A multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring.

RESEARCH QUESTION: Ovarian stimulation during IVF cycles involves close monitoring of oestradiol, progesterone and ultrasound measurements of follicle growth. In contrast to blood draws, sampling saliva is less invasive. Here, a blind validation is presented of a novel saliva-based oestradiol and progesterone assay carried out in samples collected in independent IVF clinics. DESIGN: Concurrent serum and saliva samples were collected from 324 patients at six large independent IVF laboratories. Saliva samples were frozen and run blinded. A further 18 patients had samples collected more frequently around the time of HCG trigger. Saliva samples were analysed using an immunoassay developed with Salimetrics LLC. RESULTS: In total, 652 pairs of saliva and serum oestradiol were evaluated, with correlation coefficients ranging from 0.68 to 0.91. In the European clinics, a further 237 of saliva and serum progesterone samples were evaluated; however, the correlations were generally poorer, ranging from -0.02 to 0.22. In the patients collected more frequently, five out of 18 patients (27.8%) showed an immediate decrease in oestradiol after trigger. When progesterone samples were assessed after trigger, eight out of 18 (44.4%) showed a continued rise. CONCLUSIONS: Salivary oestradiol hormone testing correlates well to serum-based assessment, whereas progesterone values, around the time of trigger, are not consistent from patient to patient.

Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility.

Inactivating variants in the centrosomal CEP78 gene have been found in cone-rod dystrophy with hearing loss (CRDHL), a particular phenotype distinct from Usher syndrome. Here, we identified and functionally characterized the first CEP78 missense variant c.449T>C, p.(Leu150Ser) in three CRDHL families. The variant was found in a biallelic state in two Belgian families and in a compound heterozygous state-in trans with c.1462-1G>T-in a third German family. Haplotype reconstruction showed a founder effect. Homology modeling revealed a detrimental effect of p.(Leu150Ser) on protein stability, which was corroborated in patients' fibroblasts. Elongated primary cilia without clear ultrastructural abnormalities in sperm or nasal brushes suggest impaired cilia assembly. Two affected males from different families displayed sperm abnormalities causing infertility. One of these is a heterozygous carrier of a complex allele in SPAG17, a ciliary gene previously associated with autosomal recessive male infertility. Taken together, our data indicate that a missense founder allele in CEP78 underlies the same sensorineural CRDHL phenotype previously associated with inactivating variants. Interestingly, the CEP78 phenotype has been possibly expanded with male infertility. Finally, CEP78 loss-of-function variants may have an underestimated role in misdiagnosed Usher syndrome, with or without sperm abnormalities.

Telemonitoring in IVF/ICSI.

PURPOSE OF REVIEW: Traditionally, ovarian stimulation for IVF/intracytoplasmic sperm injection is performed by healthcare professionals, requiring the patient to make frequent visits to these centres. We describe the rationale, research findings and early clinical experience with home-based sonography for IVF patients. RECENT FINDINGS: Published experience indicates that selected patients are able to procure video sequences themselves; they value the empowerment, discretion and decreased stress involved in these visits; partner involvement increases as well. SUMMARY: Experience is still limited but consistently indicate patients' willingness and competence to procure sonograms; home sonography is positive from the patients' perspective but may be disruptive form the healthcare provider's point of view.

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. METHODS: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. RESULTS: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

A systematic analysis of the suitability of preimplantation genetic diagnosis for mitochondrial diseases in a heteroplasmic mitochondrial mouse model.

STUDY QUESTION: What is the reliability of preimplantation genetic diagnosis (PGD) based on polar body (PB), blastomere or trophectoderm (TE) analysis in a heteroplasmic mitochondrial mouse model? SUMMARY ANSWER: The reliability of PGD to determine the level of mitochondrial DNA (mtDNA) heteroplasmy is questionable based on either the first or second PB analysis; however, PGD based on blastomere or TE analysis seems more reliable. WHAT IS KNOWN ALREADY: PGD has been suggested as a technique to determine the level of mtDNA heteroplasmy in oocytes and embryos to avoid the transmission of heritable mtDNA disorders. A strong correlation between first PBs and oocytes and between second PBs and zygotes was reported in mice but is controversial in humans. So far, the levels of mtDNA heteroplasmy in first PBs, second PBs and their corresponding oocytes, zygotes and blastomeres, TE and blastocysts have not been analysed within the same embryo. STUDY DESIGN, SIZE AND DURATION: We explored the suitability of PGD by comparing the level of mtDNA heteroplasmy between first PBs and metaphase II (MII) oocytes (n = 33), between first PBs, second PBs and zygotes (n = 30), and between first PBs, second PBs and their corresponding blastomeres of 2- (n = 10), 4- (n = 10) and 8-cell embryos (n = 11). Levels of mtDNA heteroplasmy in second PBs (n = 20), single blastomeres from 8-cell embryos (n = 20), TE (n = 20) and blastocysts (n = 20) were also compared. PARTICIPANTS/MATERIALS, SETTING, METHODS: Heteroplasmic mice (BALB/cOlaHsd), containing mtDNA mixtures of BALB/cByJ and NZB/OlaHsd, were used in this study. The first PBs were biopsied from in vivo matured MII oocytes. The ooplasm was then subjected to ICSI. After fertilization, second PBs were biopsied and zygotes were cultured to recover individual blastomeres from 2-, 4- and 8-cell embryos. Similarly, second PBs were biopsied from in vivo fertilized zygotes and single blastomeres were biopsied from 8-cell stage embryos. The remaining embryo was cultured until the blastocyst stage to isolate TE cells. Polymerase chain reaction followed by restriction fragment length polymorphism was performed to measure the level of mtDNA heteroplasmy in individual samples. MAIN RESULTS AND THE ROLE OF CHANCE: Modest correlations and wide prediction interval [PI at 95% confidence interval (CI)] were observed in the level of mtDNA heteroplasmy between first PBs and their corresponding MII oocytes (r(2) = 0.56; PI = 45.96%) and zygotes (r(2) = 0.69; PI = 37.07%). The modest correlations and wide PI were observed between second PBs and their corresponding zygotes (r(2) = 0.65; PI = 39.69%), single blastomeres (r(2) = 0.42; PI = 48.04%), TE (r(2) = 0.26; PI = 54.79%) and whole blastocysts (r(2) = 0.40; PI = 57.48%). A strong correlation with a narrow PI was observed among individual blastomeres of 2-, 4- and 8-cell stage embryos (r(2) = 0.92; PI = 11.73%, r(2) = 0.86; PI = 18.85% and r(2) = 0.85; PI = 21.42%, respectively), and also between TE and whole blastocysts (r(2) = 0.90; PI = 23.58%). Moreover, single blastomeres from 8-cell stage embryos showed a close correlation and an intermediate PI with corresponding TE cells (r(2) = 0.81; PI = 28.15%) and blastocysts (r(2) = 0.76; PI = 36.43%). LIMITATIONS, REASONS FOR CAUTION: These results in a heteroplasmic mitochondrial mouse model should be further verified in patients with mtDNA disorders to explore the reliability of PGD. WIDER IMPLICATIONS OF THE FINDINGS: To avoid the transmission of heritable mtDNA disorders, PGD techniques should accurately determine the level of heteroplasmy in biopsied cells faithfully representing the heteroplasmic load in oocytes and preimplantation embryos. Unlike previous PGD studies in mice, our results accord with PGD results for mitochondrial disorders in humans, and question the reliability of PGD using different stages of embryonic development. TRIAL REGISTRATION NUMBER: Not applicable.

Self-operated endovaginal telemonitoring versus traditional monitoring of ovarian stimulation in assisted reproduction: an RCT.

STUDY QUESTION: Does self-operated endovaginal telemonitoring (SOET) of the ovarian stimulation phase in IVF/ICSI produce similar laboratory, clinical, patient reported and health-economic results as traditional monitoring (non-SOET)? SUMMARY ANSWER: SOET is not inferior to traditional monitoring (non-SOET). WHAT IS KNOWN ALREADY: Monitoring the follicular phase is needed to adapt gonadotrophin dose, detect threatening hyperstimulation and plan HCG administration. Currently, patients pay visits to care providers, entailing transportation costs and productivity loss. It stresses patients, partners, care providers and the environment. Patients living at great distance from centres have more difficult access to treatment. The logistics and stress during the follicular phase of assisted reproduction treatment (ART) is often an impediment for treatment. STUDY DESIGNS, SIZE, DURATION: The study was a non-inferiority RCT between SOET and non-SOET performed between February 2012 and October 2013. Sample size calculations of number of metaphase II (MII) oocytes (the primary outcome): 81 patients were needed in each study arm for sufficient statistical power. Block randomization was used with allocation concealment through electronic files. The first sonogram was requested after 5 days of stimulation, after that mostly every 2 days and with a daily sonograms at the end. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Inclusion criteria were age <41 years, undergoing ICSI, no poor response and having two ovaries. We used a small laptop with USB connected vaginal probe and developed a specific web site application. Sonographic training was given to all women at the initiation of a treatment attempt at the centre. The website contained demonstration material consisting of still images and video sequences, as well as written instructions regarding the use of the instrument and probe handling. In total, 185 eligible patients were recruited in four centres: 123 were randomized; 121 completed SOET (n = 59) or non-SOET (n = 62), and 62/185 (33%) eligible patients declined participation for various reasons. MAIN RESULTS AND THE ROLE OF CHANCE: Patient characteristics were comparable. The clinical results showed similar conception rates (P = 0.47) and ongoing pregnancy rates (SOET: 15/59 = 25%; non-SOET: 16/62 = 26%) (P = 1.00) were obtained. Similar numbers of follicles >15 mm diameter at oocyte retrieval (OR), ova at OR, MII oocytes, log2 MII oocytes, embryos available at transfer, top quality embryos and embryos frozen were obtained in the two groups, indicating non-inferiority of SOET monitoring. Regarding patient-reported outcomes, a significantly higher contentedness of patient and partner (P < 0.01), a higher feeling of empowerment, discretion and more active partner participation (P < 0.001) as well as a trend towards less stress (P = 0.06) were observed in the S versus the NS group. In the economic analysis, the use of SOET led to reduced productivity loss, lower transportation costs, and lower sonogram and consultation costs (all P < 0.001 but higher personnel cost than NS). LIMITATIONS, REASONS FOR CAUTION: The study was stopped (no further funding) before full sample size was reached. There were also a few cases of unexpected poor response, leading to a wider SD than anticipated in the power calculation. However, although the study was underpowered for these reasons, non-inferiority of SOET versus non-SOET was demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: Home monitoring using SOET may provide a patient-centred alternative to the standard methods. ART sonograms can be made, and then sent to the care provider for analysis at any appropriate time and from anywhere if an internet connection is available. This approach offers several advantages for patients as well as care providers, including similar results to the traditional methods with less logistical stress and potentially bringing care to patients in poor resource settings. STUDY FUNDING/COMPETING INTERESTS: Supported by an IOF (industrial research fund) of Ghent University (full protocol available at iBiTech) and as a demonstration project of Flanders Care (Flemish Government). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: EC/2011/669 (Ghent University Hospital), B670201112232 (Belgian registration) and NCT01781143 (clinical trials number).

Delaying the oocyte maturation trigger by one day leads to a higher metaphase II oocyte yield in IVF/ICSI: a randomised controlled trial.

BACKGROUND: The negative impact of rising progesterone levels on pregnancy rates is well known, but data on mature oocyte yield are conflicting. We examined whether delaying the oocyte maturation trigger in IVF/ICSI affected the number of mature oocytes and investigated the potential influence of serum progesterone levels in this process. METHODS: Between January 31, 2011, and December 31, 2011, 262 consecutive patients were monitored using ultrasound plus hormonal evaluation. Those with > =3 follicles with a mean diameter of > =18 mm were divided into 2 groups depending on their serum progesterone levels. In cases with a progesterone level < = 1 ng/ml, which was observed in 59 patients, 30-50% of their total number of follicles (only counting those larger than 10 mm) were at least 18 mm in diameter. These patients were randomised into 2 groups: in one group, final oocyte maturation was triggered the same day; for the other, maturation was triggered 24 hours later. Seventy-two patients with progesterone levels > 1 ng/ml were randomised in the same manner, irrespective of the percentage of larger follicles (> = 18 mm). The number of metaphase II oocytes was our primary outcome variable. Because some patients were included more than once, correction for duplicate patients was performed. RESULTS: In the study arm with low progesterone (<= 1 ng/ml), the mean number of metaphase II oocytes (+/-SD) was 10.29 (+/-6.35) in the group with delayed administration of the oocyte maturation trigger versus 7.64 (+/-3.26) in the control group. After adjusting for age, the mean difference was 2.41 (95% CI: 0.22-4.61; p = 0.031). In the study arm with elevated progesterone (>1 ng/ml), the mean numbers of metaphase II oocytes (+/-SD) were 11.81 (+/-9.91) and 12.03 (+/-7.09) for the delayed and control groups, respectively. After adjusting for PCOS (polycystic ovary syndrome) and female pathology, the mean difference was -0.44 (95% CI: -3.65-2.78; p = 0.79). CONCLUSIONS: Delaying oocyte maturation in patients with low progesterone levels yields greater numbers of mature oocytes.

Adding serum estradiol measurements to ultrasound monitoring does not change the yield of mature oocytes in IVF/ICSI.

In a non-randomized, comparative prospective study (416 patients) we compared the outcome of IVF/ICSI in two parallel control groups: one in which patients were followed up using combined monitoring (ultrasound plus serum estradiol monitoring, the UHM group) and one in which only ultrasound monitoring was used (the UM group). This study has taken the number of mature oocytes at the moment of egg retrieval as its primary end variable. After adjustment for age, gravidity, antagonist protocol, AMH and infertility diagnosis, the average difference in number of mature oocytes between the UHM group and the UM group was -0.4 (95% CI: -1.7 to 1.0), which met our definition of clinical equivalence (95% CI for the adjusted mean difference between -2 and 2). Larger studies are still needed to evaluate the differences in the live birth rates per cycle and to further confirm that blood sampling definitively has no added value in monitoring ovarian stimulation for IVF/ICSI.

Toxic effects of Hoechst staining and UV irradiation on preimplantation development of parthenogenetically activated mouse oocytes.

Parthenogenetic activation of oocytes is a helpful tool to obtain blastocysts, of which the inner cell mass may be used for derivation of embryonic stem cells. In order to improve activation and embryonic development after parthenogenesis, we tried to use sperm injection and subsequent removal of the sperm head to mimic the natural Ca2+ increases by release of the oocyte activating factor. Visualization of the sperm could be accomplished by Hoechst staining and ultraviolet (UV) light irradiation. To exclude negative effects of this treatment, we examined toxicity on activated mouse oocytes. After activation, oocytes were incubated in Hoechst 33342 or 33258 stain and exposed to UV irradiation. The effects on embryonic development were evaluated. Our results showed that both types of Hoechst combined with UV irradiation have toxic effects on parthenogenetically activated mouse oocytes. Although activation and cleavage rate were not affected, blastocyst formation was significantly reduced. Secondly, we used MitoTracker staining for removal of the sperm. Sperm heads were stained before injection and removed again after 1 h. However, staining was not visible anymore in all oocytes after intracytoplasmic sperm injection. In case the sperm could be removed, most oocytes died after 1 day. As MitoTracker was also not successful, alternative methods for sperm identification should be investigated.

Toward a new concept of "natural balance" in oral estroprogestin contraception.

The Pill has undergone many changes since its first appearance some 50 years ago. Key developments included the reduction of ethinylestradiol doses and the synthesis of new progestins in order to increase safety, compliance and efficiency. Low-dose combined oral contraceptives (COCs) are currently the preferred option for millions of women. Due to this widespread use, it has been argued that the safety of COCs should be even better, raising the threshold for excellence. Yet in spite of major improvements, there is still an associated risk of venous thromboembolism (VTE). The next step in COCs' evolution should take total estrogenicity and hepatic estro-androgenic balance into account. The focus on the estrogen component--which has not changed in 50 years--has yielded a new class of natural estrogen pills. Following the introduction of a first quadriphasic pill, a monophasic estradiol pill based on the concept of "natural balance" was subsequently made available. These recent achievements could represent a step forward in the evolution of COCs and pave the way for better safety.

Follicle measurements using sonography-based automated volume count accurately predict the yield of mature oocytes in in vitro fertilization/intracytoplasmic sperm injection cycles.

AIMS: We define criteria to predict the number of mature oocytes using automated three-dimensional (3D) ultrasound follicle measurements. METHODS: Fifty in vitro fertilization/intracytoplasmic sperm injection patients underwent automated 3D echographic monitoring by a single researcher following the stimulation procedure. Classic criteria for triggering oocyte maturation as defined in the literature were utilized. 3D parameters, including the follicular volume and follicle diameter calculated from the volume measurement, were related to the oocyte count, mature oocyte count and the number of observed fertilized oocytes. RESULTS: We found that when oocyte maturation was induced, 55% of the total follicles with a diameter of at least 10 mm had a volume of at least 1.5 cm³. The number of mature eggs that were retrieved was correlated with the number of follicles observed with a volume of at least 1 cm³ or a calculated follicle diameter of at least 12 mm. CONCLUSION: Sonography-based automated volume count measurements of follicle volume and reconstructed follicle diameter can be used to reliably predict the number of mature oocytes.

Maternal and paternal parenting styles: unique and combined links to adolescent and early adult delinquency.

The present study examines the cross-sectional and longitudinal associations between fathers' and mothers' parenting styles and male and female delinquency using a sample of 330 Dutch families with a mid or late adolescent son or daughter (ages 14-22), followed across two measurement waves with a 5-year interval. Parenting styles of fathers and mothers were linked to delinquency. A significant parenting style by sex interaction was found: neglectful parenting was related to higher levels of delinquency in males and permissive parenting was linked to delinquency in females. A long term relationship was found between fathers' neglectful parenting style and delinquency in males. Furthermore, results revealed that levels of delinquency were the lowest in families with at least one authoritative parent and highest in families with two neglectful parents, indicating that the level of delinquency was dependent on the combination of mother's and father's parenting styles.

Self-operated endovaginal telemonitoring (SOET): a step towards more patient-centred ART?

The need for serial vaginal sonographies to monitor ovarian stimulation for artificial reproductive technology (ART) treatments remains a major practical and organizational drawback both for patients and health-care providers. We explore the possibility of patients and/or their partners performing their own vaginal sonographies at home. To make this a reality, a portable, easy-to-use, home-applied vaginal probe for recording relevant images would have to be developed, as well as appropriate software to transfer images using modern communication technology to the centre, to analyse the recordings and to send a swift structured response, comprising dosing advice and next-step instructions. A simplification of the uncontested need to perform these sonographies, even if applicable to just a selected proportion of IVF patients, could fit in the general tendency to make IVF more patient centred and friendly, to implement telemedicine and to increase patient empowerment by supervised active participation to their treatment. The advantages of such a technology are explored in this paper, aiming at opening up a debate on whether patients themselves would, could and should achieve a further substantial simplification of ART without loss of quality while strongly curbing costs.

Developmental competence of parthenogenetic mouse and human embryos after chemical or electrical activation.

Parthenogenetic reconstruction is one major strategy to create patient-specific stem cells. The aim of this study was to find the best artificial activation protocol for parthenogenetic activation of mouse and human oocytes comparing different methods. In a first set of experiments, in-vivo matured mouse oocytes and human failed-fertilized, in-vitro and in-vivo matured oocytes were artificially activated by a chemical (ionomycin) or electrical stimulus. In a second set of experiments, a combination of activating agents (electrical pulses followed by ionomycin or SrCl(2)) was applied in an aim to improve developmental competence. All embryos were evaluated daily until day 6 after activation. Mouse blastocysts were differentially stained to evaluate blastocyst quality. For mouse oocytes and human failed-fertilized oocytes, blastocyst development was significantly higher after electrical activation (P<0.05). For human in-vitro and in-vivo matured oocytes, blastocyst formation was only obtained after electrical activation of in-vitro matured oocytes. After combining activating agents, no differences in development could be observed. In conclusion, this study revealed that for both mouse and human oocytes development to the blastocyst stage was significantly better after electrical activation compared with chemical activation. Combining activating agents had no further positive effect on developmental potential.

Value transmissions between parents and children: gender and developmental phase as transmission belts.

This study applied the gender role model of socialization theory, the developmental aging theory, and the topic salience perspective to the investigation of parent-child value transmissions. Specifically, we examined whether the bi-directionality and selectivity of value transmissions differed as a function of parents' and children's gender and children's developmental phase (adolescence versus emerging adulthood). Transmissions between parents and children from 402 Dutch families on the topics of work as duty and hedonism were studied across a 5-year period using structural equation modeling. As expected, we did not find convincing support for the general models of gender socialization and developmental aging. Instead, parent-child value transmissions appeared to be qualified by value salience. Particularly, high salience of work as duty for fathers was related with great paternal involvement in transmissions on this value orientation and high salience of hedonism for sons and adolescents was linked to transmissions from these groups to parents.

Microflora of the penile skin-lined neovagina of transsexual women.

BACKGROUND: The microflora of the penile skin-lined neovagina in male-to-female transsexuals is a recently created microbial niche which thus far has been characterized only to a very limited extent. Yet the knowledge of this microflora can be considered as essential to the follow-up of transsexual women. The primary objective of this study was to map the neo-vaginal microflora in a group of 50 transsexual women for whom a neovagina was constructed by means of the inverted penile skin flap technique. Secondary objectives were to describe possible correlations of this microflora with multiple patients' characteristics, such as sexual orientation, the incidence of vaginal irritation and malodorous vaginal discharge. RESULTS: Based on Gram stain the majority of smears revealed a mixed microflora that had some similarity with bacterial vaginosis (BV) microflora and that contained various amounts of cocci, polymorphous Gram-negative and Gram-positive rods, often with fusiform and comma-shaped rods, and sometimes even with spirochetes. Candida cells were not seen in any of the smears. On average 8.6 species were cultured per woman. The species most often found were: Staphylococcus epidermidis, Streptococcus anginosus group spp., Enterococcus faecalis, Corynebacterium sp., Mobiluncus curtisii and Bacteroides ureolyticus. Lactobacilli were found in only one of 30 women. There was no correlation between dilatation habits, having coitus, rinsing habits and malodorous vaginal discharge on the one hand and the presence of a particular species on the other. There was however a highly significant correlation between the presence of E. faecalis on the one hand and sexual orientation and coitus on the other (p = 0.003 and p = 0.027 respectively). Respectively 82%, 58% and 30% of the samples showed an amplicon after amplification with M. curtisii, Atopobium vaginae and Gardnerella vaginalis primer sets. CONCLUSION: Our study is the first to describe the microflora of the penile skin-lined neovagina of transsexual women. It reveals a mixed microflora of aerobe and anaerobe species usually found either on the skin, in the intestinal microflora or in a BV microflora.

Single-embryo transfer versus multiple-embryo transfer.

Despite the progress made in assisted reproductive technology, live birth rates remain disappointingly low. Multiple-embryo transfer has been an accepted practice with which to increase the success rate. This has led to a higher incidence of multiple-order births compared with natural conception, which not only increase the risk of mortality and morbidity to both mother and children but are also associated with social and economic consequences. Elective single-embryo transfer (eSET) was developed in an effort to increase singleton pregnancies in assisted reproduction. Studies comparing eSET with multiple-embryo transfer highlight the benefit of this approach and suggest that, with careful patient selection and the transfer of good-quality embryos, the risk of a multiple-order pregnancy can be reduced without significantly decreasing live birth rates. Although the use of eSET has gradually increased in clinical practice, its acceptance has been limited by factors such as availability of funding and awareness of the procedure. An open discussion of eSET is warranted in an effort to enable a broader understanding by physicians and patients of the merits of this approach. Ultimately, eSET may provide a more cost-effective, potentially safer approach to patients undergoing assisted reproduction technology.

Long-term assessment of the physical, mental, and sexual health among transsexual women.

INTRODUCTION: Transsexualism is the most extreme form of gender identity disorder and most transsexuals eventually pursue sex reassignment surgery (SRS). In transsexual women, this comprises removal of the male reproductive organs, creation of a neovagina and clitoris, and often implantation of breast prostheses. Studies have shown good sexual satisfaction after transition. However, long-term follow-up data on physical, mental and sexual functioning are lacking. AIM: To gather information on physical, mental, and sexual well-being, health-promoting behavior and satisfaction with gender-related body features of transsexual women who had undergone SRS. METHODS: Fifty transsexual women who had undergone SRS >or=6 months earlier were recruited. MAIN OUTCOME MEASURES: Self-reported physical and mental health using the Dutch version of the Short-Form-36 (SF-36) Health Survey; sexual functioning using the Dutch version of the Female Sexual Function Index (FSFI). Satisfaction with gender-related bodily features as well as with perceived female appearance; importance of sex, relationship quality, necessity and advisability of gynecological exams, as well as health concerns and feelings of regret concerning transition were scored. RESULTS: Compared with reference populations, transsexual women scored good on physical and mental level (SF-36). Gender-related bodily features were shown to be of high value. Appreciation of their appearance as perceived by others, as well as their own satisfaction with their self-image as women obtained a good score (8 and 9, respectively). However, sexual functioning as assessed through FSFI was suboptimal when compared with biological women, especially the sublevels concerning arousal, lubrication, and pain. Superior scores concerning sexual function were obtained in those transsexual women who were in a relationship and in heterosexuals. CONCLUSIONS: Transsexual women function well on a physical, emotional, psychological and social level. With respect to sexuality, they suffer from specific difficulties, especially concerning arousal, lubrication, and pain.

Value transmissions between fathers, mothers, and adolescent and emerging adult children: the role of the family climate.

Using structural equation modeling, this study investigates father-child, mother-child, and father-mother transmissions on "work-as-duty" and "hedonism" across a 5-year period when children traverse late adolescence and emerging adulthood (N = 402 families). We found bidirectional father-child and child-to-mother transmissions on work-as-duty and child-to-father and bidirectional father-mother transmissions on hedonism. In addition, we examined whether family adaptability and cohesion influence these value transmissions. Father-to-child transmission on work-as-duty occurred regardless of family system levels, whereas child-to-parent transmissions on work-as-duty occurred only within more structured families. Furthermore, a more connected family climate tended to facilitate inter- and intragenerational value transmissions, but multiple-group analyses did not reveal strong evidence. All in all, this study showed that value socialization in the family is not a one-way-traffic process with parents solely influencing their children. Late adolescents and emerging adults also serve to socialize their parents and parents socialize each other.

Effect of temporary nuclear arrest by phosphodiesterase 3-inhibitor on morphological and functional aspects of in vitro matured mouse oocytes.

The present study aimed to analyze detailed morphological and functional characteristics of mouse in vitro matured oocytes after a pre-maturation culture (PMC) by temporary nuclear arrest with the specific phosphodiesterase 3-inhibitor (PDE3-I) Cilostamide. In a first experiment the lowest effective dose of Cilostamide was determined. Cumulus-oocyte complexes (COCs), isolated from small antral follicles, were exposed to different concentrations of Cilostamide (ranging from 0 (control) to 10 microM) for 24 hr. Afterwards, oocytes were removed from PDE3-I-containing medium and underwent in vitro maturation (IVM) for 16-18 hr. A concentration of 1 microM Cilostamide was the lowest effective dose for maximum level of inhibition and reversibility of meiosis inhibition. This concentration was used in further experiments to evaluate oocyte quality following IVM in relation to different parameters: kinetics of meiotic progression, metaphase II (MII) spindle morphology, aneuploidy rate, fertilization, and embryonic developmental rates. The results were compared to nonarrested (in vitro control) and in vivo matured oocytes (in vivo control). Following withdrawal of the inhibitor, the progression of meiosis was more synchronous and accelerated in arrested when compared to nonarrested oocytes. A PMC resulted in a significant increase in the number of oocytes constituting a MII spindle of normal morphology. None of the oocytes exposed to PDE3-I showed numerical chromosome alterations. In addition, fertilization and embryonic developmental rates were higher in the PMC group compared to in vitro controls, but lower than in vivo controls. These results provide evidence that induced nuclear arrest by PDE3-I is a safe and reliable method to improve oocyte quality after IVM.