Uterine length and fertility outcomes: a cohort study in the IVF population.

STUDY QUESTION: What is the relationship between pre-cycle uterine length and IVF outcome (chemical pregnancy, clinical pregnancy, spontaneous abortion and live birth)? SUMMARY ANSWER: Women at extremes of uterine length (<7.0 or >9.0 cm) were less likely to achieve live birth and women with uterine lengths <6.0 cm were also more likely to experience spontaneous abortion. WHAT IS KNOWN ALREADY: A prospective study of 807 women published in 2000 found that implantation and clinical pregnancy rates were highest in women with uterine lengths between 7.0 and 9.0 cm, though the difference was not significant. The relationship between pre-cycle uterine length and live birth has not been evaluated. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of all cycles performed after uterine length measurement at an academic hospital IVF clinic from 2001 to 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 8981 fresh cycles were performed in 5120 adult women with normal uterine anatomy. Women with uterine anomalies (unicornuate, bicornuate, septate or uterus exposed to diethylstilbestrol) were excluded and women with fibroids were identified for subanalysis. Uterine length was measured by uterine sounding. Cycles were divided by uterine length into groups: <6.0 cm (very short, n = 76), 6.0-6.9 cm (short, n = 2014), 7.0-7.9 cm (referent, n = 4984), 8.0-8.9 cm (long, n = 1664) and ≥9 cm (very long, n = 243). Multivariate logistic regression (first-cycle analyses) and generalized estimating equations (all-cycle analyses) were adjusted for age, fibroids and ART treatment (assisted hatching, intracytoplasmic sperm injection) to generate relative risk (RR) of cycle outcomes by uterine length. MAIN RESULTS AND THE ROLE OF CHANCE: Median uterine length in the IVF population was 7.0 cm (interquartile range 7.0-7.8) and was positively associated with BMI (P < 0.001) and fibroids (P = 0.02). Compared with the referent group, women with uterine lengths <6.0 cm were half as likely to achieve live birth (RR: 0.53; 95% confidence interval (CI): 0.35-0.81) and women with lengths of 6.0-6.9 cm were also less likely (RR: 0.91; CI: 0.85-0.98). Cubic regression spline identified a significant inverse U-shaped association whereby women with uterine lengths <7.0 or >9.0 cm were less likely to achieve live birth. Women with lengths <6.0 cm were also more likely to experience spontaneous abortion (RR: 2.16; CI: 1.23-3.78). Results remained consistent when excluding women with a uterine factor diagnosis (n = 8823), when limiting to the first cycle at our institution (n = 5120) and when further restricting to first-ever cycles (n = 3941). LIMITATIONS, REASONS FOR CAUTION: Optimal assessment of uterine length by ultrasound was not feasible due to time and cost limitations, though uterine sounding is a clinically relevant measurement allowing for results with practical implications. Findings from our predominantly Caucasian clinic population may not be generalizable to infertile populations with different ethnic compositions. WIDER IMPLICATIONS OF THE FINDINGS: Reproducibility of results would solidify findings and inform patient counseling in women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this investigation. MD declares relationships with UpToDate (royalties) and WINFertlity (consultant).

Twin pregnancies with a 'vanished' embryo: a higher risk multiple gestation group?

BACKGROUND: Prior studies have documented increased risks to the offspring of IVF singletons that result from a vanished twin pregnancy. We aim to investigate the effect on perinatal outcomes of having an early vanished triplet in IVF twins. METHODS: This is a retrospective cohort study of twins from a large academic IVF practice. Multivariate analysis was performed to examine the perinatal risks--including small for gestational age (SGA), low-birthweight (LBW), preterm delivery and early preterm delivery--in twins that resulted from an early vanished triplet compared with twins without a vanished embryo. RESULTS: Of 829 IVF twin deliveries, 59 were a result of vanished triplet pregnancies (7.1%). There was no significant increase in SGA, LBW or delivery <37 weeks in the vanished triplets compared with other twins; however, the risk of early preterm birth (<32 weeks) was significantly higher (OR 3.09, 95% CI 1.63-5.87) and the length of gestation of these pregnancies was on average 1.5 weeks shorter (P < 0.01). In addition, the unadjusted mean birthweight was lower by nearly 200 g in the vanished triplet pregnancies (P < 0.01). CONCLUSIONS: IVF twin pregnancies with a vanished triplet are at an increased risk for early preterm birth compared with other twin pregnancies. These pregnancies should be recognized at higher risk for early preterm birth and considered for increased obstetrical monitoring. A significant limitation of this study is that the cause for preterm birth was unknown.

[Multidrug-resistant tuberculosis management in three French hospitals]. / Prise en charge de la tuberculose multirésistante dans trois hôpitaux français.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) management is based on specific WHO guidelines. OBJECTIVES: The authors report MDR-TB management, in three French hospitals. METHOD: The authors retrospectively included patients with positive sample for multidrug-resistant Mycobacterium tuberculosis (isoniazid+rifampicin) from January 1, 2000 to December 31, 2005. The management was compared to the French and international prevalent guidelines. RESULTS: Sixteen patients were initially managed for MDR-TB by eight different medical teams over 6 successive years: 12 (75%) presented with primary MDR-TB. Management advice from the national referee center (NRC) for tuberculosis was reported in seven out of 14 treated cases. The median length of the intensive treatment was 2 months (IQR: 1-3). Eight patients (58%) had an overall treatment length of 18 months. The median number of effective drugs prescribed was 4 (IQR: 4-5). Nine patients (64%) were also managed in a sanatorium. Only eight patients (57%) completed the prescribed treatment. Nine patients were clinically cured and still followed-up, six of whom were bacteriologically cured. CONCLUSION: TB-MDR management was not conform to WHO guidelines in our study. Management in a sanatorium, NRC involvement, ambulatory DOT were highly beneficial.

Mycobacterium heckeshornense: an emerging pathogen responsible for a recurrent lung infection.

Mycobacterium heckeshornense was responsible for a severe, recurrent and chronic pulmonary infection in an immunocompetent 65-year-old woman. The pathogen, initially identified as Mycobacterium xenopi and considered as a contaminant, led to a delayed adapted antimicrobial treatment. Although M. heckeshornense is phenotypically closely related to M. xenopi, its pathogenicity is noticeably higher. Accurate molecular diagnosis methods and treatment guidelines are needed to improve the management of patients infected by this uncommon pathogen.

Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop prior to human chorionic gonadotropin.

OBJECTIVE: To study the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in in vitro fertilization cycles. METHODS: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 at Brigham and Women's Hospital were reviewed, and 65 cycles in which oocyte retrieval (ER) was performed following a drop in serum estradiol (E(2)) not associated with intentional withdrawal of gonadotropins were identified. Daily gonadotropin dose was decreased at some time in 25 of these cycles, while the remaining 40 cycles did not have a reduction in gonadotropin dose. A retrospective case-control study of the respective live birth rates and pregnancy loss rates of patients with unpredictable E(2) drops in the 65 study cycles were compared to 65 age matched controls. RESULTS: Live birth rates (32% vs. 35%, p=0.72) and pregnancy loss rates (28% vs. 30%, p=0.76) were similar for all study and control groups respectively. There were no differences in live birth and pregnancy loss rates in cycles undergoing gonadotropin dose reduction (40% vs. 44%, p=0.78 and 29% vs. 39%, p=0.70) and cycles without gonadotropin dose reduction (28% vs. 30%, p=0.81 and 27% vs. 20%, p=0.72). CONCLUSIONS: In the absence of coasting, a drop in serum estradiol levels during GnRH-agonist downregulated controlled ovarian hyperstimulation for IVF prior to hCG is not associated with a decrease in live birth rates or pregnancy loss rates.

Ethnic background and in vitro fertilization outcomes.

OBJECTIVE: To compare IVF outcomes among women of different ethnic backgrounds. METHOD: This was a retrospective cohort study. Between August 1994 and March 1998, the first IVF cycles of 1039 white, 43 African American, 18 Hispanic, and 35 Asian women were examined. RESULT: Ages and day 3 FSH levels did not differ significantly among patients. African Americans weighed more than other ethnic groups and were also more likely to have tubal factor infertility than whites. IVF cycle characteristics did not vary among the ethnic groups with the exception that African Americans had a higher level of estradiol on day of HCG than whites. Pregnancy outcomes did not differ among the ethnic groups. The percentage of ectopic pregnancies, spontaneous abortions, and successful live births was similar among the groups. CONCLUSION: Our data showed no significant difference in pregnancy outcomes with IVF among the ethnic groups.

[Epidemiology and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Ile de France area during 2001]. / Epidémiologie et résistance aux antibiotiques de Streptococcus pneumoniae en Ile de France en 2001.

OBJECTIVE: The authors wanted to assess the level of Streptococcus pneumoniae antibiotic resistance in Ile de France. METHOD: In 2001, 637 clinical strains of S. pneumoniae were prospectively collected from 32 microbiology laboratories. RESULTS: Fifty one percent of strains were isolated from children under 15 years of age and 49% from adults. In children, 76% of strains came from otitis media, 20% from blood culture, in adults most strains (92%) came from blood culture. The overall prevalence of non-susceptible penicillin pneumococci was 61% higher in children (73%) than in adults (50%). Among the non-susceptible penicillin pneumococci 21.8% were resistant (CMI > 1 mg/l). Strains with decreased susceptibility to amoxicillin and cefotaxime were 38% and 17% respectively. Resistant strains to these two drugs (CMI > 2 mg/l) were rare 2.6% and 0.4% respectively. Among other antimicrobial agents, rate of resistance was 63% to erythromycin, 47% to cotrimoxazole, 40% to tetracycline, and 23% to chloramphenicol. The most frequent serogroups were serogroups 19 and 14, respectively 23% and 18%. Serotypes included in heptavalent vaccine covered 90% of children strains under 2 years of age. CONCLUSIONS: The prevalence of resistance to penicillin was high in children particularly in otitis media pus (76%).

Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

PURPOSE: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. METHODS: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. RESULTS: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. CONCLUSION: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Dynamic nuclear polarization at 9T using a novel 250GHz gyrotron microwave source.

In this communication, we report enhancements of nuclear spin polarization by dynamic nuclear polarization (DNP) in static and spinning solids at a magnetic field strength of 9T (250 GHz for g=2 electrons, 380 MHz for 1H). In these experiments, 1H enhancements of up to 170+/-50 have been observed in 1-13C-glycine dispersed in a 60:40 glycerol/water matrix at temperatures of 20K; in addition, we have observed significant enhancements in 15N spectra of unoriented pf1-bacteriophage. Finally, enhancements of approximately 17 have been obtained in two-dimensional 13C-13C chemical shift correlation spectra of the amino acid U-13C, 15N-proline during magic angle spinning (MAS), demonstrating the stability of the DNP experiment for sustained acquisition and for quantitative experiments incorporating dipolar recoupling. In all cases, we have exploited the thermal mixing DNP mechanism with the nitroxide radical 4-amino-TEMPO as the paramagnetic dopant. These are the highest frequency DNP experiments performed to date and indicate that significant signal enhancements can be realized using the thermal mixing mechanism even at elevated magnetic fields. In large measure, this is due to the high microwave power output of the 250 GHz gyrotron oscillator used in these experiments.

Smoking induces oxidative stress inside the Graafian follicle.

BACKGROUND: A growing body of evidence indicates that pro-oxidant/antioxidant balance inside ovarian follicles plays an important role in folliculogenesis. Over 20% of women of reproductive age in Europe and the USA regularly smoke cigarettes. The impact of tobacco smoking on the intrafollicular markers of oxidative stress has not been fully elucidated. The objective of the present study was to test the hypothesis that cigarette smoking affects the intrafollicular redox milieu. METHODS: In follicular fluid samples originating from 108 IVF patients, lipid peroxidation was assessed by the thiobarbituric reactive substances method and total antioxidative capacity was quantified by the luminol enhanced chemiluminescence method. The level of patients' exposure to the cigarette smoke was evaluated by measuring the follicular fluid cotinine concentration by means of radioimmunoassay. RESULTS: Intrafollicular exposure to cigarette smoke metabolites was associated with a significant increase in follicular lipid peroxidation intensity (P < 0.001), which was accompanied by a significant decrease in the local antioxidative potential (P = 0.004). CONCLUSION: The results indicate that active smoking affects the pro-oxidant/antioxidant balance inside the pre-ovulatory ovarian follicle by inducing intrafollicular oxidative stress. This provides another possible explanation for impaired folliculogenesis in female smokers.

Effects of Mullerian anomalies on in vitro fertilization outcome.

PURPOSE: To assess the effect of Mullerian anomalies on pregnancy rates in women undergoing in vitro fertilization (IVF). METHODS: The records of 37 patients with and 819 patients without Mullerian anomalies undergoing a first cycle of IVF between December 1995 and July 1998 were included in this retrospective study. Outcome variables included maximal estradiol level, number of days of stimulation, number of follicles, number of oocytes, fertilization rate, and ongoing/livebirth pregnancy rate. RESULTS: Patients with Mullerian anomalies had a significantly lower ongoing pregnancy rate (8.3%) than did controls (24.8%). No patients with diethylstilbestrol (DES)-related anomalies had an ongoing pregnancy. CONCLUSIONS: Among women with Mullerian anomalies, those with DES exposure in utero demonstrated the poorest outcome.

Uterine leiomyomas and their effect on in vitro fertilization outcome: a retrospective study.

PURPOSE: The effect of uterine leiomyomas on the outcome of in vitro fertilization (IVF) treatment has been controversial. This study was undertaken to clarify influence of fibroids on IVF success, in a large population with age and other potential confounding variables controlled for in the analysis. METHODS: A population of 141 patients with and 406 without leiomyomata undergoing their first IVF cycle was studied. RESULTS: The association between uterine leiomyomas and assisted reproduction treatment outcome was not statistically significant (OR = 0.73, 95% CI: 0.49-1.19, p = 0.21) after controlling for age and other risk factors. Also, fibroids neither affected the risk of spontaneous abortion (OR = 1.06, 95% CI: 0.44-2.60) nor the risk of ectopic pregnancy (OR = 0.78, 95% CI: 0.08-8.02). Location of fibroids (intramural vs. submucosal/subserosal) and their size had no significant effect on pregnancy outcome. CONCLUSIONS: Results from our analyses indicated that in vitro fertilization outcome was not affected by the presence of uterine leiomyomas. Therefore, in patients with normal uterine cavities and fibroids less than a certain size (i.e., < 7 cm), undergoing myomectomies as a prerequisite for assisted reproduction treatment is seriously questionable.

The prognostic value of age and follicle-stimulating hormone levels in women over forty years of age undergoing in vitro fertilization.

PURPOSE: Basal follicle-stimulating hormone (FSH) and age are predictors of successful outcome in in vitro fertilization (IVF). More recently, the clomiphene citrate challenge test (CCCT) has been proposed as a better way to predict IVF outcome than FSH alone. The purpose of this study was to determine which indicator of ovarian reserve--basal (day 3) FSH or the CCCT--is the better predictor of IVF success in the critical age group of women over the age of 40. METHODS: In this retrospective study, basal FSH and clomiphene-stimulated FSH levels from 104 women who underwent 175 cycles of IVF were analyzed. RESULTS: Neither basal FSH level nor stimulated FSH level alone were statistically significant predictors of IVF success; however, no patient with a day 3 FSH level > 11.1 mIU/ml or a stimulated day 10 FSH level > 13.5 mIU/ml conceived and carried a pregnancy. All ongoing pregnancies occurred in the first two cycles of IVF. CONCLUSIONS: Clear prognostic cutoff values were found to predict IVF success in women over age 40. IVF programs should consider limiting the number of cycles of IVF in women above age 40.

Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection.

OBJECTIVE: To determine whether clinical or laboratory factors influence development of triploid (3PN) zygotes after ICSI. DESIGN: Retrospective review. SETTING: The assisted reproductive technology program of Brigham and Women's Hospital. PATIENT(S): Patients undergoing ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycles were divided into two groups: group A, cycles with one or more 3PN zygotes after ICSI, and group B, cycles with no 3PN zygotes. Age, amount of gonadotropin administered, peak estradiol levels, number of follicles, number of oocytes retrieved and injected, time between retrieval and injection, oocyte abnormalities, sperm type and motile count, percentage of diploid zygotes, and ongoing pregnancy rates were compared between groups. RESULT(S): Compared with patients in group B, those in group A received fewer ampoules of gonadotropins, had higher estradiol levels, and had more follicles on the day of hCG administration, oocytes, immature oocytes and oocytes injected and lower percentages of diploid zygotes. However, ongoing pregnancy rates did not differ between groups. CONCLUSION(S): Patients who produce 3PN zygotes after ICSI are high responders to ovarian stimulation. The appearance of such embryos is not associated with lower ongoing pregnancy rates and should not necessarily dictate alterations in ovarian stimulation protocols.

The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer.

OBJECTIVE: To select patients for day 3 vs. day 5 embryo transfer. DESIGN: Retrospective analysis of assisted reproduction technology (ART) cycles comparing outcomes of day 3 and day 5 transfers. SETTING: ART program of Brigham and Women's Hospital. PATIENT(S): Patients with day 3 or day 5 embryo transfers (n = 221 and 141, respectively). INTERVENTION(S): Cycles with eight or more zygotes were stratified by the number of eight-cell embryos available on day 3 (none, one or two, or three or more). MAIN OUTCOME MEASURE(S): Number of blastocysts, implantation rates, ongoing pregnancy rates, and number of fetal heart beats. RESULT(S): With no eight-cell embryos on day 3, 0% and 33% pregnancies resulted from day 5 vs. day 3 transfers. With one or two eight-cell embryos on day 3, ongoing and high order multiple rates were not different between day 3 and day 5 transfers. With three or more eight-cell embryos, day 5 transfer resulted in a decrease in multiple gestations but no difference in ongoing pregnancy rates compared with day 3 transfer. CONCLUSION(S): With no eight-cell embryos on day 3, a day 3 transfer is warranted. With one or two eight-cell embryos, any benefit of day 5 transfer appears to be equivocal. With three or more eight-cell embryos, day 5 transfer is recommended.

Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis.

OBJECTIVE: To evaluate whether the presence of antiphospholipid antibodies among women undergoing IVF affects the likelihood of IVF success. DESIGN: A meta-analysis of seven eligible studies on antiphospholipid antibodies and IVF outcome. MAIN OUTCOME MEASURE(S): Odds ratios (ORs) and 95% confidence intervals (CIs) of an association between the presence of antiphospholipid antibodies and both clinical pregnancy and live birth from IVF. RESULT(S): There was no significant association between antiphospholipid abnormalities and either clinical pregnancy (OR 0.99; 95% CI 0.64-1.53) or live birth (OR 1.07; 95% CI 0.66-1.75) in IVF patients. CONCLUSION(S): The measurement of antiphospholipid antibodies is not warranted in patients undergoing IVF.

Recent trends in assisted reproductive techniques and associated outcomes.

OBJECTIVE: We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. METHODS: We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994-1998. RESULTS: Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994-1995 to 22.5% for IVF and 28.0% for GIFT in 1997-1998 (P < or = .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. CONCLUSION: There were significant improvements in the success rates for IVF and GIFT from 1994-1998 that correlated with changes in ovulation induction regimens.

Influence of age, diagnosis, and cycle number on pregnancy rates with gonadotropin-induced controlled ovarian hyperstimulation and intrauterine insemination.

OBJECTIVE: To determine whether age, diagnosis, and cycle number influence cycle fecundity associated with gonadotropin-induced controlled ovarian hyperstimulation/IUI. DESIGN: Retrospective analysis. SETTING: The Center for Reproductive Medicine at the Brigham and Women's Hospital, a tertiary care academic medical center. PATIENT(S): Two hundred seventy-four women who underwent controlled ovarian hyperstimulation with gonadotropins and IUI. INTERVENTION(S): Infertility treatment with gonadotropins and IUI. MAIN OUTCOME MEASURE(S): Pregnancy rates according to patient age, infertility diagnosis, and number of treatment cycles. RESULT(S): Pregnancy rates decreased with increasing patient age. The cumulative pregnancy rates varied greatly by diagnosis from 13% for patients with male factor infertility to 84% for patients with ovulatory factor infertility. Average cycle fecundity was considerably less varied by diagnosis. All pregnancies among patients with male factor infertility and tubal factor infertility were achieved during the first two cycles. CONCLUSION(S): There is a clear age-related decline in fecundity associated with gonadotropin-induced controlled ovarian hyperstimulation/IUI. Patients <40 years of age and those with male factor infertility or tubal factor infertility have a particularly poor prognosis.