Nick Raine-Fenning

Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles

BACKGROUND While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. METHODS Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. RESULTS The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006-2007, the predicted LBR for women with 15 eggs retrieved in age groups 18-34, 35-37, 38-39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. CONCLUSION The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.

The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review

BACKGROUND The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery. METHODS Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used ‘optimal’ and ‘suboptimal’ tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations. RESULTS We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5–8.5] in the unselected population, 8.0% (95% CI, 5.3–12) in infertile women, 13.3% (95% CI, 8.9–20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3–32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1–7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations. CONCLUSIONS Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.

The interobserver reliability and validity of volume calculation from three‐dimensional ultrasound datasets in the in vitro setting

The primary aim of this validation study was to determine the interobserver reliability and validity of measurements of phantom objects of known volume using conventional and rotational techniques of volume calculation according to measurement technique.

A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation

OBJECTIVE To compare three-dimensional ultrasound parameters, antral follicle count (AFC), ovarian volume, and ovarian vascularity indices with anti-Müllerian hormone (AMH) and other conventional endocrine markers for the prediction of poor response to controlled ovarian hyperstimulation (COH) during assisted reproduction treatment (ART). DESIGN Prospective study. SETTING University-based assisted conception unit. PATIENT(S) One hundred thirty-five women undergoing the first cycle of ART. INTERVENTION(S) Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle immediately before ART. MAIN OUTCOME MEASURE(S) Poor ovarian response and nonconception. RESULT(S) Antral follicle count (Exp(B): 0.65) and AMH (Exp(B): 0.13) were the most significant predictors of poor ovarian response on multiple regression analysis and their predictive accuracy was similar, with an area under the curve (AUC) of 0.935 and 0.905, respectively. The AFC and AMH, as a combined test, did not significantly improve the level of prediction (AUC = 0.946). The sensitivity and specificity for prediction of poor ovarian response were 93% and 88% for AFC and 100% and 73% for AMH at an optimum cutoff values of < or =10 and < or =0.99 ng/mL, respectively. Age (Exp(B): 1.191) was the only significant predictor of nonconception, although its predictive accuracy was also low (AUC = 0.674). CONCLUSION(S) The AFC and AMH are the most significant predictors of poor response to ovarian stimulation during ART. The AMH and AFC, either alone or in combination, demonstrate a similar predictive power but are not predictive of nonconception, which is dependent on the womans age.

ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages safe clinical practice and high-quality teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accept any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

The reliability of virtual organ computer‐aided analysis (VOCAL) for the semiquantification of ovarian, endometrial and subendometrial perfusion

Three‐dimensional power Doppler angiography (3D‐PDA) has been largely used for the subjective assessment of vascular patterns but semiquantification of the power Doppler signal is now possible. We examined the intraobserver and interobserver reliability of the semiquantification of ovarian, endometrial and subendometrial blood flow using 3D‐PDA, virtual organ computer‐aided analysis (VOCAL™) and shell‐imaging.

Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection.

Anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating AMH concentrations. To determine AMH gene expression in GC (q-RT-PCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (3-13 mm diameter) including both GC and the corresponding follicular fluid (FF) were collected in connection with fertility preservation of human ovaries. Further, follicle number and diameter, graded in 1 mm increments, were determined by 3D ultrasound in 113 women in their natural menstrual cycle to determine follicle number and diameter in relation to circulating AMH levels. This study demonstrates for the first time a positive association between AMH gene expression in human and both total follicular fluid AMH (P < 0.02) and follicular fluid AMH concentration (P < 0.01). AMH gene expression and total AMH protein increased until a follicular diameter of 8 mm, after which a sharp decline occurred. In vivo modelling confirmed that 5-8 mm follicles make the greatest contribution to serum AMH, estimated for the first time in human to be 60% of the circulating concentration. Significant positive associations between gene expression of AMH and FSHR, AR and AMHR2 expression (P < 0.00001 for all three) and significant negative association between follicular fluid AMH concentration and CYP19a1 expression were found (P < 0.0001). Both AMH gene expression (P < 0.02) and follicular fluid concentration of AMH (P < 0.00001) correlated negatively with estradiol concentration.

Reproductive outcomes in women with congenital uterine anomalies: a systematic review

Congenital uterine anomalies are common but their effect on reproductive outcome is unclear. We conducted a systematic review to evaluate the association between different types of congenital uterine anomaly and various reproductive outcomes.

Skin aging and menopause : implications for treatment.

The skin is one of the largest organs of the body, which is significantly affected by the aging process and menopause. The significant changes sustained by the skin during the menopause are due to the effect sustained on the skin’s individual components.The estrogen receptor has been detected on the cellular components of the skin. Accordingly, dermal cellular metabolism is influenced by the hypoestrogenoemic state of menopause leading to changes in the collagen content, alterations in the concentration of glycoaminoglycans and most importantly the water content. Consequently changes in these basic components leads to an alteration in function compatible with skin aging.Changes in the skin collagen leads to diminished elasticity and skin strength. Collagen content may be measured by various methods such as direct skin biopsy, skin blister assessment for collagen markers and skin thickness measurement. All these variables indicate a reduction in collagen content following menopause. This may be reversed with the administration of estrogen given both topically and systemically.A reduction in hydrophilic glycoaminglycans leads to a direct reduction in water content, which influences the skin turgor. These effects on glycoaminoglycans, due to the hypoestrogenia, have been clearly shown in animal studies and appeared to be rapidly reversed with the application of estrogens. The sum total of these basic effects on the skin leads to wrinkles, the skin condition typifying skin aging.Structures resident in the skin are likewise influenced by menopause. Changes to the cutaneous vascular reactivity are noted following menopause. Capillary blood flow velocity decreases significantly in postmenopausal women. Postmenopausal flushing is due to profound vasodilatation in the dermal papillae. Hair growth is also influenced by the hormonal milieu and consequently hair loss has been associated with the beginning of menopause.Treatments administered for menopause, in particular hormone replacement therapy, appear to alter its effects on the basic components of the skin as well as the more complex structures residing in the skin, consequently retarding the skin aging process.

Determining the relationship between three-dimensional power Doppler data and true blood flow characteristics: an in-vitro flow phantom experiment

Three‐dimensional (3D) ultrasound can be used to acquire power Doppler data which can be quantified to give an objective impression about blood flow within a tissue or organ. Proprietary software can be used to calculate three indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Although these indices appear to have a predictive value in the clinical setting and can be shown to vary between different patient populations and over time within the same population, their relationship with true in‐vivo blood flow characteristics has not been established. The objective was to examine the effect of flow rate, vessel number, attenuation and erythrocyte density on these indices.