Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF.

STUDY QUESTION: Are perinatal outcomes improved in singleton pregnancies resulting from fresh embryo transfers performed following unstimulated/natural cycle IVF (NCIVF) compared with stimulated IVF? SUMMARY ANSWER: Infants conceived by unstimulated/NCIVF have a lower risk of being low birthweight than infants conceived by stimulated IVF; however, this risk did not remain significant after adjusting for gestation age. WHAT IS ALREADY KNOWN: Previous studies have shown that infants born after modified NCIVF have a higher average birthweight and are less likely to be low birthweight than those infants conceived with conventional stimulated IVF. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of singleton live births in non-smoking women undergoing fresh IVF-embryo transfer cycles from 2007 to 2013 in a single IVF center. The women were stratified by stimulated (n = 174) or unstimulated (n = 190) IVF exposure status. Unstimulated/NCIVF is defined as IVF without the use of exogenous gonadotrophins, and only includes the use of HCG to time oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Demographic data including maternal age, BMI, infertility diagnosis and IVF cycle characteristics were collected. The perinatal outcomes used for comparison between the two study groups were length of gestation, birthweight, preterm delivery, very preterm delivery, low birthweight, small for gestational age and large for gestational age. MAIN RESULTS AND ROLE OF CHANCE: Although women in the NCIVF group were older than those in the stimulated group (35.0 versus 34.2 years, P < 0.05), parity and history of prior ART cycles were comparable between the groups. The mean birthweight was significantly higher in the NCIVF group by 163 g than in the stimulated group (3436 ± 420 g versus 3273 ± 574 g, P < 0.05). Consistent with this finding, there were also less low birthweight (<2500 g) infants in the NCIVF group versus stimulated group (1 versus 8.6%, P < 0.005). The reduction in risk for low birthweight in the NCIVF group remained significant after adjustment for maternal age, infertility diagnosis, ICSI, number of embryos transferred and blastocyst transfer (odds ratio (OR) 0.07; 95% CI 0.014-0.35). As NCIVF group had less preterm infants, additional adjustment for gestational age was performed and this showed a tendency towards lower risk of low birthweight in NCIVF (OR 0.11; 95% CI 0.01-1.0). While gestational age at delivery was comparable between the groups, both preterm births (<37 weeks gestation) (31 versus 42%, P < 0.05) and very preterm births (<32 weeks gestation) (0.52 versus 6.3%, P < 0.005) were significantly reduced in the NCIVF group. However, after adjustment for potential confounders, the reduction in risk of preterm and very preterm delivery associated with the NCIVF group was no longer significant (OR 1.1; 95% CI 0.48-2.5). LIMITATIONS, REASONS FOR CAUTION: Limitations of this study are the retrospective nature of the data collection and the lack of information about parental characteristics associated with birthweight. WIDER IMPLICATIONS OF THE FINDINGS: The improved perinatal outcomes following successful unstimulated/NCIVF suggest that this treatment should be considered as a viable option for infertile couples. NCIVF could reduce potential adverse perinatal outcomes such as low birthweight related to fresh embryo transfers performed following ovarian stimulation. The etiology of the improved perinatal outcomes following NCIVF needs to be explored further to determine if the improvement is derived from endometrial factors versus follicular/oocyte factors. STUDY FUNDING/COMPETING INTERESTS: The study was supported by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD K12HD047018 (W.M.), NICHD K12HD001271 (L.A.K.). The authors have no competing interests.

Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

Live births achieved via IVF are increased by improvements in air quality and laboratory environment.

Infertility is a common disease, which causes many couples to seek treatment with assisted reproduction techniques. Many factors contribute to successful assisted reproduction technique outcomes. One important factor is laboratory environment and air quality. Our facility had the unique opportunity to compare consecutively used, but separate assisted reproduction technique laboratories, as a result of a required move. Environmental conditions were improved by strategic engineering designs. All other aspects of the IVF laboratory, including equipment, physicians, embryologists, nursing staff and protocols, were kept constant between facilities. Air quality testing showed improved air quality at the new IVF site. Embryo implantation (32.4% versus 24.3%; P < 0.01) and live birth (39.3% versus 31.8%, P < 0.05) were significantly increased in the new facility compared with the old facility. More patients met clinical criteria and underwent mandatory single embryo transfer on day 5 leading to both a reduction in multiple gestation pregnancies and increased numbers of vitrified embryos per patient with supernumerary embryos available. Improvements in IVF laboratory conditions and air quality had profound positive effects on laboratory measures and patient outcomes. This study further strengthens the importance of the laboratory environment and air quality in the success of an IVF programme.

Follicular and estradiol parameters that improve success with natural cycle in vitro fertilization.

OBJECTIVE: To describe clinical thresholds for follicle size and estradiol levels to optimize success with natural cycle in vitro fertilization (NCIVF). STUDY DESIGN: Descriptive cohort of candidates for stimulated IVF, < 43 years old, with regular menstrual cycles, regardless of ovarian reserve or fertility treatment history. Patients underwent NCIVF, defined as oocyte retrieval, fertilization and embryo transfer after human chorionic gonadotropin (hCG) trigger without luteinizing hormone (LH) suppression or ovarian stimulation medications. RESULTS: A total of 422 patients underwent 821 NCIVF cycles. Clinical pregnancy rates per cycle start, retrieval, and transfer were 13%, 17%, and 32%, respectively, for all patients and 19%, 25%, and 49% for patients < 30 years old. The threshold estradiol level on day of hCG was 101 pg/mL; below that level no clinical pregnancies occurred. Likewise, a mean follicular diameter > 15 mm was the optimal threshold for hCG trigger. Anti-Müllerian hormone and follicle-stimulating hormone levels did not predict success in NCIVF, and no statistical difference in clinical pregnancy rates between day 3 or day 5 embryo transfer was observed. CONCLUSION: NCIVF is an effective therapy for infertile patients regardless of their ovarian reserve. Cycle cancellation due to a premature LH surge can be reduced, without sacrificing success, by triggering smaller follicles above a threshold level of estradiol.

Falling estradiol levels on day after human chorionic gonadotropin administration in assisted reproductive technology cycles are not predictive of decreasing oocyte maturity or pregnancy rates.

OBJECTIVE: To determine whether a fall in serum estradiol levels the day after human chorionic gonadotropin (hCG) administration correlated with the incidence of a positive serum hCG in fresh, nondonor assisted reproductive technology (ART) cycles. STUDY DESIGN: A total of 1,969 women undergoing fresh, nondonor ART cycles at a tertiary referral fertility clinic between January 1, 2003, and January 31, 2010, were included and retrospectively analyzed. Primary outcome measures were oocyte maturity and positive serum beta-hCG. RESULTS: A total of 1,969 cycles met inclusion criteria, of which 1,875 had the same or increasing serum estradiol levels and 94 had decreasing estradiol levels on the morning after hCG trigger administration (6-11 hours after hCG injection). There were no statistically significant differences between the groups with respect to age, baseline FSH levels, type of pituitary downregulation, total ampules of gonadotropin administered, days of stimulation, average number of oocytes retrieved, or oocyte maturity. Probability of pregnancy in women with declining E2 levels after hCG trigger administration did not differ from patients with the same or rising estradiol levels (53% vs. 54%, p = 0.89). CONCLUSION: Absolute change in estradiol levels the morning after beta-hCG administration were not predictive of positive hCG.

GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes.

Gonadotrophin-releasing hormone (GnRH) antagonist rescue is performed by replacing a GnRH agonist with a GnRH antagonist in patients with rapidly rising serum oestradiol who are at risk of ovarian hyperstimulation syndrome (OHSS) during stimulation. It results in a rapid reduction in serum oestradiol, allowing for the avoidance of cycle cancellation and the continuation of exogenous gonadotrophin administration. A total of 387 patients who underwent GnRH antagonist rescue for ovarian hyperresponse were compared with 271 patients who did not receive GnRH antagonist rescue and had oestradiol concentrations >4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration. GnRH antagonist rescue decreased the mean oestradiol concentration by 35% on the first day of use. There was no difference in oocyte maturity (82% versus 83%) or fertilization rate (69% versus 67%) between the antagonist rescue and comparison groups, respectively. The percentage of high-grade embryos on day 3 and the blastocyst development rate were also similar between groups. The live-birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy. Gonadotrophin-releasing hormone (GnRH) antagonist rescue is a protocol to reduce the risk of ovarian hyperstimulation syndrome (OHSS) in assisted reproduction treatment. Patients who have a hyperresponse to medication during their treatment cycle have their GnRH agonist discontinued and a GnRH antagonist started in its place. This causes a rapid reduction in oestrogen concentrations and allows for the continuation of stimulation medication. We evaluated the effectiveness of this protocol by comparing patients who had GnRH antagonist rescue against high-responding patients who did not receive GnRH antagonist rescue. GnRH antagonist rescue resulted in a 35% reduction in oestrogen concentration and only a 1.5% cycle cancellation rate. There were no differences in oocyte maturity or fertilization between the two groups. There were no differences in the quality of day-3 and day-5 embryos between the two groups. The live birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue reduced serum oestradiol concentrations and enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy.

Epidemiology of myomas.

Fibroids are a prevalent disorder occurring in at least half of American reproductive-age women. In general, the incidence and size increases with age. Most women never attribute or report any symptoms from their fibroids, and because of this the actual contribution of disease to symptoms of pelvic pain,menstrual symptoms, and infertility is poorly understood. The presence of fibroids can lead to multiple and disabling difficulties. Fibroids may cause pain and menstrual bleeding to the point of anemia. Fibroids clearly reduce fertility,increase preterm labor and delivery, and markedly increase the risk for cesarean delivery. Because the incidence varies according to population of interest, fibroids may explain some health disparities in different populations. For example,African Americans have a relatively poor outcome with assisted reproductive techniques compared with whites. Controlling for fibroid disease may explain this disparity, at least in part. Fibroids represent a tremendous public health burden on women and economic cost on society. Strategies to prevent, limit growth, and treat nonsurgically are needed. Fundamental and significant questions remain about fibroid disease,such as whether different clinical disease phenotypes (multiple versus single leiomyomas) contribute equally to symptoms and possess an equal likelihood of disease progression. For epidemiologic assessment of disease, a scoring system is urgently needed. Well-designed, controlled, prospective studies are still needed to define the natural history and correlate the presence of disease with symptomatology in women.

Impact of a prior cesarean delivery on embryo transfer: a prospective study.

OBJECTIVE: To determine whether a history of prior cesarean delivery (CD) makes ET more difficult and impacts pregnancy outcomes. DESIGN: Prospective cohort study. SETTING: Tertiary care military facility. PATIENT(S): One hundred ninety-four patients with previous delivery undergoing IVF/intracytoplasmic sperm injection (ICSI)-ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth (primary), positive hCG, clinical pregnancy, and time to perform ET. RESULT(S): There was no statistically significant difference between patients with a history of only vaginal deliveries versus those with a history of CD for live birth (39% vs. 32%), positive hCG (56% vs. 53%), or clinical pregnancy (49% vs. 41%). Embryo transfers took longer in the history of CD group (157 vs. 187 seconds) and were more likely to have mucus (27% vs. 45%) or blood (8% vs. 21%) on the catheter. CONCLUSION(S): Embryo transfers performed on patients with a prior CD took 30 seconds longer. They were also more likely to have blood or mucus on the catheter. Despite the apparently more difficult transfers, pregnancy outcomes were not different between the two groups.

Strategy for elucidating differentially expressed genes in leiomyomata identified by microarray technology.

OBJECTIVE: cDNA microarray technology identifies genes that are differentially expressed between tissues. Our previous study identified several genes that might contribute to the fibroid phenotype. We therefore sought to confirm genes involved in three distinct signal transduction pathways. DESIGN: Evaluation of differential mRNA and protein expression of Dlk, Frizzled-2, and CD-24 in fibroids compared with adjacent myometrium. University hospital. PATIENT(S): Five women undergoing medically indicated hysterectomy for symptomatic fibroids. INTERVENTION(S): Microarray analysis of up to 33000 genes, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time RT-PCR, Western blot, and immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of mRNA transcripts and protein in fibroid compared with myometrium.A more extensive microarray confirmed differential expression of Frizzled-2 and CD-24 but did not confirm Dlk overexpression. RT-PCR and real-time PCR demonstrated equivalent Dlk mRNA expression between fibroid and myometrium (ratio, 1.02), a slight Frizzled-2 overexpression (ratio, 2.09), and robust CD-24 overexpression in fibroids (ratio, 12.35). Western blot and immunohistochemistry confirmed Frizzled-2 overexpression, but did not confirm Dlk overexpression. CONCLUSION(S): Microarray technology is the first phase of tissue evaluation, but changes in gene expression must be confirmed. Confirmed genes can then be used to generate hypotheses testing their involvement in fibroid development.

Utilization and success rates of unstimulated in vitro fertilization in the United States: an analysis of the Society for Assisted Reproductive Technology database.

OBJECTIVE: To examine the utilization and outcomes of natural cycle (unstimulated) IVF as reported to the Society of Assisted Reproductive Technology (SART) in 2006 and 2007. DESIGN: Retrospective analysis. SETTING: Dataset analysis from the SART Clinical Outcome Reporting System national database. PATIENT(S): All patients undergoing IVF as reported to SART in 2006 and 2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Utilization of unstimulated IVF; description of patient demographics; and comparison of implantation and pregnancy rates between unstimulated and stimulated IVF cycles. RESULT(S): During 2006 and 2007 a total of 795 unstimulated IVF cycles were initiated. Success rates were age dependent, with patients <35 years of age demonstrating clinical pregnancy rates per cycle start, retrieval, and transfer of 19.2%, 26.8%, and 35.9%, respectively. Implantation rates were statistically higher for unstimulated compared with stimulated IVF in patients who were 35 to 42 years old. CONCLUSION(S): Unstimulated IVF represents <1% of the total IVF cycles initiated in the United States. The pregnancy and live birth rates per initiated cycle were 19.2% and 15.2%, respectively, in patients <35 years old. The implantation rates in unstimulated IVF cycles compared favorably to stimulated IVF. Natural cycle IVF may be considered in a wide range of patients as an alternative therapy for the infertile couple.

Enough is enough! Patients who do not conceive on 600 IU/d of gonadotropins show no improvement from an additional 150 IU of LH activity.

Studies have suggested that supplemental LH improves outcomes in assisted reproductive technology (ART) cycles. In this retrospective review, an additional 150 IU of LH activity did not improve ART outcomes in women undergoing a second round of IVF/ intracytoplasmic sperm injection (ICSI) after an initial failed cycle using 600 IU of gonadotropins.

Are there ethnic differences in pregnancy rates in African-American versus white women undergoing frozen blastocyst transfers?

OBJECTIVE: To determine whether frozen-thawed blastocyst transfer pregnancy rates (PR) are lower in African-American compared with white women. DESIGN: Retrospective review of frozen blastocyst cycles. SETTING: University-based assisted reproductive technology (ART) program. PATIENT(S): All patients who underwent a frozen blastocyst transfer between 2003 and 2008. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): One hundred sixty-nine patients underwent transfer of a frozen-thawed blastocyst. African-American women had a higher incidence of leiomyoma (40% vs. 10%) and tubal and uterine factor infertility. There was no difference in the live birth rate for African-American patients (28.0%) compared with white patients (30.2%). Of the patients who underwent a frozen-thawed blastocyst transfer, 58% (n=98) had their fresh, autologous IVF cycle, which produced the cryopreserved blastocyst, at Walter Reed Medical Center. A higher peak serum E2 level was noted in African-American patients (5,355 pg/mL) compared with white patients (4,541 pg/mL). During the fresh cycle, the live birth rates between African-American and white patients were significantly different at 16.7% versus 39.7%, respectively. CONCLUSION(S): Live birth rates after frozen blastocyst transfer are not different between African-American and white women despite a fourfold higher incidence of leiomyomas in African-American women.

Proficiency in oocyte retrieval: how many procedures are necessary for training?

OBJECTIVE: To determine a minimum number of procedures required for proficiency in oocyte retrieval and to characterize skill acquisition. DESIGN: Retrospective analysis. SETTING: Reproductive endocrinology and infertility fellowship training program. SUBJECT(S): Fellows in training from 2005 to 2007 and 2008 to 2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proficiency scores were calculated by dividing the number of oocytes retrieved by oocytes expected. The 2005 to 2007 trainees were grouped and proficiency scores calculated as an average during specific points in their training. The 2008 to 2010 trainees were compared individually to determine differences in individual skill acquisition. RESULT(S): A greater number of oocytes were retrieved than expected, 8.6 versus 7.6. A relatively lower proficiency score was noted during the first 10 trainee aspirations (proficiency score=1.1) compared with subsequent aspirations (proficiency score=1.25 for retrievals 11-20, proficiency score=1.21 for retrievals 21-30 and >31). When individual fellows' scores were calculated, the majority achieved proficiency by 20 aspirations, and all but one trainee achieved the mean staff proficiency score by 50 retrievals. CONCLUSION(S): Regardless of a trainee's initial proficiency in oocyte retrieval, there were no statistically significant differences in the learning curve between trainees. The majority of individual fellows in training demonstrate proficiency in follicular aspirations within 20 procedures; however, a minority may require 50 procedures to achieve the proficiency of an attending physician.

Experience with a patient-friendly, mandatory, single-blastocyst transfer policy: the power of one.

OBJECTIVE: To determine whether a mandatory single-blastocyst transfer (mSBT) algorithm reduced multiple gestation rates without sacrificing clinical pregnancy rates. DESIGN: Retrospective review. SETTING: U.S. university-based assisted reproductive technology (ART) program. PATIENT(S): All women younger than 38 years undergoing their first ART cycle from 2009 to 2010 with ≥4 high-grade embryos on day 3 after oocyte retrieval (patients from 2009 were the "before" group, and patients completing ART under the mSBT policy in 2010 were the "after" group). INTERVENTION(S): mSBT algorithm. MAIN OUTCOME MEASURE(S): Multiple gestation and clinical pregnancy rates. RESULT(S): Of the qualified patients, 136 women met inclusion criteria (62 from 2009, 74 from 2010). The baseline demographics were similar between the groups. Statistically significantly fewer blastocysts were transferred per patient in 2010 compared with 2009 (1.5 vs. 1.9). The clinical pregnancy rates before (67.7%) or after (63.5%) the mSBT policy were not statistically significantly different. Multiple gestation rates were statistically significantly reduced, from 43.8% (2009) to 14.6% (2010) after the mSBT policy was instituted. More patients from 2010 had ≥1 blastocyst cryopreserved compared with 2009 (52.9% vs. 30.6%). CONCLUSION(S): A novel single-blastocyst transfer algorithm reduced multiple gestation rates and improved cryopreservation rates without compromising clinical pregnancy rates in good-prognosis patients.

The pathophysiology of ovarian hyperstimulation syndrome: an unrecognized compartment syndrome.

OBJECTIVE: To compare and contrast the pathophysiology of ovarian hyperstimualtion syndrome (OHSS) with known syndromes of increased intraabdominal pressure (IAP), and to explore the relationship of increased IAP with symptom severity in OHSS. DESIGN: Literature review. MAIN OUTCOME MEASURE(S): Correlation of OHSS symptoms with IAP; effects of paracentesis on IAP in patients with OHSS. SETTING: Academic Research Institution. INTERVENTION(S): None. RESULT(S): OHSS involves a rapid accumulation of volume (from 1.5-17 liters) in the peritoneal cavity that can lead to organ dysfunction, including respiratory impairment and oliguria. In published reports of 20 moderate-to-severe OHSS patients in whom IAP was measured, IAP was found to be elevated to a pathologic range. The increased IAP indicates that OHSS may be considered a compartment syndrome and meets criteria for abdominal compartment syndrome in advanced cases. For this reason, management of OHSS should include reduction of pressure by paracentesis to avoid morbidity and syndrome progression. In addition, measurement of IAP may help to classify the stage of OHSS. CONCLUSION(S): IAP was found to be elevated in the few cases of OHSS in which it was measured, substantiating the conclusion that OHSS may be considered a compartment syndrome. An understanding of the pathophysiology of increased intrabdominal pressure is useful in the management of OHSS.

Ovarian follicular flushing among low-responding patients undergoing assisted reproductive technology.

A randomized comparison trial was performed to evaluate whether follicular reaspiration with use of a double-lumen retrieval needle improves oocyte recovery when compared with direct follicular aspiration among low-responding patients undergoing ART. There were no differences observed in the number of oocytes retrieved (single lumen: 6.5 +/- 2.2 oocytes, double lumen: 7.2 +/- 2.3 oocytes) whereas follicular reaspiration with the double-lumen retrieval needle resulted in a twofold increase in procedure time.

Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression.

OBJECTIVE: To determine if curcumin has an antiproliferative effect on leiomyoma cells via apoptosis induction and whether curcumin impacts extracellular matrix (ECM) production by assessing the fibronectin expression in leiomyoma cells treated with curcumin. DESIGN: Tissue culture study of immortalized human leiomyoma and patient-matched myometrial cells treated with curcumin. SETTING: University hospital. PATIENT(S): Immortalized leiomyoma and myometrial cells from patients with symptomatic leiomyomata. INTERVENTION(S): Tissue culture, followed by proliferation studies, RNA, and protein analysis. MAIN OUTCOME MEASURE(S): Cell proliferation, alteration in apoptotic signaling pathways. RESULT(S): Curcumin demonstrated an antiproliferative effect on leiomyoma cell lines (IC50 = 20 muM). Importantly, no statistically significant inhibition of growth was observed when patient-matched myometrial cells were exposed to equivalent concentrations of curcumin. Curcumin stimulated caspase-3 and caspase-9 expression while inhibiting extracellular signal-regulated kinase 1 (ERK 1), ERK 2, and nuclear factor kappa B (NF-kappaB), suggesting regulation of leiomyocyte apoptosis. Finally, curcumin inhibited expression of fibronectin in leiomyoma cells. CONCLUSION(S): Our findings demonstrate that curcumin inhibited uterine leiomyoma cell proliferation via regulation of the apoptotic pathway, and inhibited production of the ECM component fibronectin. Curcumin provides a novel direction for leiomyoma therapies.

Activating transcription factor 3 gene expression suggests that tissue stress plays a role in leiomyoma development.

OBJECTIVE: To determine whether expression of the stress response gene ATF3 and related members of activator protein complex-1, cJun and cFos, were altered in leiomyoma compared with myometrium, and whether this difference might correlate with leiomyoma size or race. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): Fifteen women undergoing hysterectomy for symptomatic leiomyoma. INTERVENTION(S): Tissue procurement, RNA isolation, reverse-transcriptase polymerase chain reaction, real-time reverse-transcriptase polymerase (RT-PCR) chain reaction, immunohistochemistry, Western blot. MAIN OUTCOME MEASURE(S): Expression of mRNA and protein in leiomyoma and patient-matched myometrium. RESULT(S): mRNA transcripts of ATF3 were decreased in leiomyoma compared with matched myometrium by both RT-PCR and real-time RT-PCR. The decrease was greater than fivefold in a majority of samples. The reduction seen in ATF3 mRNA expression did not show a correlation with race and leiomyoma size. Surprisingly, immunohistochemistry and Western blot analysis demonstrated an elevation of ATF3 protein expression by a mean of 2.9-fold. Transcripts of related AP-1 genes, cJun and cFos, were significantly decreased by a mean of -29.57 for cJun and -23.78 for cFos, but there was no significant change in protein expression of the two transcription factors. CONCLUSIONS: Alterations in ATF3 gene expression resemble the response to mechanical and ischemic stress reported in other tissues. Results suggested that ATF3 protein expression was increased in leiomyoma, and may reflect increased tissue stress.

Balloon fluoroscopy as treatment for intrauterine adhesions: a novel approach.

OBJECTIVE: To report a unique fluoroscopically guided approach to treat severe intrauterine adhesions and cervical stenosis using balloon hysteroplasty. DESIGN: Case report. SETTING: Military-based fertility center. PATIENT(S): A 33-year-old woman undergoing assisted reproductive technology whose uterus could not be cannulated because of the development of intrauterine synechiae and cervical stenosis after a post-IUI infection that was further complicated by a prominent lower uterine segment-filling defect in the location of a prior cesarean delivery scar. INTERVENTION(S): Fluoroscopic cannulation and balloon uterine dilation. MAIN OUTCOME MEASURE(S): Resolution of synechiae by hysterosalpingogram and successful uterine cannulation. RESULT(S): A postprocedure hysterosalpingogram demonstrated a normalized uterine cavity with the exception of a persistent prominent lower uterine segment-filling defect from a prior cesarean delivery. A frozen ET cycle was performed successfully. CONCLUSION(S): Hysteroplasty, using standard interventional radiographic techniques, may provide an alternative treatment modality for patients with intrauterine adhesions and lower uterine defects from prior cesarean deliveries in select cases. While treating intrauterine adhesions improves pregnancy outcome, the effect of lower uterine segment-filling defects from cesarean deliveries on pregnancy outcome in assisted reproductive technology cycles warrants further investigation.