There have been concerns about validity and accuracy of the measurement of sHLA-G in embryo culture supernatants. In this systematic review, we quantified the diagnostic accuracy of sHLA-G for predicting the ability to achieve clinical pregnancy in women who are undergoing infertility treatment.
Medline and Embase were searched up to 7 September 2007, for full English and non-English articles concerning cohort studies evaluating sHLA-G in embryo culture for predicting clinical pregnancy in women undergoing IVF and ICSI.
Eleven studies including 1813 patients met our inclusion criteria. In the individual studies, sensitivity ranged from 0.01 to 0.97, specificity from 0.18 to 0.98, the positive likelihood ratio from 0.34 to 3.21 and the negative likelihood ratio from 0.08 to 1.01. These values were highly heterogeneous with, in each case, I2 values of >75%, and P-values for the Q statistic of <0.001, arguing against generating a pooled estimate for these diagnostic test properties. The diagnostic odds ratios (DORs) ranged from 0.92 to 24.82 in the individual studies with an I2 value of 49% indicating moderate heterogeneity. Therefore, the meta-analysis combined the logs of the DORs, which are derived from sensitivity and specificity. A random-effects model yielded a summary DOR of 4.38 (95% CI, 2.93–6.55), consistent with modest diagnostic accuracy. Interestingly, an a priori defined subgroup analysis restricted to six studies with good quality embryos showed a better diagnostic performance with a DOR of 12.67 (95% CI, 3.66–43.80) to predict the ability to achieve clinical pregnancy in women undergoing infertility treatment. CONCLUSIONS: Further research is needed with single-embryo culture, single-embryo transfer and highly sensitive detection techniques to determine the potential application of measuring sHLA-G in culture supernatant.
The effect of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) on the developing human brain is unclear. The objective of this study is to evaluate neurodevelopmental (ND) outcome of children born following these techniques.
This systematic review includes studies which compare a group of children born following IVF/ICSI to children born after natural conception by assessing outcome in terms of neuromotor development, cognition, speech/language and behaviour. Specific attention is paid to the studies’ methodological quality based on study design, attrition, blinding of the assessor, validity of ND tests used, confounders included and group size or power analysis.
Twenty-three out of 59 studies had a good methodological quality including 9 register-based (RB) and 14 controlled studies. RB studies suggested that IVF/ICSI per se does not increase the risk for severe cognitive impairment (i.e. mental retardation) or neuromotor handicaps such as cerebral palsy (CP), the association of IVF/ICSI and CP being brought about by the association of assisted conception with risk factors, like preterm birth. In general, controlled studies of good quality did not report an excess of ND disorders in IVF/ICSI-children. However, the majority of studies followed the children during infancy only, thereby precluding pertinent conclusions on the risk of ND disorders that come to the expression at older ages, such as fine manipulative disability or dyslexia.
A negative effect of assisted conception on the developing human brain is not identified; however, further research of high methodological quality in children beyond pre-school age is needed.
To review the accuracy of multivariate models for the prediction of ovarian reserve and pregnancy in women undergoing IVF compared with the antral follicle count (AFC) as single test.
We performed a computerized MEDLINE and EMBASE search to identify articles published on multivariate models for ovarian reserve testing in patients undergoing IVF. In order to be selected, articles had to contain data on the outcome of IVF in terms of either pregnancy and/or poor response and on the prediction of these events based on a multivariate model. For the selected studies, sensitivity and specificity of the test in the prediction of poor ovarian response and non-pregnancy were calculated. Overall performance was assessed by estimating a summary receiver operating characteristic (ROC) curve, which was compared with the ROC curve for the AFC as the current best single test.
We identified 11 studies reporting on the predictive capacity of multivariate models in ovarian reserve testing. All studies reported on the prediction of poor ovarian response, whereas none reported on the occurrence of pregnancy. The sensitivity for prediction of poor ovarian response varied between 39% and 97% and the specificity between 50% and 96%. Logistic regression analysis indicated that cohort studies provided a significantly better discriminative performance than case–control studies. As cohort studies are superior to case–control studies, further analysis was limited to the cohort studies. For the cohort studies, a summary ROC curve could be estimated, which had a shape similar to that previously made for the AFC.
The accuracy of multivariate models for the prediction of ovarian response in women undergoing IVF is similar to the accuracy of AFC. No data are available on the capacity of these models to predict pregnancy, let alone live birth. On the basis of these findings, the use of more than one single test for the assessment of ovarian reserve cannot currently be supported.
Recurrent pregnancy loss (RM) affects 0.5–1% of couples. The pathophysiology of RM is complex. The suggested causes include anatomical, genetic and molecular abnormalities, endocrine disorders, thrombophilias and anti-phospholipid syndrome. In ~50% of the cases neither of the above can be identified. We aimed at examining the evidence on the role of progesterone in the pathophysiology of RM, and the clinical evidence on effectiveness of progestogen treatment.
We searched PubMed and the Cochrane database covering the period of 1968–2007. The search terms progestogens and recurrent miscarriage, NK cells and recurrent miscarriage as well as cytokines and recurrent miscarriage were used.
Progesterone is indispensable for creating a suitable endometrial environment for implantation. RM may be due to subnormal progesterone secretion and retarded endometrial development in the peri-implantation period. Progesterone also acts on the immune system, mainly by affecting cytokine synthesis and the function of NK cells. A recent meta-analysis showed that though progesterone treatment did not affect pregnancy outcome in women with miscarriages in general, separate analysis of three small and dated studies including altogether 91 patients with RM revealed a small but significant effect. It is noteworthy that the design of these 40 years old studies does not meet modern requirements.
Standardized laboratory protocols for identifying potential targets of progestogen treatment as well as implementation of well-designed randomized studies are needed to establish the usefulness of progesterone supplementation in the treatment of RM.