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Category Archives: Human Reproduction

Assessment of acrosome and nuclear abnormalities in human spermatozoa with large vacuoles

BACKGROUND

Spermatozoa with large vacuoles (SLV) may have a negative impact on embryo development. The origin of these vacuoles is unknown. We evaluated acrosome and nucleus alterations in isolated SLV, versus unselected spermatozoa.

METHODS

We studied 20 patients with teratozoospermia. Spermatozoa from the native semen sample and spermatozoa presenting a vacuole occupying >13.0% total head area, isolated under high magnification (x6600), were assessed. Confocal and transmission electron microscope evaluations were performed on SLV and native sperm, respectively. Acrosome morphology and DNA fragmentation were analysed using proacrosin immunolabelling (monoclonal antibody 4D4) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Chromatin condensation was evaluated with aniline blue staining. Sperm aneuploidy was assessed using fluorescence in situ hybridization.

RESULTS

SLV represented 38.0 ± 5.10% of motile spermatozoa obtained after gradient density centrifugation. Vacuoles were mainly in the anterior and median sperm head (45.7 ± 2.90 and 46.1 ± 3.00%, respectively). Abnormal acrosomes were increased in SLV compared with unselected spermatozoa (77.8 ± 2.49 versus 70.6 ± 2.62%; P = 0.014). Microscopic observations showed an exclusively nuclear localization of large vacuoles. Complete DNA fragmentation was higher in native spermatozoa (P < 0.0001) than SLV, while chromatin condensation was altered in SLV (P < 0.0001). Aneuploidy and diploidy rates were increased in SLV (P < 0.0001).

CONCLUSIONS

Sperm vacuoles were exclusively nuclear. In our selected teratozoospermic population, aneuploidy and chromatin condensation defects were the main alterations observed in SLV. Based on results from this small sample of spermatozoa, we propose a global impairment of the spermatogenesis process as a common origin of the morphological alterations.

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ESHRE PGD Consortium/Embryology Special Interest Group–best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS)

In 2005, the European Society for Human Reproduction and Embryology (ESHRE) Preimplantation Genetic Diagnosis (PGD) Consortium published a set of Guidelines for Best Practice to give information, support and guidance to potential, existing and fledgling PGD programmes (Thornhill AR, De Die-Smulders CE, Geraedts JP, Harper JC, Harton GL, Lavery SA, Moutou C, Robinson MD, Schmutzler AG, Scriven PN et al. ESHRE PGD Consortium best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod 2005;20:35–48.). The subsequent years have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of ESHRE's recent advice on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme; Organization of a PGD centre, fluorescence in situ hybridization-based testing, amplification-based testing and polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Here we have updated the sections that pertain to embryology (including cryopreservation) and biopsy of embryos prior to PGD or PGS. Topics covered in this guideline include uses of embryo biopsy, laboratory issues relating to biopsy, timing of biopsy, biopsy procedure and cryopreserving biopsied embryos.

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Insulin-like growth factor binding protein-1 in PCOS: a systematic review and meta-analysis

BACKGROUND

Despite extensive research, the pathogenesis of polycystic ovary syndrome (PCOS) remains unclear. Putatively, an elevated circulating concentration of insulin inhibits the production of insulin-like growth factor binding protein-1 (IGFBP-1), thus increasing the level of free IGF-I in serum and stimulating ovarian androgen production. Decreased IGFBP-1 has been reported in PCOS and in obesity; however, there are inconsistencies in the evidence. This systematic review and meta-analysis aimed to determine whether IGFBP-1 is decreased in PCOS when controlling for the influence of BMI.

METHODS

Articles published between 1988 and 2008 were searched using MEDLINE, PubMed, SCOPUS and Web of Knowledge. Unpublished literature, trials in progress, and recent reviews were also searched. Original articles were selected by two investigators. To be included, the study must have compared serum IGFBP-1 in two populations: either PCOS versus controls, or an overweight subgroup versus the normal weight subgroup in either population. From 617 identified articles, 12 were included in the meta-analysis. Data were abstracted by two reviewers independently and standardized for errors.

RESULTS

The population difference is presented as the Weighted Mean Difference (95% CI). PCOS subjects had a significantly lower serum concentrations of IGFBP-1 compared with controls [P< 0.00001; –36.6 (–52.0, –21.2) µg/l]. Overweight PCOS subjects also had lower IGFBP-1 levels compared with normal weight PCOS subjects [P < 0.006; –30.6 (–52.3, –8.8) µg/l]. No significant difference was found between overweight PCOS patients and overweight controls [P = 0.23; –5.1 (–13.5, 3.2) µg/l] or between normal weight PCOS patients and normal weight controls [P = 0.50; –3.8 (–14.9, 7.3) µg/l]. Overweight controls had significantly lower IGFBP-1 concentrations than normal weight controls [P = 0.03; –18.0 (–34.4, – 1.5) µg/l].

CONCLUSION

These data indicate that a decreased serum level of IGFBP-1 is unlikely to be a mechanism for ovarian hyperandrogenism in PCOS. BMI may be the major determinant of serum IGFBP-1.

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Strategies to prevent unintended pregnancy: increasing use of long-acting reversible contraception

BACKGROUND

Despite increasing contraceptive availability, unintended pregnancy remains a global problem, representing as many as 30% of all known pregnancies. Various strategies have been proposed to reverse this disturbing trend, especially increased use of long-acting reversible contraceptive (LARC) methods. In this review we aim to discuss the role of LARC methods and importance of contraceptive counseling in reducing unintended pregnancy rates.

METHODS

References/resources cited were identified based on searches of medical literature (MEDLINE, 1990–2009), bibliographies of relevant publications and the Internet.

RESULTS AND CONCLUSIONS

LARC methods—copper intrauterine devices (IUDs), progestogen-releasing intrauterine system and injectable and implantable contraceptives—are safe and effective contraceptive options (unintended pregnancy rates with typical versus perfect use: 0.05–3.0 versus 0.05–0.6%) that are appropriate for a wide range of women seeking to limit or space childbearing. Despite their safety and efficacy records, these methods remain underutilized; injectable and implantable methods are used by an estimated 3.4% and intrauterine methods by 15.5% of women worldwide. LARC methods require no daily or coital adherence and avoid the adverse events and health risks of estrogen-containing contraceptives. The copper IUD and progestin-only injections and implants have been shown to be more cost-effective than more commonly used methods, such as condoms and the pill (5-year savings: $13 373–$14 122, LARC; $12 239, condoms; $12 879, pill). Women who are considering use of LARC methods should receive comprehensive contraceptive counseling, as women who receive counseling before use demonstrate higher rates of after-use method satisfaction, continuation and acceptance than those who do not.

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Global variations in the uptake of single embryo transfer

BACKGROUND

Single embryo transfer (SET) is the most effective way of reducing multiple pregnancy rates associated with assisted reproductive technology (ART). Despite published evidence suggesting that the judicious use of elective SET can lead to near-elimination of multiples without compromising cumulative live birth rates, the uptake of this strategy has been variable.

METHODS

Medline, EMBASE and the Cochrane Database of Systematic Reviews (1978–2010) were searched using appropriate MeSH headings. Leading fertility journals along with appropriate cross references were hand searched and information retrieved from national ART registers and websites of national fertility societies in order to determine current rates of SET. We explored social, economic and clinical factors determining the uptake of SET.

RESULTS

It was not possible to distinguish elective from non-elective SET from national ART reports. Data from 31 countries suggest that there has been a gradual increase in SET rates over a 3 year period (2003–2005) but major geographical differences were noted. SET rates are highest in Sweden (69.4%) but are as low as 2.8% in the USA. Access to public funding for ART, availability of good cryopreservation facilities and legislation appear to be the most important reasons favouring the uptake of SET. Personal choice plays a significant role as many subfertile couples have a strong preference for twins. Awareness that double embryo transfer (DET) increases live birth per fresh treatment cycle, inability to accurately identify women at high risk for twins and limitations of existing embryos selection criteria are barriers to a wider acceptance of SET.

CONCLUSIONS

The current variation in the uptake of elective SET is likely to persist until there are major changes in the way ART is viewed, funded and legislated.

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Risk for postpartum depression associated with assisted reproductive technologies and multiple births: a systematic review

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.

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