Human chorionic gonadotrophin stimulation test as a predictor of ovarian response and pregnancy in IVF cycles stimulated with GnRH agonist gonadotrophin treatment: a pilot study.

BACKGROUND: Recent evidence supports a specific and broad role of androgen produced by theca cells in reproductive physiology. This pilot study evaluated the usefulness of hCG theca stimulation test in predicting ovarian response and pregnancy. METHODS: Prospective cohort study including 80 infertile women treated with IVF/ICSI. On Day 3 of the menstrual cycle preceding, the first IVF/ICSI cycle a blood sample was drawn to evaluate baseline FSH, estradiol (E(2)), 17-hydroxy-progesterone, androstenedione and testosterone levels. All women then received 250 µg recombinant hCG s.c. and underwent a second blood sampling 24 h after hCG injection to measurement steroid serum levels. RESULTS: Percentage increment of E(2) but not its precursors was significantly higher in normo-responders and pregnancy cycles than in poor responders and non-pregnancy cycles (P = 0.03 and P = 0.02, respectively) diagnostic accuracy being 67 and 75%, respectively. The percentage increase in E(2) thus still fails in as many as 33 and 25% of patients in predicting ovarian response and pregnancy, respectively. In addition, E(2) concentrations are poorly reproducible and a wide range of variation in all serum steroids investigated-including E(2)-after hCG injection was observed. CONCLUSIONS: The predictive power of the hCG test is based on E(2) but not androgen response to hCG injection. This test cannot be recommended in routine clinical practice because it is too laborious for screening purposes, shows great variability in the response obtained and its overall accuracy is not better than that reported for other available markers of ovarian reserve. The use of the currently available markers, antral follicle count and anti-Müllerian hormone, is therefore recommended.

Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome.

OBJECTIVE: To evaluate the perinatal and neurodevelopmental outcome of small-for-gestational-age fetuses with normal umbilical artery Doppler managed expectantly during pregnancy and delivery. STUDY DESIGN: Perinatal and neurodevelopmental outcome was assessed from a cohort of singleton small-for-gestational-age fetuses with normal umbilical artery Doppler and normally grown controls matched by gestational age at delivery, parity and parental socio-economic level. Neurodevelopmental outcome was prospectively evaluated by means of the 24-month Age&Stage Questionnaire (ASQ). RESULTS: A total of 129 small-for-gestational-age fetuses and 259 controls were included. Small-for-gestational-age fetuses had a higher risk for neonatal intensive care unit admission (15.5% versus 3.9%; p<0.001) and significant neonatal morbidity (2.3% versus 0%; p=0.04) than controls. At 24-months, these fetuses showed significantly lower neurodevelopmental centile in the problem solving (42.8 versus 52.1; p=0.001) and personal-social (44.4 versus 54.6; p<0.001) areas than controls. CONCLUSION: Perinatal and neurodevelopmental outcome in small-for-gestational-age fetuses with normal umbilical artery Doppler is suboptimal, which may challenge the role of umbilical artery Doppler to discriminate between normal-SGA and growth-restricted fetuses.

Evaluation of two doses of recombinant human luteinizing hormone supplementation in down-regulated women of advanced reproductive age undergoing follicular stimulation for IVF: a randomized clinical study.

OBJECTIVES: To evaluate the effects of mid-follicular recombinant human luteinizing hormone (rhLH) supplementation in down-regulated women of advanced reproductive age undergoing in vitro fertilization (IVF). STUDY DESIGN: This was a prospective, randomized parallel-group study (allocation 1:1) including 187 normogonadotrophic infertile patients aged ≥ 35 years. Subcutaneous triptorelin was used for pituitary desensitization, and ovarian stimulation was achieved with recombinant human follicle-stimulating hormone (rhFSH) either alone (Group 1) or in combination with rhLH in one of two daily doses: 37.5 IU (Group 2) or 75 IU (Group 3). Ovarian stimulation characteristics and IVF outcome were evaluated. The main outcome was pregnancy rate. RESULTS: A total of 62, 62 and 63 patients were randomized to groups 1, 2 and 3 respectively, and 56, 54 and 55 patients respectively were available for final analysis of the results. Follicular development and oocyte yield were significantly higher in group 1 patients compared with patients in groups 2 and 3. Oocyte maturity and number of oocytes fertilized were also higher in group 1 patients; this difference almost reached statistical significance. No significant difference in implantation and clinical pregnancy rates was found among the three treatment groups. CONCLUSIONS: rhLH supplementation is not a useful tool for patients of advanced reproductive age in ovarian stimulation protocols using an appropriate gonadotrophin-releasing hormone agonist and a step-down regimen of rhFSH.

Growth deficit in term small-for-gestational fetuses with normal umbilical artery Doppler is associated with adverse outcome.

AIM: The association between the growth deficit and the occurrence of adverse outcome was analyzed in a cohort of small-for-gestational age fetuses delivered at term. METHODS: A cohort of consecutive singleton fetuses suspected of being SGA during the late third trimester and delivered beyond 37 weeks was selected. Growth deficit area was calculated as that between the individual 10(th) centile curve of the customized optimal fetal weight and the individual fetal growth curve. RESULTS: A total of 55 women were included. Of these, 16 had 28 adverse events: eight cases of umbilical artery pH<7.15, 9 cases of caesarean section for fetal distress and 11 cases of admission to neonatal intensive care unit. Whereas the mean area of growth deficit was 8.8 kg x week units (SD 7.6) for cases with normal outcomes, it was 13.9 (SD 8.04) for cases with adverse outcomes (P=0.03). A growth area deficit >10 units, predicted the occurrence of adverse outcome with a sensitivity and specificity of 62% and 68%, respectively. CONCLUSION: In term growth restricted fetuses the degree of growth deficit from the optimal customized growth may be used to identify a subgroup of fetuses at high-risk for adverse outcomes.

Prediction of adverse perinatal outcome at term in small-for-gestational age fetuses: comparison of growth velocity vs. customized assessment.

OBJECTIVE: To explore the ability of growth velocity and customized standards of fetal weight to predict adverse outcomes in small fetuses delivered at term. METHODS: We evaluated a cohort of 86 consecutive singletons suspected to be small for gestational age during the third trimester (estimated fetal weight <10(th) centile), who had normal umbilical artery Doppler and ultimately delivered at term. Conditional growth velocity and customized fetal growth were compared for the prediction of adverse outcome. RESULTS: Overall, customized growth assessment showed better sensitivity than growth velocity assessment (57.1% vs. 42.9% for a 10(th) centile cut-off) for the prediction of adverse outcome, but with comparable specificity. The odds of having an adverse outcome for women with a positive test compared with women with a negative test were 1.54 and 3.22 for the 10(th) centile growth velocity and customized definitions, respectively. The area under the curve for the prediction of adverse outcome was larger for customized than for growth velocity standards (0.65 vs. 0.59), albeit without statistical significance. CONCLUSIONS: Our study suggests that customized growth assessment may have better accuracy in predicting adverse perinatal outcome than growth velocity in small fetuses with normal umbilical Doppler delivered at term.