Defining polycystic ovary syndrome phenotype in Vietnamese women.

AIM: This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. METHODS: In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. RESULTS: The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). CONCLUSION: The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.

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.

Effects of different frozen embryo transfer regimens on abnormalities of fetal weight: a systematic review and meta-analysis.

BACKGROUND: Reported increases in maternal and perinatal morbidity (including macrosomia, large for gestational age (LGA), cesarean section, hemorrhage and hypertensive disorders of pregnancy) following frozen embryo transfer (FET) cycles may be associated with the lack of a corpus luteum seen in programmed FET. Given the growing number of studies comparing outcomes between natural FET and programmed FET cycles, a meta-analysis would prove useful to detect the presence of abnormalities in fetal birth weight in patients undergoing natural and programmed FET cycles. OBJECTIVE AND RATIONALE: The aim of this study was to provide a systematic review and meta-analysis of the effects of natural versus programmed methods of endometrial preparation for FET cycles on fetal weight and the risks of LGA and macrosomia. SEARCH METHODS: A literature search using MEDLINE, SCOPUS, EMBASE and clinicaltrials.gov was conducted for published research comparing neonatal outcomes in natural FET and programmed FET cycles. Primary outcomes of interest were fetal weight, macrosomia and LGA. Studies were included if the following criteria were met: study contained cohorts of NFET and programmed FET with outcome data of birth weight, large for gestational data and/or macrosomia. The data are presented as average weight and odds ratio (OR) with 95% confidence interval (CI) with fixed- or random-effects meta-analysis between cohorts of NFET and programmed FET cycles. Bias was assessed using Newcastle-Ottawa quality assessment scale for the 14 included studies. Multiple subgroup analyses were performed to assess for effect of the true natural cycle (defined as no ovulation trigger medication use) and the day of embryo transfer on fetal weight parameters compared with programmed cycle FET. OUTCOMES: A total of 879 studies were identified, with 15 meeting inclusion the criteria. The studies varied with respect to country of origin, definition of natural cycle FET and type of progesterone supplementation used. The included studies had similar gestational ages at the time of birth. Programmed FET cycles resulted in a higher fetal weight compared with natural FET cycles (mean difference 47.38 gp = 0.04). Programmed FET cycles were also at higher risk for macrosomia (OR 1.15, 95% CI 1.06-1.26) and LGA (OR 1.10, 95% CI 1.02-1.19) compared with natural FET cycles. Subgroup analyses demonstrated that programmed FET cycles resulted in a higher fetal weight compared with true natural FET (mean difference 62.18 gp = 0.0001) cycles. Cleavage stage embryo transfers had an increased risk of LGA (OR 1.27, 95% CI 1.00-1.62) and an increased risk of macrosomia (OR 1.25, 95% CI 1.08-1.44) in programmed FET cycles compared with natural FET cycles. Blastocyst transfer in programmed FET cycles resulted in no difference in risk of macrosomia but an increased risk of LGA (OR 1.13, 95% CI 1.06-1.21) compared with natural FET cycles. WIDER IMPLICATIONS: Programmed endometrial preparation for FET cycles had a significant effect, causing increased fetal birth weight and increased risks of LGA and macrosomia. The numbers of studies in the subgroup analyses were too low to determine reliable results. Further prospective randomized trials are needed to determine whether the changes seen in the observational trials are indeed accurate.

Characterization of the role of Activator Protein 1 signaling pathway on extracellular matrix deposition in uterine leiomyoma.

OBJECTIVE: To characterize the role Activator Protein 1 (AP 1) family members play in mediating extracellular matrix deposition in uterine leiomyoma. DESIGN: Laboratory study. SETTING: University research laboratory. INTERVENTION(S): Exposure of leiomyoma and myometrial cell lines to either an AP 1 inhibitor alone, AP 1 inhibitor plus transforming growth factor (TGF)ß3, or TGFß3 alone. MAIN OUTCOME MEASURE(S): Western immunoblot analysis was performed to assess for changes in AP 1 family member protein expression. RESULT(S): In patient-matched myometrial and leiomyoma cell lines, the only AP 1 member found to be elevated significantly in leiomyoma compared with myometrium was FOSB (3.47 ± 0.12-fold), whereas others were decreased significantly: FRA1 (0.67 ± 0.02-fold), FRA2 (0.45 ± 0.01-fold), c FOS (0.37 ± 0.01-fold), Phos c FOS (0.19 ± 0.02-fold), Phos c JUN (0.75 ± 0.02-fold), JUNB (0.81 ± 0.04-fold), and JUND (0.65 ± 0.03-fold). c JUN (0.93 ± 0.03-fold) concentration was reduced but at nonsignificant levels. Following stimulation with TGF ß 3, fibronectin (2.16 ± 0.14-fold) and versican (4.71 ± 0.15-fold) protein concentrations were increased at 24 hours. Collagen 1A demonstrated a time-dependent significant increased concentration beginning at 6 hours (1.32 ± 0.01-fold) and increased to (6.49 ± 0.02-fold) at 24 hours. Following treatment with AP 1 inhibitor (SR11302), there were significant reductions in Collagen 1A concentration at 4 hours (0.59 ± 0.03-fold) and 6 hours (0.42 ± 0.05-fold). Activator Protein 1 inhibition did not reduce significantly versican concentration until 6 hours of treatment (0.84 ± 0.04-fold). SR11302 also decreased significantly fibronectin concentration (0.68 ± 0.05-fold) at 8 hours of treatment. CONCLUSION(S): Activator Protein 1 signaling is well described in fibrotic diseases, and, herein, we demonstrated that signaling via AP 1 family members promotes extracellular matrix deposition in leiomyoma.

Steroid hormones and hormone antagonists regulate the neural marker neurotrimin in uterine leiomyoma.

OBJECTIVE: To characterize the role of steroid hormone and antihormone exposure on neurotrimin (NTM) expression in human leiomyoma and myometrial tissue and cells. DESIGN: Laboratory study of placebo and ulipristal acetate (UPA)-treated patient tissue. In vitro assessment of immortalized myometrial and leiomyoma cell lines after hormone and antihormone exposure. SETTING: Academic research center. PATIENT(S): Not applicable. INTERVENTIONS(S): Exposure of leiomyoma cell lines to 17ß-E2, medroxyprogesterone acetate (MPA), UPA, and fulvestrant. MAIN OUTCOME MEASURE(S): Messenger RNA expression quantified with the use of RNASeq analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels quantified by means of Western blot analysis. Immunohistochemistry (IHC) on placebo- and UPA-treated patient uterine tissue specimens. RESULT(S): Expression of NTM in human uterine leiomyoma specimens according to RNASeq was increased compared with myometrium (5.22 ± 0.57-fold), which was confirmed with the use of qRT-PCR (1.95 ± 0.05). Furthermore, NTM protein was elevated in leiomyoma tissue compared with matched myometrium (2.799 ± 0.575). IHC revealed increased staining intensity in leiomyoma surgical specimens compared with matched myometrium of placebo patients. Western blot analysis in immortalized leiomyoma cell lines demonstrated an up-regulation of NTM protein expression (2.4 ± 0.04). Treatment of leiomyoma cell lines with 17ß-E2 yielded a 1.98 ± 0.11-fold increase in NTM protein expression; however, treatment with fulvestrant showed no significant change compared with control. Leiomyoma cell lines demonstrated a 1.91 ± 0.97-fold increase in NTM protein expression after progesterone treatment. RNASeq analysis demonstrated a reduced expression in patient leiomyoma after UPA treatment (0.75 ± 0.14). Treatment of leiomyoma cells with UPA demonstrated a reduced total NTM protein amount (0.54 ± 0.31) in patients, which was confirmed with the use of IHC (UPA10 147.2 ± 9.40, UPA20 182.8 ± 8.98). In vitro studies with UPA treatment revealed a concentration-dependent effect that supported these findings. CONCLUSION(S): NTM, a neural cell adhesion molecule, is increased in leiomyoma compared with myometrium in patient tissue and in vitro models after estrogen and progesterone treatment. Down-regulation of expression occurs after UPA treatment, but not after fulvestrant exposure. CLINICAL TRIAL REGISTRATION NUMBER: NCT00290251.

Assisted Reproductive Technology and the Reproductive Endocrinology and Infertility Specialist in the U.S. Military.

The U.S. military mirrors the U.S. population given the diverse ethnic and cultural backgrounds of the service members. Active-duty military members, veterans, and Department of Defense beneficiaries can be negatively impacted by infertility.

Embryo transfer simulation improves pregnancy rates and decreases time to proficiency in Reproductive Endocrinology and Infertility fellow embryo transfers.

OBJECTIVE: To design and evaluate an ET simulator to train Reproductive Endocrinology and Infertility (REI) fellows' techniques of ET. DESIGN: Simulation model development and retrospective cohort analysis. SETTING: Not applicable. PATIENT(S): Patients undergoing IVF. INTERVENTION(S): Simulation model evaluation and implementation of ET simulation training. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): The REI fellow and faculty evaluation responses (n = 19/21 [90%]) of the model demonstrated realistic characteristics, with evaluators concluding the model was suitable for training in almost all evaluated areas. A total of 12 REI fellows who performed ET were analyzed: 6 before ET trainer and 6 after ET trainer. Pregnancy rates were 31% in the initial 10 ETs per fellow before simulator vs. 46% after simulator. One of six pre-ET trainer fellows (17%) had pregnancy rates ≥40% in their first 10 ETs; whereas four of six post-ET trainer fellows had pregnancy rates ≥40% in their first 10 ETs. The average number of ETs to obtain >40% pregnancy efficiency was 27 ETs before trainer vs. 15 ETs after trainer. Pregnancy rates were similar in the two groups after 20 ETs, and collective terminal pregnancy rates were >50% after 40 ETs. CONCLUSION(S): Embryo transfer simulation improved REI fellow pregnancy rates in their first 10 transfers and led to a more rapid ET proficiency. These data suggest potential value in adopting ET simulation, even in programs with a robust history of live ET in fellowship training.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity.

OBJECTIVE: To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. DESIGN: Retrospective cohort study. SETTING: Military assisted reproductive technology (ART) program. PATIENT(S): Fresh autologous ART cycles. INTERVENTION(S): Serum hCG level the day before oocyte retrieval. MAIN OUTCOME MEASURE(S): Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. RESULT(S): A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. CONCLUSION(S): Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful.