High-quality embryos maintain high pregnancy rates in passive smokers but not in active smokers.

This study assesses the effect of passive and active smoking on pregnancy rates after IVF with transfer of high-quality embryos. In a cohort study, women attending the IVF unit in 2006­2007 with favourable parameters for pregnancy (<38 years; less than three IVF cycles, transfer of two highest-grade embryos) grouped by smoking status were included. The cohort included 237 patients/cycles: 42 smokers, 195 non-smokers. The clinical pregnancy rate was significantly lower in smokers (35.7% versus 55.4%,P = 0.021, OR = 0.44 (95% CI 0.22­0.89)), even after conditional stratification on covariates (passive smoker, passive or partner smoker, age group). The live-birth rate was lower in smokers (28.6% versus 42.6%), but the difference was not statistically significant(OR = 0.54 (0.26­1.11)). Among non-smokers, there was no difference in pregnancy rate by passive or partner smoking. On logistic regression, variables predicting pregnancy were age <35 years (P = 0.008, OR = 2.58 (1.2­5.2)) and non-smoking (P = 0.003,OR = 3.47 (1.51­7.98)). In conclusion, transfer of high-quality embryos does not overcome the negative effect of active smoking on pregnancy rate in IVF treatment. The endometrium is apparently involved in the mechanism underlying IVF failure in smokers.

High-quality embryos retain their implantation capability in overweight women.

To assess the effect of obesity on implantation rate, pregnancy rate and course of pregnancy in young women undergoing IVF in whom only high-quality embryos were transferred, a cohort study included women attending the IVF unit in 2006-2007 with favourable parameters to achieve pregnancy (<38years, fewer than three IVF cycles, transfer of two high-quality embryos), grouped by body mass index (BMI). Of 230 women, 160 had a BMI ⩽25kg/m(2) (mean 21.6±2.2) and 73 had BMI >25kg/m(2) (mean 29.5±3.7). The overweight group had a higher consumption of gonadotrophins during stimulation. There were no between-group differences in treatment protocols, duration of gonadotrophin stimulation, maximal oestradiol concentrations, endometrial thickness and number of oocytes retrieved/fertilized, or in rates of pregnancy (51.3%, 52.1%), implantation (34.5%, 37.5%), multiple pregnancy, and abortion. Rate of gestational diabetes or pregnancy-induced hypertension was higher in the overweight group (23.3%, 8.2%; P=0.045). Within the overweight group, those with multiple pregnancies were at highest risk (31.3%, 6.9%; P=0.031). In conclusion, implantation and pregnancy rates are not compromised in overweight women when high-quality embryos are transferred. However, in overweight women, pregnancy complications remain high, mainly in those with multiple pregnancies.

High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation.

The study was designed to evaluate the isolated effect of high serum oestradiol concentration on human chorionic gonadotrophin (HCG) day in IVF cycles on endometrial receptivity and placentation. A retrospective cohort included all women attending the IVF unit in 2006 and 2007, with the best prognosis to achieve pregnancy: age (<38 years), less than three IVF cycles, transfer of two highest grade embryos and no evidence of factors known to impair implantation or that are associated with increased risk of pregnancy complications. The total included 280 patients were categorized into three groups according to their serum oestradiol concentration on HCG day: group 1, oestradiol <5000 pmol/l, group 2, oestradiol in the range 5000-10,000 pmol/l and group 3, oestradiol in the range of 10,000-15,000 pmol/l. No significant differences were found between the groups in implantation, pregnancy and abortion rates. The high oestradiol group was characterized by high rate (20.8%) of pregnancy complications related to abnormal placentation--fetal growth restriction, pregnancy-induced hypertension and abnormal implantation of the placenta. Hence, the decision to perform embryo transfer in high-responder patients should take into consideration both possible risks of ovarian hyperstimulation syndrome and pregnancy complications related to abnormal placentation.

Ovarian stimulation in polycystic ovary syndrome patients: the role of body mass index.

In an attempt to examine whether body mass index (BMI) may influence IVF outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either gonadotrophin-releasing hormone (GnRH)-agonist (agonist group) or antagonist (antagonist group), 100 IVF cycles were studied: 35 in the agonist and 65 in the antagonist groups. In both agonist and antagonist groups, patients with BMI < or = 25 kg/m(2) had a significantly higher fertilization rate compared with patients with BMI > 25 kg/m(2) (P < 0.02 and P < 0.01, respectively). Lean patients (BMI < or = 25) undergoing ovarian stimulation using the GnRH-agonist, demonstrated the highest pregnancy rate. In conclusion, in this series of PCOS patients undergoing IVFembryo transfer cycles, ovarian stimulation utilizing the midluteal long GnRH-agonist suppressive protocol yielded a higher pregnancy rate in lean patients, probably due to its ability to lower the high basal LH milieu and its detrimental effect on oocyte quality and implantation potential.

The influence of body mass index on in vitro fertilization outcome.

OBJECTIVE: To examine whether body mass index (BMI) influences the outcome of in vitro fertilization (IVF). METHODS: We studied 516 IVF cycles, 438 undergone by nonobese (BMI < or = 30) and 78 by obese (BMI > 30) women who all had an a priori favorable prognosis (age < 40 years and first, second, or third IVF cycle). RESULTS: Pregnancy was achieved in 122 (27.9%) nonobese and 12 (15.4%) obese women. The obese women required significantly longer stimulation and more gonadotropin ampoules, and had lower peak estradiol levels and a significantly lower fertilization rate; obese poor responders had a significantly lower pregnancy rate than nonobese poor responders; and the prevalence of poor responders was significantly higher among obese than nonobese women (28.2% vs 16.9%, P < 0.04). CONCLUSION: While the likelihood of poor responders was increased among obese women, reasonable conception rates were achieved in nonobese poor responders, and were comparable to the rates in nonobese and obese normal responders.

Immediate ambulation after embryo transfer: a prospective study.

OBJECTIVE: To assess whether bed rest following the embryo transfer (ET) procedure contributes to the implantation process and pregnancy rate. DESIGN: A prospective (patient-influenced) study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENT(S): Four hundred six patients undergoing controlled ovarian hyperstimulation and IVF. INTERVENTION(S): All women undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles in our unit were given a special individual counseling session before the ET procedure in which they were informed that our previous experience showed no advantage for bed rest over immediate ambulation after ET. The women were allowed to select the practice of their choice, and they were assured that their decision would have no influence on their further treatment. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcome were compared between the two groups (bed rest and immediate ambulation). RESULT(S): Of the 406 patients counseled during the study period, 167 preferred immediate ambulation and 239 opted to stay in the unit for 1 hour's bed rest. There were no significant differences between the groups in mean patient age, number of embryos transferred, and other variables of the assisted reproductive technique cycles. Pregnancy rates did not differ between the groups: 41 out of 167 (24.55%) in the immediate-ambulation group and 51 out of 239 (21.34%) in the bed-rest group. CONCLUSION(S): Immediate ambulation following the ET procedure has no adverse influence on the ability to conceive.

Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective, randomized study.

OBJECTIVE: To compare the use of two depot GnRH-a, leuprolide and triptorelin, in long-suppression GnRH-a protocols. DESIGN: Prospective, randomized study. SETTING: An IVF unit of an academic medical center.Fifty-two women who underwent controlled ovarian hyperstimulation and IVF. INTERVENTION(S): Patients were prospectively randomized to receive 3.75 mg depot formulations of either leuprolide or triptorelin on days 21-23 of the menstrual cycle. Stimulation with gonadotropins was initiated after pituitary desensitization was achieved. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcomes were compared between the two groups. RESULT(S): Twenty-six patients were included in each group. No significant differences were observed in the patient age, estrogen, and P levels on day of hCG administration, gonadotropin dosage, number of oocytes retrieved, fertilization rate, percentage of high-quality embryos, and number of embryos transferred. However, significantly higher clinical implantation and pregnancy rates were found in the leuprolide group compared with the triptorelin group. CONCLUSION(S): A depot preparation of leuprolide is associated with higher implantation and pregnancy rates than a depot preparation of triptorelin when it is used in the midluteal phase as part of the long-suppression GnRH-a protocol in IVF.

What is the preferred GnRH analogue for polycystic ovary syndrome patients undergoing controlled ovarian hyperstimulation for in vitro fertilization?

In an attempt to evaluate the influence of the GnRH analogue used during controlled ovarian hyperstimulation (COH) on the outcome of IVF cycles of polycystic ovary syndrome (PCOS) patients, we studied 152 IVF cycles. The PCOS patients undergoing COH using the GnRH agonist protocol (n = 50) showed a significantly higher pregnancy rate (36% vs. 19.6%, respectively), compared with the GnRH antagonist protocol (n = 102).

Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?

In an attempt to examine and compare the effect of the two commercially available recombinant FSH on ovarian stimulation characteristics and IVF cycle outcome, we studied 264 IVF cycles in patients with a favorable prognosis a priori, 198 in patients using follitropin-alpha, and 68 in patients using follitropin-beta. Although both groups achieved a comparable number of retrieved oocytes, the use of follitropin-beta was associated with a tendency toward a lower clinical pregnancy rate (PR), and with significantly higher E(2) levels despite the use of significantly lower total gonadotropin dose.

Repeated in vitro fertilization cycle attempts in patients undergoing controlled ovarian hyperstimulation with use of gonadotropin-releasing hormone antagonists.

To examine pregnancy rate in patients undergoing controlled ovarian hyperstimulation (COH) with use of multidose GnRH antagonists in multiple repeated IVF cycle attempts, we conducted a survey in 785 consecutive IVF cycles in our unit. Although pregnancy rate significantly decreased beyond the second IVF cycle attempt, no significant decrease was noted between cycle attempts 3 and 4 and 5 to 8.

Serum androgen levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycles.

AIM: To investigate androgen behavior during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: A prospective, observational study. SETTING: An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 consecutive patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). RESULTS: There was a significant increase in serum sex steroid levels during gonadotropin treatment. After hCG administration, there was a significant increase in levels of serum 17-hydroxyprogesterone (17-OHP) and ovarian androgens (total and free testosterone and androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone sulfate). Significant correlations were observed between plasma estradiol (E(2)) and androgen levels during COH and until hCG administration, but not after hCG administration. The E(2)/testosterone ratio increased significantly during COH and until hCG administration, and then decreased significantly. The number of oocytes retrieved correlated significantly with serum 17-OHP, E(2) and E(2)/testosterone ratio. The number of gonadotropin ampoules used correlated inversely only with serum E(2) levels. CONCLUSION: In patients undergoing COH for IVF, androgen levels increase in response to gonadotropin, and then again after hCG administration. Although the E(2)/testosterone ratio correlates with the number of oocytes retrieved, androgen levels do not.

Controlled ovarian hyperstimulation: does prolonged stimulation justify cancellation of in vitro fertilization cycles?

BACKGROUND: In daily practice, assisted reproductive technology (ART) cycles are often cancelled under the assumption that a prolonged stimulation period lowers the likelihood of an appropriate ovarian response. The aim of the present study was to determine whether a prolonged cycle has an adverse effect on achievement of pregnancy. METHODS: The study sample included consecutive women enrolled in our ART unit between 1999 and 2001 who were treated with the mid-luteal long suppressive gonadotropin-releasing hormone protocol. Data were collected prospectively on a computerized database and evaluated at the end of the study. Prolonged stimulation was defined as a stimulation period of more than two standard deviations (SD) above the mean. Outcome was compared between patients who required prolonged stimulation and those who did not. RESULTS: A total of 1015 consecutive in vitro fertilization (IVF) cycles were performed with the mid-luteal long suppressive protocol during the study period. Thirty-four women required prolonged stimulation. No difference in clinical pregnancy rate was detected between women who received prolonged stimulation and those who did not (9/34, 26.5% vs. 291/981, 29.7%), despite the significantly fewer oocytes retrieved in the prolonged-stimulation group (7.1 +/- 5.2 and 11.6 +/- 6.7 (mean +/- SD), respectively, p < 0.001). CONCLUSION: The likelihood of achieving pregnancy is not influenced by the length of stimulation. We recommend that IVF cycles should not be discontinued on the grounds of prolonged stimulation alone.

Does intravaginal probiotic supplementation increase the pregnancy rate in IVF-embryo transfer cycles?

This study investigated the effect of intravaginal administration of probiotics immediately after oocyte retrieval on vaginal colonization and outcome of the IVF-embryo transfer cycle. One hundred and seventeen women who underwent ovarian stimulation and IVF were randomized immediately after oocyte retrieval into two groups: those who received intravaginal probiotics (study group, n = 50) and those who did not (control group, n = 67). Vaginal colonization with lactobacilli and pregnancy rate were compared between the two groups. No significant between-group differences were observed in patient age, oestrogen and progesterone concentrations on day of human chorionic gonadotrophin administration, number of oocytes retrieved, fertilization rate, number of embryos transferred, or pregnancy rate. The presence of lactobacilli in the vagina during oocyte retrieval or embryo transfer did not improve the pregnancy rate. Furthermore, intravaginal administration of lactobacilli following oocyte retrieval did not affect the prevalence of lactobacilli during embryo transfer, or the pregnancy rate. Intravaginal probiotic supplementation immediately after oocyte retrieval has no effect on vaginal colonization or pregnancy rate in IVF cycles.

Significance of increased endometrial thickness in assisted reproduction technology treatments.

PURPOSE: The purpose of this study was to evaluate the relationship between thick endometrium and both implantation and pregnancy rates in ART treatments. METHODS: The study group was composed of consecutive women undergoing ultrasonographic evaluation on the day of hCG administration in our ART unit. Endometrial thickness was measured at the thickest part of the midsagittal plane. On the basis of the findings, patients were divided into two groups: A--endometrial thickness >14 mm (above the 95th percentile) and B--endometrial thickness 7-14 mm (between the 5th and 95th percentiles). Patients with a thickness of less than 7 mm were excluded from the study. RESULTS: In all, 1218 cycles were included in the study (50 in Group A and 1168 in Group B). There was no significant difference between the groups in mean patient or mean number of embryos transferred. Similar pregnancy and implantation rates were noted in Group A (24 and 11.3%, respectively) and Group B (27.7 and 14.7%, respectively). Endometrial thickness was found to have a significant positive correlation with the duration of follicular stimulation, and an inverse correlation with woman's age. CONCLUSIONS: Increased endometrial thickness (>14 mm) is not associated with decreased implantation or pregnancy rates in assisted reproduction.

C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle.

BACKGROUND: The aim of the present study was to determine serum and follicular fluid C-reactive protein (CRP) levels in patients undergoing controlled ovarian hyperstimulation (COH) for IVF-embryo transfer cycle, and their possible correlation to COH variables. PATIENTS AND METHODS: The subjects were 16 consecutive patients undergoing our routine IVF long GnRH agonist protocol. Blood was drawn three times during the COH cycle: (i) the day on which adequate suppression was obtained (Day-S); (ii) the day of, or prior to HCG administration (Day-HCG); and (iii) the day of (and before) oocyte pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid CRP were compared among the three time points. Serum and follicular fluid CRP were measured with a commercial immunoturbidimetric assay. RESULTS: Serum levels of CRP were significantly higher on Day-OPU and Day-HCG than on Day-S, and significantly higher on Day-OPU than on Day-HCG. No difference was observed between follicular and serum CRP levels on Day-OPU. No significant correlations were found between serum and follicular fluid CRP, or between serum CRP-to-BMI ratio and serum sex steroid levels or IVF treatment variables. CONCLUSIONS: The significant increase in serum CRP levels during COH, especially after HCG administration, suggests that COH potentiates a state of systemic inflammation.

Serum P-selectin level during controlled ovarian hyperstimulation--a preliminary report.

OBJECTIVE: To measure levels of serum P-selectin in patients undergoing controlled ovarian hyperstimulation (COH) cycles and to determine their possible correlation to COH variables. SETTING: Large university-based infertility and in vitro fertilization unit. PATIENTS: Fourteen consecutive patients undergoing our routine COH protocol for unexplained infertility. INTERVENTIONS AND MAIN OUTCOME MEASURES: Blood was drawn three times during the COH cycle: (1) day 2 or 3 of the menstrual cycle, before gonadotropin treatment (Day-0); (2) day of or prior to human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) day of ovulation (Day-OVU). Serum levels of sex steroids and P-selectin were compared among the three time points. P-selectin was measured with a commercial quantitative sandwich immunoassay technique. To reduce interpatient variability, the percent difference between the Day-0 (non-stimulated, basal) level and the Day-hCG and Day-OVU levels was calculated. RESULTS: P-selectin level on Day-hCG was significantly higher than on Day-0 (P < 0.05) and non-significantly higher than on Day-OVU (P < 0.12). No significant correlations were observed between serum P-selectin and patient age, amount of gonadotropins used, or estradiol or progesterone level. CONCLUSION: The increase in serum P-selectin level during COH until peak estradiol suggests that COH may potentiate a state of platelet activation which is substantially attenuated after hCG administration.