FSH administration at 12-hour intervals for the first 2 days, combined with mandatory GnRH-agonist trigger and blastocyst vitrification in women (<80Kg) with high AMH levels, results in higher cumulative live birth rates and is safer.

We aimed to determine if a programme change to 12 hourly injections of FSH (150 IU per injection) for the first 2 days of stimulation in women with high ovarian reserve (AMH ≥ 30 pmol/L), followed by 24 hourly injections, would elicit increased earlier follicular recruitment, higher egg yields and blastocyst embryos for cryopreservation, leading to potential higher cumulative pregnancy rates, than conventional daily injections throughout. For safety reasons, the approach required mandatory cryopreservation of all blastocysts (mFET group; n = 74), after ovulation trigger with GnRH-agonist, in GnRH-antagonist controlled cycles. The 'Comparator group' (n = 91) comprised women with the same high AMH levels treated with the same base dose of FSH, with the aim of fresh blastocyst transfer and cryopreservation of supernumerary embryos, treated over the preceding 2 years. There was no difference in age, AMH, weight or BMI between the groups. The mFET group achieved higher egg (17.7 versus 11.7; p < 0.001) and embryo (10.9 versus 7.2; p < 0.001) yields and fewer cases with sub-optimal embryo yields (7% versus 22%; p = 0.018). The cumulative live birth rate was superior in the mFET group (73% versus 43%), as was the safety profile, and negligible rate of treatment plan modification.

Soluble LH-HCG receptor and oestradiol as predictors of pregnancy and live birth in IVF.

RESEARCH QUESTION: Circulating soluble LH-HCG receptor (sLHCGR) is a first-trimester marker for screening pregnancy pathologies and predicts premature or multiple births before fertility treatment. Oestradiol per oocyte at ovulation induction predicts IVF treatment outcomes. We asked whether sLHCGR levels are stable during fertility treatment and whether, alone or with oestradiol, they could improve prediction of fertility treatment outcomes. DESIGN: Serum sLHCGR, anti-Müllerian hormone [AMH] and oestradiol were measured in patients undergoing IVF. Antral follicle count before ovarian stimulation and oocyte yield were used to establish sLHCGR- oocyte ratio (SOR), sLHCGR- antral follicle ratio (SAR), oestradiol at trigger per oocyte (oestradiol-oocyte ratio [EOR]) and oestradiol at trigger per antral follicle (oestradiol-antral follicle ratio [EAR]). RESULTS: The relatively stable sLHCGR was negatively related to AMH when oocyte yield was high. The sLHCGR levels were proportional (r = 0.49) to oestradiol at early cycle (day-3). Pregnancy and live birth were highest at low sLHCGR (≤1.0 pmol/ml) and SOR (≤ 0.1 pmol/ml/oocyte). A total of 86-89% of live births in IVF treatment were within the cut-off parameters of SAR and SOR (0.5 pmol/ml) and EAR and EOR (380 pg/ml). For failed pregnancy, age, SOR and EOR together had positive and negative predictive values of 0.841 and 0.703, respectively. CONCLUSIONS: sLHCGR levels are negatively related to AMH when oocyte yield is high. High early cycle sLHCGR is associated with elevated day-3 oestradiol. Low sLHCGR and SOR are indicators of increased clinical pregnancy and live birth rates. Patient age and SOR, combined with EOR, might improve prediction of IVF treatment outcomes.

Objective multicentre performance of the automated assays for AMH and estimation of established critical concentrations.

The measurement of AMH has now become widespread practice within the field of fertility treatment and research, despite technical issues with some of the original assays. The two new automated assays, with their potentially improved technical performance, require detailed examination and comparison under different conditions. In addition, the determination of categories of responses to ovarian stimulation, require re-evaluation for these new tests. The performance of the assays across numerous laboratories, and over a protracted timeframe, has been examined through the UK NEQAS published results. The automated assays show high quality performance figures over a broad concentration range, with exceptionally low variance figures, and they also yield very similar absolute concentration values. Critical response diagnostic concentrations have been re-evaluated by determination of age-related concentrations from within large population datasets.

Premature and multiple births in IVF are associated with pretreatment circulating LH/hCG receptor concentration.

The luteinizing hormone (LH) and pregnancy hormone, human chorionic gonadotrophin (hCG), share a common receptor: LH/hCG-R or LHCGR. In this prospective study involving 290 patients undergoing in vitro fertilization (IVF) and embryo transfer, we have examined whether pretreatment circulating LHCGR (sLHCGR) influences the course of pregnancy and perinatal outcome after embryo transfer. The blood samples were collected before the fertility treatment began and sLHCGR concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) test. We demonstrate that extreme pretreatment sLHCGR concentrations (low & high) were linked to abnormal birth weights for singleton births, while very low concentrations of sLHCGR were associated with premature delivery (≤34 weeks) of singletons and multiple births following transfer of ≥2 embryos.

Antimüllerian hormone levels and antral follicle count as prognostic indicators in a personalized prediction model of live birth.

OBJECTIVE: To compare antimüllerian hormone (AMH) and antral follicle count (AFC) separately and in combination with clinical characteristics for the prediction of live birth after controlled ovarian stimulation. DESIGN: Retrospective development and temporal external validation of prediction model. SETTING: Outpatient IVF clinic. PATIENT(S): We applied the boosted tree method to develop three prediction models incorporating clinical characteristics plus AMH or AFC or the combination on 2,124 linked IVF cycles from 2006 to 2010 and temporally externally validated predicted live-birth probabilities with an independent data set comprising 1,121 cycles from 2011 to 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Predictive power (posterior log of odds ratio compared to age, or PLORA), reclassification, receiver operator characteristic analysis, calibration, dynamic range. RESULT(S): Predictive power, was highest for the AMH model (PLORA = 29.1), followed by the AMH-AFC model (PLORA = 28.3) and AFC model (PLORA = 22.5). The prediction errors were 1% to <5% in each prognostic tier for all three models, except for the predicted live-birth probabilities of <10% in the AFC model, where the prediction error was 8%. The improvement in predictive power was highest for the AMH model: 76.2% improvement over age alone relative to 59% improvement for AFC and 73.3% for the combined model. Receiver operating characteristic analysis demonstrated that the AMH and the combined model had comparable discrimination (area under the curve = 0.716) and similar prediction error for high and low strata of live-birth prediction, with an improvement of 6.3% over age alone. CONCLUSION(S): The validated prediction model confirmed that AMH when combined with clinical characteristics can accurately identify the likelihood of live birth with a low prediction error. AFC provided no added predictive value beyond AMH.

Stability of AMH measurement in blood and avoidance of proteolytic changes.

The new Gen II assay for anti-Müllerian hormone (AMH) shows good stability and reliability in serum, but analyses of stability in whole blood are lacking. Testing the effects of storage of whole-blood samples at room temperature revealed significant increases in the measured value of AMH of 31% over 4 days (P<0.001). The effect is temperature dependent, with storage at 4°C showing markedly reduced increments. Further, samples collected into serum tubes with gel separators and centrifuged within 5h (blood cells and serum physically separated within the collection tube) showed reliable stability over a period of more than 5 days.

Women with recurrent postmenopausal bleeding should be re-investigated but are not more likely to have endometrial cancer.

OBJECTIVES: We aimed to determine the prevalence of endometrial cancer in patients presenting with recurrent postmenopausal bleeding (PMB) after initial negative investigations. STUDY DESIGN: This was a retrospective study carried out in a dedicated PMB clinic. All patients presenting with recurrent PMB between 1 January 2003 and 31 May 2009 were studied. All patients had transvaginal ultrasound, speculum examination and endometrial sampling attempted. Main outcome measure The prevalence of endometrial cancer in patients presenting with recurrent PMB after initial negative investigations. RESULTS: A total of 1536 women with PMB were seen over a period of 56 months. Sixty-six required definitive treatment after their first visit. One hundred and twenty-six re-presented with recurrent bleeding. The prevalence of endometrial cancer in women presenting for the first time with PMB was 3.04% whereas that in women presenting with recurrent PMB after initial negative investigations was 4%. One of these women re-presented within six months of initial visit and another within one year. All the other cancers were diagnosed more than one year after initial negative investigations (range 19.6-57.1 months). One woman had an endometrial cancer even though the endometrial thickness was less than 3 mm. CONCLUSIONS: Women with recurrent PMB after initial negative investigations are no more likely to have endometrial cancer than those presenting for the first time but re-investigation is indicated if six months has elapsed.

Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception.

BACKGROUND: Individualization of controlled ovarian stimulation (COS) for assisted conception is complicated by variable ovarian response to follicle stimulating hormone. We hypothesized that anti-Müllerian hormone (AMH), a predictor of oocyte yield, may facilitate treatment strategies for women undergoing COS, to optimize safety and clinical pregnancy rates. METHODS: Prospective cohort study of 538 patients in two centres with differential COS strategies based on a centralized AMH measurement. RESULTS: AMH was associated with oocyte yield after ovarian stimulation in both centres, and a 'reduced' AMH (1 to <5 pmol/l) was associated with a reduced clinical pregnancy rate. Women with a 'normal' AMH (5 to <15 pmol/l) treated with a long GnRH-agonist protocol (both centres) showed a low incidence of excess response (0%) and poor response (0%). In women with 'high' AMH (>15 pmol/l), the antagonist protocol eliminated the need for complete cryopreservation of embryos due to excess response (P < 0.001) and showed a higher fresh cycle clinical pregnancy rate than agonist cycles [OR 4.40 (95% CI 1.95-9.93), P < 0.001]. CONCLUSIONS: The use of circulating AMH to individualize treatment strategies for COS may result in reduced clinical risk, optimized treatment burden and maintained pregnancy rates, and is worthy of prospective randomized examination.

Effectiveness of a nurse-led pregnancy termination clinic.

A new nurse-led service was developed for women requesting pregnancy termination. Compared with the previous service, the nurse-led clinic reduced waiting times and cost almost 40 per cent less.

Routine ultrasound for pregnancy termination requests increases women's choice and reduces inappropriate treatments.

This prospective observational study aimed to determine the correlation between gestational age based on menstrual dates and ultrasound scan in women requesting pregnancy termination and the proportion of cases where first trimester medical termination might be offered. Two hundred and sixty-two women (93%) had ongoing pregnancies. Two hundred and thirty-seven women (90%) were certain of their menstrual dates but there was a discrepancy of more than one week in gestational age in 38%. Calculated from their menstrual dates, 138 women might have been offered first trimester medical termination but this rose to 173 if gestation was based on ultrasound scan. From this study, we believe ultrasound should be performed routinely for all women requesting pregnancy termination.

Ovulation induction/intrauterine insemination in infertile couples is associated with low-birth-weight infants.

OBJECTIVE: The study was undertaken to determine the outcome of singleton pregnancies conceived through ovulation induction and intrauterine insemination using a partner's (OI/IUI) or donor sperm (OI/IUID) by comparison with naturally conceived singletons within a national cohort. STUDY DESIGN: Retrospective cohort study in primigravid women who were treated with OI/IUI (n = 97) or OI/IUID (n = 35) at Glasgow Royal Infirmary between March 1993 and March 1997 and identified within the Scottish national cohort (n = 109,443) delivering during the same period. Univariate and multivariate logistic regression models were used to examine outcomes and to determine the factors associated with infertility treatment and low birth weight. RESULTS: OI/IUI singletons were more likely to be lighter, of clinically low birth weight, and born more prematurely than natural conceptions. After adjustment for associated factors, these infants were 4.85 times (95% CI 2.25-10.48) more likely to be of low birth weight. We could not demonstrate any differences between OI/IUID and natural conceptions. CONCLUSION: The perinatal outcome of singletons born to subfertile mothers conceived through OI/IUI is poorer than that of matched natural conceptions. We suggest that intrinsic factors in subfertile couples predispose them to having smaller infants and that "infertility" should be added to the list of recognized factors associated with low birth weight.