Use of double decidual sac sign to confirm intrauterine pregnancy location prior to sonographic visualization of embryonic contents.

OBJECTIVES: To determine the diagnostic accuracy of the double decidual sac sign (DDSS) for predicting an intrauterine pregnancy (IUP) prior to visualization of embryonic contents, using modern high-resolution transvaginal sonography (TVS). METHODS: The study was conducted following STARD guidelines and participants were recruited prospectively from Nurture Fertility, Nottingham, UK, following in-vitro fertilization/intracytoplasmic sperm injection treatment between 1 January 2015 and 31 October 2015. Women were excluded if there was no evidence of intrauterine fluid collection during the index test, a yolk sac or fetal pole was visible during the index test, no outcome data were available or pregnancy location could not be determined by the reference standard. The index test consisted of TVS at 32-34 days' gestation using a high-frequency transvaginal probe. Reference standard was TVS at 7 weeks' gestation. The outcome of interest was an IUP. RESULTS: A total of 67 intrauterine fluid collections were observed and included in the analysis, of which 61 exhibited the DDSS and 65 were proven to be IUPs. Two ectopic pregnancies were included, neither of which demonstrated the DDSS. The DDSS therefore had a sensitivity of 93.9% (95% CI, 85.0-98.3%), specificity of 100% (95% CI, 15.8-100%) and overall diagnostic accuracy of 94.0% (95% CI, 88.3-99.7%) for predicting an IUP. The negative likelihood ratio and positive and negative predictive values were 0.06 (95% CI, 0.02-0.16), 100% (95% CI, 94.1-100%) and 33.3% (95% CI, 4.3-77.7%), respectively. CONCLUSION: With modern high-resolution TVS, presence of the DDSS can be used to confirm accurately IUP location prior to sonographic visualization of embryonic contents, and therefore to exclude effectively ectopic pregnancy. Absence of the DDSS, however, does not preclude an IUP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effect of ethnicity on live birth rates after in vitro fertilisation or intracytoplasmic sperm injection treatment.

OBJECTIVE: To assess the relationship between the ethnicity of women and the clinical success of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Observational cohort study. SETTING: Nottingham University Research and Treatment Unit in Reproduction (NURTURE), UK. SAMPLE: A total of 1517 women, of which 1291 were white Europeans and 226 belonged to an ethnic minority group. All the women were undergoing their first cycle of assisted reproductive technology (ART) between 2006 and 2011. METHODS: All of the women underwent their first cycle of ART between 2006 and 2011. MAIN OUTCOME MEASURES: Live birth rates following IVF or ICSI treatment. RESULTS: Although pre-treatment ovarian reserve variables [mean age, basal follicle stimulating hormone (FSH), and total antral follicle count] were significantly favourable in the ethnic group, the live birth rates were significantly lower in this group (35%) compared with the white European group (43.8%) (relative risk 0.8; 95% CI 0.66-0.97). On logistic regression analysis, ethnicity was an independent predictor of live birth rate (OR 0.688; 95% CI 0.513-0.924). After controlling for the other independent variables (age and FSH), the significant association between ethnicity and live birth rate remained strong (OR 0.591; 95% CI 0.425-0.822) on multivariate logistic regression analysis. CONCLUSIONS: Live birth rates following IVF or ICSI treatment were significantly lower in the ethnic minority group compared with white European women, which suggests that ethnicity is a major determinant of live birth following IVF treatment.

Brief communication: assessment and validation of nonspermicidal condoms as specimen collection sheaths for semen analysis and assisted conception.

The choice of nonspermicidal sheaths for specimen collection for diagnosis and/or fertility treatment is limited. Those that are available tend to be relatively expensive and as a results, offered selectively to patients. This study describes the evaluation of three over-the-counter nonspermicidal condoms as alternatives to specialized specimen collection sheaths. Sheaths were incubated with motile sperm for up to 2 h and the percent Grade A motility, percent progressive motility and progressive velocity assessed using an 'in-house' computer-assisted semen analysis system every 30 min. Two of the sheaths tested, Pasante Naturelle (PN) and the Durex Avanti Ultima were shown to be highly toxic to sperm, leading to immobilization of most specimens within 1 h. However the loss of sperm motility when sperm were incubated with the Pasante Unique (PU) condom was no greater than with either the control (rigid 60 ml specimen container) or the Male Factor Pak (MFP), a commercially available specialized semen collection sheath. In conclusion, the PU brand of condom could be used as a cheaper alternative to the specimen collection sheaths currently available. Furthermore, some brands of condom sold as nonspermicidal are in fact toxic to sperm and will immobilize most specimens within 1 h.

Initial evaluation of a new device for gynaecological laparoscopic surgery: the Atiomo-Laparoscopic Assistant™.

The aim of this study was to evaluate the number of surgeons required to successfully complete a range of gynaecological laparoscopic procedures using a new device (the Atiomo-Laparoscopic Assistant™), which enables one surgeon to easily simultaneously manipulate the uterus and the laparoscope. The number of surgeons required to complete the operation in 15 women undergoing a range of laparoscopic procedures using the Atiomo-Laparoscopic Assistant™ was compared with data retrospectively collected from theatre records. It was possible for one surgeon to assess the pelvis during laparoscopy in 10 (67%) of the 15 procedures where the Atiomo-Laparoscopic Assistant™ was used, compared with 177 of the 599 (30%) procedures where it was not used (p = 0.005). However, with the Mark 3 device, it was possible for one surgeon to perform the procedure in all seven procedures (100%) where it was used. Surgeons felt that the device was easy to use and no complications occurred.

A randomised controlled trial of 300 versus 225 IU recombinant FSH for ovarian stimulation in predicted normal responders by antral follicle count.

OBJECTIVE: To test the hypothesis that among women predicted to have a normal ovarian response, ovarian stimulation using 300 IU follicle-stimulating hormone (FSH) results in the retrieval of more mature oocytes than 225 IU during in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Prospective randomised controlled study. SETTING: University-based assisted conception unit. POPULATION: A cohort of 131 women predicted to have a normal ovarian response to gonadotrophin stimulation, based on antral follicle count. METHODS: Subjects undergoing their first cycle of IVF/ICSI were randomised to receive a fixed daily dose of 300 (experimental arm) or 225 IU (control arm) of recombinant FSH (Gonal-F). MAIN OUTCOME MEASURES: Number of mature oocytes retrieved and live birth rates. RESULTS: The number (mean +/- standard deviation) of mature oocytes retrieved (8.2 +/- 5.0 versus 9.0 +/- 4.8, for 300 and 225 IU, respectively; P = 0.34) was similar in each group. There were no differences between the 300- and 225 IU arms in live birth rates (31 versus 41%, respectively; P = 0.25), cycle cancellations resulting from insufficient ovarian response (0 versus 6.1%, respectively; P = 0.12), and prevalence of moderate (3.1 versus 3.0, respectively; P = 1.0) and severe (0 versus 1.5%, respectively; P = 1.0) ovarian hyperstimulation syndrome. CONCLUSIONS: The use of a higher daily dose of 300 IU of recombinant FSH for ovarian stimulation does not improve the number of mature oocytes retrieved, or live birth rates, among women with a predicted normal response during conventional IVF/ICSI.

The predictive value of the automated quantification of the number and size of small antral follicles in women undergoing ART.

BACKGROUND: Sono-automatic volume calculation (SonoAVC) automatically identifies and measures the dimensions of hypoechogenic areas within datasets acquired using three-dimensional ultrasound. The objective of this study was to evaluate the predictive value of automated antral follicle counts according to their relative sizes in women undergoing assisted reproduction treatment (ART). METHODS: A total of 156 subjects aged < or =40 years with a baseline FSH < or =15 IU that undergo their first cycle of ART were prospectively recruited. SonoAVC was used to measure the datasets and record the number of antral follicles measuring < or =9 mm in diameter. These follicles were then grouped into subsets according to their relative sizes: < or =2.0, 2.1-4.0, 4.1-6.0, 6.1-8.0 and 8.1-9.0 mm. The primary outcome was viable pregnancy confirmed on ultrasound 5 weeks following embryo transfer. RESULTS: A total of 142 subjects were included for analysis of primary end-point. Those subjects who conceived had significantly more antral follicles measuring < or =2 (P = 0.041) and 2.1-4.0 mm (P < 0.001) than those who had unsuccessful treatment. There were no significant differences between the groups in the number of antral follicles measuring 4.1-6.0 (P = 0.191), 6.1-8.0 (P = 0.203) and 8.1-9.0 mm (P = 0.601). Multiple logistic regression showed that antral follicles measuring 2.1-4.0 mm were an independent predictor of pregnancy [Exp(B) = 1.234, 95% CI = 1.092-1.491; P = 0.004; AUC = 0.693]. CONCLUSION: SonoAVC provides automated measures of antral follicle number and size. Using this technique, the number of antral follicles measuring 2.1-4.0 mm in diameter is an independent, significant predictor of pregnancy following in vitro fertilization treatment.

Effect of pituitary desensitization on the early growing follicular cohort estimated using anti-Mullerian hormone.

BACKGROUND: This study evaluated the effect of pituitary desensitization on the early growing follicle population through assessment of serum anti-Mullerian hormone (AMH) concentration. Other markers of ovarian reserve, basal follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin-B and three-dimensional ultrasound ovarian parameters were also assessed for comparison. METHODS: One hundred and two subjects aged <40 years with FSH levels <12 IU/l underwent venepuncture and transvaginal ultrasound in the early follicular phase of the menstrual cycle and after 14 days of down-regulation using gonadotrophin releasing hormone (GnRH) agonists. Serum levels of AMH and other markers of ovarian reserve measured during the early follicular phase were compared with those measured following down-regulation. RESULTS: While AMH levels increased significantly by approximately 32% (P < 0.01), there was a significant decline of approximately 40-50% (P < 0.01) in the levels of inhibin-B, FSH, LH and estradiol. Down-regulation treatment was also associated with a decrease (P < 0.01) in mean ovarian volume and in ovarian blood flow, but no difference was seen in the antral follicle count. CONCLUSIONS: Pituitary desensitization results in a significant increase in AMH levels, which implies that either the secretion of AMH by early growing follicles is enhanced or that the size of this follicle cohort is increased. The number of antral follicles visualized on ultrasound in the early follicular phase and at down-regulation appears unchanged, suggesting that any effect is restricted to the smaller selectable follicles. Our results may explain the enhanced ovarian response to conventional controlled ovarian stimulation and higher pregnancy rates when pretreatment with GnRH-agonists is employed.

Quantification of the effect of pituitary down-regulation on 3D ultrasound predictors of ovarian response.

BACKGROUND: This study evaluated the effect of pituitary desensitization on ovarian volume, antral follicle count (AFC), and ovarian blood flow indices and their value as predictors of ovarian response during assisted reproduction treatment. METHODS: A total of 115 subjects aged <40 years with follicle-stimulating hormone (FSH) levels <12 IU/l underwent transvaginal ultrasound in the early follicular phase of the menstrual cycle and after 14 days of down-regulation using gonadotrophin-releasing hormone agonists. 3D power Doppler was used to quantify ovarian volume, AFC and ovarian blood flow. The relationship between these ultrasound variables and treatment outcome was evaluated using multiple regression analysis. RESULTS: Although a significant decrease in the ovarian volume (P < 0.05) and flow index (FI; P < 0.01) was demonstrated after pituitary desensitization, no differences were seen in the AFC. The total AFC, regardless of whether this was measured before or after down-regulation, was a significantly better predictor of the number of oocytes retrieved (P < 0.001) and poor ovarian response (P < 0.05) than age, FSH, ovarian volume and vascular indices although pre-treatment ovarian volume (P < 0.05) and FI (P < 0.05) were also predictive of the number of oocytes retrieved. CONCLUSIONS: Pituitary desensitization results in a significant reduction in ovarian volume and vascularity, but has no effect on the AFC. AFC is the single best predictor of ovarian response regardless of whether the assessment is performed before or after down-regulation.

Does 3D ultrasound offer any advantage in the pretreatment assessment of ovarian reserve and prediction of outcome after assisted reproduction treatment?

BACKGROUND: This study compared the predictive value of the antral follicle count (AFC) measured from stored 3D data by three methods including a '2D equivalent technique' and two 3D techniques, the 'multiplanar view' and 'rendered inversion mode', as a test of ovarian reserve and treatment outcome. METHODS: One hundred consecutive subjects aged<40 years with basal FSH levels<12 IU/l underwent transvaginal ultrasound in the early follicular phase prior to their first cycle of assisted reproduction treatment. The relationship between the AFC made with each method and outcome was evaluated. RESULTS: The AFC as measured by the 'inversion mode' method (r=0.777) showed a higher, but statistically insignificant, correlation with the number of retrieved oocytes than did comparable measurements made with the '2D equivalent' (r=0.665) and '3D multiplanar' (r=0.687) techniques. Multiple regression analysis showed the AFC measured using any of the three methods was a significantly better predictor of the number of oocytes retrieved (P<0.001) than age, FSH or ovarian volume. AFC was not predictive of non-conception regardless of the measurement technique. CONCLUSIONS: For predicting ovarian respone and outcome, the AFC measured using techniques based on 3D ultrasound offers no statistically significant advantage over a measurement which is limited to information available with conventional 2D imaging.

Integrins alpha 3 and alpha 6 are differentially expressed in endometrium and endometriosis.

The expression of integrin subunits has been investigated in the stroma and epithelium of eutopic and ectopic endometrial tissues, using immunohistochemistry and fluorescently activated cell-sorting techniques. Integrin subunits exhibited tissue-specific expression in both eutopic and ectopic endometrium. Integrin alpha 3 subunit was up-regulated in ectopic endometrium compared with the eutopic counterpart, whereas alpha 6 integrin subunit was down-regulated in the ectopic tissues. Cycle stage-dependent expression of alpha v and beta 3, observed in eutopic endometrium, was absent in the ectopic counterpart. It is concluded that the development and regeneration of the endometrium involve complex integrin-ligand interactions and that regulation of specific adhesive events is lost in endometriosis.

Expression of heparin-binding epidermal growth factor messenger RNA in the human endometrium.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the epidermal growth factor family. In rodents HB-EGF has been found to mediate the mitogenic effects of oestrogen on the endometrial glandular cells and those of progesterone on the stromal cells. HB-EGF has also been found to be expressed at the site of implantation before any other discernible sign of blastocyst attachment in rodents. Our aim was to determine whether HB-EGF mRNA was expressed in the human pregnant and non-pregnant endometrial tissues. Normal endometrial tissues at different stages of the menstrual cycle, first trimester chorionic villi and decidua, second trimester chorionic villi and term placental tissues were snap frozen and stored at -80 degrees C. Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyse the expression of HB-EGF mRNA in these tissues. HB-EGF mRNA was found to be expressed in human endometrium throughout the menstrual cycle. It was also present in first trimester chorionic villi and decidua, second trimester villi and term placenta. These findings suggest that HB-EGF may have a role in the growth or function of the human uterus, and that it may be important at the feto-maternal interface throughout pregnancy.