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Biomedical subjects

T D'Hooghe

Publications and source records attributed to T D'Hooghe.

At least 19 recordsLinked to original sources

Multi-disciplinary centres/networks of excellence for endometriosis management and research: a proposal.

Centres/networks of excellence are the only way forward to ensure that women with endometriosis receive consistent, evidence-based care, ensuring excellence, continuity of care, multi-disciplinarity, research, training and cost-effectiveness. Clinical excellence should be achieved by proper training, adherence to evidence-based guidelines, quality management and continuous measurement of patient outcome as a central focus. To ensure continuity of care, the first step is to assign to each patient a central gynaecologist who must have continuously updated knowledge regarding all diagnostic and management options for endometriosis and who must set priorities and realistic expectations together with the woman using a long-term multi-disciplinary treatment plan. Scientific research within and scientific collaboration between centres/networks of excellence will create the critical mass of patients and tissue samples that is needed to make progress. Centres/networks of excellence should be accredited as training centres by professional bodies. They should aim at improving the cost-effectiveness of the management of endometriosis by a reduction in the time to diagnosis, a reduction in the time before individualized specialist care is invoked, a reduction of expensive hit-and-miss treatments and a reduction in expensive fertility treatments, if the disease is under control before fertility is impaired.

Accreditation↗

Implantation of the human embryo: research lines and models. From the implantation research network 'Fruitful'.

Infertility is an increasing problem all over the world, and it has been estimated that 10-15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women's health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The 'Fruitful' research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors.

Animals↗

The type of catheter has no impact on the pregnancy rate after intrauterine insemination: a randomized study.

BACKGROUND: This study was done to test the hypothesis that intrauterine insemination (IUI) using a soft-tip catheter results in a higher live birth rate than IUI using a hard-tip catheter. METHODS: Five hundred and forty patients were randomized into those inseminated with a soft-tip catheter (group 1, n = 267) and those inseminated with a hard-tip catheter (group 2, n = 269). Four patients were excluded. Main outcome measures included pregnancy rate and live birth rate per cycle. RESULTS: Both groups were similar with regard to female age, duration of infertility, ovarian stimulation and sperm quality. No significant differences were observed between group 1 and group 2 regarding clinical pregnancy rate per cycle (20 versus 19%), live birth rate per cycle (15 versus 14%), multiple live birth rate per cycle (4 versus 6%) and multiple live birth per total of live births (5 versus 8%, overall 6%), respectively. CONCLUSION: Our hypothesis that IUI using a soft tip catheter results in a higher live birth rate per cycle than IUI using a hard-tip catheter was not confirmed in this study. Multiple live birth rate after treatment with low-dose gonadotrophins and IUI can be kept low (6%).

Age Factors↗

Validation of real-time RT-PCR assays for mRNA quantification in baboons.

Real-time RT-PCR has been used widely, both in fundamental research and in clinical diagnostics, for instance for quantification of RNA levels in human tissues and tissue biopsies. In the present study we provide a strategy to validate primers/probes for real-time RT-PCR quantification of baboon samples. The method is based on the TaqMan system and uses primers/probes that have been designed and validated for human real-time RT-PCR. A prerequisite for the accuracy of this strategy is a similar amplification efficiency between human and baboon PCR reactions. We propose two different methods, i.e. by calculating PCR efficiencies from the slope of a dilution curve or by using the linear regression method, to compare the amplification efficiency between human and baboon samples. In conclusion, by performing a simple validation experiment, real-time PCR assays based on human sequences, which are easily available, can be applied for analysis of baboon samples.

Animals↗

Preimplantation genetic diagnosis for an insertional translocation carrier.

BACKGROUND: While preimplantation genetic diagnosis (PGD) is well established for carriers of reciprocal terminal translocations, reports on PGD for insertional translocation carriers are lacking. Here, we report on the PGD of an insertional translocation carrier with karyotype 46,XX,ins(14;2)(q21;q31q35). Due to the possibility of crossovers within the inserted region, rather than a single probe, four probes are required for proper embryo selection. METHODS: Probes were generated for PGD using fluorescence in situ hybridization and two PGD cycles. RESULTS: Analysis of 10 embryos revealed four embryos to be normal diploid. Two embryos were consistent with 3:1 segregation of the theoretical quadrivalent and one was consistent with 2:2 or 1:1 segregation. Furthermore, one embryo was mosaic abnormal and one remained without diagnosis. CONCLUSIONS: With increased acceptance of PGD, it is likely that more carriers of complex translocations will enter PGD programmes. The present results suggest that a careful genetic work-up of complex translocations is essential for proper embryo selection. While theoretical modelling may predict that quadrivalents will form during the meiosis of insertional translocations, experimental proof for the occurrence of quadrivalents is still lacking and more research on the meiotic process of both female and male insertional translocation carriers is warranted.

Blastocyst↗

Coping with infertility: a body-mind group intervention programme for infertile couples.

BACKGROUND: The recognition of the distressing character of infertility diagnosis and treatment has led to the development of several psychosocial interventions for infertile couples. At the Leuven University Fertility Centre, a body-mind marital group intervention was developed to help infertile couples cope with the distress related to infertility. METHODS AND RESULTS: This treatment programme was originally adapted from a mind-body approach, but integrated concepts and techniques from body-oriented therapy, art therapy and multi-family group therapy. In this paper, the therapeutic foundations, treatment goals and practical implications of the mind-body marital group intervention are outlined. Further, the treatment procedure is explained in detail and illustrated by clinical vignettes. CONCLUSIONS: Although the first clinical impressions about the usefulness of the body-mind group programme in fertility clinics seem promising, further research is needed to assess its effectiveness.

Adaptation, Psychological↗

The risk of endometriosis and exposure to dioxins and polychlorinated biphenyls: a case-control study of infertile women.

BACKGROUND: A case-control study was designed to determine the possible association between chronic exposure to dioxins and polychlorinated biphenyls (PCBs), and the occurrence of endometriosis. The study group consisted of 42 infertile endometriosis cases and 27 mechanical infertile controls, both groups attending one of the collaborating Centres for Reproductive Medicine, enrolled between 1996-1998. METHODS: Exposure assessment to dioxin-like compounds was determined through CALUX (chemical-activated luciferase gene expression)-bioassay to measure dioxin-like total toxic equivalents (dioxins and co-planar PCBs), whereas non-co-planar PCBs were determined through chemical analysis. RESULTS: No association was found between median dioxin-like total toxic equivalents (TEQ) and the occurrence of endometriosis in infertile women [cases (n = 34): 29; controls (n = 27): 24; NS]. When patients were subdivided based on an arbitrary cut-off value of 100 pg TEQ/g serum lipids, no statistically significant association between very high exposure to dioxin-like compounds and endometriosis was found [crude odds ratio (OR) = 4.33; confidence interval (CI) 0.49-38.19; NS]. After adjusting for body mass index, and alcohol consumption, the risk increased slightly to OR = 4.6 (CI 0.48-43.62; NS). There was no confounding by age, ovulatory dysfunction, caffeine intake, smoking or exposure to non-co-planar PCBs. CONCLUSIONS: The study results showed no statistically significant association between exposure to dioxin-like compounds and the occurrence of endometriosis in infertile women.

Adult↗

Superovulation of female mice delays embryonic and fetal development.

Mouse and human embryos, cultured in vitro, undergo a delay in development compared with those grown in vivo. This delay can be caused by suboptimal culture conditions, but possible influences of ovarian stimulation cannot be excluded. The objective of this study was to test the hypothesis that both in vitro and in vivo, preimplantation embryonic development and postimplantation fetal development are impaired in superovulated female mice when compared with naturally cycling controls. A delay in in-vitro blastocyst hatching and in-vivo blastocyst formation (P < 0.03 and P < 0.0001 respectively) and a 40% fetal growth retardation (P < 0.0001) were observed after superovulation in comparison with naturally cycling controls. After transfer to non-stimulated foster mothers, blastocysts from stimulated females had a lower implantation rate (P < 0.005), and developed into fewer living fetuses (P < 0.02), more resorption sites (P < 0.02) and had more pronounced growth retardation (P < 0.0001) when compared with blastocysts from naturally cycling controls. In conclusion, superovulation in the mouse causes a delayed embryonic development in vitro and in vivo, an increased abnormal blastocyst formation, a pronounced fetal growth retardation, and an increased number of resorption sites. If this observation in mice can be extrapolated to humans, it may offer an explanation for the delay in embryonic development and the low birth weight observed after IVF.

Animals↗

Comparison of persistent organic pollutant residues in serum and adipose tissue in a female population in Belgium, 1996-1998.

This study was performed to determine and compare persistent organic pollutant (POP) levels in different matrices in a female population. A total of 96 serum and 46 adipose tissue samples were collected from infertile women (n = 101) attending Centers for Reproductive Medicine in Belgium from 1996 to 1998. Gas chromatography with electron-capture detection was used to quantify residue levels on a lipid basis of seven organochlorine pesticides (OCPs) and seven polychlorinated biphenyls (PCBs). There was a strong association between adipose tissue and serum residues. The adipose tissue levels of CB-138, 153, 180 and p,p'-DDE were explained by the serum residues. Besides, the accumulation pattern for CB-153 and CB-180 in serum and adipose tissue are mirror images of each other.

Adipose Tissue↗

Alpha-glycosidase activity in seminal plasma: predictive value for outcome in intrauterine insemination and in vitro fertilization.

OBJECTIVE: To test the hypothesis that alpha-glycosidase activity in seminal plasma can predict the outcome of both IUI and IVF. DESIGN: A retrospective cohort study. SETTING: Tertiary fertility center in a university hospital. PATIENT(S): Eighty-three subfertile couples who underwent IUI and 125 subfertile couples who underwent IVF. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Determination of the alpha-glycosidase activity in seminal plasma before an IUI or IVF attempt, correlation of alpha-glycosidase activity and other semen parameters, and prediction of pregnancy using alpha-glycosidase activity in seminal plasma. RESULT(S): Alpha-glycosidase activity correlated with sperm count. In the IUI group, alpha-glycosidase activity of >23.9 mU/mL predicted pregnancy with a sensitivity of 100% and a specificity of 55.2%. In the IVF group, the outcome could not be predicted with use of any of the semen parameters. CONCLUSION(S): Alpha-glycosidase activity measured in mU/mL probably can be used as a predictor for IVF and pregnancy in an IUI program but has no predictive value with regard to pregnancy rate in an IVF program.

Adult↗

Coping style and depression level influence outcome in in vitro fertilization.

OBJECTIVE: To examine the influence of depression levels and coping on IVF outcome in women, taking into account the cause of infertility. DESIGN: Prospective clinical study. SETTING: A university hospital. PATIENT(S): Ninety-eight women undergoing IVF treatment. INTERVENTION(S): Psychometric tests were administered at the first visit (day 3) of the investigated treatment cycle. MAIN OUTCOME MEASURE(S): Achievement of pregnancy. RESULTS: The nonpregnant group reported increased expression of negative emotions. In the subgroup with a female indication for IVF, increased depressive symptomatology (correlated with increased expression of negative emotions) was associated with lower pregnancy rates (PRs), whereas in the subgroup with a male indication for IVF, increased depressive symptomatology (correlated with decreased expression of negative emotions) was associated with higher PRs. CONCLUSION(S): Expression of negative emotions predicts depression levels and outcome in IVF. The cause of infertility should be taken into account when investigating the relation between psychologic functioning and outcome in IVF.

Adaptation, Psychological↗

Genetic abnormalities and male infertility. A comprehensive review.

The development of assisted reproductive technologies, such as intracytoplasmic sperm injection (ICSI) substantially improved the outlook for patients with severe male fertility problems. However this implies that for the first time genetic defects associated with male in- or subfertility might be transmitted to offspring and result in genetic disease [de Kretser DM, The potential of intracytoplasmic sperm injection (ICSI) to transmit genetic defects causing male infertility. Reprod. Fertil. Dev. 1995;7:137-142]. The knowledge of male specific fertility genes on the Y chromosome increased enormously in the last decade. The SRY gene plays a critical role in gonadal differentiation. DAZ, SPGY and related genes on the Y chromosome are very important for spermatogenesis. Interstitial Y-chromosomal microdeletions encompassing the AZFa, b or c region have become an additional class of genetic abnormalities causing male infertility. A review is given of the different genetic aspects of male infertility.

DNA-Binding Proteins↗

Successful treatment of idiopathic anejaculation with electroejaculation after microsurgical vas aspiration.

This case report describes a couple suffering from infertility secondary to psychogenic anejaculation, which was refractory to all conservative treatment modalities. A first trial of microsurgical vas aspiration in combination with in-vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more trials of microsurgical vas aspiration in combination with either IVF or subzonal insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after 3 years, spermatozoa obtained by rectal probe stimulation under general anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI) procedure using these cryopreserved spermatozoa also resulted in a second pregnancy. Although sperm concentration was in the normal range, in all samples obtained by either rectal probe electrostimulation or microsurgical vas aspiration, motility was <30% in all but two samples.

Adult↗

Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice.

The aim of this experiment was to design a suitable mouse model for male subfertility in which to study the effect of decreased sperm quality on embryo quality in vivo and in vitro. To achieve male subfertility, testes of adult male mice were immersed in water at either 42 degrees C (heated) or 33 degrees C (controls) during 20 min. Twenty-eight days after treatment, all heat stressed males showed a significant decrease in relative testis weight [384.7 mg in controls (286.7-460.6) versus 323 mg in stress heated groups (117.9-405.6); P < 0.001], sperm concentration [3.75 x 10(6)/ml (2.75-7.25) versus 1.00 x 10(6)/ml (0-4.00); P < 0.001] and progressive sperm motility [57.5% (48.0-79.0) versus 42.5% (14.0-66.0); P < 0.001]. Moreover, after mating to heat exposed males, not only the number of pregnant females (20/22 versus 18/30) but also the weight of their embryos [275.4 mg (78.7-339.4) versus 261.8 mg (68.1-339.0); P < 0.001] was significantly lower at 14.5 days post coitum when compared to controls. Neither the number of resorption sites nor the number of viable embryos per pregnant female was significantly different between groups. Also, the in-vitro fertilization rate of oocytes, fertilized by spermatozoa collected from heat stressed males, was significantly lower (44.9%; P < 0.0001) when compared to controls (65.1%; P < 0.0001). In conclusion, the results of this study suggest that male subfertility induced by acute scrotal heating may result in impaired sperm quality, reduced embryo weight in vivo and decreased fertilization rate in vitro.

Animals↗

Low birth weight and subsequent male subfertility.

Male subfertility often remains unexplained. Severe intrauterine growth retardation has previously been linked to hypergonadotropic hypogonadism. We examined whether reduced fetal growth, as judged by low birth weight, is associated with unexplained male subfertility later in life. Birth weight and gestational age were obtained by questionnaire from male partners of couples consulting for subfertility, and were transformed into birth weight SD scores. Men with normal semen analysis (n = 128) had a median birth weight SD score of 0.0 (P25-P75 range: -0.7 to 1.0), comparable to that of men with explained subfertility (n = 28), and higher (p = 0.012) than that of men with unexplained subfertility (n = 32; median -0.5 SD score; P25-P75 range: -0.9 to -0.1). These results extend the link between reduced fetal growth and male subfertility to a range of birth weight that is well within normality. The pathophysiologic mechanism governing this association now remains to be unraveled.

Adult↗

Evaluation of trophoblast invasion in placental bed biopsies of the baboon, with immunohistochemical localisation of cytokeratin, fibronectin, and laminin.

Biopsies of placentas (n = 21), placental bed (n = 17) and decidua (n = 26) of various gestation periods (30 to 140 days) were used to study trophoblast invasion in the baboon. Application of immunohistochemical staining for cytokeratin allowed proper identification of trophoblast. Earlier reports showing restricted trophoblast invasion in this species were confirmed by the finding that endovascular trophoblast was present in only one third of biopsies containing spiral arteries. Moreover, immunostaining for cytokeratin revealed that in several arteries only a few isolated trophoblastic cells were present, while the vessel had not undergone the normal physiological change. Trophoblast invasion could only be detected within decidual, but not in myometrial, segments of spiral arteries. Interstitial trophoblast invasion was very limited and multinuclear giant cells were absent. Immunohistochemical staining suggested a contribution of laminin to the fibrinoid deposition within the physiologically changed spiral arteries, while fibronectin was present intracellularly in the invaded trophoblast. Because of differences in the trophoblast invasion pattern, the baboon cannot be regarded as a satisfactory experimental model to explore results of inadequate endovascular trophoblast invasion which, in the human, leads to pregnancy complications such a preeclampsia.

Animals↗

Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease.

Deeply infiltrating endometriosis can be defined as endometriosis infiltrating deeper than 5 mm under the peritoneal surface. Type I is a conical lesion suggested to be caused by infiltration; type II is mainly caused by retraction of the bowel over the lesion; type III is the most severe lesion suggested to be caused by adenomyosis externa. Severe cases are clinically apparent by nodularities in the pouch of Douglas, whereas mild and subtle forms of deep endometriosis are easily missed. Clinical examination during menstruation and scrutiny at laparoscopy for indurations, followed, preferably, by CO2-laser-excision are the key features for diagnosis and treatment. It is important to realize that depth of infiltration and lateral spread cannot be evaluated by laparoscopic inspection but only during excision, that CA125 concentration but not ultrasound or nuclear magnetic resonance can be helpful in the diagnosis, and that in the most severe cases medical pretreatment is advocated. Results of excision, as evaluated by disappearance of pain in some 80% of women, by a cumulative pregnancy of some 70% and a low recurrence rate, are excellent. The peritoneal fluid is thought to play a key role in the physiopathology of deep endometriosis which is considered to be endometriosis which has escaped from the influence of the peritoneal fluid. This concept is clinically important for the medical treatment of endometriosis, which is suggested to shrink deep lesions and to bring them back under peritoneal fluid control. A model of endometriosis is proposed and discussed. Subtle lesions are considered a natural condition occurring intermittently in all women, whereas we question whether mild endometriosis is a disease. In some women endometriosis has an aggressive behavior and develops into cystic ovarian endometriosis or into deeply infiltrating endometriosis. In this model subtle and mild forms would be called "endometriosis," whereas deep and cystic ovarian forms could be called "endometriotic disease." It is stressed that deep and cystic ovarian endometriosis are two distinct entities, which is important for our understanding of endometriosis, for classification and for treatment of endometriosis.

Endometriosis↗