), receiving an FSH dose of 225 U/day. In group III (Asn/Asn, n=44), the FSH dose was 150 U/day. Age and basal FSH levels were not different between groups. At ovulation induction, total FSH doses were comparable in group I (1631+/-96 U) and group III (1640+/-57 U) but significantly higher in group II (2421+/-112 U) (P<0.001). Peak oestradiol levels on the day of human chorionic gonadotrophin (hCG) administration were significantly lower in group I (5680+/-675 pmol/l) compared to group III (8679+/-804 pmol/l) (P=0.028). Increasing the FSH dose from 150 to 225 U/day overcame the lower oestradiol response in women with Ser/Ser (group II, 7804+/-983 pmol/l). In women undergoing controlled ovarian hyperstimulation, the p.N680S sequence variation results in lower oestradiol levels following FSH stimulation. This lower FSH receptor sensitivity can be overcome by higher FSH doses.

The effect of multiple cycles in oocyte donors

The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.

Fertility Preservation in Breast Cancer Patients: A Prospective Controlled Comparison of Ovarian Stimulation With Tamoxifen and Letrozole for Embryo Cryopreservation

To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy. Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF. Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 +/- 0.3 v 6 +/- 1 and 7.8 +/- 0.9, respectively; P < .0001), mature oocytes (1.5 +/- 0.3 v 5.1 +/- 1.1 and 8.5 +/- 1.6, respectively; P < .001), and embryos (1.3 +/- 0.2 v 3.8 +/- 0.8 and 5.3 +/- 0.8, respectively; P < .001). Peak estradiol (E2) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 +/- 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage. The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E2 levels.

Estradiol and leptin as conditional prognostic IVF markers

We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/- 9.8 ng/ml) leptin levels were associated with a high number of 'good-quality' embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems.

Fertility preservation and pregnancy outcome after malignancy

The overall survival and cure rates of patients with childhood and adult malignancies have improved dramatically, but cancer treatment can be associated with diminished reproductive potential. However, research on the preservation of fertility in these patients has given patients new options. This article discusses the mechanisms of reproductive failure after cancer therapy and the currently available fertility preservation strategies. Ovarian transposition is still a viable option if radiotherapy is to be used alone. Modifications in assisted reproductive technology that decrease peak estradiol levels are ideal for breast cancer survivors. Embryo freezing technology offers excellent pregnancy rates. Oocyte freezing is available for women without a partner, but there is more limited experience with this technique. Understanding the concepts of graft function after the autotransplantation of frozen-thawed ovarian tissue has resulted in great strides in the technical requirements for success. Gonadotropin-releasing hormone analogues are the only available medical protection means for gonadotoxic chemotherapy. Assisted reproductive technology offers excellent results, but the protocols require a delay in implementing chemotherapy. Despite recent reports of embryo development after the transplantation of cryopreserved-thawed ovarian tissue, clinical experience is limited and the technique remains experimental.

A randomized prospective trial comparing alternate day GnRH agonist versus GnRH antagonist in IVF cycles

Gonadotrophin releasing hormone (GnRH) antagonists may have helped to overcome some disadvantages of GnRH agonists especially of long protocol, which is currently the standart protocol for ovarian stimulation. Aim of this study was to compare the effects of the modified long agonist protocol which called alternate day agonist protocol and multiple dose antagonist protocol on the IVF results. Prospective randomized study Total of 80 IVF patients who have normal day 3 FSH levels (<10IU/L), under 36 of age, first IVF cycle, no previous ovarian surgery, no history of endometriosis and polycystic ovarian disease were enrolled in the study. Patients were randomized in two groups: Group A (alternate day triptorelin protocol, 40 patients) and Group B (multiple dose cetrorelix protocol, 40 patients). Group A patients received a daily sc. injection of 100μg triptorelin for 7 days starting from day 21 of pre treatment cycle. After than dose was reduced to alternate fashion and continued until the day of the hCG administration. Group B patients received daily 0.25 mg cetrorelix started on day 6 of gonadotrophin stimulation and continued until the day of the hCG. Gonadotrophin stimulation was started on cycle day 3 in both groups. Variables which analyzed and compared were as follows: average age of patients, peak estradiol levels, total dose of gonadotrophins used, length of gonadotrophin stimulation, number of mature oocyte, number of transferred embryos, total agonist or antagonist dose and clinical pregnancy rate per embryo transfer. Independent samples t test and chi square analysis used to determine significance. Total 80 IVF cycles were analyzed and results were summarized in table I. Both protocols yielded similiar numbers of mature oocytes and transferable embriyos. Pregnancy rates were also similiar in both groups. Peak estradiol levels were statistically higher in group A. Length of gonadotrophin stimulation and total antagonist dose were statistically lower as compared to agonist group. Altough statistically was not different totally used gonadotrophin dose was tended to lower in group B. Although clinical pregnancy rates are similiar, GnRH antagonist protocol is patient friendly and cost effective as compared to alternate day GnRH agonist protocol.

Removal of Endometriomas Before in vitro Fertilization Does Not Improve Fertility Outcomes: A Matched, Case-Control Study

Debate continues about the effect of ovarian endometriomas on techniques of assisted reproduction. Possibly, an ovarian endometriotic cyst could impair oocyte quality and limit the response to ovarian hyperstimulation. Alternately, previous surgery may be the problem, not the endometriosis itself. This retrospective case-control study, conducted in connection with 2 academic in vitro fertilization (IVF) programs, examined outcomes in 189 women with endometriosis who underwent IVF with embryo transfer. Of these patients, 133 had previously undergone laparoscopic cystectomy for an ovarian endometrioma. The remaining 56 women proceeded directly to IVF. The diagnosis of endometrioma was confirmed histologically in all surgical cases. None of the participants had a known infertility factor other than endometriosis. The case and control women were similar with respect to age and ovarian reserve, and there were no significant differences in the duration of stimulation. There were, however, significant differences in the total dose of gonadotropins administered and peak estradiol levels on the day of giving human chorionic gonadotropin. These differences favored the women who went directly to controlled ovarian hyperstimulation. Comparable numbers of mature oocytes were obtained from women in the 2 groups. No significant group differences were found in fertilization rate, the number of embryos obtained per cycle, or the number of embryos transferred. Finally, rates of implantation, pregnancy, and miscarriage were similar in the 2 groups. Although laparoscopic cystectomy for ovarian endometriosis does not impair oocyte quality, it also does not offer superior fertility outcomes to asymptomatic women. Proceeding directly to controlled ovarian hyperstimulation in women who lack symptoms might reduce the time to pregnancy and lower patient costs as well as avoiding possible surgical complications. Symptomatic women may be told that conservative ovarian surgery does not lessen the chance of successful IVF.