Significant Predictors Of Clinical Pregnancy Research Articles

Associations of post-warming embryo or blastocyst development with clinical pregnancy in vitrified embryo or blastocyst transfer cycles.

Objective To investigate whether the degree of post-warming embryo or blastocyst development is associated with clinical pregnancy in vitrified embryo or blastocyst transfer cycles.Methods Ninety-six vitrified cleavage-stage embryos and 58 vitrified blastocyst transfer cycles were selected. All transfer cycles were performed from February 2011 to March 2019, and all vitrified embryos or blastocysts were warmed from 4 PM to 6 PM and then transferred the next morning from 9 AM to 10 AM. The scores of the cleavage-stage embryos and blastocysts were assessed at warming and at transfer using the modified Steer method and the Gardner method, respectively. The mean embryo or blastocyst score, score of the single top-quality embryo or blastocyst, and the difference in the score between warming and transfer were compared between nonpregnant and pregnant women.Results In the cleavage-stage embryo transfer cycles, both the top-quality embryo score at transfer and the difference in the score between warming and transfer were significantly associated with clinical pregnancy. A top-quality embryo score at transfer of ≥60.0 (area under the curve [AUC], 0.673; 95% confidence interval [CI], 0.531–0.815) and a difference in the score between warming and transfer of ≥23.0 (AUC, 0.675; 95% CI, 0.514–0.835) were significant predictors of clinical pregnancy. In blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor associated with clinical pregnancy. A top-quality blastocyst score at transfer of ≥38.3 was a significant predictor of clinical pregnancy (AUC, 0.666; 95% CI, 0.525–0.807).Conclusion The top-quality embryo score at transfer and the degree of post-warming embryo development were associated with clinical pregnancy in vitrified cleavage-stage embryo transfer cycles. In vitrified blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor affecting clinical pregnancy.

Predictive factors influencing pregnancy rate in frozen embryo transfer.

PurposeTo evaluate the outcomes of embryo transfer (ET) and to identify the parameters influencing pregnancy outcomes.MethodsThis study included 938 ET cycles involving single frozen and thawed good‐quality blastocyst (Gardner grade ≥3BB) between August 2017 and January 2018. The significance of several parameters including endometrial thickness, position of the transferred air bubble, self‐evaluation score by physicians, and uterus direction at ET as predictors of clinical pregnancy was evaluated using univariate and multivariate analyses.ResultsAmong 938 ET cycles, 462 (49.3%) resulted in a clinical pregnancy. Endometrial thickness was positively associated with clinical pregnancy in a linear trend. Between the variable position of the transferred air bubble and clinical pregnancy rate showed a curvilinear relationship. Clinical pregnancy rate was higher in cases with good self‐evaluation score, whereas there was no difference between groups with different uterus directions. Univariate analysis of predictive parameters identified endometrial thickness, self‐evaluation score by physicians, and position of air bubbles as significant predictors of clinical pregnancy, of which endometrial thickness and position of air bubbles appeared to be independently related to clinical pregnancy.ConclusionEndometrial thickness and the position of transferred air bubbles influenced clinical pregnancy in ET cycles.

Serum Albumin Level Adjusted Progesterone Level on the Trigger Day is Not a Significant Predictor of Clinical Pregnancy

Objective: We aimed to assess the effect of serum albumin level adjusted progesterone levels on the trigger day on clinical pregnancy rate in ICSI cycles.Study Design: A total of 100 women undergoing ICSI cycles due to poor ovarian reserve or tubal factor infertility were included in this study. Serum progesterone and albumin levels on the trigger day were utilized to predict clinical pregnancy among normal and poor responders.Results: There were significant differences between groups with and without successful clinical pregnancy in terms of serum albumin (4.6 vs. 4.3 g/dl), progesterone levels (0.5 ng/mL vs. 0.7 ng/mL) on the trigger day and endometrial thickness (11.5 mm vs. 9.3 mm) (p<0.05, p<0.05 and p<0.05, respectively). In ROC analyses, progesterone level on the trigger day was found to be a significant predictor of clinical pregnancy (AUC=0.652, p=0.015). An optimal cut-off value of 0.55 ng/mL was obtained with 65% sensitivity and 57% specificity. Albumin level adjusted progesterone concentrations on the trigger day were 0.67 ng/mL versus 0.64 ng/mL, but this difference was not statistically significant (p>0.05). Conclusion: Albumin adjusted progesterone concentrations may be utilized to determine cases for a freeze-all policy.

The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles

ABSTRACTOur objective was to assess the role of laparoscopic removal of ovarian endometriomas and ablation of peritoneal endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) - Embryo Transfer cycles by comparing with the results of patients with untreated endometriomas and tubal factor without underlying endometriosis confirmed by laparoscopy. For this purpose, between 2002 and 2015, outcomes of 257 ICSI cycles of 150 patients, including 91 cycles of 48 patients in minimal endometriosis, 57 cycles of 25 patients in endometrioma removal, 65 cycles of 53 patients in non-operated endometrioma, and 44 cycles of 24 patients in tubal factor groups were retrospectively analyzed. Basal ovarian reserve was significantly lower, mean starting and total gonadotropin consumption was significantly higher, and mean serum E2 on the day of hCG injection, number of dominant follicles, number of retrieved total, and MII oocytes were all significantly lower in the endometrioma cystectomy group. Fertilization and embryo cleavage rates were also significantly the lowest in the endometrioma cystectomy group, whereas clinical pregnancy and live birth rates were comparable among all groups. The number of transferred embryos and duration of infertility were the most significant predictors of clinical pregnancy and live birth. Basal antral follicle count was also significant in predicting live birth.

Comparison of pregnancy outcomes between obese and non-obese polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) cycles

PCOS is commonly associated with metabolic abnormalities and obesity. Obesity has been shown to have adverse effects on both assisted reproductive technology (ART) cycles and pregnancy outcomes. The primary objective of this study was to determine whether there was a difference in reproductive outcomes between obese and non-obese PCOS patients undergoing IVF. A secondary objective was to determine demographic and clinical factors that may predict clinical pregnancy among women with PCOS. Historical cohort study in an academic setting. Women (n=79) meeting the Rotterdam PCOS criteria and undergoing IVF from 2007 to 2016 were included in the study. Data collected included baseline demographics, clinical parameters, and treatment outcomes. Obesity was defined as BMI>=30kg/m2. Clinical pregnancy was defined as the presence of fetal heart beat on ultrasound. Bivariate analysis was done using Student’s t, Pearson’s chi-squared, and Wilcoxon rank sum tests as appropriate. Logistic regression and generalized estimating equations (GEE) were performed to control for confounding variables and to account for multiple cycles from the same patients. A total of 108 IVF cycles (obese group n=63 and non-obese group n=45) were included in the analysis. Baseline demographics and clinical parameters were similar when examining pregnant versus non-pregnant women except for age (32.3 vs. 35 years old, p=0.007), baseline antral follicle count (AFC) (24.1 vs. 17.7, p=0.003), and progesterone level on day of trigger (0.6 vs. 0.8 ng/mL, p=0.06). The obese group had lower serum peak estradiol level (1898 vs. 2623 pg/mL, p=0.001), required more total gonadotropins (2907 vs. 2187 units, p<0.001), and needed a longer stimulation course (11.7 vs. 10.6 days, p=0.02) compared to the non-obese group. After adjusting for confounding variables, the pregnancy rates were similar in the obese (37.5%) compared to the non-obese group (41.7%) (p=0.7). After adjusting for age and serum progesterone level on day of trigger, AFC was the only significant predictor of clinical pregnancy (OR 2.1, 95% CI 1.1-4.1; p=0.02). Obesity does not affect clinical pregnancy rates in PCOS patients undergoing IVF. On the other hand, AFC seems to be associated with clinical pregnancy in PCOS patients. Further investigation is needed to determine if AFC is an accurate predictor of clinical pregnancy in women with PCOS.

Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial

To determine if the addition of continuous morphokinetic data improves reproductive outcomes when all embryos are cultured in a closed system. Prospective, randomized, controlled study. Single academic center. A total of 235 patients undergoing fresh autologous IVF cycles with at least four embryos, cultured in the Embryoscope: 116 patients randomized to conventional once-daily morphologic embryo screening (CS) and 119 to additional time-lapse kinetic monitoring (TLM) for selection. TLM versus CS. Intrauterine clinical pregnancy (CPR) and implantation (IR) rates. CPR and IR were similar overall (TLM vs. CS, respectively: CPR 68% vs. 63%; IR 51% vs. 45%) and with blastocyst transfers (CPR 74% vs. 67%; IR 56% vs. 51%). CPR with day 5 transfer was threefold higher than day 3 transfer, but group (TLM vs. CS) was not a significant predictor of clinical pregnancy or implantation. Significantly more multinucleation was detected when CS embryos were retrospectively reviewed with the use of TLM (7.0% vs. 35.3%), and multinucleation was independently associated with decreased rates of implantation. Time to the start of blastulation of <100hours after insemination and the morphokinetic scoring system used in the TLM group were independently associated with implantation. The addition of time-lapse morphokinetic data did not significantly improve clinical reproductive outcomes in all patients and in those with blastocyst transfers. Absence of multinucleation, timing of blastulation, and morphokinetic score were found to be associated with blastocyst implantation rates. NCT02081859.

Patient-specific predictions of outcome after gonadotropin ovulation induction/intrauterine insemination

To use patient-specific and cycle-specific characteristics to predict clinical pregnancy, multiple pregnancy, and spontaneous abortion rates after gonadotropin ovulation induction (OI)/IUI. Retrospective chart review. Academic fertility center. A total of 1,438 women who underwent 3,375 gonadotropin OI/IUI cycles. Individual and cycle-specific characteristics were evaluated to determine predictors of the rates of clinical pregnancy, multiple pregnancy, and spontaneous abortion. Logistic regression using individual parameters was used to create predictive models. Clinical pregnancy (CPR), multiple pregnancy (MPR), and spontaneous abortion rates (SABR). Multiple predictors were identified for CPR, MPR, and SABR. The presence of at least two follicles ≥ 13 mm at ovulation trigger significantly increased CPR (odds ratio [OR], 95% confidence interval [CI] = 1.45, 1.18-1.78) and MPR (OR, 95% CI = 5.17, 2.16-12.41). An E2 level >400 pg/mL significantly increased MPR (OR, 95% CI = 9.54, 2.31-39.42). Logistic regression models were developed for individualized predictions of outcome. Regression analysis reveals the patient and cycle-specific characteristics that are significant predictors of CPR, MPR, and SABR after OI/IUI. Logistic models using significant or nearly significant predictors for CPR, MPR, and SABR offer improved predictive power relative to simpler models, and allow for the development of a risk calculator for personalized patient counseling.

Semen Parameters are Unrelated to BMI But Vary With SSRI Use and Prior Urological Surgery

Male infertility affects approximately 6% of reproductive-aged men. It has been suggested that overweight men or men with obese body mass index (BMI) experience prolonged time to pregnancy, though the influence of male BMI on fertility remains understudied. We hypothesized that BMI is inversely correlated with fertility, manifested by reduced sperm concentration, motility, and morphology. Males of age 18 to 50 with semen analyses and self-reported BMI were included (n = 530). Patient parameters analyzed included age, BMI, smoking, urological, and fertility history. Leutinizing hormone (LH), Follicle-stimulating hormone, testosterone, steroid hormone-binding globulin (SHBG) and free androgen index (FAI) levels (n = 55), and selective serotonin reuptake inhibitor (SSRI) use (n = 12) were also measured. The men in this study had a mean BMI of 28.2 ± 4.9 kg/m(2) (range = 15-60), which is considered overweight, and a mean semen concentration of 55.4 ± 46.8 million/mL, which is in normal range, according to WHO standard. No consistent relationship was observed between increasing BMI and sperm concentration, motility, or morphology, although the testosterone levels trended downward with increasing BMI; there was a suggestion for decreased sperm concentration in current smokers. Men treated with combination SSRI and other psychotropic agent therapy (n = 12) had significantly reduced sperm motility (P = .009). Not unexpectedly, prior urological surgery (n = 77) was associated with lower sperm concentration (P = .0001) and morphology (P = .0008). When in vitro fertilization-embryo transfer (IVF-ET) was used as a treatment modality (n = 121), male BMI was not a significant predictor of clinical pregnancy (P = .06). In our study, we did not observe a significant association between male BMI and sperm concentration, motility or morphology, or clinical pregnancy following IVF-ET. Significantly, SSRI use may affect sperm parameters negatively.

Impact of GnRH ovarian stimulation protocols on intracytoplasmic sperm injection outcomes

BackgroundAlthough a large number of studies have been conducted in relation to ovarian response and pregnancy after GnRH agonist and GnRH antagonist controlled ovarian hyperstimulation protocols, most of them used single or combinations of a few predictive factors, and none included the stimulation protocol in the multivariable analysis. The present study was thus primarily designed to investigate the predictive value of the stimulation protocol and to analyze the possible relationships between stimulation protocols and treatment outcomes after adjusting for a large set of variables that potentially affect reproductive outcomes. Factors related to pregnancy achievement and predictive of the number of oocytes retrieved and high quality of the embryos obtained were also analyzed.MethodsTo analyze the impact of GnRH ovarian stimulation protocols on the independent predictors of ovarian response, high quality embryos and clinical pregnancy, two groups out of 278 ICSI treatment cycles were compared prospectively, 123 with a GnRH agonist and 155 with a GnRH antagonist, with multivariable analysis assessing outcomes after adjusting for a large set of variables.ResultsAntagonists were significantly associated with lower length and total dose of GnRH, lower length of rFSH, and higher numbers of oocytes and high quality embryos, whereas the agonist presented a higher fertilization rate and probability of pregnancy. Significant predictors of retrieved oocytes and high quality embryos were the antagonist protocol, lower female age, lower serum levels of basal FSH and higher total number of antral follicles. Significant predictors of clinical pregnancy were the agonist protocol, reduced number of attempts, increased endometrial thickness and lower female age. The probability of pregnancy increased until 30 years-old, with a decline after that age and with a sharp decline after 40 years-old.ConclusionThe models found suggest that not only the protocol but also factors as female age, basal FSH, antral follicles, number of attempts and endometrial thickness should be analyzed for counselling patients undergoing an ICSI treatment.

The hyaluronan binding assay HBA™: a novel and statistically significant predictor of clinical pregnancy (CP) in in vitro fertilization (IVF) and assisted reproductive technology (ART)

OBJECTIVE: Established andrology assays assist in directing the clinician towards the selection of the optimal ART for each couple facing infertility. The HBA assay assesses the ability of the seminal population to bind to an immobilized substrate of hyaluronan. H-bound (HB) sperm carry reduced levels of chromosomal aberrations and enhanced levels of developmental maturity. This relationship led to the current study examining sperm binding potential, descriptive parameters of the male and female partners and their individual contribution to IVF outcome. The study sought to explore the potential association between the HBA index, morphology (M), total number of motile sperm (MS), ART treatment, age, follicle stimulating hormone (FSH) level, number of dominant follicles (DF) and the likelihood of CP.DESIGN: A retrospective analysis of 253 infertility couples examined each parameter as to its contribution to a positive CP. Data collection followed an IRB-approved protocol. The sample consisted of patients requiring intracytoplasmic sperm injection (ICSI) (n=84), IVF (n=93) and intrauterine insemination (IUI) (n=76).MATERIALS AND METHODS: The HBA score, M, MS, ART treatment, age, FSH and DF were the independent variables (IV) recorded for each patient. The HBA score was calculated as # bound MS/# total MS. With CP as the dependent variable, all IV were entered into a logistic regression model (LRM). Descriptive analyses included ANOVA and Pearson's χ 2 (chi square) using SPSS 15.0.RESULTS: Overall, 11.8% of IUI, 68% of IVF and 72.6% of ICSI patients demonstrated a CP. There was a statistically significant difference in mean HBA scores of IUI and IVF patients (79.87, 78.58, respectively (resp.)) as compared to ICSI patients (62.26, p<0.001). The LRM showed that the HBA score, female age and ART method had a statistically significant role in contributing to CP (p=.003, p=.001, p<.001, resp.). Male age, MS, M and FSH level showed no statistical significance (p>0.05) in contributing to CP.CONCLUSIONS: The use of the HBA index in the evaluation of the infertile couple merits strong consideration in the selection of the most appropriate ART to achieve a CP. The statistically significant value of the HBA index in predicting CP suggests the influence HB-sperm exert on preimplantation embryogenesis. Use of refined criteria for the HBA index may better direct the ART technologies selected for infertile patients thus optimizing CP and improving patient care. OBJECTIVE: Established andrology assays assist in directing the clinician towards the selection of the optimal ART for each couple facing infertility. The HBA assay assesses the ability of the seminal population to bind to an immobilized substrate of hyaluronan. H-bound (HB) sperm carry reduced levels of chromosomal aberrations and enhanced levels of developmental maturity. This relationship led to the current study examining sperm binding potential, descriptive parameters of the male and female partners and their individual contribution to IVF outcome. The study sought to explore the potential association between the HBA index, morphology (M), total number of motile sperm (MS), ART treatment, age, follicle stimulating hormone (FSH) level, number of dominant follicles (DF) and the likelihood of CP. DESIGN: A retrospective analysis of 253 infertility couples examined each parameter as to its contribution to a positive CP. Data collection followed an IRB-approved protocol. The sample consisted of patients requiring intracytoplasmic sperm injection (ICSI) (n=84), IVF (n=93) and intrauterine insemination (IUI) (n=76). MATERIALS AND METHODS: The HBA score, M, MS, ART treatment, age, FSH and DF were the independent variables (IV) recorded for each patient. The HBA score was calculated as # bound MS/# total MS. With CP as the dependent variable, all IV were entered into a logistic regression model (LRM). Descriptive analyses included ANOVA and Pearson's χ 2 (chi square) using SPSS 15.0. RESULTS: Overall, 11.8% of IUI, 68% of IVF and 72.6% of ICSI patients demonstrated a CP. There was a statistically significant difference in mean HBA scores of IUI and IVF patients (79.87, 78.58, respectively (resp.)) as compared to ICSI patients (62.26, p<0.001). The LRM showed that the HBA score, female age and ART method had a statistically significant role in contributing to CP (p=.003, p=.001, p<.001, resp.). Male age, MS, M and FSH level showed no statistical significance (p>0.05) in contributing to CP. CONCLUSIONS: The use of the HBA index in the evaluation of the infertile couple merits strong consideration in the selection of the most appropriate ART to achieve a CP. The statistically significant value of the HBA index in predicting CP suggests the influence HB-sperm exert on preimplantation embryogenesis. Use of refined criteria for the HBA index may better direct the ART technologies selected for infertile patients thus optimizing CP and improving patient care.

Large blastocyst diameter, early blastulation, and low preovulatory serum progesterone are dominant predictors of clinical pregnancy in fresh autologous cycles

To identify dominant predictors of clinical pregnancy in IVF cycles. Retrospective study. Private fertility center. The study included 580 fresh autologous IVF cycles with blastocyst transfer. None. Clinical pregnancy rate. A set of 25 suspected predictors was used to develop predictive models of clinical pregnancy in a set of 361 blastocyst transfer cycles. Initial bivariate analysis identified 14 of these variables that were significant enough to be candidate variables for multiple logistic regression. Similar sets of significant variables were identified by using alternative approaches for model construction. The final model included blastocyst diameter, day of blastulation, and preovulatory serum P level as significant predictors of clinical pregnancy. Specifically, clinical pregnancy was predicted by preovulatory serum P of <1.0 ng/mL, blastulation on day 5, and large blastocyst diameter. Of these variables, blastocyst diameter was the most significant predictor of clinical pregnancy in the multivariate models. The final model was validated against a separate set of 219 subsequent blastocyst transfer cycles. Pre-ovulatory serum P level, blastulation day, and embryo diameter are simultaneously predictive of clinical pregnancy, and their relationships with clinical pregnancy are consistent with an effect of embryo-endometrium synchrony.

Zona pellucida thickness does not predict pregnancy outcomes in patients less than 38 years of age undergoing in vitro fertilization: results from a prospective, randomized trial on assisted hatching

“Thickened zona pellucida” is a commonly cited, but poorly defined, indication for the assisted hatching (AH) procedure. We sought to determine the effect of zona pellucida (ZP) thickness on clinical pregnancy rates in younger patients undergoing in vitro fertilization (IVF), and furthermore to define a ZP thickness at which assisted hatching may be beneficial. A prospective, randomized, controlled, double-blind trial of AH in patients less than 38 years of age undergoing IVF. Between April 2004 and February 2007, 162 patients were consented and enrolled in our study. The Zona Laser Treatment System (Hamilton Thorne, Beverly, MA) was used to measure the thickness of each ZP. Patients whose embryos had a ZP thickness ≥13 microns were randomized to undergo assisted hatching or to remain unhatched; those whose embryos had a ZP thickness <13 microns were classified as “thin” and were not randomized. Each patient's mean ZP thickness was calculated for use in the final analysis. Hatching procedures were performed using acidic Tyrode's medium. To examine mean ZP thickness as a predictor of pregnancy outcomes, a receiver operator curve (ROC) was generated using a log-binomial model. A total of 98 recorded ZP measurements from 55 IVF cycles were compared. 11 embryos (11%) had a mean ZP <13 microns. The mean ZP thickness of the remaining 87 embryos was 17.36 microns ± 3.09 (SD). Among patients whose embryos did not undergo AH, there was no difference (P=0.28) between mean ZP thickness of those embryos with resultant clinical pregnancies (17.6 ± 3.3, n = 8) vs. mean ZP thickness of those without clinical pregnancies (16.8 ± 3.3, n = 5). After adjusting for assisted hatching, the ROC showed a one unit increase in mean ZP to be associated with a small increase in the odds of pregnancy, but this difference was not statistically significant (RR = 1.11, 95% CI 0.96–1.28). The area under the curve was 0.77; there was no ZP thickness that sensitively and specifically predicted the outcome of clinical pregnancy. ZP thickness is not a significant predictor of clinical pregnancy in patients less than 38 years of age undergoing IVF. Our results therefore do not support the use of “thickened ZP” as an indication for AH in this patient population. On the contrary, the evidence suggests that “thickened ZP” is not a clinically useful concept in this setting.

Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer

To define and validate metrics of embryo progression and morphology during extended embryo culture and to compare the effects of early cleavage (EC) vs. blastulation stages on clinical pregnancy. Retrospective observational study. University-affiliated assisted reproduction center. One thousand two hundred ninety-two intracytoplasmic sperm injection and 842 IVF blastocyst-transfer cycles. The embryo progression index (EPI) was calculated as the area under the curve of total cell number (TCN) over time, by using observed TCN for cleavage-stage embryos and estimated blastocyst TCN according to morphology. The EPI from days 1-3 measured early cleavage, and blastulation was assessed by EPI over extended embryo culture. Blastocyst morphology was converted into numerical blastocyst quality scores (BQSs). Receiver operating characteristic curve analysis was used to evaluate predictors for clinical pregnancy. Clinical pregnancy. Per-cycle mean EPI and mean BQS for all embryos developing into blastocysts, as well as mean BQS of the transferred embryos, were significant predictors of clinical pregnancy in intracytoplasmic sperm injection and IVF cycles. Mean EPI for days 1-3 did not predict outcome. Early cleavage is a putative marker of embryo quality. Late-stage embryo development is more sensitive and specific in predicting clinical pregnancy than is early cleavage, supporting the use of extended embryo culture for embryo selection. The embryo progression index and BQS may also be used for this purpose.

GnRH Antagonist Use in IVF and ICSI Cycles Decreases Implantation and Clinical Pregnancy Rates Without Affecting Embryo Quality and Blastulation

We aimed to compare the outcome of ovarian stimulation protocols using GnRH antagonist to those incorporating GnRH agonist in IVF or ICSI, non-donor fresh blastocyst transfer cycles. Retrospective comparison of GnRH antagonist IVF or ICSI cycles to GnRH agonist cycles from a university-affiliated private ART program. Cycles were included only if they resulted in blastocyst transfer. A total of 750 IVF and 1288 ICSI, fresh non-donor blastocyst transfer cycles were included. Patients on GnRH agonists received daily leuprolide acetate injections using either long luteal phase or flare protocols. Patients on GnRH antagonist received cetrorelix acetate 3 mg administered 4 days before the start of FSH stimulation for synchronization of the antral follicle cohort and a repeat dose was given when a lead follicular diameter of 13-14 mm was reached. Embryo Progression Index (EPI) was calculated from the area under the curve of numerical conversion of the available embryo progression data by trapezoidal integration. Gardner/Schoolcraft blastocyst grades were converted into numerical Blastocyst Quality Scores (BQS). Mean EPI for day 3 and day 5/6 for all blastocysts and mean BQS of developed and transferred embryos were used as separate variables to serve as measures of embryo progression and blastulation. IVF and ICSI cycles were analyzed separately. The comparisons were made by independent t- and chi-square tests where appropriate. The significant predictors of clinical pregnancy were analyzed by logistic regression. Cycle outcomes were summarized in the following table (Table 1.). Cycles with GnRH antagonists had reduced implantation and clinical pregnancy rates although the embryo progression and blastulation parameters were comparable in IVF cycles and were superior in ICSI cycles which employed GnRH antagonists. Evaluation of first treatment cycles did not change these findings. Logistic regression models further supported the negative impact of GnRH antagonist on clinical pregnancy in both IVF and ICSI cycles. Tabled 1 Non-donor IVF or ICSI cycles with fresh blastocyst transfer using GnRH antagonist result in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation scores are comparable or superior in GnRH antagonist cycles. These findings suggest potential adverse effects of GnRH antagonist on endometrial receptivity which justifies further investigation.

Endocrine and ultrasonographic assessment of the ovarian reserve and their predictive potential for IVF outcome

Objective: The assessment of basal cycle day 3 FSH, LH and E2 levels (usually referred to as ovarian reserve) has been demonstrated to predict response to controlled ovarian hyperstimulation and chances of conception in IVF. Recent studies have also shown that such predictability can be enhanced by ultrasonographic examination of basal ovarian follicle count. The objective of this study was to investigate the correlations between ovarian reserve, basal ovarian volume and antral follicle count, the main parameters reflective of ovarian response, and pregnancy outcome in IVF. Design: Prospective cohort analysis. Materials and Methods: A total of 135 consecutive women undergoing IVF (with or without ICSI) between January and December 2002 were enrolled independently of their age and the etiology of infertility. Pretreatment transvaginal ultrasound measurements and basal levels of FSH, LH and E2 on basal cycle day 3 were correlated with the parameters of subsequent ovarian response (peak E2, numbers of mature oocytes, number of ampoules of gonadotropins used) and cycle outcome (clinical pregnancy). Ovarian response outcomes were analyzed by ordinary least squares regression. Pregnancy outcome was analyzed by logistic regression. Univariate analyses were made for each predictor; a multivariable analysis was also made to adjust for the other predictors. Results: Peak E2 demonstrated a negative correlation with basal cycle day 3 FSH (r = −0.22, p = 0.01) and a positive correlation with both basal cycle day 3 LH and basal antral follicle count after correcting for other variables (r = 0.20, p = 0.004 and r = 0.27, p = 0.05, respectively). After adjustment for other variables, only age and basal antral follicle count correlated with the total number of ampoules of gonadotropins used (r = 0.43, p < 0.001 and r = −0.37, p < 0.001, respectively) with age being the strongest predictor. The number of mature oocytes obtained at retrieval showed a positive correlation with basal cycle day 3 LH and basal antral follicle count (r = 0.32, p < 0.001 and r = 0.29, p = 0.01, respectively), and a negative correlation with basal cycle day 3 FSH and E2 (r = 0.–30, p < 0.001 and r = −0.16, p < 0.001, respectively). Only age was a significant predictor of clinical pregnancy, but when adjusted for all other variables it was no longer statistically significant. Conclusion: Basal cycle day 3 assessment of ovarian reserve through hormonal evaluation of FSH, LH and E2, and determination of the basal antral follicle count, were equally predictive of response to controlled ovarian hyperstimulation using gonadotropins in IVF therapy. Basal ovarian volume did not correlate with such response.

Statistical analysis of factors affecting fertilization rates and clinical outcome associated with intracytoplasmic sperm injection

ObjectiveTo identify and evaluate the statistically significant predictors of intracytoplasmic sperm injection (ICSI) fertilization rates and clinical pregnancy in a single population using appropriate statistical techniques. DesignRetrospective study. SettingFertility and Endocrinology Center, University of Washington Medical Center, Seattle, Washington. Patient(s)Four hundred forty-one patients undergoing their first attempt at IVF-ICSI from January 1, 1999, to May 21, 2001. Intervention(s)Each ICSI procedure for an individual patient was performed by a single operator. Sperm parameters, oocyte age, culture condition, ICSI technique, and ICSI operator were assessed as variables influencing the fertilization rate. We also assessed the impact of patient age, serum E2 concentration on the day of hCG administration, embryo quality, and number of embryos transferred on the probability of achieving a clinical pregnancy. Main outcome measure(s)Fertilization rate and clinical pregnancy. Result(s)The 2 pronuclei (2PN) rate was significantly correlated with sperm motility, and there were significant differences in the 2PN rates among the ICSI operators. There was no difference in the 2PN rate among different sperm types or among the eight laboratory incubators or whether the eggs were cultured individually or in groups. Patient age, serum E2 concentration on the day of hCG administration, embryo quality, and number of embryos transferred were all statistically significant predictors of clinical pregnancy. Conclusion(s)In our program, sperm motility and ICSI operator are the two most important predictors for the ICSI fertilization rate in vitro. Patient age, serum E2 concentration on the day of hCG administration, embryo quality, and number of embryos transferred were all statistically significant predictors of clinical pregnancy.

Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial

Objective: To compare the efficacy of intracytoplasmic sperm injection and IVF in women with a tuboperitoneal factor as their sole cause of infertility. Design: Prospective, randomized study. Setting: Hacettepe University Assisted Reproduction Unit, Ankara, Turkey. Patient(s): Seventy-six consecutively seen patients with tuboperitoneal factor infertility were randomized on an alternate basis to undergo either intracytoplasmic sperm injection (38 patients and cycles) or IVF (38 patients and cycles). Intervention(s): Intracytoplasmic sperm injection and IVF. Main Outcome Measure(s): Fertilization, implantation, and clinical pregnancy rates. Result(s): A comparable number of oocytes and embryos were obtained with intracytoplasmic sperm injection and IVF. The two-pronuclei fertilization rates per metaphase II oocyte or mature cumulus-oocyte complex were similar in the two groups. The numbers of total and grade I embryos transferred also were similar. Comparisons of intracytoplasmic sperm injection and IVF did not reveal any statistically significant differences in individual implantation rates (38.75% ± 24.46% and 34.58% ± 16.97%, respectively) clinical pregnancy rates per cycle (21.05% and 21.05%, respectively), or take-home infant rates (18.42% and 15.79%, respectively). The type of procedure performed was not a significant predictor of clinical pregnancy. Conclusion(s): When a decision is made to proceed with an assisted reproductive technique in patients with a tubal factor as their sole cause of infertility, IVF should be the initial treatment of choice.