BACKGROUND

Women with fertility problems often experience higher levels of stress, anxiety and depressive symptoms associated with both the infertility diagnosis and eventual fertility treatment. The authors investigated whether women who do not succeed in having a child after an infertility evaluation are at a higher risk of suicide than women who succeed in having a child after an infertility evaluation.

METHODS

A cohort of 51 221 Danish women with primary or secondary infertility and referred to hospitals or private fertility clinics in Denmark during 1973–1998 was established. The cohort was linked to four Danish administrative population-based registries. Each woman was followed from the date of her initial fertility evaluation at the clinic or hospital until 2006. Cox proportional hazards regression analyses was used to calculate hazard ratios (HRs) for suicide and their corresponding 95% confidence intervals (CIs) adjusted for potential confounders.

RESULTS

Women who did not have a child after an initial fertility evaluation had a >2-fold (HR: 2.43; 95% CI: 1.38–3.71) greater risk of suicide than women who had at least one child after a fertility evaluation. Women with secondary infertility, i.e. women who had a child before a fertility evaluation but did not succeed in having one after, also had an increased risk for suicide (HR: 1.68; 95% CI, 0.82–3.41) compared with women who succeeded in having another child, although the risk estimate failed to reach significance.

CONCLUSIONS

Health-care personnel treating women with fertility problems should be aware of the emotional response of their patients in order to recognize and treat possible psychiatric morbidity after fertility problems.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

This study examines the findings from the largest survey to date of donor-inseminated (DI) offspring and focuses on respondents’ learning of the method of their conception and their desire to contact their donor.

METHODS

Online questionnaires were completed by 741 DI offspring, of whom 61.8% have heterosexual parents and 38.2% have lesbian parents. Respondents were recruited via the Donor Sibling Registry, a non-profit US-based international registry that facilitates communication between donor-conceived offspring and their non-biological and biological relatives. Data were collected on family composition, offspring's feelings regarding the method of their conception, communication within families, donor anonymity and their search for their donors. This investigation focuses on the relationship between family type (single or dual-parent and lesbian or heterosexual parent/s) and offspring's reactions to learning of their DI conception.

RESULTS

Offspring of lesbian parents learned of their DI origins at earlier ages than offspring of heterosexual parents. In the latter families, disclosure tended to occur earlier in single-parent than in dual-parent families. Disclosure was most likely to be confusing to offspring of heterosexual parents, particularly when it occurred at an older age. The vast majority of offspring in all types of families desired contact with their donor; however, comfort in expressing curiosity regarding one's donor was lowest in dual-parent heterosexual families, with about one-quarter reporting an inability to discuss their origins with their social father.

CONCLUSIONS

Although the findings are not based on a random sample, the desire among offspring surveyed here is for greater openness and contact with their donor. A variety of strategies are needed for offspring of heterosexual couples to benefit optimally from the general trend toward openness in gamete donation.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Little is known about psychological processes of infertile couples pursuing medical treatment in comparison with fertile couples and adoption candidates who also suffer from infertility but are not seeking medical help. This study aims to contribute to a better understanding of these individuals in terms of psychological processes (such as external shame, internal shame and self-judgment) and their association with psychopathology, also attending to gender differences.

METHODS

One hundred control couples without known fertility problems [fertile group (FG)], 100 couples with an infertility diagnosis and pursuing medical treatment [infertile group (IG)], and 40 couples with an infertility diagnosis who are applying for adoption [adoption group (AG)] completed the instruments: Beck Depression Inventory, Spielberger State-Trait Anxiety Inventory, Others as Shamer, Experience of Shame Scale and the Self-compassion Scale. One-way analysis of variances were used to compare the three groups demographic and study variables. Pearson correlations and linear multiple regression analysis were performed to investigate the associations between shame, self-judgment, depression and anxiety. To explore gender differences, T-tests were used.

RESULTS

The IG group scored higher than FG and AG in measures of depression, anxiety, external shame, internal shame and self-judgment. In infertile couples, self-judgment, external shame and internal shame emerged as significant predictors of depressive symptomatology. Women with an infertility diagnosis tend to present higher levels of depressive and anxiety symptoms in comparison with fertile controls and adoption candidates.

CONCLUSIONS

This study highlights the importance of emotional regulation processes such as internal and external shame, and self-judgment, to the understanding of psychopathological symptomatology associated with infertility. Our results suggest that these issues should be addressed in a therapeutic context with these couples. Nevertheless, the heterogeneity of the infertile group, in what concerns different stages of medical diagnosis and treatment, might represent a limitation in the interpretation of our findings.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Existing definitions of infertility lack uniformity, rendering comparisons in prevalence between countries or over time problematic. The absence of an agreed definition also compromises clinical management and undermines the impact of research findings. The aim of this study was to perform a systematic review of the literature to determine how infertility has been defined in prevalence studies and to come up with suggestions for a feasible and clinically relevant definition.

METHODS

MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews were searched for relevant population-based prevalence studies published between 1975 and 2010.

RESULTS

A total of 39 articles were included in the current review. The results highlight the heterogeneity of criteria used to define infertility and critical differences between demographic and epidemiological definitions. Demographers tend to define infertility as childlessness in a population of women of reproductive age, while the epidemiological definition is based on ‘trying for’ or ‘time to’ a pregnancy, generally in a population of women exposed to the risk of conception. There is considerable variation in terms of the duration of ‘trying for pregnancy’, the age of women sampled and their marital or cohabitation status. This leads to inconsistencies in determining the numerator and denominator used to calculate the prevalence of infertility.

CONCLUSIONS

There is a need for an agreed definition for infertility. We suggest a clinically relevant definition based on the duration of trying for pregnancy coupled with female age.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking.

METHODS

Observational studies published 1959–2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls.

RESULTS

Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02–1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05–1.27); limb reduction defects (OR 1.26, 95% CI 1.15–1.39); missing/extra digits (OR 1.18, 95% CI 0.99–1.41); clubfoot (OR 1.28, 95% CI 1.10–1.47); craniosynostosis (OR 1.33, 95% CI 1.03–1.73); facial defects (OR 1.19, 95% CI 1.06–1.35); eye defects (OR 1.25, 95% CI 1.11–1.40); orofacial clefts (OR 1.28, 95% CI 1.20–1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18–1.36); gastroschisis (OR 1.50, 95% CI 1.28–1.76); anal atresia (OR 1.20, 95% CI 1.06–1.36); hernia (OR 1.40, 95% CI 1.23–1.59); and undescended testes (OR 1.13, 95% CI 1.02–1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85–0.95) and skin defects (OR 0.82, 0.75–0.89). For all defects combined the OR was 1.01 (0.96–1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects).

CONCLUSIONS

Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy.

METHODS

Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register.

RESULTS

From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1–2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6–4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1–2.0), miscarriage (OR 3.73, 95% CI 1.8–7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5–3.5), preterm birth (OR 1.9, 95% CI 1.1–3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6–24) when compared with the absence of thyroid antibodies.

CONCLUSIONS

Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is determined by the analysis of a single cell from that embryo.

METHODS

Here we report a systematic review and meta-analysis of studies on the chromosomal constitution of human preimplantation embryos. In 36 studies, out of 2117 citations that met our search criteria, data were provided extensively enough to allow classification of each analysed embryo with prespecified criteria for its chromosomal makeup. The main outcome of this classification was the prevalence of chromosomal mosaicism in human preimplantation embryos.

RESULTS

A total of 815 embryos could be classified. Of these, 177 (22%) were diploid, 599 (73%) were mosaic, of which 480 (59% of the total number of embryos) were diploid–aneuploid mosaic and 119 (14% of the total number of embryos) were aneuploid mosaic, and 39 (5%) contained other numerical chromosomal abnormalities. The distribution of the embryos over these categories was associated with the developmental stage of the embryos, the method used for analysis and the number of chromosomes analysed.

CONCLUSIONS

Diploid–aneuploid mosaicism is by far the most common chromosomal constitution in spare human preimplantation embryos after IVF. This undermines the reliable determination of the ploidy status of a cleavage-stage embryo based on the analysis of a single cell. Future research should determine the origin and developmental potential of mosaic embryos.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Endometriosis is a complex disease with a multifactorial pathogenesis, which is crucially dependent on the development of new blood vessels. Based on the current literature, the present review highlights the fact that the neovascularization of endometriotic lesions is not only driven by angiogenesis, but also involves de novo formation of microvessels from circulating endothelial progenitor cells (EPCs). This process, termed post-natal vasculogenesis, is a characteristic of various pathogenic conditions, such as tumour growth and atherosclerosis, and typically comprises the activation, mobilization and recruitment of bone marrow-derived EPCs to the sites of tissue hypoxia.

METHODS

Literature searches were performed in PubMed, MEDLINE and ISI Web of Knowledge for publications focusing on vasculogenesis in the endometrium and endometriotic lesions.

RESULTS

Recent studies indicate that up to 37% of the microvascular endothelium of ectopic endometrial tissue originates from EPCs, partly controlled by the stromal-cell-derived factor-1/chemokine receptor type 4 axis. Accordingly, blockade of EPC recruitment effectively inhibits the formation of microvascular networks in developing endometriotic lesions, indicating that vasculogenesis represents an integral part of the pathogenesis of endometriosis.

CONCLUSIONS

The involvement of vasculogenesis in endometriosis may offer the exciting opportunity for the future establishment of novel diagnostic and therapeutic strategies for this frequent gynaecological disease.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Endometriosis is usually diagnosed by an invasive procedure such as a laparoscopy. Great interest therefore lies in the potential to identify biomarkers which may be surrogates of disease presence or activity, especially relating to the effects of therapy. We have reviewed the existing literature on endometrial differences in women with endometriosis, and assess their potential use as disease biomarkers.

METHODS

We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to conduct a systematic review of published papers over the past 25 years on the subject of endometrial differences in endometriosis. We searched for all studies assessing differences between eutopic endometrium of women with and without endometriosis.

RESULTS

We identified 182 relevant articles that are summarized in the review. These studies assess over 200 potential biomarkers, including hormones and their receptors (n = 29), cytokines (n = 25), factors identified using proteomics (n = 8) and histological analysis (n = 10) of endometrial tissue. Sensitivity and specificity were reported or could be calculated for only 32 articles, and ranged from 0 to 100%. Of the nine highest quality studies, six identified putative biomarkers related to nerve fibre growth or cell cycle control, highlighting these areas as promising candidates for future biomarker research.

CONCLUSIONS

This systematic review identified several reports of endometrial differences which have the potential to be biomarkers of endometriosis. However, larger studies in well-defined populations are clearly required to determine their true usefulness.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

The increase in the incidence of obesity has a substantial societal health impact. Contrasting reports have been published on whether overweight and obesity affect male fertility. To clarify this, we have reviewed published data on the relation between overweight/obesity, semen parameters, endocrine status and human male fertility. Subsequently, we have used results obtained in animal models of obesity to explain the human data.

METHODS

Pubmed, Scopus, Web of Science and Google Scholar databases were searched between September 2009 and October 2010 for a comprehensive publication record. Available studies on adult human males were examined. The included animal studies examined obesity and fertility, and focused on leptin, leptin receptor signaling, kisspeptins and/or NPY.

RESULTS

Most overweight/obese men do not experience significant fertility problems, despite the presence of reduced testosterone alongside normal gonadotrophin levels. Only a subgroup of subjects suffers from hypogonadotropic hypogonadism. Animal models offer several explanations and show that reduced leptin signaling leads to reduced GnRH neuronal activity. This may be due to decreased hypothalamic Kiss1 expression, a potent regulator of GnRH/LH/FSH release. As the Kiss1 neurons express leptin receptors, the Kiss1 system may participate in transmitting metabolic information to the GnRH neurons, thus providing a bridge between metabolic regulation and fertility.

CONCLUSIONS

Infertility in overweight/obese males may be explained by leptin insensitivity. This implies a possible role for the KISS1 system in human obesity-related male infertility. If substantiated, it will pave the way for methods to restore fertility in these subjects.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

Background

The purpose of this study was first to give an overview of the historical development of polarization microscopy, second to describe the various applications of this technique in assisted reproduction techniques (ART) and third to discuss the potential benefit of polarization microscopy as a predictor for IVF success.

Methods

The history of polarization microscopy was undertaken by performing a backward search in the scientific literature using Google and internet sites of several Societies for Microscopy and Cell Biology. Studies of polarization microscopy in ART were identified by using a systematic literature search in PubMed and Scopus.

Results

A total of 62 articles were identified by the direct search and further relevant articles were found by screening the cited literature in these articles. The topics relevant for assisted reproduction were spindle and zona imaging in combination with IVF success, meiotic cell cycle progression, pharmaceutical studies and cryopreservation. A separate topic was the use of sperm birefringence in ART.

Conclusions

The majority of studies are observational studies and were not performed in a randomized manner and there is no direct comparison of techniques using other gamete selection markers. Despite this, most studies show that polarization microscopy may help us to further increase our knowledge on gametes and meiosis. Whether certain applications such as spindle or zona imaging may lead to an increase in IVF success is unclear at present. Publications on the use of polarization microscopy on sperm are still very limited.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

A correct classification of malformations of the female genital tract is essential to prevent unnecessary and inadequate surgical operations and to compare reproductive results. An ideal classification system should be based on aetiopathogenesis and should suggest the appropriate therapeutic strategy.

METHODS

We conducted a systematic review of relevant articles found in PubMed, Scopus, Scirus and ISI webknowledge, and analysis of historical collections of ‘female genital malformations’ and ‘classifications’. Of 124 full-text articles assessed for eligibility, 64 were included because they contained original general, partial or modified classifications.

RESULTS

All the existing classifications were analysed and grouped. The unification of terms and concepts was also analysed. Traditionally, malformations of the female genital tract have been catalogued and classified as Müllerian malformations due to agenesis, lack of fusion, the absence of resorption and lack of posterior development of the Müllerian ducts. The American Fertility Society classification of the late 1980s included seven basic groups of malformations also considering the Müllerian development and the relationship of the malformations to fertility. Other classifications are based on different aspects: functional, defects in vertical fusion, embryological or anatomical (Vagina, Cervix, Uterus, Adnex and Associated Malformation: VCUAM classification). However, an embryological-clinical classification system seems to be the most appropriate.

CONCLUSIONS

Accepting the need for a new classification system of genitourinary malformations that considers the experience gained from the application of the current classification systems, the aetiopathogenesis and that also suggests the appropriate treatment, we proposed an update of our embryological–clinical classification as a new system with six groups of female genitourinary anomalies.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Lifestyle changes around the time of menopause have the potential to impact on morbidity and eventual mortality. Here we review this topic to identify how such changes may improve health at perimenopause and beyond.

METHODS

Searches were performed in Medline and other databases. Each subject summary was presented to the ESHRE Workshop Group, where omissions or disagreements were resolved by discussion.

RESULTS

Body weight increases because the decline in physical activity during the perimenopause is greater than the concomitant decline in energy intake. It is imperative to stop smoking before menopause because the risk of acute myocardial infarction rises sharply thereafter. Cardiovascular events can be reduced by managing risk factors, such as hypertension and increased lipids and body weight. Breast cancer risk is increased to a similar extent by hormone use, decreased physical activity, increased calorie intake and alcohol use, all reflecting lifestyle decisions. Smoking, alcohol and exercise may increase or decrease risk of aging brain disorders, especially dementia and Parkinson's disease, while stress is consistently associated with increased risk and a prudent diet is consistently associated with reduced risk. Osteoarthritis frequency increases after 50 years of age and risk is elevated 3-fold by obesity, while risk of osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise.

CONCLUSIONS

Lifestyle changes around the time of the perimenopause can reduce the likelihood and severity of heart disease and chronic illness in later years and the cost of care of elderly women.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Complete asthenozoospermia, i.e. 100% immotile spermatozoa in the ejaculate, is reported at a frequency of 1 of 5000 men. Its diagnosis implies a poor fertility prognosis even with ICSI. It is extremely important to distinguish between two different groups of patients with complete asthenozoospermia, i.e. virtual or absolute asthenozoospermia. With the former group having some motile spermatozoa after extensive processing of the semen, absolute asthenozoospermia can be associated with metabolic deficiencies, ultrastructural abnormalities of the sperm flagellum, necrozoospermia otherwise it can be idiopathic. In the management of persistent absolute asthenozoospermia, it is very important to elucidate its nature and whenever possible to correct the potential causes.

METHODS

We reported data published in the literature on the aetiology of absolute asthenozoospermia and the different techniques to improve ICSI outcome. We propose an algorithm for diagnosis and treatment of this condition.

RESULTS

Different results regarding fertilization, cleavage and pregnancy rate have been published in patients with absolute asthenozoospermia undergoing ICSI. However, the results vary widely depending on the sperm origin and the technique applied for immotile sperm selection. The percentage of viable spermatozoa varies between 0 and 100%.

CONCLUSIONS

Absolute immotile spermatozoa is one of the most important causes of reduced fertilization and pregnancy rates after ICSI and different techniques are used to improve ICSI outcomes. However, it still remains unclear which is the best technique to improve the pregnancy outcomes in these couples.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

BACKGROUND

Couples with recurrent miscarriage (RM) have an increased risk of one of the partners carrying a structural chromosome abnormality. On the basis of four independent risk factors, an evidence-based model was developed, which allows limiting karyotyping to high-risk couples. The aim of this study was to assess the level of adoption of selective karyotyping, its clinical consequences and the factors at the patient and hospital level that determine adoption.

METHODS

A retrospective cohort study was performed in nine Departments of Obstetrics and Gynaecology, the Netherlands, in 2006. Selective karyotyping was defined as offering karyotyping to high-risk couples and refraining from karyotyping in low-risk couples. Data were collected for risk factors as described in the model for selective karyotyping, cytogenetic results as a measure for clinical consequences, and information about determinants and costs.

RESULTS

A total of 530 couples were included; 252 (48%) high-risk couples and 278 (52%) low-risk couples. Among the high-risk couples, 186 (74%) were offered karyotyping. Although not advised, karyotyping was still performed in 198 (71%) low-risk couples. Overall, selective karyotyping was offered to 50% of the couples. The main determinants for adoption of the model were maternal age, obstetric history, treatment by specialists in RM and the number of patients per centre. If selective karyotyping was adopted adequately, a potential reduction of 34% of all karyotyping tests performed is possible.

CONCLUSION

Selective karyotyping is applied in only half of the couples with RM in daily practice. Implementation of selective karyotyping should be a topic of future research.

BACKGROUND

Although infertility is a serious concern in survivors of pediatric cancers, little is known about the influence of the degree of sexual maturation at the time of irradiation on spermatogenic recovery after treatment. Thus, we address this question in a non-human primate model, the rhesus monkey (Macaca mulatta).

METHODS

Two pubertal (testis size 3 and 6.5 ml, no sperm in ejaculate) and four prepubertal (testis size 1 ml, no sperm in ejaculate) macaques were submitted to a single fraction of testicular irradiation (10 Gy). Unilateral autologous transfer of cryopreserved testis cells was performed 2 months after irradiation. Testicular volume, histology and semen parameters were analyzed to assess irradiation effects and testicular recovery.

RESULTS

Irradiation provoked acute testis involution only in the two pubertal monkeys. Subsequently, testis sizes recovered and sperm was present in the ejaculates. Longitudinal outgrowth of seminiferous tubules continued, and, in testes without autologous cell transfer, 4–22% of tubular cross sections showed spermatogenesis 2 years after irradiation. In contrast, the four prepubertal monkeys showed neither a detectable involution as direct response to irradiation, nor a detectable growth of seminiferous tubules later. However, two of these animals showed spermarche 2 years after irradiation, and 8–12% of tubules presented spermatogenesis. One prepubertally irradiated monkey presented fast growth of one testis after cell transfer, and showed spermarche 1 year after irradiation. The infused testis had spermatogenesis in 70% of the tubules. The contralateral testis remained smaller.

CONCLUSION

We conclude that irradiation before puberty has a severe detrimental effect on outgrowth of seminiferous tubules. But, within the seminiferous epithelium, spermatogenetic recovery occurs at a low rate with no detectable relation to the maturity of the epithelium at irradiation. We also show that autologous testis cell transplantation can enhance spermatogenesis, but only in isolated cases.

BACKGROUND

The purpose of this study was to optimize the electrophoretic conditions that should be used for the effective isolation of functional human spermatozoa and to determine whether this method of isolating cells was associated with oxidative stress and DNA damage.

METHODS

Human spermatozoa were prepared by repeated centrifugation, discontinuous density gradient centrifugation and electrophoresis followed by assessments of sperm quality.

RESULTS

Systematic analysis of optimal electrophoresis conditions demonstrated that field strength was positively correlated with sperm recovery rates but negatively correlated with sperm movement, irrespective of whether the current or the voltage was held constant. This loss of functionality observed at high power settings was not associated with a major increase in superoxide generation or the induction of oxidative DNA damage. In contrast, discontinuous Percoll gradient centrifugation was shown to produce a significant rise in oxidative DNA base adduct expression in live cells (P < 0.05). As a result of these analyses, optimized electrophoretic conditions were defined that permitted sperm recovery rates of around 20%. These electrophoretically isolated cells were not only free of oxidative stress but exhibited significantly enhanced motility (P < 0.01) and vitality (P < 0.001) compared with the original samples.

CONCLUSIONS

We conclude that while field strength is positively correlated with sperm recovery rates; it is negatively associated with sperm motility. Optimized conditions are described that represent a balance between these opposing forces and permit the isolation of highly motile, vital sperm populations, free from the oxidative DNA damage associated with conventional density gradient centrifugation technologies.

BACKGROUND

Peripheral natural killer (pNK) and uterine NK (uNK) cells have been associated with reproductive failure. We systematically reviewed the literature to assess whether numbers or activity of pNK or uNK cells predicted subsequent pregnancy and outcome.

METHODS

We searched the electronic MEDLINE database from 1950 to April 2010 for relevant publications by using MeSH terms ‘natural killer cells’, ‘reproduction’ and ‘pregnancy complications’. We included studies that measured pre-pregnancy pNK and uNK cell numbers or activity in women with recurrent miscarriage (RM) or infertility, and reported subsequent pregnancy outcomes of miscarriage or failure to conceive after assisted reproductive technology (ART).

RESULTS

The search identified 783 publications and 12 fulfilled the inclusion criteria. There were too few women entered into the observational studies to assess whether high pNK cell percentages or activity predicted subsequent miscarriage in women with idiopathic RM (numbers: n = 32, OR 17, 95% CI 0.82–350.6, activity: n = 92, OR 2.51, 95% CI 0.16–40.29), or implantation failure (n = 203, OR 1.35, 95% CI 0.28–6.46), or miscarriage in infertile women after ART (n = 79, OR 2.48, 95% CI 0.50–12.32). Similarly, the studies of uNK cells were not large enough to assess whether abnormal uNK cell density predicted subsequent miscarriage in women with idiopathic RM (n = 72, OR 1.33, 95% CI 0.16–11.11). None of the uNK cell studies in women with infertility reported pregnancy outcomes dichotomized for uNK cell numbers.

CONCLUSIONS

The prognostic value of measuring pNK or uNK cell parameters remains uncertain. More studies are needed to confirm or refute the role of NK cell assessments as a predictive test for screening women who may benefit from immunotherapy.

BACKGROUND

The aim of this study was to determine the relationship between nutrient utilization by the human embryo and its subsequent viability after transfer.

METHODS

The embryos of 50 patients having single blastocyst transfer were cultured individually from Day 3 in 10 µl drops of medium G2 under Ovoil in 5%O₂, 6%CO₂, 89%N₂. Patient inclusion in the study was maternal age ≤38. Embryos were moved to fresh drops of medium every 24 h. Spent media samples, including controls containing no embryo, were coded, frozen and subsequently analysed blind. Analysis of glucose was performed by microfluorimetry. The sex of children born was recorded.

RESULTS

Clinical pregnancy and live birth rates were 58 and 56%, respectively. Glucose consumption by embryos which resulted in a pregnancy was significantly higher on both Day 4 and Day 5 than that by embryos which failed to develop post-transfer (P< 0.01). Furthermore, on Day 4 female embryos consumed 28% more glucose compared with males (P< 0.05). Glucose uptake was independent of embryo grade.

CONCLUSIONS

The rapid screening of glucose metabolism by the human embryo on Day 4 and 5 may prove to be a useful metric in the development of algorithms for the selection of embryos for transfer in human IVF. Also, the observed sex-related metabolic difference provides preliminary data to support the hypothesis that male and female human embryos differ in their physiology due to the presence of two active X chromosomes and an altered proteome for a finite time during the preimplantation period.

BACKGROUND

Intact frozen-thawed embryos have a greater potential than damaged embryos to establish successful pregnancies. This study aimed to determine whether elevated concentrations of sucrose during freezing would increase the proportion of patients with ≥50% of embryos intact after thawing (primary outcome), and improve clinical outcome.

METHODS

In a two arm, parallel group, pragmatic trial, IVF/ICSI couples were randomized prospectively to have their supernumerary embryos frozen in a medium containing 0.1 M sucrose (control; n = 99) or 0.3 M sucrose (intervention; n = 102).

RESULTS

More control (74/99) than intervention (63/102) couples had at least one embryo thawed (P = 0.07). Significantly more (P = 0.005) intervention (53/63) than control (45/74) couples had ≥50% of embryos intact. Freezing in a medium containing 0.3 M sucrose increased by 3.4-fold [95% confidence interval (CI) (1.45, 7.82)] the likelihood of a couple having ≥50% of their embryos intact. In the fresh cycle, live birth rate per transfer was similar in the control (35/95) and intervention (36/93) groups (P = 0.91). More control (19/63) than intervention (9/59) couples had a live birth after frozen embryo transfer (P = 0.08). When fresh and frozen cycles were combined, fewer intervention (n = 102) than control (n = 99) couples had at least one live birth (42 versus 53%). The difference in cumulative live birth rate was not significant [hazard ratio = 0.75, 95% CI (0.49, 1.13); P = 0.17].

CONCLUSIONS

Increasing the concentration of sucrose in the freezing medium improves embryo survival, but this is not reflected by increased cumulative birth rates.

Clinical Trials Registration number: ISRCTN93314892.