This study aimed to evaluate the potential benefit, in terms of pain relief, of the new oral fast-release orodispersible galvanic form of tramadol in women undergoing hysterosalpingography (HSG) with either a metal cannula or a balloon catheter.
METHODS
In a randomized, double-blind, placebo-controlled, 2 x 2 factorial-design trial, conducted at a single academic centre, 128 women were assigned into groups: (I) tramadol and a metal cannula, (II) tramadol and a balloon catheter, (III) placebo and a metal cannula or (IV) placebo and a balloon catheter. The primary end-point was pain registered by the patients on 10-cm visual analogue scales (VASs) at various times during and after the procedure. Secondary end-points included side effects and pain as assessed by the same physician during HSG.
RESULTS
The main effect of tramadol versus placebo medication (i.e. I and II versus III and IV) was a statistically significant difference (P < 0.001) in self-reported VAS of –0.91 (–1.35 to –0.47) on the absolute and –33% (–48% to –17%) on the relative scale in favour of tramadol. Likewise, there was a significant benefit for tramadol against placebo medication for physician-perceived VAS pain scores (39% relative reduction; P < 0.001). The main effect of the balloon catheter versus metal cannula (i.e. II and IV versus I and III) was a non-significant (P = 0.82) difference in patient-reported VAS of –0.05 (–0.49 to +0.39) and –2% (–21% to +17%). There were no medication–HSG device interactions and no differences in side effects.
CONCLUSIONS
During and after HSG, fast-release orodispersible tramadol significantly reduces pain without increasing side effects.
The present study was designed to evaluate whether the alteration of aquaporin-9 (AQP-9) expression in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS) was associated with the hyperandrogenism in follicular fluid (FF).
METHODS
We recruited infertile women with PCOS (n = 14) and infertile women with tubal blockage (controls, n = 31) for this study. We examined total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), FSH, LH and estradiol in FF. Real-time PCR and western blotting were performed to assess AQP-9 expression in GCs, including effects of dihydrotestosterone (DHT) in vitro.
RESULTS
AQP-9 protein was localized in the nucleus, cytoplasm and cell membrane of the human GCs. The TT, FAI and LH levels were all higher, and SHBG levels lower, in the FF of women with PCOS versus controls (P = 0.0145, 0.0001, 0.0191, 0.0001, respectively). AQP-9 mRNA level in GCs of patients with PCOS was tightly correlated with the TT, SHBG levels and FAI in FF (P = 0.0020, 0.0001, 0.0020, respectively). In vitro, DHT (10–9 mol/l) decreased AQP-9 mRNA (lowest at 12 h) and protein levels in control GCs (P = 0.0005, 0.0247, respectively). The inhibitory effect of DHT on AQP-9 mRNA was attenuated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor (P = 0.0013). Fifty micromolar 4-(hydroxymercuri) benzoic acid sodium salt (PMB) and 10–9 mol/l DHT blunted the swelling of GCs in hypotonic medium, respectively (P = 0.0350, 0.0027).
CONCLUSION
Hyperandrogenism in FF of women with PCOS inhibited AQP-9 in GCs through the PI3K pathway.
This study explores the differences in prenatal maternal expectations, coping resources and maternal stress between first time mothers of IVF twins and first time mothers of spontaneously conceived twins. The role of prenatal maternal expectations in the prediction of maternal stress was examined, as well as the mediating and moderating effect of coping resources on the association between pregnancy-type group and maternal stress.
METHOD
Mothers of twins from various regions in Israel were included in this prospective and cross-sectional study in which 88 mothers of IVF-conceived twins and 98 mothers of spontaneously conceived twins were interviewed twice. First, at 33–36 weeks of their pregnancy they completed a socio-demographic questionnaire and the maternal expectations questionnaire; then at 6 months after birth they completed a questionnaire regarding the delivery and medical condition of the infants, and their coping resources and maternal stress.
RESULTS
Compared with mothers who conceived spontaneously, IVF mothers had more positive prenatal maternal expectations, but poorer coping resources and higher levels of maternal stress 6 months after birth. Maternal expectations had no predictive power regarding maternal stress, although the mother's coping resources were significantly related to maternal stress and mediated the association between pregnancy type and maternal stress.
CONCLUSIONS
IVF-pregnant women bearing twins should be considered a high-risk group. Early identification of these mothers is essential for timely psychosocial interventions in order to enhance their resources and decrease maternal stress. Further longitudinal studies are required to determine causality in more ethnically-diverse mothers of twins.
Women often enter preimplantation genetic diagnosis (PGD) treatment following traumatic reproductive and genetic histories, the detrimental psychological effects of which are known to be long lasting in some cases. In addition, attempting IVF with PGD requires an in-depth understanding of the aspects of the technology. The level of information that is required and retained by women entering treatment is important for clinicians to understand. To date, neither of these issues has been explored empirically. To address this, we assessed mood and information-seeking behavior in a sample of women entering PGD.
METHODS
Fifty women entering PGD treatment completed self-administered questionnaires that assessed anxiety, depression, knowledge of technical aspects of PGD, expectancy of establishing a pregnancy and unmet information needs.
RESULTS
Anxiety and depression rates were similar to normal population data. State anxiety was associated with degree of financial worry [β = 0.36, t = 2.60, P = 0.01, 95% confidence interval (CI): 0.03–0.23], and living in an inner metropolitan area (β = 0.30, P = 0.03, 95% CI: 0.32–10.81). Unmet information needs were positively associated with women's education (β = 0.97, P = 0.01, 95% CI: 0.22–1.73). Lastly, expectancy of establishing a pregnancy was above that of what clinicians provide as realistic PGD pregnancy chances and, unexpectedly, was also associated with degree of financial worry (β = 0.36, P = 0.01, 95% CI: 0.07–0.56).
CONCLUSIONS
Women entering PGD are emotionally well adjusted although the financial costs associated with PGD are associated with increases in anxiety. The study is limited by its small sample size and the fact that partners were not assessed.
The distress that couples experience in IVF treatment is well-documented though research exploring factors that might contribute to the distress is scarce and the role of infertility-specific versus more general psychological characteristics in predicting psychological distress remains unexplored. This exploratory study aimed to describe, explore and test a self-constructed conceptual framework designed to understand the relative impact of infertility-specific and general psychological characteristics, in predicting psychological distress.
METHODS
Validated self-report questionnaires that measured the concepts of the encompassing framework (personality characteristics self-criticism and dependency, attachment in the partner relationship, child wish, coping, intrusiveness, infertility-related stress and general psychological distress) were completed by 106 women and 102 men before starting the first IVF/ICSI treatment at a university hospital-based fertility centre. Data were analysed by hierarchical multivariate linear regression analysis and path analysis.
RESULTS
The overall conceptual psychological framework explained 55% of the variance in psychological distress. The strongest predictors of psychological distress were general psychological characteristics: passive and active coping, self-criticism and dependency and intrusiveness. A path analysis confirmed the framework and highlighted the mediating role of coping and intrusiveness. In the final analysis, none of the infertility-specific variables significantly predicted psychological distress.
CONCLUSIONS
The current study of patients starting IVF-treatment demonstrated that general psychological characteristics, specifically active and passive coping, personality characteristics, dependency and self-criticism and intrusiveness, are more important in predicting the variability in psychological distress than infertility-specific concerns. The results raise important questions for infertility counselling. However, the cross-sectional nature of the study only allows for insight into baseline measurement (before starting the first IVF-treatment) and therefore this area of research could benefit from additional longitudinal studies.
The use of quarantined cryopreserved semen is mandatory in donor insemination programs. Whether sperm cells can survive and retain their ability to fertilize after long-term storage remains a controversial issue. The objective of this study was to determine the effect of the duration of cryostorage in liquid nitrogen on the sperm cells’ progressive motility concentration (PMC) in a large study group.
METHODS
A total of 2525 thawed sperm specimens, packed in straws and donated by 72 sperm bank donors for intrauterine insemination (IUI), were evaluated in an assisted reproduction institute. PMC was recorded after 0.5–14.4 years of cryostorage.
RESULTS
The mean (±SD) value of PMC of all study samples was 10.8 ± 3.3 x 106/ml after freezing/thawing and before cryostorage (T0), and 12.3 ± 2.9 x 106/ml after storage and before using the specimen for IUI (T1, P < 0.0001). Specimen storage for different lengths of time revealed that storage duration had no significant influence on the PMC of the specimens (r = –0.03, P = 0.08). The PMC of partially filled straws was lower than in full straws. Cryostorage duration made no difference in the PMC of raw and washed sperm specimens.
CONCLUSION
Prolonged storage of donated sperm in liquid nitrogen had no influence on the PMC of the specimens and therefore should not alter the fertilization potency of donated sperm. The high post-storage values of the PMC compared with the pre-storage PMC values was probably an artifact of the small volume of the pre-storage sample.
The majority of countries that support the use of donor insemination (DI) in artificial reproductive technology (ART) limit the number of children born from one donor. The setting of these donor limits, though intended to control for the risk of inadvertent half-sibling unions between the offspring of anonymous donors, actually have no evidence base. Controlling for the risk of inadvertent half-sibling unions may soon become unnecessary due to the increasing world-wide use of open-identity sperm donors and the revocation of donor anonymity in many countries. With the shift from anonymous to open-identity donation, the central issue is not the risk of genetic abnormality from inadvertent half-sibling consanguinity; it is the psycho-social impact of the multiple use of open-identity sperm donors. Despite this, the jurisdictions that allow or mandate the use of open-identity donors continue to observe existing limits that do not consider nor specifically control for the psycho-social impact of the multiple use of open-identity sperm donors. It is proposed that: (i) conservative interim donor limits be placed on the multiple use of open-identity donors, while research into the psycho-social impact of disclosure is undertaken to inform the establishment of evidence-based limits; and (ii) the existing limits in jurisdictions where anonymity is still commonly practiced or protected could be raised, if an updated mathematical model was used for calculating evidence-based anonymous donor limits.
The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well-being as well as sexarche.
METHODS
Patients (n = 1148) underwent standardized clinical evaluation. Psychological well-being was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed.
RESULTS
Amenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively).
CONCLUSIONS
Our results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics.
Obesity has been identified as a risk factor for spontaneous miscarriage although the mechanism is unclear. The purpose of this study is to better understand the effect of obesity on early pregnancy success by examining the cytogenetic results of miscarriages in women with normal and elevated body mass index (BMI).
METHODS
We conducted a retrospective case–control study in an academic infertility practice. Medical records of women ages <40 years with first trimester missed abortion (n = 204), who underwent dilatation and curettage between 1999 and 2008, were reviewed for demographics, BMI, diagnosis of polycystic ovary syndrome (PCOS) and karyotype analysis. 2 and Student's t-test analysis were used for statistical analysis, with P < 0.05 considered significant.
RESULTS
A total of 204 miscarriages were included, from women with a mean age of 34.5 years. The overall rate of aneuploidy was 59%. Women with BMI ≥ 25 kg/m2 had a significant increase in euploid miscarriages compared with women with lower BMI (P = 0.04), despite a similar mean age (34.4 years for both).
CONCLUSIONS
We found a significant increase in normal embryonic karyotypes in the miscarriages of overweight and obese women (BMI ≥ 25). These results suggest that the excess risk of miscarriages in the overweight and obese population is independent of embryonic aneuploidy. Further studies are needed to assess the impact of lifestyle modification, insulin resistance and PCOS on pregnancy outcomes in the overweight and obese population.
Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts.
METHODS AND RESULTS
Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development.
CONCLUSIONS
Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.
A key step in studying the biology of spermatogonia is to determine their global gene expression profile. However, disassociation of these cells from the testis may alter their profile to a considerable degree. To characterize the molecular phenotype of human spermatogonia, including spermatogonial stem cells (SSCs), within their cognate microenvironment, a rare subtype of human defective spermatogenesis was exploited in which spermatogonia were the only germ cell type.
METHODS
The global expression profile of these samples was assessed on the Affymetrix microarray platform and compared with tissues showing homogeneous Sertoli-cell-only appearance; selected genes were validated by quantitative real-time PCR and immunohistochemistry on disparate sample sets.
RESULTS
Highly significant differences in gene expression levels correlated with the appearance of spermatogonia, including 239 best candidates of human spermatogonially expressed genes. Specifically, fibroblast growth factor receptor 3 (FGFR3), desmoglein 2 (DSG2), E3 ubiquitin ligase c-CBL (casitas B-cell lymphoma), cancer/testis antigen NY-ESO-1 (CTAG1A/B), undifferentiated embryonic cell transcription factor 1 (UTF1) and synaptosomal-associated protein, 91 kDa homolog (SNAP91) were shown to represent specific biomarkers of human spermatogonia.
CONCLUSIONS
These biomarkers, specifically the surface markers FGFR3 and DSG2, may facilitate the isolation and enrichment of human stem and/or progenitor spermatogonia and thus lay a foundation for studies of long-term maintenance of human SSCs/progenitor cells, spermatogonial self-renewal, clonal expansion and differentiation.
Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers the dendritic cell-mediated TH2 response and regulatory T cell expansion. The aim of this study is to evaluate whether TSLP and TSLP receptor (TSLPR) are expressed in primary human extravillous trophoblast (EVT), how proimflammatory cytokines (tumor necrosis factor (TNF)-, IL-1β), TH2 and TH3 cytokines (IL-4, TGF-β) and pregnancy-associated hormones regulate TSLP production by EVT and whether the SLP–TSLPR interaction affects the biological behavior of trophoblsts.
METHODS
We assessed TSLP mRNA and protein expression by real-time RT–PCR, ELISA and immunochemistry, respectively. We further investigated effects of TSLP on the proliferation and invasion of trophoblast cells in vitro.
RESULTS
The primary EVTs constitutively expressed TSLP and TSLPR. IL-4 and TNF- or pregnancy-associated hormones result in a significant increase in TSLP mRNA expression and protein release from EVT, and TSLP promotes primary EVT proliferation and invasion in vitro.
CONCLUSIONS
This study has demonstrated that the first-trimester human trophoblast cells express TSLP and TSLPR, that cytokine milieu which mimics the maternal–fetal interface modulates expression of TSLP in trophoblast and that TSLP stimulates trophoblast proliferation and invasion. This suggests that TSLP plays an important role in human EVT invasion and placentation in human early pregnancy.
Extravillous trophoblast (EVT) cell invasion of uterine decidua and the inner third of myometrium is critical for successful pregnancy. Many decidual factors are likely to play a role in regulating this process. We have previously shown that cytokines, known to be produced by uterine natural killer (uNK) cells, such as TNF-, TGF-β1 and IFN- inhibit EVT invasion. We therefore hypothesized that supernatants from purified uNK cells would inhibit EVT invasion.
METHODS AND RESULTS
Total unfractionated decidual cell supernatants from 8 to 10 weeks gestation increased EVT invasion from placental villous explants, although uNK cell supernatants from 8 to 10 weeks gestation had no effect. In contrast, both total decidual and uNK cell supernatants from 12 to 14 weeks gestation stimulated EVT invasion. MMP-2, uPA, PAI-1 and PAI-2 levels did not differ under any of the conditions tested, whereas MMP-9 levels were increased in the presence of both total decidual and uNK cell supernatants from both gestational age groups. There was a decrease in the level of EVT apoptosis in the presence of uNK cell supernatant from 12 to 14 weeks, but not 8–10 weeks, gestation.
CONCLUSIONS
Decidual uNK cell supernatants from 12 to 14 weeks gestational age stimulated EVT invasion, potentially by increasing MMP9 levels and reducing apoptosis. Total decidual cell isolates stimulated EVT invasion at both gestational ages investigated, potentially reflecting the complex nature of these cell culture supernatants.
Routes of trophoblast invasion seem to be clear, whereas specific invasive pathways need further elucidation. Extravillous trophoblasts (EVTs) transform spiral arteries to guarantee appropriate blood flow to the placenta in the second trimester. Embryo nutrition during the first trimester is thought to be histiotrophic, whereas proof that EVTs also invade uterine glands is lacking. We developed novel three-dimensional confrontation co-culture models to elucidate invasion of EVTs into uterine glands.
METHODS
First trimester decidua parietalis and placental villous explants were directly confronted and co-cultured for 72 h, or confronted indirectly after 72 h pre-culture for re-epithelialization of decidua pieces. Cryosections were stained by immunohistochemistry or immunofluorescent/immunohistochemical double labelling and compared with first trimester placentation sites in situ.
RESULTS
EVTs deeply invaded decidual tissues in direct confrontation assays and were found between the decidual epithelial cells and epithelial basement membrane. EVTs were also detected in the decidual stroma in direct proximity to glands, sometimes even replacing glandular epithelial cells. Similar observations were made in sections from the first trimester decidua/placental bed. In the invaded parts of sections of decidua basalis, 55% ± 7% (mean ± SEM; n = 10, range 6–11 weeks) of glandular cross sections were associated with or infiltrated by EVTs.
CONCLUSIONS
Using novel confrontation co-culture assays, a potential new route of EVT invasion was detected. EVTs appear to break through the basement membrane of uterine glands to open their lumen towards the intervillous space. These data support the hypothesis of histiotrophic nutrition of the embryo prior to onset of maternal blood flow within the placenta.
We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane.
METHODS
Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity.
RESULTS
Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at ≥0.002% concentration with hyper-polarization of sperm membrane potential (P < 0.001), intracellular alkalinization (P < 0.01), ROS generation (P < 0.05) and no apparent effect on sperm (n = 150) membrane structure. Isoxazolecarbaldehyde compounds required ≥0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P < 0.001), intracellular acidification (P < 0.01) and ROS generation (P < 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at ≥0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P < 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 µg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg).
CONCLUSIONS
The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal contraceptive.
The levonorgestrel-releasing intrauterine system (LNG-IUS) induces amenorrhoea, and its effect on bone mineral density (BMD) may constitute a concern. This study evaluated BMD in long-term users of the LNG-IUS or intrauterine device (IUD).
METHODS
BMD was evaluated at the midshaft of the ulna and ultra-distal radius using dual-energy X-ray absorptiometry in 37 women at 7 or 10 years of use following placement of a second LNG-IUS. The groups were paired for duration of use, age, body mass index (BMI), ethnicity and number of pregnancies.
RESULTS
The mean age of both LNG-IUS and IUD users at the 7th and 10th year was ~34 and 38 years, respectively. Mean BMI was ~25 in both groups, increasing to ~26 at the 10th year. Amenorrhoea occurred in 51.4 and 91.9% of LNG-IUS users at the 7th and 10th year, respectively. Estradiol levels in LNG-IUS users were normal at both evaluations. There were no differences in BMD (g/cm2) at the midshaft of the ulna nor ultra-distal radius between LNG-IUS and IUD users or between the 7th and 10th years of use in LNG-IUS users. A Z-score below –2SD at the ultra-distal radius was observed in only one LNG-IUS user and in none of the IUD users at the 10th year. Higher BMI and BMD at the seventh year and amenorrhoea were predictors of higher BMD at the 10th year.
CONCLUSIONS
BMD at the midshaft of the ulna and ultra-distal radius in LNG-IUS users were similar to that of IUD users and remained unchanged between the 7th and the 10th years of use.
Home use of misoprostol for termination of pregnancy is still controversial in many countries. Acceptability of home use of misoprostol has been investigated in pregnancies below 49 days gestation. In this study, we aimed to assess efficacy, feasibility and acceptability of home use of vaginal misoprostol for medical termination of pregnancy at 50–63 days compared with gestation of below 50 days among women who chose to administer misoprostol at home.
METHODS
In this prospective study, mifepristone 200 mg was given in hospital under nursing supervision in the university hospital outpatient family planning clinic. Women self-administered misoprostol 800 µg vaginally 36–48 h later at home. Follow-up was 2 weeks later. Women with gestation of 50–63 days on the day of mifepristone administration were compared with women with gestation of below 50 days. Efficacy and feasibility were assessed by review of patient records and questionnaires. Acceptability was assessed using questionnaires where women reported on future choice of abortion method were they to have another abortion.
RESULTS
Among the 2992 women who had a medical abortion during the study period, 395 women chose to administer misoprostol at home and were included in the study. A total of 203 women were below 50 days gestation and 192 were between 50 and 63 days gestation. Efficacy was 97.5% and did not differ between the groups. Surgical intervention was needed in 10 patients, of whom four were in the lower gestational band (P = 0.36). No serious adverse events or blood transfusions were reported. Preference for home administration of misoprostol, were they to have another induced abortion in the future, was high, 92.3 and 86.6% respectively, and did not differ between the groups (P = 0.097). Need for extra analgesia significantly influenced women's experiences in both gestational groups.
CONCLUSIONS
Medical abortion with mifepristone followed by home administration of vaginal misoprostol is safe and highly acceptable also to women with gestational length of 50–63 days as compared with shorter gestations. Efficacy, acceptability and preference for future place of administration of misoprostol, were women to have another abortion, did not differ between women with gestation below 50 days or between 50 and 63 days.
Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis.
METHODS
From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared.
RESULTS
Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls.
CONCLUSIONS
Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.
This is a prospective long-term extension study of a randomized controlled trial aimed to assess the risk–benefit ratio of an ultra-conservative fertility-sparing approach in patients with bilateral borderline ovarian tumours (BOTs).
METHODS
The experimental group (n = 15) was treated with an ultra-conservative surgical approach consisting of bilateral cystectomy, whereas the control group (n = 17) received a less conservative surgery consisting of oophorectomy plus controlateral cystectomy alone. All patients received a complete laparoscopic staging followed by a fertility enhancement programme. Patients who completed childbearing were treated with a non-conservative standard treatment at the first recurrence.
RESULTS
After a follow-up period of 128 (9 interquartile range (IQR); 115–150 range) and 132 (7 IQR; 117–152 range) months for the experimental and control groups, respectively (P = 0.25), the time to first baby-in-arm (P < 0.02) and the relative rate (RR) of baby-in-arm (8.05 [95% confidence interval (CI), 1.20–9.66; P < 0.01]) were significantly lower and higher, respectively, for the experimental compared with the control group. Although the time to first recurrence was significently (P < 0.01) shorter for the experimental group, in the regression analysis the difference did not reach the statistic significance (P = 0.14), and the RR of recurrence (1.23 [95% CI, 0.62–3.17; P = 0.41]) was not significant. Finally the number needed to treat for pregnancy was three, the number needed to harm for radical surgery was only two.
CONCLUSIONS
The ultra-conservative fertility-sparing approach is more effective than the standard approach in terms of reproductive outcomes, but presents a higher oncological risk.
Whether implantation occurs after in vitro fertilization (IVF) depends on the embryo, uterine receptivity or a combination of both. The prevalence of minor intrauterine abnormalities identified at hysteroscopy in cases with a normal transvaginal sonography (TVS) has been recorded to be as high as 20–40%. Diagnosing and treating such pathology prior to initiating IVF/intra-cytoplasmic sperm injection (ICSI), has been widely advocated without high-quality evidence of a beneficial effect. The objective of the current study was to assess, by screening office hysteroscopy, the prevalence of unsuspected intrauterine abnormalities in an asymptomatic population of IVF patients, in whom TVS had not revealed any pathology.
METHODS
The prevalence of unsuspected intrauterine abnormalities in patients allocated for a randomized controlled trial was prospectively assessed at two tertiary infertility care units: Academic Hospital at the Dutch-speaking Brussels Free University and University Medical Center Utrecht. A total of 678 unselected, asymptomatic, infertile women with a regular indication for a first IVF/ICSI treatment underwent office hysteroscopy. Only asymptomatic patients, aged ≤42 years, with a normal TVS and no previous hysteroscopy were included. The presence of predefined intrauterine abnormalities was recorded and described in a standardized manner.
RESULTS
Endometrial polyps were identified in 41 (6%) women and submucous myomas in 6 women (1%). Some women were also diagnosed with intrauterine adhesions (2%) or septa (2%). The overall prevalence of any predefined intrauterine abnormality in this IVF/ICSI population was 11%.
CONCLUSIONS
The observed prevalence of unsuspected intrauterine abnormalities in asymptomatic patients indicated for their first IVF/ICSI treatment appeared to be clearly lower than previously reported (11 versus 20–45%). This may have implications for the significance of these abnormalities regarding prospects in IVF/ICSI treatment cycles.
