Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 8–12% of women. Lifestyle modification, including increased physical activity, is the first-line approach in managing PCOS. A systematic review was performed to identify and describe the effect of exercise as an independent intervention on clinical outcomes in PCOS.
METHODS
Five databases were searched with no time limit. A pre-specified definition of PCOS was not used. Studies were included if exercise therapy (aerobic and/or resistance) could be evaluated as an independent treatment against a comparison group. Outcomes measured included cardiovascular risk factors [insulin resistance (IR), lipid profiles, blood pressure and weight] and reproductive measures (ovulation, menstrual regularity and fertility outcomes). Quality analysis was performed based on the Cochrane Handbook of Systematic Reviews and the Quality of Reporting of Meta-Analyses checklist.
RESULTS
Eight manuscripts were identified (five randomized controlled trials and three cohort studies). All studies involved moderate intensity physical activity and most were of either 12 or 24 weeks duration with frequency and duration of exercise sessions ranging between studies. The most consistent improvements included improved ovulation, reduced IR (9–30%) and weight loss (4.5–10%). Improvements were not dependant on the type of exercise, frequency or length of exercise sessions.
CONCLUSIONS
Exercise-specific interventions in PCOS are limited. Studies vary considerably in design, intensity and outcome measures; therefore conclusive results remain elusive. Larger, optimally designed studies are needed to both gain insights into the mechanisms of exercise action and to evaluate the public health impact of exercise of PCOS.
Combined oral contraceptives (OCs) inhibit ovulation, substantially reduce the volume of menstrual flow and may hypothetically interfere with implantation of refluxed endometrial cells. The aim of this review is to establish if OC use influences the risk of endometriosis.
METHODS
We performed a MEDLINE search to identify all studies published in the last four decades (January 1970 to January 2010) in the English language on the relationship between OC exposure and risk of endometriosis. Two authors abstracted data on standardized forms.
RESULTS
We identified 608 potentially relevant studies and 18 studies (6 cross-sectional, 7 case–control and 5 cohort) were selected. Pooling of the results derived from all the included reports independently from study design, yielded a common relative risk of 0.63 [95% confidence interval (CI), 0.47–0.85] for current OC users, 1.21 (95% CI, 0.94–1.56) for past users and 1.19 (95% CI, 0.89–1.60) for ever users. Methodological drawbacks, such as uncertain temporal relationship between exposure and outcome in cross-sectional studies and suboptimal selection of controls in case–control studies, limit the quality of the available evidence.
CONCLUSIONS
The risk of endometriosis appears reduced during OC use. However, it is not possible to exclude the possibility that the apparent protective effect of OC against endometriosis is the result of postponement of surgical evaluation due to temporary suppression of pain symptoms. Confounding by selection and indication biases may explain the trend towards an increase in risk of endometriosis observed after discontinuation, but further clarification is needed. To date, the hypothesis of recommending OCs for primary prevention of endometriosis does not seem sufficiently substantiated.
Implantation is a complex initial step in the establishment of a successful pregnancy. Although embryo quality is an important determinant of implantation, temporally coordinated differentiation of endometrial cells to attain uterine receptivity and a synchronized dialog between maternal and embryonic tissues are crucial. The exact mechanism of implantation failure is still poorly understood.
METHODS
This review summarizes the current knowledge about the proposed mechanisms of implantation failure in gynecological diseases, the evaluation of endometrial receptivity and the treatment methods to improve implantation.
RESULTS
The absence or suppression of molecules essential for endometrial receptivity results in decreased implantation rates in animal models and gynecological diseases, including endometriosis, hydrosalpinx, leiomyoma and polycystic ovarian syndrome. The mechanisms are diverse and include abnormal cytokine and hormonal signaling as well as epigenetic alterations.
CONCLUSIONS
Optimizing endometrial receptivity in fertility treatment will improve success rates. Evaluation of implantation markers may help to predict pregnancy outcome and detect occult implantation deficiency. Treating the underlying gynecological disease with medical or surgical interventions is the optimal current therapy. Manipulating the expression of key endometrial genes with gene or stem cell-based therapies may some day be used to further improve implantation rates.
Understanding the aetiology of subfertility and female reproductive tract disorders at a molecular level may improve success rates in fertility treatment. Such understanding may be gained by the application of metabonomics technologies to tissues or biofluids. Metabonomics is concerned with the quantification of molecules in the metabolome and uses nuclear magnetic resonance (NMR) spectroscopy as one of the main technological platforms. This review concentrates on NMR studies of the female reproductive tract and discusses further possible applications. While full metabolic profiling is relatively recent, targeted NMR studies of biofluid and tissue has a longer history.
METHODS
Searches were carried out on MEDLINE®, PubMed, SciFinder® Scholar 2007 and ISI Web of KnowledgeSM for papers about NMR spectroscopy or metabonomics of the female reproductive tract and subfertility.
RESULTS
NMR spectroscopy has been employed for the compositional analysis of various elements of the female reproductive tract, including cervical mucus, follicular fluid (FF), ovarian tissue, fallopian tubes and uterine matter. NMR was used to document for the first time a change in FF lipoprotein concentration during follicular development. NMR analysis of granulosa cells from rats has revealed that follicle-stimulating hormone increases the activity of the pentose pathway, having crucial implications for ovarian stimulation regimens. In the uterine matter work, it has been shown by NMR that glycolysis is rapidly stimulated by estrogen, and in another study, citrate in uterine fluid was found as a potential biomarker for adenomyosis. NMR has also been used to show that chlamydiae are able to achieve higher energy reserves by stimulating glucose transport in host cells.
CONCLUSIONS
A range of NMR spectroscopic techniques have been applied to the analysis of the female reproductive tract, however great potential remains for further studies. Incorporation of metabonomics techniques into female fertility research may be valuable for understanding subfertility and predicting outcomes of assisted conception treatments.
The impact of gr/gr deletions on male fertility is unclear. These partial deletions of the AZFc region of the Y chromosome have been detected more frequently in infertile patients. However, few individual studies have demonstrated a statistically significant association. This study aims to quantify the strength of association between gr/gr deletions and male infertility, and to explore potential sources of heterogeneity, including ethnicity and geographical location.
METHODS
Medline was searched up to 31 December 2009 for full articles investigating the prevalence of gr/gr deletions in infertile and control men. A pooled odds ratio (OR) was estimated by a random-effects model. Heterogeneity was assessed by the Cochran's Q test, and quantified by I2 statistic.
RESULTS
A total of 18 case–control studies, including 6388 cases and 6011 controls, met our inclusion criteria and showed that gr/gr deletions were present in 6.86% of cases and 4.69% of controls. The association between gr/gr deletions and infertility was significant (P < 0.001), with a pooled random-effects OR of 1.76 (1.21–2.66) for infertile men versus normozoospermic controls (13 studies). The test for heterogeneity among studies yielded a Q test P = 0.089 with I2 value of 37%, indicating moderate heterogeneity. The association between gr/gr deletions and infertility was dependent on ethnicity and geographic region.
CONCLUSIONS
Our meta-analysis comprising >12 000 men demonstrates that gr/gr deletions occur more frequently in infertile than control men. The association between gr/gr deletions and infertility varies according to ethnicity and geographic region, with an association reaching significance among Caucasian men, in Europe and the Western Pacific region.
Recurrent implantation failure (RIF) following embryo transfer (ET) is a major continuing problem in IVF. Women with haemostatic defects may be at increased risk of miscarriage and preclinical pregnancy loss. The fibrinolytic system is considered, at present, the key to new thrombotic pathogenic mechanisms. Patients with unexplained recurrent miscarriage have an impairment of fibrinolysis, as demonstrated by prolonged clot lysis time (CLT) in association with increased plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI). In this study, we investigated fibrinolytic potential in patients with RIF.
METHODS
Three groups of patients were studied: 30 women with RIF (RIF group), 60 patients undergoing a first successful IVF–ET cycle (IVF group) and 60 healthy fertile women (FER group). Plasma CLT was measured using a global fibrinolysis assay. TAFI antigen plasma levels and polymorphisms in the TAFI gene (+505A/G and +1542C/G) were analysed using enzyme-linked immunosorbent assay and allele-specific PCR, respectively.
RESULTS
CLT was significantly longer (P< 0.0001 and P< 0.0009, respectively) and TAFI antigen levels were significantly higher (both P< 0.0001) in the RIF versus the IVF and FER groups. A direct relationship between CLT and TAFI antigen levels (r = 0.40; P = 0.001) was detected in the whole study population. There were no differences in distribution of TAFI polymorphisms between groups.
CONCLUSIONS
Patients with RIF have reduced plasma fibrinolytic potential, as shown by a prolonged CLT, and this may be explained, at least in part, by increased TAFI antigen levels.
The first week of human embryonic development comprises a series of events that change highly specialized germ cells into undifferentiated human embryonic stem cells (hESCs) that display an extraordinarily broad developmental potential. The understanding of these events is crucial to the improvement of the success rate of in vitro fertilization. With the emergence of new technologies such as Omics, the gene expression profiling of human oocytes, embryos and hESCs has been performed and generated a flood of data related to the molecular signature of early embryo development.
METHODS
In order to understand the complex genetic network that controls the first week of embryo development, we performed a systematic review and study of this issue. We performed a literature search using PubMed and EMBASE to identify all relevant studies published as original articles in English up to March 2010 (n = 165). We also analyzed the transcriptome of human oocytes, embryos and hESCs.
RESULTS
Distinct sets of genes were revealed by comparing the expression profiles of oocytes, embryos on Day 3 and hESCs, which are associated with totipotency, pluripotency and reprogramming properties, respectively. Known components of two signaling pathways (WNT and transforming growth factor-β) were linked to oocyte maturation and early embryonic development.
CONCLUSIONS
Omics analysis provides tools for understanding the molecular mechanisms and signaling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single-embryo transfer program.
Pluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from teratocarcinomas and from male germ cells. The recent development of induced pluripotent stem cells demonstrates that somatic cells can be reprogrammed to a pluripotent state in vitro.
METHODS
This review summarizes our current understanding of the origins of mouse and human pluripotent cells. We pay specific attention to transcriptional and epigenetic regulation in pluripotent cells and germ cells. Furthermore, we discuss developmental aspects in the germline that seem to be of importance for the transition of germ cells towards pluripotency. This review is based on literature from the Pubmed database, using Boolean search statements with relevant keywords on the subject.
RESULTS
There are distinct molecular mechanisms involved in the generation and maintenance of the various pluripotent cell types. Furthermore, there are important similarities and differences between the different categories of pluripotent cells in terms of phenotype and epigenetic modifications. Pluripotent cell lines from various origins differ in growth characteristics, developmental potential, transcriptional activity and epigenetic regulation. Upon derivation, pluripotent stem cells generally acquire new properties, but they often also retain a ‘footprint’ of their tissue of origin.
CONCLUSIONS
In order to further our knowledge of the mechanisms underlying self-renewal and pluripotency, a thorough comparison between different pluripotent stem cell types is required. This will progress the use of stem cells in basic biology, drug discovery and future clinical applications.
Conflicting results have been reported regarding the use of polarized microscopy as a predictive tool for human oocyte quality.
METHODS
Oocytes from 121 ICSI cycles were analysed with polarized microscopy. Both qualitative (spindle presence) and quantitative (retardance) data were correlated to the key assisted reproduction technology outcome parameters. Second, polarized microscopy was applied on in vitro matured (IVM) oocytes from germinal vesicle oocytes that matured after 24 or 48 h and from metaphase I oocytes matured after 3 or 24 h. These data were correlated with confocal analysis of spindle-chromosome complex.
RESULTS
Spindles were detected in 82% of in vivo matured oocytes and in 64% adjacent to the first polar body (PB). Fertilization rate was higher in oocytes with a visible spindle (P = 0.0002). In patients aged over 35 years, the percentage of a visible spindle and mean spindle retardance was lower than in younger patients (P < 0.03). A higher number of spindles were located adjacent to the first PB in IVM matured oocytes (94%) versus in vivo matured oocytes (P < 0.0001). Confocal imaging revealed that spindle absent IVM metaphase II (MII) oocytes had a higher degree of aberrant spindle and chromosomal configurations versus IVM MII oocytes with a visible spindle (P = 0.002).
CONCLUSIONS
Oocytes with absent spindles were associated with lower fertilization rates and advanced female age. Other important outcome parameters (embryo quality, pregnancy rates) were not correlated to spindle nor zona inner layer analysis. Interestingly, confocal imaging showed that polarized microscopy might be used as a qualitative predictive tool of human oocyte quality but no correlation could be demonstrated with quantitative polarized microscopy.
In order to optimize blastocyst cryopreservation, vitrification was introduced as the routine procedure instead of slow freezing. The outcome of a closed blastocyst vitrification system was evaluated in relation to the blastocyst score before cryopreservation in single embryo transfers (SETs).
METHODS
Supernumerary blastocysts of IVF/ICSI patients with a fresh Day 5 transfer were vitrified using CBS-VIT High Security (HS) straws. In 759 warming cycles, morphological survival and transfer rates were assessed in relation to the blastocyst score and the day of vitrification. Pregnancy rates were assessed in 530 SET and 156 double embryo transfer (DET) cycles. Implantation rates per embryo transferred in SET cycles were analysed according to blastocyst quality and day of cryopreservation.
RESULTS
Immediate morphological survival was 77.8% (921/1185) and the transfer rate per warmed blastocyst was 70.7% (838/1185). Survival rates were higher for Day 5 early blastocysts (86.7%) compared with full (78.7%) or expanded blastocysts (72.7%). A reduced survival rate of 70.1% was found for Day 6 blastocysts compared with Day 5 blastocysts (80.6%, P < 0.001). The overall clinical/ongoing pregnancy rate after SET was 16.4/14.2% and 24.4/20.5% after DET with an ongoing multiple pregnancy rate of 21.8% (7/32) after DET. Significantly lower implantation rates were found for Day 5 early blastocysts (10.6%) compared with advanced blastocysts (17.5%, P< 0.05). Similar implantation potentials for Day 5 and 6 blastocysts (14.3 versus 13.7%) were found.
CONCLUSIONS
Successful cryopreservation of blastocysts from the early cavitating up to expanded blastocyst stages is possible using a closed HS device. The choice between single or double frozen blastocyst transfer should depend on blastocyst expansion after vitrification.
The maternal–fetal interface has a unique immunological response towards the implanting placenta. It is generally accepted that a T-helper type-2 (Th-2) cytokine prevailing environment is important in pregnancy. The proportion of Th-2 cells in the peripheral blood and decidua is significantly higher in pregnant women in the first trimester than in non-pregnant women. Glycodelin-A (GdA) is a major endocrine-regulated decidual glycoprotein thought to be related to fetomaternal defence. Yet the relationship between its immunoregulatory activities and the shift towards Th-2 cytokine profile during pregnancy is unclear.
METHODS
GdA was immunoaffinity purified from human amniotic fluid. T-helper, T-helper type-1 (Th-1) and Th-2 cells were isolated from the peripheral blood. The viability of these cells was studied by XTT assay. Immunophenotyping of CD4/CD294, cell death and GdA-binding were determined by flow cytometry. The mRNA expression, surface expression and secretion of Fas/Fas ligand (FasL) were determined by quantitative polymerase chain reaction, flow cytometry and ELISA, respectively. The activities of caspase-3, -8 and -9 were measured. The phosphorylation of extracellular signal-regulated kinases (ERK), p38 and, c-Jun N-terminal kinase was determined by western blotting.
RESULTS
Although GdA bound to both Th-1 and Th-2 cells, it had differential actions on the two cell-types. GdA induced cell death of the Th-1 cells but not the Th-2 cells. The cell death was mediated through activation of caspase -3, -8 and -9 activities. GdA up-regulated the expression of Fas and inhibited ERK activation in the Th-1 cells, which might enhance the vulnerability of the cells to cell death caused by a trophoblast-derived FasL.
CONCLUSIONS
The data suggest that GdA could be an endometrial factor that contributes to the Th-2/Th-1 shift during pregnancy.
Myolysis is one of the procedures that is claimed to provide significant improvement in myoma status without hysterectomy. Myolysis procedures have been generally performed via laparoscopy, and there are limited data on transvaginal radiofrequency (RF) myolysis. This study investigated the feasibility, efficacy and safety of transvaginal ultrasound-guided RF myolysis.
METHODS
Transvaginal ultrasound-guided RF myolysis was performed on 69 premenopausal women with symptomatic uterine myomas as an outpatient procedure. Outcomes were assessed 1, 3, 6 and 12 months after RF myolysis. Myoma volumes were measured by ulrasonography. Menorrhagia was evaluated by the number of soaked normal-sized sanitary products used per menstrual period and overall symptoms were evaluated using the symptom severity subscale of the uterine fibroids symptom questionnaire.
RESULTS
Mean (± SD) age of patients was 39.8 ± 6.5 years. Mean baseline volume of the dominant myomas was 304.6 ± 229.1 cm3 and its volume at 3 months following RF myolysis decreased compared with the previous examination (P = 0.002). An improvement of menorrhagia occurred 1, 3, 6 and 12 months after operation (all P < 0.001 versus baseline). Overall symptoms at 1, 3, 6 and 12 months after RF myolysis also improved (all P < 0.001 versus baseline). No major complications were observed or reported. After 12 months, three patients had successfully conceived and delivered and there were no complications during labor or delivery.
CONCLUSIONS
Transvaginal ultrasound-guided RF myolysis might be a safe, effective and minimally invasive outpatient procedure for uterine myoma in terms of size reduction, symptom improvement and safety.
Uterus transplantation (UTx) research aims towards the introduction of UTx as a treatment for uterine factor infertility. The rat model is the principal rodent model used and this study aims to assess the potential for pregnancy and to assess effects on pregnancy outcome.
METHODS
Female Lewis rats underwent hysterectomy and received syngeneic uterine transplants (with one horn removed) by end-to-side anastomosis between the common iliac vessels of the recipient and the graft. The graft was placed in an orthotopic position with anastomosis to the upper part of the native uterine horn and vagina to allow for pregnancy by mating. Controls had only one uterine horn removed. Mating and pregnancy frequencies, successful deliveries and pup weight trajectory were compared.
RESULTS
Pregnancy was achieved in rats after UTx with the pregnancy rate, number of pups and growth trajectory of pups being similar to controls. However, numbers of resorbed pregnancies and arrested parturitions were more common in the UTx group.
CONCLUSIONS
A model for orthotopic UTx was developed and pregnancies with live offspring were for the first time demonstrated in the rat model of UTx. The model will be useful in future studies of fertility after UTx.
Unusual and consistent defects in infertility patients merit attention as these may indicate an underlying genetic abnormality, in turn necessitating tailored management strategies. We describe a case of repeated early pregnancy loss from in vivo conceptions, followed by cancelled embryo transfers after one IVF and one ICSI/PGD cycle. Following the unexpected presence of cleaved embryos at the fertilization check in the first IVF attempt, oocytes and embryos were subsequently analyzed in an ICSI/PGD case. Part of the oocyte cohort was fixed at retrieval for a cellular evaluation of microtubules, microfilaments and chromatin. The remaining oocytes were injected with sperm, and resultant embryos were biopsied for genetic analysis by fluorescence in situ hybridization (FISH), single-nucleotide polymorphism (SNP) microarray for 23 chromosome pairs, as well as with PCR for sex chromosomes. The presence of interphase microtubule networks and pronuclear structures indicated that oocytes were spontaneously activated by the time of retrieval. FISH revealed aneuploidy in all seven blastomeres analyzed, with all but two lacking Y chromosomes. Microarray SNP analysis showed an exclusively maternal origin of all blastomeres analyzed, which was further confirmed by PCR. From our multi-faceted analyses, we conclude that spontaneous activation, or parthenogenesis, was probably the pathology underlying our patient's recurrent inability to maintain a normal pregnancy. Such analyses may prove beneficial not only in diagnosing case-specific aberrations for other patients with similar or related failures, but also for furthering our general understanding of oocyte activation.
Controlled ovarian hyperstimulation with intrauterine insemination (COH/IUI) is an established tool in medically assisted conception for many infertility factors. However, the proper timing of IUI after hCG trigger and the frequency of IUI are still debated. We aimed to examine the association between the cycle pregnancy rate (CPR) and: (i) single IUI timed at 36 ± 2 h post-hCG (pre- or post-ovulation) (ii) the number of IUI (single or double) for pre-ovulatory cases both aims in male, anovulatory and unexplained infertility.
METHODS
The study included a total 1146 first-stimulated cycles in infertile couples due to male factor, anovulation or unexplained infertility. Cycles were stimulated by clomiphine citrate (CC) or sequential CC–hMG or hMG and monitored by transvaginal ultrasound. When the leading follicle reached ≥18 mm mean diameter, 10000 IU hCG was given to trigger ovulation and IUI was timed for 36 ± 2 h later. Semen was processed and ovulation was checked at the time of IUI. Post-ovulatory cases received single IUI, while pre-ovulatory cases were sequentially randomized to receive either single or double IUI. The end-point of the cycle was CPR.
RESULTS
Overall CPR in the whole cohort was 10.1%. When ovulation was present before IUI, CPR was 11.7% compared with 6.7% when ovulation was absent [OR (95% CI): 1.85 (1.12–3.06), P = 0.015]. When this OR was computed according to infertility etiology, it was 1.26 (0.52–2.95) (P =0.82) for male factor infertility and 2.24 (1.23–4.08) (P = 0.007) for non-male factor infertility. Comparing the CPR for double versus single IUI in pre-ovulatory cases, the OR for all cycles was 1.9 (0.76–4.7) (P = 0.22), but according to etiology, it was 4.667 (0.9–24.13) (P = 0.06) in male factor and 1.2 (0.43–3.33) (P = 0.779) for non-male factors.
CONCLUSIONS
Single IUI timed post-ovulation gives a better CPR when compared with single pre-ovulation IUI for non-male infertility, whereas for male factors, pre-ovulation, double IUI gives a better CPR when compared with single IUI.
IVF treatments carry a high risk of twin pregnancy which confers a higher risk to the mother and child than singletons. Increased use of elective single embryo transfer (eSET) can reduce this twin rate. We aimed to utilize a previously published data set and statistical model based on routinely collected clinical data to predict the outcomes of policies that increase the proportion of eSET.
METHODS
The models allow simultaneous prediction of outcomes from double embryo transfer (DET) and SET. These models were used to predict outcomes for different scenarios using SET in both the initial (fresh) transfer and over a complete cycle (transfer of all embryos created, with cryopreservation). A total of 16 096 cycles (12 487 fresh and 3609 frozen) from 9040 couples treated between 2000 and 2005 were included in the final analyses.
RESULTS
For any transfer, SET has about a one-third lower live birth rate relative to DET: this can be partially mitigated by appropriate patient and treatment cycle selection, with several realistic policies performing similarly. However, if we consider complete cycles with embryo cryopreservation, it is possible for repeat SET to produce more live births per egg retrieval than repeat DET.
CONCLUSIONS
All patients receiving SET would have a higher chance of successful treatment in that cycle if they received DET. The selection of appropriate patients for SET can partially ameliorate the overall loss. For complete cycles, repeat SET could produce more live births per egg retrieval than repeat DET. All treatments involving SET will increase the number of treatments required to achieve a successful outcome and this extra treatment burden will be a significant barrier to the implementation of such treatments.
Torsion of the ovary is a rare but serious cause of gynecologic surgical emergency. Specific laboratory markers that support the preoperative diagnosis of ovarian torsion are not currently available in the clinical routine. The aim of this study was to investigate the diagnostic value of plasma D-dimer level as an early indicator of ovarian torsion in an experimental rat ovarian torsion model.
METHODS
Sixteen female adult Sprague–Dawley rats were used for this controlled experimental study. Eight rats in the sham operation group (Group I) underwent a surgical procedure similar to Group II but the ovary was not occluded. In Group II (eight rats), a torsion model was created by using atraumatic vascular clips just above and below the right ovary for a 2-h period of ischemia. Right ovaries were surgically removed at the end of the procedure in each group. Blood was sampled before and after operation to assess plasma D-dimer levels. The main outcome measure was ovarian histopathologic findings scores and plasma D-dimer levels.
RESULTS
There was no significant difference in pre-operative plasma D-dimer levels (0.5963 ± 0.2047 mg/l in Group I, 0.6344 ± 0.1348 mg/l in Group II, P = 0.815, Mann–Whitney U-test). However, mean plasma D-dimer value for Group II was significantly higher than that in the control group (1.2267 ± 0.3099 versus 0.6213 ± 0.2346 mg/l, respectively, Mann–Whitney U-test, P < 0.001), following 2 h of ovarian torsion. Ovarian tissue damage scores were also statistically significantly different among groups.
CONCLUSIONS
If the observations made in a rat model are extended to humans, plasma D-dimer measurement may be a valuable parameter in the early diagnosis of ovarian torsion.
Subfertility is a common but hidden source of anxiety, depressive symptoms and hopelessness. Counselling reduces this emotional burden and may even enhance the likelihood of pregnancy. Art therapy may be a useful intervention, because it facilitates the expression of feelings, both visually and verbally, and may ease emotional distress.
METHODS
Weekly 2-h art therapy group courses were held for a total of 21 subfertile women. The impact of subfertile women's support systems and barriers to coping were all explored. The effectiveness of art therapy was assessed using Beck Hopelessness, Depression and Anxiety Inventories, administered before and after participation, as well as a qualitative exit questionnaire.
RESULTS
The mean age of participants was 35.7 (SD 2.1) years and duration of infertility was 64 (12.0) months. Mean Beck Hopelessness Scale fell from 6.1 (3.8) to 3.5 (3.1, P = 0.01) after therapy. Beck Depression Inventory-II Score fell from 19.8 (11.0) to 12.5 (10.2, P = 0.01) and Beck Anxiety Inventory Score changed from 12.4 (8.4) to 8.4 (5.2, P = 0.3). Based on the exit questionnaire, women felt the course was insightful, powerful and enjoyable.
CONCLUSIONS
Art therapy is an inexpensive, non-pharmacological intervention, which was associated with decreased levels of hopelessness and depressed mood in subfertile women. It also provides insight into the meaning and emotional implications of subfertility for patients and caregivers. This pilot study highlights the need for further research in this field.
Advanced glycation end-products (AGE) are pivotal in aging and diabetes. Aging and polycystic ovary syndrome, a diabetes-associated disease, often cause infertility. We examined how AGE accumulation affects assisted reproductive technology (ART) outcomes.
METHODS
In this retrospective analysis, toxic AGE (TAGE), pentosidine (Pent) and carboxymethyl lysine (CML) in blood and follicular fluid (FF) were measured in 157 ART-patients. We analyzed associations of AGE with ART outcomes and pre-ART clinical factors.
RESULTS
TAGE, Pent and CML in FF and TAGE in serum, showed significant negative correlations with estradiol and numbers of follicles larger than 12 mm in diameter, retrieved oocytes, fertilized oocytes and embryos. AGE, Pent in FF and TAGE in serum showed significant negative correlations with ongoing pregnancy. Areas under receiver-operating characteristic curves for AGE (0.709), Pent in FF (0.686) and TAGE in serum (0.667) were significantly larger than for the reference (0.5). Women with serum TAGE above 7.24 U/ml showed decreased oocyte numbers and ongoing pregnancy rates, even with younger age or lower Day-3 FSH. Serum TAGE correlated positively with leptin (R = 0.51), BMI, low-density lipoprotein, triglyceride, glucose, homeostasis model assessment-insulin resistance and insulin.
CONCLUSIONS
Serum TAGE and FF Pent accumulations correlated highly with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy. Serum TAGE predicts poor ART outcomes independent of age and Day-3 FSH.
High-quality healthcare should be effective, safe and patient-centred. How important patient-centredness is in relation to effectiveness of fertility care has never been investigated. This study aimed to determine and compare the importance of patient-centredness, relative to pregnancy rates, to patients and physicians.
METHODS
A discrete choice experiment (DCE) was designed. Participants had to choose between hypothetical fertility clinics differing in following attributes: travel time; pregnancy rate (effectiveness); physicians' attitude; information on treatment; and continuity of physicians (the latter three represent patient-centredness). A total of 1378 patients and 268 physicians from eight Dutch and Belgian fertility clinics received the DCE-questionnaire. The attributes' relative importance was analysed using multinomial logistic regression. Additionally, patients' actual choice behaviour was investigated.
RESULTS
In total, 925 patients and 227 physicians participated. Pregnancy rates were relatively more important to physicians. Patients assigned more value to patient-centredness (P< 0.001) and were willing to trade-off a higher pregnancy rate for patient-centredness than physicians recommended them to do (P< 0.05). For example, patients considered pregnancy rates 1.5 times as important as an interested physician's attitude, whereas physicians considered this 2.4 times as important (P< 0.001). The willingness to trade-off pregnancy rate for this attitude was 9.8% for patients and 6.3% for physicians (P< 0.001). A lack of patient-centredness was the most cited non-medical reason for changing fertility clinics.
CONCLUSIONS
Patients and physicians put considerable value on pregnancy rates. However, physicians significantly undervalue the importance of patient-centredness to patients. Clinics aiming to optimize the quality of their services should be aware of the substantial importance their patients assign to patient-centredness.
