Peak E2 Levels Research Articles

Annual variation in the reproductive hormone and behavior rhythm in a population of the Asian short-toed lark: Can spring temperature influence activation of the HPG axis of wild birds?

Although a number of studies have demonstrated a correlation between ambient temperature and the timing of reproductive behavior in many bird species, the relationships between temperature, activation of the hypothalamus–pituitary–gonad (HPG) axis, laying, and hatching in free-living birds, remain unclear. We investigated the relationships between spring temperature, reproductive hormones, and behavior, in a population of the Asian short-toed lark (Calandrella cheleensis) on the Inner Mongolian Grasslands in 2014, 2015 and 2016. LH and T levels peaked earliest in the year with the highest April temperature (2014) and latest in the year with the lowest April temperature (2016), and rose faster in 2014 than in 2015 or 2016. Laying and hatching occurred earliest in 2014 and latest in 2016. E2 also peaked earlier in 2014 than in the other two years but there was no significant difference in peak E2 levels among the three years. The peak of hatching only coincided with the peak in grasshopper nymph (the main food of nestlings) abundance in 2015 and the nestling fledging rate in 2015 was significantly higher than that in 2014 and 2016. We also conducted a controlled experiment on the effect of temperature on plasma LH, T and E2 levels in wild-caught larks, which shows that mean plasma LH, T and E2 levels in the 16°C group all peaked 4days earlier than in the 13°C group. All these results suggest that activation of HPG endocrine axis in the Asia short-toed lark population is closely related to ambient temperature, and that this subsequently influences the timing of laying and hatching. The HPG axis' endocrine function is a physiological factor that mediates effects of ambient temperature on the timing of breeding. Temperature induced annual variation in the timing of hatching was, however, insufficient to synchronize the nestling period with the annual peak in grasshopper nymph abundance. Unusually warm, or cold, spring temperatures advanced, or delayed, grasshopper nymph development to an extent that exceeded the Asian short-toed lark's capacity to advance or delay the onset of breeding and reproductive success was lower in the two years of the study in which the nestling period was asynchronous with the peak of grasshopper nymph abundance. Long-term research on the relationship between the timing of reproduction and population demographics of the Asian short-toed lark is required to understand the effects of climate change on this species and on temperate birds in general.

Are there any differences between antagonist administration on days

BackgroundThe aim of this study was to investigate the cost-effectiveness of antagonist administration on stimulation on days <6 and ≥6 of COH on assisted reproductive technique (ART) outcomes. MethodsIn this retrospective cohort study, 412 patients who were admitted to the ART Department were evaluated. In group 1 (203 patients), antagonist administration was provided on days <6 of COH. For group 2 (209 patients), antagonist administration was provided on days ≥6 of COH. We preferred a flexible antagonist protocol in clinical practice and added an antagonist treatment regimen when dominant follicles were enlarged to 13 mm or the serum blood E2 was >300 pg/mL. ResultsThere were no differences between antagonist administration on days <6 and days ≥6 of COH in terms of age, BMI, duration and etiology of infertility, AFC, serum FSH, LH, peak E2 levels, the number of MII oocytes, 2PN, FR, the number of transferred embryos, and CPR per woman. However, there were statistically significant differences between the duration of stimulation, the total gonadotropin dose required, and progesterone levels on day hCG [8.26 ± 1.83 vs 9.56 ± 1.51 (p = 0.001); 2173.71 ± 860.00 vs 2749.17 ± 1079.51 (p = 0.001); 0.75 ± 0.44 vs 0.92 ± 0.59 (p = 0.002), respectively]. ConclusionOur results have demonstrated that there was no effect of antagonist administration on days <6 and ≥6 of COH on ART outcomes. However, taking cost-effectiveness into consideration, we suggest an antagonist administration on days <6 of COH since the necessary gonadotropin dose is lower.

Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial

BackgroundChemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. Methods/designRandomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18–43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. DiscussionConcerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis.Trial Registration: NTR4108.

Peak Serum Estradiol Level During Controlled Ovarian Stimulation Is not Associated with Lower Levels of Pregnancy-Associated Plasma Protein-A or Small for Gestational Age Infants: A Cohort Study

ObjectiveDuring controlled ovarian stimulation in IVF, supraphysiologic levels of estradiol (E2) have been associated with poor placentation and adverse pregnancy outcomes. This study aimed to investigate whether high peak E2 on the day of human chorionic gonadotropin trigger is associated with low pregnancy-associated plasma protein-A (PAPP-A) and adverse perinatal outcomes. MethodsWe performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. We enrolled 216 patients with a singleton pregnancy after fresh embryo transfer who also underwent first trimester screening. Adverse perinatal outcomes were collected from a local registry and included preterm birth, hypertension in pregnancy, antepartum hemorrhage, intrauterine growth restriction, SGA, stillbirth, admission to the NICU, and neonatal death. ResultsHigh serum E2 (≥13 035 pmol/L) at controlled ovarian stimulation was not correlated with low PAPP-A (<0.4 multiples of the median) at first trimester screening (P = 0.46). When each adverse outcome was analysed separately, there was no association between high E2 and any of the outcomes (P > 0.05 for all). High peak E2 was not associated with a total composite of maternal and neonatal adverse birth outcomes (P = 0.30). ConclusionOur results do not support the theory that high E2 at fresh embryo transfer impedes placentation. We found no association between peak E2 and low PAPP-A levels or adverse pregnancy outcomes.

Predicting the outcome of different protocols of invitro fertilization with anti-Muüllerian hormone levels in patients with polycystic ovary syndrome.

ObjectiveThis study evaluated associations of basal serum and follicular fluid (FF) anti-Muüllerian hormone (AMH) levels with in vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients.MethodsThis prospective study included 179 consecutive women undergoing IVF, including 59 with PCOS and non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF outcomes were assessed.ResultsMedian serum and FF AMH levels, antral follicle count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and retrieved oocyte numbers were higher in PCOS patients than in controls (all P < 0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS patients than in controls (P < 0.01), but both groups had similar fertilization, implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH-ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels were correlated with AFC in PCOS patients (P < 0.01). Peak E2 and FF AMH levels were independent predictors of oocyte number. Peak E2 predicted the fertilization rate.ConclusionSerum basal AMH levels are predictive of oocyte quantity, but not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar among protocols.

Impact of the number of retrieved oocytes on pregnancy outcome in in vitro fertilization

ObjectiveTo evaluate the impact of the number of retrieved oocytes on pregnancy outcome. Materials and MethodsWe retrospectively examined the cycles of 2491 women undergoing in vitro fertilization therapy at Taipei Medical University (Taipei, Taiwan) from August 1995 to March 2009. We divided them into three groups based on their response rate (where H = high, M = middle, and L = low). We conducted this study to evaluate and compare pregnancy outcome in these three groups. ResultsThe total number of retrieved oocytes had a significantly positive correlation with peak E2 levels, and the number of fertilized oocytes, good quality embryos, and available frozen embryos. The number of retrieved oocytes had a positive correlation with pregnancy rates and a negative correlation with fertilization rates. The implantation and abortion rates among the three groups were essentially the same. Compared to the middle and higher responders, the pregnancy rates for lower responders were significantly lower. The pregnancy rates for middle responders and higher responders were not significantly different. ConclusionThe benefits of more retrieved oocytes between the lower and the middle responders were obvious. However, the benefits and risks for retrieving more oocytes for the middle and the higher responders remained controversial.

Hyperestrogenic milieu during fresh in vitro fertilization cycles and low birth weight: does a supraphysiologic threshold exist?

Recent studies have suggested a detrimental effect of the hyperestrogenic milieu during ovarian stimulation on perinatal outcomes. To this effect, we investigate the existence of a supraphysiologic estradiol (E2) threshold for the pathogenesis of adverse perinatal outcomes. Retrospective cohort study. All patients <40 years undergoing fresh IVF-embryo transfer (ET) at our center between 2004 and 2013 resulting in live singleton births were included. Patients with vanishing twins or multiple gestations were excluded. Demographics and ovarian stimulation parameters of the study cohort were recorded. Perinatal outcomes analyzed included LBW (<2500 grams), very LBW (<1500 grams), early PTB (<34 weeks), and late PTB (>34 to <37 weeks). LBW was further classified as term LBW or term very LBW. Rates of the aforementioned perinatal outcomes were plotted against peak E2 levels, in increments of 500 pg/mL (<500 to >4000 pg/mL). Odds ratios (OR) for perinatal outcomes at various peak E2 levels were calculated by using the median E2 level of study cohort as the referent group. A receiving-operator-characteristic (ROC) curve was constructed to identify a E2 threshold, with a corresponding area-under-the-curve (AUC) calculation. A total of 4071 patients with live singleton births were included. The median age, peak E2 level and birth weight for the study cohort was 36 (33-39) years, 1554 (1112.7-2179) pg/mL, and 3289 (2920-3628) grams, respectively. The overall rate of LBW was 209/4071 (5.14%) and PTB was 378/4071 (9.29%). Although there was no difference in the odds of PTB across all E2 quartiles, the odds of LBW were higher in the top E2 quartile compared to the median E2, suggesting an E2-dependent effect. Upon analyzing the LBW group as term LBW or term very LBW, the odds of term LBW with E2 levels >2500 pg/mL were 6.11-7.89 times higher compared to the median E2. In contrast, the odds of term very LBW remained unchanged across all E2 quartiles. The ROC curve indicated an E2 level of 2900 pg/mL as the threshold beyond which statistically significant odds of term LBW was observed (AUC=0.83). Using term LBW as a surrogate, our results suggest that an E2 level >2900 pg/mL may serve as a supraphysiologic threshold for adverse perinatal outcomes in fresh IVF-ET cycles. These results emphasize the importance of utilizing conservative step-down stimulation protocols and careful monitoring of serum E2 to minimize the supraphysiologic elevations of E2 levels in fresh IVF-ET cycles, and thereby circumvent adverse perinatal outcomes.Tabled 1Odds of Term LBW According to Various E2 Cut-offsComparisonOdds Ratio (95% CI)PE2 1501-2000 vs. E2 1554 pg/mL1.74 (0.24-2.8)0.58E2 2001-2500 vs. E2 1554 pg/mL3.37 (0.55-4.8)0.17E2 2501-3000 vs. E2 1554 pg/mL6.11 (1.8-7.33)0.02E2 3001-3500 vs. E2 1554 pg/mL7.35 (1.33-9.42)0.001E2 3501-4000 vs. E2 1554 pg/mL7.28 (1.32-9.03)<0.001E2>4000 vs. E2 1554 pg/mL7.89 (1.44-9.43)<0.001 Open table in a new tab

Revisiting oolemma characteristics during ICSI in relation to fertilization patterns and embryo development and implantation

The oolemma response during ICSI has been linked to membrane and cytoplasmic maturity. The former is evidenced by the depth of the funnel and can manifest in the unextrusion of the second polar body and oocyte lysis, while the latter in absent fertilization. We investigate the occurrence of normal and abnormal fertilization patterns, as well as oocyte survival in relation to ovarian stimulation and eventual reproductive outcomes. In couples with an adequate cohort of mature oocytes and varying degrees of fertilization, we measured the occurrence of immature membrane and ooplasm (as evident by oocyte lysis), impaired cytoplasmic maturity (as evident by no fertilization), lower membrane maturity (as evident by 3PN embryos) and complete membrane and cytoplasmic maturity (2PN). Only ICSI cycles with >5 oocytes at MII stage were included. Unextrusion of the second polar body, characterized by digynic 3PN, is associated with sudden breakage of the membrane, short funnel, and indicates ooplasmic maturity but membrane dysmaturity. Oocyte lysis is characterized by absence of funnel development and therefore severe membrane dysmaturity. Absent fertilization presented with adequate funnel development up to the center of the oocyte therefore allowing oocyte survival, but unfortunately with ooplasmic immaturity. ICSI cycles were stratified by fertilization rates, in increments of 20%. The rates of 3-PN embryos and oocyte lysis were plotted against increasing fertilization rates. Demographics and ovarian stimulation parameters were compared across fertilization groups. 11911 ICSI cycles were identified. The rate of digynic 3PN embryos decreased with increasing fertilization rate [7.19% (<20%) to 1.10% (81-100%)]. Similar trends in the rate of oocyte lysis were observed as well. There was no difference in the median age of patients (36), number of oocytes (9), or total stimulation days (10) across different fertilization groups. Patients with oocyte lysis had a progressively lower dose of gonadotropins (P=0.007) and peak E2 levels (P<0.001) in comparison to those that had no fertilization, digynic 3PN embryos, and both membrane and cytoplasmic maturity (all 2PN). To assess the impact of oolemma/ooplasmic maturity within the cohort of oocyte injected on the embryo developmental outcome, we compared patients with oocyte lysis to those who had normal fertilization (n=384). Lower implantation (16.7% vs. 32.4%; P<0.001) and clinical pregnancy rates (7.01% vs. 34.6%; P<0.001) were noted in the former group compared to the latter. During ICSI, membrane funnel characteristics may provide insight into oolemma maturity. Oocyte survival, absent/abnormal fertilization provides invaluable information about ooplasmic maturity and embryo developmental competence. Our study highlights the potential link between oolemma behavior, absent/abnormal fertilization and ovarian stimulation.

Does salpingectomy have a deleterious impact on ovarian response in in vitro fertilization cycles?

To investigate the impact of salpingectomy in patients with IVF treatment on ovarian response. Meta-analysis. Not applicable. Patients under treatment for infertility, during the cycles before and after treatment by salpingectomy for hydrosalpinx or ectopic pregnancy. PubMed, MEDLINE, EMBASE databases, and CENTRAL in Cochrane Library up to July 2015. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. The subgroup analysis was planned a priori before data were collected and analyzed. The amount of gonadotropin administered, the peak E2 level, the number of oocytes retrieved, and the number of pregnancies. After the final screening, 12 of the studies were retrospective and six were prospective. In this meta-analysis, 1,482 patients were enrolled, including a total of 657 patients with salpingectomy and 825 without salpingectomy. The comparisons before and after salpingectomy of the peak E2 level (standardized mean difference [SMD] = -0.182; 95% confidence interval [CI], -0.166, 0.101; I2, 85.45%), the total gonadotropin dose used for stimulation (SMD = 0.127; 95% CI, -0.054 0.308; I2, 84.49%), and number of oocytes retrieved (SMD = -0.060; 95% CI, -0.189, 0.070; I2, 63.93%) did not reveal any significant differences. The number of pregnancies before and after salpingectomy did not differ significantly (odds ratio [OR] = 1.180; 95% CI, 0.854, 1.630; I2, 34.01%). Salpingectomy in infertile patients does not have any negative effect on their subsequent fertility treatment, but further studies should be performed before this result can be considered definitive.

Effect of Coasting on Success of In-Vitro Fertilization Cycles

Introduction: “Coasting” is a method used in prevention of Ovarian Hyperstimulation Syndrome (OHSS) during In Vitro Fertilization (IVF) cycles. Coasting refers to witholding exogenous gonodotropine usage and delaying the administration of hCG in high risk cycles until serum estradiol levels falls into an acceptable range. The aim of our study is to evaluate coasting effect on IVF oucomes in patients with E2 levels of 4000-5000 pikogram. Metod: This study was a single centered, retrospective and a case-control study. Study population were selected from women applied Zeynep Kamil Research Hospital IVF department between January 2003 and December 2013(n= 7850). Patients taking GnRH aganist or antagonist protocol, having BMI between 23-28 kg/m2, having E2 levels between 4000-5000 pikogram and age ≤43 were included in the study. Patients were divided in 2 groups as conrol group (Group 1, n=48) and coasted group (Group 2, n=34) according to whether or not coasting performed. Peak E2 levels before coasting, follicle count before oocyte pick up, collected M2 oocyte count, fertilized oocyte count, OHSS incidince and pregnancy incidence were compared between groups.Statistical analysis was performed using Student’s t test for continuous variables and chi-square test for categorical variables. Results: While most of patients in group 2 needed less than 2 days of coasting, only two patient needed 4 days of coasting. E2 levels on the day of hCG in group 2 were significiantly lower than group 1 (4332.6±256.6 and 3180.8±702.9; p

Correlation of serum estradiol level on the day of ovulation trigger with the reproductive outcome of intracytoplasmic sperm injection.

BACKGROUND:Serum estradiol (E2) levels are measured in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), to assess the ovarian response and to predict ovarian hyperstimulation syndrome. The impact of peak E2 levels on IVF-ICSI outcome was found to be inconsistent in the previous studies.AIM:To evaluate the impact of the serum E2 levels on the day of ovulation trigger with the reproductive outcome of ICSI.SETTINGS AND DESIGN:Retrospective observational study. ART Center, at a Tertiary Care University Teaching Hospital.SUBJECTS AND METHODS:Eighty-nine infertile women, who underwent ICSI with fresh embryo transfer over a period of 3 years, were included in the study. The study subjects were grouped based on the serum E2 level on the day of ovulation trigger:- Group I - <1000 pg/ml, Group II - 1000–2000 pg/ml, Group III – 2000.1-3000 pg/ml, Group IV – 3000.1–4000 pg/ml, and Group V >4000 pg/ml. The baseline characteristics and controlled ovarian hyperstimulation (COH) outcome were compared among the study groups.STATISTICAL ANALYSIS USED:Chi-square test, Student's t-test, ANOVA, and logistic regression analysis.RESULTS:The study groups were comparable with regard to age, body mass index, ovarian reserve. Group V had significantly higher number of oocytes retrieved than I and II (18.90 vs. 11.36 and 11.33; P = 0.009). Group IV showed significantly higher fertilization rate than I, III, and V; (92.23 vs. 77.43, 75.52, 75.73; P = 0.028). There were no significant differences in the implantation rates (P = 0.368) and pregnancy rates (P = 0.368).CONCLUSION:Higher E2 levels on the day of ovulation trigger would predict increased oocyte yield after COH. E2 levels in the range of 3000–4000 pg/ml would probably predict increased fertilization and pregnancies in ICSI cycles.

Maximum basal FSH predicts reproductive outcome better than cycle-specific basal FSH levels: waiting for a "better" month conveys limited retrieval benefits.

BackgroundElevated follicle stimulating hormone (FSH) is associated with poor vaginal oocyte retrieval (VOR) outcomes and cycle cancellations but intercycle variability in basal FSH reportedly does not predict ovarian response.MethodsWe conducted a retrospective cohort study of basal FSH (n = 15573 cycles) in couples (n = 9132) who initiated IVF cycle(s) with basal estradiol (E2) <100 pg/mL between 2002 and 2014 to reevaluate this hypothesis.The most recent (current) FSH, maximum FSH (Max FSH) and prior cycle maximum basal FSH (PMax FSH) were computed for each cycle. Metaphase II (MII) oocyte counts were modeled by age, stimulation type, prior peak E2 level, prior MII count, Max FSH, PMax FSH and current FSH. Antral follicle counts, pregnancy, clinical pregnancy and live birth rates were modeled as secondary outcomes.ResultsMax FSH level distinguished completed cycles from cancelled cycles better than PMax FSH or current FSH (AUC of 0.72, 0.71 and 0.61, respectively, p < 0.001). Fewer MIIs were retrieved (5.7 ± 3.8) in cycles with Max FSH >13 mIU/mL (n = 1475) than those with ≤13 mIU/mL (n = 11978) (11.6 ± 7.1) (p < 0.001). Max FSH was a better predictor of MII count than PMax FSH or current FSH after controlling for age, stimulation type, prior peak E2 level and prior MII count.Additional MIIs were retrieved on average in cycles with PMax FSH >13 mIU/mL (n = 1930) whose current FSH was ≤13 mIU/ml rather than >13 mIU/ml (p < 0.01) after controlling for age, cycle number and stimulation type. However, no improvement in pregnancy or live birth rate was detected.ConclusionsMax FSH is the best FSH-based predictor of ovarian reserve. Retrieval benefits from waiting for a "better" month appear to exist but are limited.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0078-0) contains supplementary material, which is available to authorized users.

Cryopreserved embryo transfer is an independent risk factor for placenta accreta

To explore the association between cryopreserved embryo transfer (CET) and risk of placenta accreta among patients utilizing invitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). Case-control study. Academic medical center. All patients using IVF and/or ICSI, with autologous or donor oocytes, undergoing fresh or cryopreserved transfer, who delivered a live-born fetus at ≥24weeks of gestation at our center, from 2005 to 2011 (n = 1,571), were reviewed for placenta accreta at delivery. Cases of accreta (n = 50) were matched by age and prior cesarean section to controls (1:3) without accreta. The association between CET and accreta was modeled using conditional logistic regression, controlling a priori for age and placenta previa. Receiver operating characteristic curves were used to determine thresholds of endometrial thickness and peak serum E2 levels related to accreta. Placenta accreta. Univariate predictors of accreta were non-Caucasian race (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.25-6.47); uterine factor infertility (OR 5.80, 95% CI 2.49-13.50); prior abdominal or laparoscopic myomectomy (OR 7.24, 95% CI 1.92-27.28); and persistent or resolved placenta previa (OR 4.25, 95% CI 1.94-9.33). In multivariate analysis, we observed a significant association between CET and accreta (adjusted OR 3.20, 95% CI 1.14-9.02), which remained when analyses were restricted to cases of accreta with morbid complications (adjusted OR 3.87, 95% CI 1.08-13.81). Endometrial thickness and peak serum E2 level were each significantly lower in CET cycles and those with accreta. Cryopreserved ET is a strong independent risk factor for accreta among patients using IVF and/or ICSI. A threshold endometrial thickness and a "safety window" of optimal peak E2 level are proposed for external validation.

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles.

To investigate the impact of elevated serum estradiol (E2) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E2 levels on day of hCG trigger above or below the 95 % cutoff for E2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02-5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22-3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11-5.64; P = .023). Peak E2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile(49)Ser) and Anti-Müllerian hormone type II receptor (AMHRII -482 A>G) as genetic markers in assisted reproduction technology.

The aim of the study was to evaluate whether the presence Antimullerian hormone (AMH) and Antimullerian hormone type II receptor (AMHRII) single nucleotide polymorphisms (SNPs) Ile(49)Ser and -482A>G respectively are related to the assisted reproduction outcome. A prospective cross-sectional observational study was conducted in order to assess the distribution of AMH and AMHRII SNPs in two cohorts, one of healthy women (N = 100) and the control group and the IVF/ICSI group (N = 151) consisted of women undergoing IVF/ICSI treatment for infertility. Furthermore, a prospective longitudinal observational study was performed on the latter group to assess possible associations of these SNPs with patients' characteristics and controlled ovarian stimulation (COS) and pregnancy outcome. Among non-carriers of the AMH (Ile(49)Ser) polymorphism, basal FSH levels were lower in those with more than two of previous IVF attempts and fertilization rate wasstatistically higher in those with peak serum E2 levels below 1500pg/ml, whereas among non-carriers of the AMHRII (-482 A>G) polymorphism, number of follicles was higher in those with more than two previous IVF attempts and total dose of gonadotropins was lower in those with peak serum E2 levels above 1500pg/ml. There was evidence that in specific subgroups of women undergoing IVF/ICSI, AMH and AMHRII SNPs may be related to patients' characteristics and controlled ovarian stimulation and pregnancy outcome and thus may provide a means for the prediction of ovarian response in specific subgroups of women entering an IVF/ICSI program.

Letrozole as an adjunct in GnRH antagonist cycles improves IVF outcome in poor responders

Letrozole as an adjunct in GnRH antagonist cycles improves IVF outcome in poor responders

Tamoxifen co-administration during controlled ovarian hyperstimulation for in vitro fertilization in breast cancer patients increases the safety of fertility-preservation treatment strategies

To evaluate the safety and efficacy of tamoxifen co-administration during conventional controlled ovarian hyperstimulation (COH) protocols for a fertility-preservation IVF cycle in breast cancer patients. Two groups: retrospective descriptive cohort study and prospective study. Breast cancer oncology and fertility-preservation centers in a tertiary hospital. Two groups of breast cancer patients: premenopausal patients treated with adjuvant tamoxifen; and patients undergoing invitro fertilization (IVF) for fertility preservation. Fertility-preservation cycles, tamoxifen co-administration during conventional IVF. Endocrine records, and IVF results. Estradiol (E2) levels were chronically high (mean 2663 pmol/L, maximum: 10,000 pmol/L) in 38 of 46 breast cancer patients treated with adjuvant tamoxifen. Co-administration of tamoxifen (48 cycles) during conventional IVF or without tamoxifen (26 cycles), using either the long gonadotropin-releasing hormone-agonist or-antagonist protocols, resulted, respectively, in a mean of 12.65 and 10.2 oocytes retrieved, and 8.5 and 6.4 embryos cryopreserved. Average peak E2 levels were 6,924 pmol/L and 5,093 pmol/L, respectively, but long-term recurrence risk (up to 10years) was not increased. In breast cancer patients, co-administration of tamoxifen during conventional COH for fertility preservation does not interfere with IVF results. The high serum E2 levels during COH should be considered safe, as it simulates the high prevalence of persistently high serum E2 levels in premenopausal breast cancer patients safely treated with adjuvant tamoxifen.

Comparison between two protocols for thawed embryo transfer: natural cycle versus exogenous hormone replacement

Introduction: There are two most popular protocols for Frozen Embryo Transfer: the natural and the E2&P4 replacement cycles. There is still a controversy whether one is superior over the other.Purpose: To compare the outcome in patient groups undergoing FET following these protocols.Methods: About 1235 FET cycles were retrospectively analyzed during a period of 12 years. In 798 cycles (group A), the natural cycle protocol was used, and in 437 cycles (group B), the exogenous E2&P4 administration protocol was used.Results: The average patient age was 32.11 ± 0.27 years in group A and 32.94 ± 0.19 years in group B (p < 0.05). The endometrial thickness was 9.54 ± 0.11 mm and 8.95 ± 0.13 mm in groups A and B, respectively (p < 0.001). The peak serum E2 level was 162.51 ± 8.97 pg/mL and 250.78 ± 33.67 pg/mL in groups A and B, respectively (p < 0.001). The implantation, clinical pregnancy, and ongoing pregnancy rates in groups A and B were 6.47%, 12.91%, and 10.4% versus 4.26%, 8.47%, and 5.95%, respectively (p < 0.05).Conclusions: Natural endometrial preparation yields better outcome in compare with exogenous E2&P4 in FET cycles with higher endometrial thickness, implantation, and clinical pregnancy rates.

Mini-dose long gonadotropin-releasing hormone (GnRH) agonist versus agonist flare stimulation protocol for in vitro fertilization poor responders

Abstract Objectives To compare 2 stimulation protocols, mini-dose long gonadotropin releasing hormone (GnRH) agonist versus agonist flare for in vitro fertilization poor responders. Design Prospective comparative nonrandomized clinical trial. Setting Dr. Samir Abasss IVF center, Jeddah, Kingdom of Saudi Arabia from april 2012 to December 2012 on 50 women undergoing IVF/ICSI fulfilling the criteria of poor responders. Material and methods Patients were allocated into 2 groups, group 1 ( n = 25) received mini-dose long agonist and group 2 ( n = 25) received agonist flare protocol. Main outcome Number of oocytes retrieved (primary outcome), duration of stimulation (days), peak E2 level on the day of hCG injection, number of fertilized oocytes, number of transferred embryos and pregnancy rate/cycle. Results Both groups were comparable regarding age, body mass index and duration of infertility (years). The difference in basal FSH and duration of stimulation (days) does not reach statistical significance ( p value 0.833 and 0.373 respectively). There was a high statistical difference between both groups regarding peak E2 on day of hCG injection, number of oocytes retrieved, number of fertilized oocytes, number of transferred embryos; which is higher in the mini-dose agonist group ( p value 0.00). Pregnancy rate/cycle was higher in the mini-dose agonist group (9/25 vs. 6/25) however this difference does not reach statistical significance ( p value 0.355) which may be attributed to small sample size or advanced maternal age. Conclusion Mini-dose long GnRHa stimulation protocol appears to be more beneficial for poor responders than GnRHa agonist flare.

GnRH agonist (GnRHa) priming increases the number of in vitro matured (IVM) oocytes available for cryopreservation in cancer patients seeking urgent fertility preservation (FP)

E2 and follicular size and may complicate clinical decision making. This study seeks to determine whether continuous AI use throughout stimulation impacts oocyte maturity and function. DESIGN: Retrospective. MATERIALS AND METHODS: FP patients with breast cancer treated with an AI (letrozole) were compared to FP patients with other malignancies not using AIs. The AI group had oocyte maturation induced when leading follicles reached 20mm as suggested by Oktay et al, compared with the standard of 18mm. Endocrine levels, oocyte maturity (MII/retrieved oocytes), MII yield (MII/follicles R14mm) and fertilization rates were compared. RESULTS: 24 AI patients were compared with 22 controls. The age, AMH, and antral follicle counts were equivalent. In contrast to prior reports, total gonadotropin usage was similar. The AI group had lower peak E2 levels (536 vs 1972 pg/mL; P 400 pg/mL). The AI group had higher peak P levels (1.1 vs 0.7 ng/mL; P<0.01) and a trend toward a higher risk of premature P rise R1.5 ng/mL (29% vs 5%; P1⁄40.06). Despite larger follicles, the AI group had a lower maturity rate (68% vs 80%; P<0.001). The MII yield was lower in the AI group (P1⁄40.04). Among those who underwent ICSI (15 AI, 14 noAI), the fertilization rate was lower in the AI group (76% vs 84%; P1⁄40.03). CONCLUSION: Despite efforts to prevent supraphysiologicE2 inbreast cancer FP cycles, most AI stimulations result in elevated E2 levels. Although the impact of elevated P on oocyte quality in FP cycles is not established, it may reflect an altered intrafollicular endocrine milieu and post-maturity. Caution shouldbe exercisedwhenchangingdecisionmaking inFPpatients receivingAIs.