M.L. Uhler

Body mass index: impact on IVF success appears age-related †

BACKGROUND The objective of this study was to examine the effect of BMI on IVF outcomes. METHODS This was a retrospective analysis of all patients undergoing IVF from 1st January 2005 to 1st March 2006 in a large private practice using a single IVF laboratory. The patients underwent standard protocols for controlled ovarian hyperstimulation and embryology parameters. The main outcome measure was clinical pregnancy rate. RESULTS A total of 2167 fresh, non-donor IVF cycles were queried, but to minimize bias, only the first treatment cycle for each patient was analyzed (n = 1273). The data were examined by multiple regression models that included BMI and Age as main effects plus a BMI x Age interaction. When examined as a main effect, BMI did not appear to have a major effect on IVF outcome, but there was a significant BMI x Age interaction. At younger ages, a high BMI had a pronounced negative influence on fertility, but this effect diminished as the patient age increased. Clinical pregnancy rates decreased with increasing BMI and increasing Age. CONCLUSIONS In younger patients undergoing IVF, BMI has a significant negative impact on fertility that diminishes as patients reach their mid thirties. After Age 36, BMI has a minimal impact on fertility.

Relationship between sperm characteristics and hormonal parameters in normal couples

OBJECTIVE To examine the relationships between hormone profiles and semen analysis measures and fertility in the male partners of presumed normal couples. DESIGN Prospective clinical study. SETTINGS Healthy volunteers in an academic research environment. PATIENT(S) One hundred forty-five reproductive age couples without known risk factors for infertility and who had discontinued contraception to achieve pregnancy completed this component of this study. Each couple was followed for < or =12 menstrual cycles while they attempted to conceive. INTERVENTION(S) Semen quality measures for the first ejaculates were obtained at the start of the study along with a single blood sample. Levels of FSH, bioactive FSH, inhibin B, LH, and T were measured for each man. MAIN OUTCOME MEASURE(S) Semen analysis, FSH, inhibin B, LH, T, and clinical pregnancy. RESULTS Significant positive relationships were observed between the two measures of FSH as well as between both of the FSH measures and LH. Follicle-stimulating hormone as measured by RIA was significantly negatively correlated with inhibin B. Inhibin B showed a marginally significant negative correlation with LH, and LH and T had a marginally significant positive correlation. Inhibin B increased significantly, and both measures of FSH activity showed significant decreases, with increasing levels in several semen quality measures. There was no significant relationship between the measured hormones and the pregnant and nonpregnant groups or time to pregnancy. CONCLUSION(S) These results contribute additional information on the utility of reproductive hormone measurements for predicting semen quality in couples without known reduced fertility.

The effect of nonsteroidal anti-inflammatory drugs on ovulation: a prospective, randomized clinical trial☆

OBJECTIVE To assess the effect of ibuprofen, a nonspecific inhibitor of prostaglandin synthesis, on ovulation. DESIGN Prospective, randomized, double-blind, placebo-controlled cross-over study. SETTING University Medical Center. PATIENT(S) Twelve normally cycling women between ages 20 and 40. INTERVENTION(S) Subjects were randomized to either oral ibuprofen (800 mg) or placebo three times per day, beginning when the maximum diameter of the leading follicle reached 16 mm by ultrasound, and continuing for 10 days total. The second cycle was a washout period, and in the third cycle, the subjects were crossed over to the alternate regimen from the first cycle. The probability of delayed follicular collapse was determined using the binomial distribution, and changes in P levels were compared using the paired t test. MAIN OUTCOME MEASURE(S) Urinary LH surge, follicular collapse by serial transvaginal ultrasonography, and serum midluteal P levels. RESULT(S) Eleven of 12 subjects detected an LH surge with both ibuprofen and placebo. Five of 11 women demonstrated a >or=2-day increase in time interval from detection of the LH surge to follicular collapse, and 3 of those 5 had been randomized to ibuprofen. This represents a 27% (3 of 11; 95% confidence limits: 1%, 53%) rate of delay for follicular collapse for ibuprofen. There was no difference in average midluteal P levels for ibuprofen or placebo. CONCLUSION(S) If ibuprofen inhibits follicular collapse, this effect is seen in a small group of study subjects, and this information should be clinically reassuring to patients who take nonsteroidal anti-inflammatory drugs. Serum midluteal P levels were unaffected by administration of ibuprofen.

Racial disparities in in vitro fertilization outcomes

OBJECTIVE To evaluate the impact of race on in vitro fertilization (IVF) outcomes. DESIGN Retrospective analysis. SETTING Private practice. PATIENT(S) All women who underwent a first autologous IVF cycle at Fertility Centers of Illinois from January 2010 to December 2012. INTERVENTION(S) Information was collected on baseline characteristics, cycle parameters, and outcomes. Race was self-reported. MAIN OUTCOME MEASURE(S) Clinical intrauterine pregnancy and live birth rates. RESULT(S) A total of 4,045 women were included: 3,003 white (74.2%), 213 black (5.3%), 541 Asian (13.4%), and 288 Hispanic women (7.1%). A multivariable logistic regression was performed to control for confounders. Compared with white women, the adjusted odds ratio for clinical intrauterine pregnancy was 0.63 (95% confidence interval [CI] 0.44-0.88) in black women, 0.73 (95% CI 0.60-0.90) in Asian women, and 0.82 (95% CI 0.62-1.07) in Hispanic women. The adjusted odds ratio for live birth was 0.50 (95% CI 0.33-0.72) in black women, 0.64 (95% CI 0.51-0.80) in Asian women, and 0.80 (95% CI 0.60-1.06) in Hispanic women compared with white women. The spontaneous abortion rate was 14.6% in white women versus 28.9% in black women, 20.6% in Asian women, and 15.3% in Hispanic women. CONCLUSION(S) Black and Asian women had lower odds of clinical intrauterine pregnancy and live birth and higher rates of spontaneous abortion compared with white women. Further research is needed to better characterize the mechanisms associated with this racial disparity and to improve treatment options for black and Asian women.

Adding human menopausal gonadotrophin to antagonist protocols - : is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.

Endometrin as luteal phase support in assisted reproduction

OBJECTIVE To compare clinical pregnancy rate (PR) and live birth rate (LBR) between Endometrin monotherapy versus Endometrin and P in oil combination therapy in assisted reproductive technology (ART) cycles. DESIGN Retrospective analysis. SETTING Large private practice. PATIENT(S) Patients undergoing autologous fresh IVF cycles, autologous frozen ET cycles, and fresh oocyte donor cycles were included for analysis. INTERVENTION(S) Endometrin as a single agent for luteal support, Endometrin monotherapy or Endometrin with P in oil used at least once every 3 days for luteal support, Endometrin combination therapy. MAIN OUTCOME MEASURE(S) Clinical PR and LBR. RESULT(S) A total of 1,034 ART cycles were analyzed. Endometrin monotherapy was used in 694 of 1,034 (67%) cycles and Endometrin combination therapy was used in 340 of 1,034 (33%) cycles. In all fresh cycles, clinical PR was not significantly different (IVF autologous: Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor oocyte endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%). Frozen ET cycles had a significantly higher clinical PR and LBR with combination therapy group compared with monotherapy (clinical PR 47.9% vs. 23.5%; LBR 37.5% vs. 17.3%). CONCLUSION(S) Endometrin monotherapy was sufficient for the P component of luteal support and provided high PRs for fresh cycles in both autologous and donor oocyte cycles. Clinical PR and LBR in frozen ET cycles were significantly improved with the addition of IM P to Endometrin therapy. This may reflect the fact that lesser quality embryos are transferred in frozen ET cycles, and more intense P support is required for comparable PRs.

Age-matched comparison of recombinant and urinary HCG for final follicular maturation

This age-matched retrospective analysis compared the clinical outcomes of recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down-regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in combination with human menopausal gonadotrophin. When two or more follicles had attained a mean diameter of 20 mm, follicular triggering was achieved with either Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were considered subjects, and they were age-matched in a 1:2 ratio to patients receiving uHCG, who were designated as controls. The main outcome measures were number of oocytes retrieved, number of mature oocytes obtained, number of oocytes fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched and compared with 546 controls. Recombinant HCG had a minimal effect on the number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3) and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0 versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular maturation in IVF cycles.

Reproductive Outcome After Sterilization Reversal in Women of Advanced Reproductive Age

Objective:Our objective was to assess the clinical outcome of tubal reversal in women of advanced reproductive age.Methods:A multicenter retrospective chart review of 153 patients who underwent a tubal ligation reversal was carried out. Patients were evaluated according to age. All patients had documented ovulation and a partner with a normal semen analysis by WHO criteria. Outcome measures included rates of clinical pregnancy, ectopic pregnancy, spontaneous abortion, and live birth, and the time to conception.Results:Clinical pregnancy rates were significantly lower in women ≥40 compared to younger groups. The time to conception was significantly shorter for women <30 compared to women ≥35. No pregnancies occurred in women ≥42.Conclusions:Our data support the judicious use of sterilization reversal for infertile women with no male factor through their early forties. Women ≥42 years should be especially counseled as to the very low success rates.

High Intercycle Variability of Day 3 FSH Levels is Useful for Predicting Ovarian Responses But Not Pregnancy Outcomes in IVF

OBJECTIVE: To determine if intercycle variability in day 3 FSH (D3FSH) levels is useful in predicting IVF outcomes. DESIGN: Retrospective analysis of patients undergoing IVF from January 2004 to March 2005 in a large private practice setting. MATERIALS AND METHODS: A total of 2504 fresh, nondonor IVF cycles were available for analysis. This group encompassed a broad spectrum of patients representing typical infertility patients presenting for assisted reproduction. The patients ranged in age from 21-44 and underwent controlled ovarian hyperstimulation by standard midluteal phase GnRH agonist down regulation or GnRH antagonist protocol using recombinant FSH or FSH in combination with HMG. Adjustments were made based on individual responses, and when two or more follicles had attained a minimum mean diameter of 19-20mm, follicular triggering was achieved with hCG and oocyte retrieval was performed 36 hours later. Standard laboratory protocols were followed, including intracytoplasmic sperm injection, assisted hatching for cleavage embryos and extended culture for blastocyst transfer, as clinically appropriate. Ultrasound guided embryo transfer was performed, and all patients received luteal progesterone support. Serum hCG levels were measured 15 days after retrieval, and a clinical pregnancy was defined as the presence of a gestational sac on ultrasound. An estimate of normal intercycle D3FSH variability was derived by regressing standard deviations of replicate measurements against mean FSH in patients 35 years old with D3FSH 10. Patients were placed in the high variability category when their calculated standard deviation was significantly higher than normal. Comparisons were made between patients with normal and high D3FSH variability as well as patients with a single treatment cycle. Continuous and categorical data were analyzed by ANOVA and Chi Square tests, respectively. A value of P 0.05 was considered to be statistically significant. Results are expressed as mean SD. RESULTS: Patients with replicate cycles were older. Relative to patients with normal variability, patients with high D3FSH variability had significantly diminished ovarian responses, with fewer retrieved and mature oocytes but similar fertilization, pregnancy and clinical pregnancy rates. All patients with replicate cycles had significantly lower pregnancy outcomes than patients with single cycles.

Assessment of human sperm acrosome reaction by flow cytometry: validation and evaluation of the method by fluorescence-activated cell sorting**Presented in part at the 48th Annual Meeting of The American Fertility Society, New Orleans, Louisiana, November 2 to 5, 1992.

OBJECTIVE To determine the applicability of flow cytometry to assess human sperm acrosome reaction. DESIGN Prospective evaluation of semen samples incubated overnight for the development of spontaneous acrosome reaction or exposed to the calcium ionophore A23187 (5 microM) for 3 hours for induction of the acrosome reaction. SETTING University-affiliated tertiary care center. PATIENTS Normal healthy volunteers. INTERVENTIONS The spermatozoa were stained with fluorescein isothiocyanate (FITC)-labeled pea agglutinin. The labeled samples were assessed visually and also subjected to analytic flow cytometry and fluorescence-activated cell sorting. MAIN OUTCOME MEASURES Acrosome reaction assessed visually and by flow cytometry. RESULTS Flow cytometric analysis showed a single peak of FITC fluorescence in the washed semen samples. A second peak of lower FITC fluorescence intensity was noted after overnight incubation or exposure to A23187, suggesting loss of fluorescence, which indicated the occurrence of the acrosome reaction. There was a statistically significant correlation between the assessment by the two methods (n = 41). However, although the mean difference between the methods was small (2.49%), the difference between the two methods for each individual sample can vary between -24% to +29%. When the sperm cells were subjected to cell sorting based on green fluorescence intensity, reanalysis and visual scoring verified that the low intensity peak contained a majority of acrosome-reacted spermatozoa (77.52% +/- 2.39%). CONCLUSION These results validated the flow cytometric method for assessment of acrosome-reacted spermatozoa. Although flow cytometry is more objective and less time consuming when many samples are assessed at the same time, the visual method remains a useful and practical procedure in the clinical andrology laboratory.