Category Archives: Human Reproduction

BACKGROUND

It has been hypothesized that certain obstetrical populations, including women who conceive using assisted reproductive technologies (ART) and women with multiple births, may be at increased risk for postpartum depression. In this systematic literature review, we examine the published evidence for this hypothesis.

METHODS

The databases Medline, CINAHL, EMBASE, PsycINFO and the Cochrane Library were searched from their start dates through to April 1, 2009 using relevant keywords. All published, peer-reviewed articles in English, Spanish or French including a standardized assessment of depression administered between 2 and 52 weeks postpartum were considered for inclusion. Two independent reviewers abstracted and critically appraised a total of 13 eligible articles.

RESULTS

The data indicate little or no increased risk for postpartum depression among women who use ART to conceive. In contrast, most studies of adequate quality indicate that mothers of multiples may be at elevated risk for symptoms of depression. However, existing data do not permit differentiation between transient maternal distress and clinically significant postpartum depression.

CONCLUSIONS

Studies included in this review were often limited by small samples and lack of appropriate comparison groups, making further research in this area essential. In particular, lack of control for maternal psychiatric history and other important sociodemographic predictors of depression is a serious limitation of existing research on this topic. Further, the use of reproductive technologies and multiple births often co-occur, and few study designs enabled separation of the effects of these two variables. However, evidence of increased risk for symptoms of postpartum depression among women with multiple births, if confirmed, may warrant targeted interventions for this population.

BACKGROUND

Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions.

METHODS

We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies.

RESULTS

Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility.

CONCLUSIONS

All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

BACKGROUND

During meiosis, mammalian oocytes undergo two successive cell divisions without an intermediate replicative phase. This brief period, called ‘meiotic maturation’, is crucial for the formation of an egg capable of being fertilized and of generating viable and euploid offspring.

METHODS

We review our current knowledge of the cellular and molecular mechanisms that control asymmetry and appear to be shared between mammalian species, as well as the associated misfunctions that impair the formation of functional female gametes.

RESULTS AND CONCLUSIONS

The two successive divisions that comprise mammalian oogenesis are asymmetric. They lead to the formation of small polar bodies and the large and polarized egg. This asymmetry depends upon the dynamic organization of the oocyte cytoskeleton during both divisions. During meiosis I, microfilaments and associated molecules ensure the targeting of the microtubule spindle at the oocyte periphery. During meiosis II, they anchor the spindle under the plasma membrane. In parallel, the cortex overhanging the spindle is dramatically reorganized. Establishment and maintenance of this cortical domain are crucial for the completion of fertilization. Loss of this differentiated area is characteristic of ageing or low-quality gametes and associated with increased maternal age or post-ovulatory ageing.

BACKGROUND

Anti-Mullerian hormone (AMH) is a marker of ovarian reserve status and represents a good predictor of ovarian response to ovarian hyperstimulation. The aim of this study was to assess the accuracy of AMH and antral follicle count (AFC) as predictors of an excessive response in IVF/ICSI treatment.

METHODS

A systematic review and meta-analysis of the existing literature was performed. Studies were included if 2 x 2 tables for the outcome excessive response in IVF patients in relation to AMH/AFC could be constructed. Using a bivariate meta-analytic model, both summary point estimates for sensitivity and specificity were calculated, as well as summary ROC curves. Clinical value was analysed by calculating post-test probabilities of excessive response at optimal cut-off levels, as well as the corresponding abnormal test rates.

RESULTS

Nine studies reporting on AMH and five reporting on AFC were found. Summary estimates of sensitivity and specificity for AMH were 82 and 76%, respectively, and 82 and 80%, respectively, for AFC. Comparison of the summary estimates and ROC curves for AMH and AFC showed no statistical difference. Abnormal test rates for AMH and AFC amounted to ~14 and 16%, respectively, at cut-off levels where test performance is optimal [likelihood ratio for a positive result (LR + )>8], with a post-test probability of ±70%.

CONCLUSIONS

Both AMH and AFC are accurate predictors of excessive response to ovarian hyperstimulation. Moreover, both tests appear to have clinical value. This opens ways to explore the potential of individualized FSH dose regimens based on ovarian reserve testing.

BACKGROUND

The retinoic acid metabolizing enzyme Cyp26a1 plays a pivotal role in vertebrate embryo development. Cyp26a1 was characterized previously as a differentially expressed gene in peri-implantation rat uteri via suppressive subtracted hybridization analysis. However, the role of Cyp26a1 in rat embryo implantation remained elusive.

METHODS

The expression of Cyp26a1 in the uteri of early pregnancy, pseudopregnancy and artificial decidualization was detected by northern blotting, real time-PCR, in situ hybridization, western blotting and immunofluorescent staining. The effect of Cyp26a1 on apoptosis of endometrial stromal cells (ESCs) isolated from rat uteri was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst staining. Apoptosis-related proteins in ESCs were detected by western blotting.

RESULTS

Cyp26a1 showed distinctive expression patterns in embryos and uteri during the peri-implantation period, with a remarkable increase (P < 0.01 versus Days 4–5) in mRNA and protein in the implantation phase (Days 5.5–6.5 of pregnancy). CYP26A1 was specifically localized in glandular epithelium, luminal epithelium and decidua basalis. The level of CYP26A1 protein was significantly increased in uteri of artificial decidualization (P < 0.01 versus control). Forced Cyp26a1 overexpression significantly reduced the sensitivity of ESCs to etoposide-induced apoptosis, with reductions in p53 (P < 0.01) and Fas (P < 0.05) proteins versus control, while in contrast, FasL (P < 0.01) and proliferating cell nuclear antigen (P < 0.05) proteins increased.

CONCLUSIONS

Cyp26a1 is spatiotemporally expressed in the uterus during embryo implantation and decidualization. Overexpression of Cyp26a1 attenuates the process of uterine stromal cell apoptosis, probably via down-regulating the expression of p53 and FasL.

BACKGROUND

The association among hereditary thrombophilia, recurrent pregnancy loss (RPL) and obstetric complications is yet uncertain. The objective of the study was to assess the prognostic value of the factor V Leiden (FVL) and prothrombin (PT) mutations for the subsequent chance of live birth for women with RPL.

METHODS

Pregnancy outcome was recorded in a retrospective cohort of 363 women with a minimum of three consecutive pregnancy losses (early miscarriage, late miscarriage or stillbirth/neonatal death) who were not treated with anticoagulation therapy.

RESULTS

Of the 363 women, 29 were FVL-mutation carriers and 6 were PT-mutation carriers. The unadjusted live birth rate was 45.7% in FVL/PT carriers versus 63.4% in FVL/PT non-carriers, P = 0.04. The adjusted odds ratio for live birth in FVL/PT carriers was 0.48 (95% CI = 0.23–1.01), P = 0.05. Among the obstetric complications, only excessive bleeding was found to be associated with FVL/PT mutations.

CONCLUSIONS

In the unadjusted analysis, FVL and PT mutations have a negative prognostic impact on the live birth rate in women with RPL; however, when adjusting for significant covariates, the results no longer reach statistical significance. Strong conclusions on the association between obstetric complications and hereditary thrombophilia cannot be drawn from this study. Whether anticoagulation therapy would improve the prognosis in women with RPL and FVL/PT mutations remains to be documented in large randomized controlled trials.