Cross-border reproductive care in Belgium.

BACKGROUND: Cross-border reproductive care indicates the cross-border movements made by patients to obtain infertility treatment they cannot obtain at home. The problem at present is that empirical data on the extent of the phenomenon are lacking. This article presents the data on infertility patients going to Belgium for treatment. METHODS: A survey was conducted among the centres for reproductive medicine that are allowed to handle oocytes and create embryos (B-centres). Data were collected on the nationality of patients and the type of treatment for which they attended during the period 2000-2007. RESULTS: Sixteen of 18 centres responded to the questionnaire. The flow of foreign patients has stabilized since 2006 at approximately 2100 patients per year. The majority of foreign nationals seeking treatment in Belgium were French women for sperm donation. The next highest group was patients entering the country to obtain ICSI with ejaculated sperm. CONCLUSIONS: There are clear indications that numerous movements are motivated by the wish to evade legal restrictions in one's home country, either because the technology is prohibited or because the patients have characteristics, which exclude them from treatment in their own countries.

Histologic reaction to four synthetic microsutures in the rabbit.

Histologic reaction to nylon, polypropylene, polyglactin-910, and polydioxanone microsutures was assessed in the uterine horn of the rabbit. At 24 days after insertion of the microsuture, a marked infiltration of histiocytes was seen around the nylon, polypropylene, and polydioxanone microsutures, whereas the reaction to polyglactin-910 was characterized by the presence of giant cells. At 80 days after insertion of the microsutures, the polydioxanone was almost entirely absorbed and the reaction to polyglactin-910 was minimal. Moderate histiocytic infiltration persisted around the nylon and polypropylene sutures. Fibrosis was also detected around the nylon and polypropylene sutures at 80 days, but not at all around the polydioxanone and polyglactin-910 sutures. We conclude that polydioxanone leaves little or no tissue reaction at 80 days in the uterine horn of the rabbit.

Disturbances in dexamethasone suppression test and lower availability of L-tryptophan and tyrosine in early puerperium and in women under contraceptive therapy.

This study investigates the function of the hypothalamic-pituitary-adrenal (HPA)-axis and the availability of L-tryptophan and tyrosine to the brain in postpartum women and in women taking long-term oral contraceptives. To this end, we have measured the following parameters in 50 women (i.e. 9 normal controls, 10 women taking oral contraceptives, and 31 postpartum females): plasma cortisol, L-tryptophan, tyrosine and the amino acids (CAA) known to compete with them for transport through the blood-brain barrier. We have determined the effects of 1 mg of dexamethasone on the above-mentioned biological markers in postpartum females. Plasma cortisol and tyrosine were significantly higher and lower, respectively, in puerperium and in women under contraceptive therapy as opposed to normal controls. L-Tryptophan was significantly lower in postpartum females, whilst the L-tryptophan/CAA ratio did not differ across the three study groups. Postpartum females revealed a significant negative relationship between the availability of L-tryptophan to the brain and postpartum mood, as measured by Zung's Depression and Anxiety Scales and State Anxiety Inventory. Dexamethasone had a significant suppressive effect on L-tryptophan/CAA and tyrosine/CAA ratios, with cortisol nonsuppression appearing in 82% of the postpartum females.

PIP: The possible role of amino acid availability and a functional hypothalamic-pituitary-adrenal axis in the mood disturbances often reported in postpartum women and in users of the oral contraceptive was examined by measuring amino acids and doing a dexamethasone suppression test. Plasma cortisol, tryptophan, tyrosine, their competing amino acids in brain uptake (CAA), and the effect of 1mg dexamethasone were determined in 10 women taking oral contraceptives, 31 women 3 days postpartum, and 9 controls. The pill contained 30 mcg ethinyl estradiol and .075 mg gestodene (2 women), and 30 mg ethinyl estradiol and .15 mg desogestrel (8 women). The subject also took self-rating mood scales: Zung Depression, Zung Anxiety, Beck Depression and State Anxiety Inventory. Cortisol was significantly higher in postpartum women and pill users than in normal controls. Tryptophan, valine, isoleucine and leucine were lower in postpartum women. Tyrosine and tyrosine CAA were lower in postpartum women and pill users. 80% of the postpartum group had negative dexamethasone suppression tests, i.e., cortisol 5 mcg/dl 24 hours after 1 mg dexamethasone. After dexamethasone valine was significantly higher and tryptophan/CAA and tyrosine/CAA ratios were lower, as a result of slightly lower tryptophan and tyrosine and slightly higher CAAs. Furthermore, effects on the amino acid ratios were only evident in women exhibiting dexamethasone suppression. There was a significant negative correlation between depression and anxiety scores and the tryptophan/CAA ratio. The results indicated first that the dexamethasone suppression test is an invalid marker for major depression, and also that availability of the amino acid precursors of brain neurotransmitters may affect mood in the puerperium.

Equine estrogen-dydrogesterone therapy in the management of postmenopausal women.

The clinical and metabolic effects of equine estrogen and dydrogesterone combined therapy were investigated in twenty healthy women aged 45 to 59 years with menopausal complaints. Equine estrogens (0.625 mg per day) were given for 2 months, then dydrogesterone (20 mg daily) was cyclically added for 12 days per month, during an additional period of 6 months. The combination was very efficacious in reducing complaints, with a limited number of side effects. Blood pressure, body weight and cervical smears were unaffected. No influence on glucose tolerance, liver or blood coagulation parameters was seen. A VLDL cholesterol decrease of 41% and an increase in apo AI concentrations of 41% was observed. Total, HDL and LDL cholesterol remained almost unaltered, as well as the total:HDL cholesterol ratio. We conclude that the use of the equine estrogen-dydrogesterone combination provides an efficacious, acceptable and probably safe therapy for menopausal complaints.

Antenatal ultrasonographic diagnosis of trisomy 18 (Edwards syndrome).

A 35-yr-old G7P6A0 presented at 28 weeks of gestation with an acute polyhydramnios. On ultrasonographic examination the diagnosis of trisomy 18 in the fetus was suspected. This was confirmed by chromosome analysis of the cultured amniocytes. The value of a systematic ultrasonographic examination, especially in every abnormal pregnancy, is briefly discussed.

Management and outcome of 21 triplet and quadruplet pregnancies.

The course of gestation and the outcome of fifteen triplet and six quadruplet pregnancies are reviewed. Twenty pregnancies followed induction of ovulation and only one was spontaneous. Bed rest, the use of beta-mimetics and betamethasone, and prolonged hospitalisation were part of the management. Elective cervical suture was not used. The most frequent antenatal complications were preterm labor, preterm rupture of membranes and pregnancy-induced hypertension. The median gestational age was 33.5 weeks in the triplets and 32 weeks in the quadruplets. The overall perinatal and neonatal mortality was 4.9%. The neonatal complications resulted from prematurity and sepsis.

The relation between levels of selected PCB congeners in human serum and follicular fluid.

Individual congener and total PCB concentrations were determined in serum and follicular fluid obtained from women undergoing assisted reproductive technologies (in-vitro fertilization and embryo replacement). Although the mean individual PCB levels revealed varying degrees of contamination, the results fall in the same range as that observed by other investigators. Except for PCB 118, correlations between levels in serum and follicular fluid were strong, and statistically significant at p < 0.05. Moreover PCB 153, a major and very stable PCB congener has been shown to correlate to the total amount of PCBs (r = 0.994, and r = 0.987, for serum and follicular fluid, respectively). The same accumulation patterns of PCBs for serum and follicular fluid have been observed.

Decreasing the number of ovulations in the rabbit with surgical division of the blood vessels between the fallopian tube and ovary.

The effect of surgical division of the anastomotic blood vessels between the ovary and the fimbria upon the number of ovulations in that ovary was tested in 32 New Zealand white rabbits. A significant reduction in the number of ovulations occurred, from an average of 5.6 for the control ovary to 3.3 for the experimental ovary (p less than 0.01). This finding suggests that every effort be made to preserve the tuboovarian blood supply in women at the time of reconstructive fertility surgery.

Conjoint measurement in psychiatric research.

In order to study complex drug-patient-milieu interactions, conjoint measurement models can be of great help in finding out whether there are any interaction patterns in the data and, if so, in specifying the kind of interaction. Some examples are given. The possible applications as well as the limitations of this technique are discussed.

Acute puerperal uterine inversion: two-step management with a beta-mimetic and a prostaglandin.

Sequential administration of a beta 2-mimetic and a prostaglandin, the latter preferably injected into the uterus, is a simple and highly effective method for managing acute puerperal uterine inversion.

Quantification of insulin-like growth factor I receptors on granulosa cells with flow cytometry after follicular stimulation.

The presence of insulin-like growth factor I (IGF-I) receptors on granulosa cells was investigated by flow cytometric analysis. Granulosa cells were retrieved from follicular fluid after oocyte retrieval during assisted reproduction technology procedures. Whole samples of follicular fluid were pooled and the cellular fraction analysed. In order to analyse granulosa cells only we developed a dual labelling technique whereby granulosa cells were identified as CD45 negative cells, distinguishing them from leukocytes which are CD45 positive. Analysis of the IGF-I receptor was done by staining the sample with a monoclonal anti-IGF-I receptor antibody (alphaIR3 clone) and goat anti-mouse phycoerythrin labelled antibody. After identification of the presence of IGF-I receptors, receptor expression was quantified by calibration of the fluorescence signals. We analysed 10 patients' samples and showed 559-1774 binding sites per granulosa cell with a mean value of 1125 +/- 382 (SD).

Danazol treatment of chronic cystic mastopathy: a clinical and hormonal evaluation.

Danazol, a new synthetic steroid, was administered at a dose of 400 mg daily for two months to 16 premenopausal women with chronic cystic mastopathy. The clinical and hormonal effects (serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, progesterone, testosterone and urinary oestrogens, pregnanediol, pregnanetriol, androsterone and etiocholanolone) were evaluated after 4 and 8 weeks of treatment. Using the same dosage and duration of treatment, danazol (13 patients) was compared with placebo (12 patients) in a double blind randomized clinical trial. Danazol proved to be significantly more effective than placebo in relieving symptoms. Combining the open and double blind study (27 patients), danazol treatment resulted in complete relief in 14 patients and improvement in 11. The main endocrine changes during danazol treatment were related to the drug's ovulation inhibiting effect. Amenorrhoea, irregular bleeding and weight gain (mean 2.1 kg) were significant side effects.

Preovulatory ovum harvest and transfer to sterile and infective hydrosalpinges in the rabbit.

Preovulatory ova were harvested from ovarian follicles of eight doe rabbits and transferred into chronic sterile hydrosalpinges induced by infundibular ligation in four rabbits and into chronic infective hydrosalpinges in another four rabbits. Afterwards, normal pregnancies implanted in the uterine horns on the side of the transfer procedures in all four sterile hydrosalpinx rabbits, but in none of the uterine horns of the chronic infective hydrosalpinx group. This points to sequelae of infection rather than simple dilation of the oviductal ampulla as the more potent cause of infertility in the rabbit.

The value of intrauterine insemination with washed husband's sperm in the treatment of infertility.

Twenty-nine infertile couples were treated by intrauterine insemination (IUI) of washed sperm from a sub-fertile husband (n = 16), in cases of gynaecological (n = 3), combined (n = 4) or idiopathic (n = 6) infertility; 116 treatment cycles resulted in 11 ongoing pregnancies. Between 0.25 and 0.45 ml of capacitation medium, containing at least 500,000 pretreated spermatozoa, were inseminated. Pre-treatment of first split fractions was performed by centrifugation and swimming up of motile spermatozoa. The pregnancy per cycle index (P/C) for IUI was 9.5% for a total of 37.9% of all couples treated achieving pregnancy. These results suggest a substantial benefit compared with a calculated six months' cumulative pregnancy rate of 4.2% independent of treatment, for this infertile population. The value of IUI in selected cases of infertility seems obvious but needs further investigation.

Comparison of HMG/HCG superovulation for AID with or without superactive GnRH agonist.

New methods of ovulation induction have been discovered and perfected in recent years. Among others, gonadotrophin-releasing hormone (GnRH) agonists are being used increasingly in the treatment of ovulatory infertility. In a prospective study, 24 women undergoing artificial insemination with donor sperm (AID) and facing failure of treatment because of ovulation disorders, were treated with human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG) superovulation with or without pituitary densensitization using a superactive luteinizing hormone-releasing hormone (LHRH) agonist, buserelin (BUS), Suprefact (Hoechst, Frankfurt a/Main, FRG). In 86 cycles stimulated with HMG/HCG no pregnancy occurred, whereas 12 pregnancies occurred in the same group of patients after a total of 43 BUS/HMG/HCG stimulation cycles. Superactive LHRH agonists have a definite place in the treatment of AID patients presenting with refractory ovulation disorders and/or luteal insufficiency.

Immediate postpartum insertion of a copper-wired intrauterine contraceptive device, the MLCu250.

The MLCu250, a copper-wired intrauterine contraceptive device, was inserted in 600 women immediately after delivery of the placenta. Thirty months after insertion, 9843 woman months of experience were computerized and the data analysed according to the life-table method. The gross cumulative pregnancy and expulsion rates were 1.3 and 6.0 respectively. No serious complications were observed and the puerperium was uncomplicated.

PIP: In a Belgium study, MLCu250 IUDs were inserted in 600 women immediately after delivery. The women were followed for a total of 9843 women months of use, and the results were analyzed using the life table method. Cumulative continuation rates/100 users were 87.2 at 6 months, 72.7 at 12 months, and 55.8 at 30 months. Expulsion rates/100 users were 3.7 at 6 months, 5.8 at 12 months, and 6.0 at 18, 24, and 30 months. Removal rates for bleeding and pain/100 users were 4.3 at 6 months, 7.1 at 12 months, 9.1 at 18 months, 10.7 at 24 months, and 11.8 at 30 months. Removal rates decreased as the age of the patient increased. Parity did not greatly influence removal rates. 6 pregnancies occurred during the study period, none of which were ectopic. No serious complications were reported but inversion of the devices in the uterine cavity could result in perforation. Efforts to diagnosis inversion should be made, and the device removed if inversion has occurred. The regular MLCu250 inserter was found to be satisfactory while attempts to use a longer inserter proved cumbersome. Tables provide gross cumulative event rates/100 users at 6, 12, 18, 24, and 30 month intervals and at 12 and 24 month intervals by age and by parity. An additional table describes each of the unplanned pregnancies in terms of age, parity, previous IUD use, IUD position, IUD removal time, and interval between insertion and last menstrual cycle.

Six years' experience with the T Cu 220C intrauterine contraceptive device.

PIP: A 6-year long evaluation of interval insertion of the T Cu 220C has proven the efficacy, safety, and acceptability of a multisleeved copper-T IUD model. A sample of 947 insertions covers 37,669 woman months of experience. Gross cumulative event rates at 6 years were: pregnancy, 5.6; expulsions, 6.3; removals for bleeding/pain and other medical reasons, 11.4 and 5.2, respectively. Age, parity, and method of insertion influence the performance of the T Cu 220C. The T Cu 220C is an experimental model designed by Tatum to increase the efficacy by delivering copper ions higher up in the uterine cavity and extend the effective life span by using sleeves instead of filamental copper. The device has a T-shaped skeleton of polyethylene into which 20% barium sulfate is incorporated. The total amount of copper is ca. 503 mg and the total surface area ca. 220 mm squared. The IUDs were inserted during or immediately after menstruation, not earlier than 6 weeks after delivery or abortion. Gynecologists performed all insertions using either a push-in or a retraction technique.^ieng

Comparative performance of two copper-wired IUDs (ML Cu 250 and T Cu 200: immediate postpartum and interval insertion.

PIP: A comparative randomized study of the ML Cu 250 and the T Cu 200 was conducted; the results of 1956 insertions (of which 957 concerned the ML Cu 250) are reported. All recipients were women requesting an IUD (Department of Obstetrics, University of Gent, Belgium) and lacking contraindication to its use. The IUDs were inserted at interim or immediately after delivery of placenta at, or about term. When inserted at interim the 2 IUDs had a comparable anti-fertility effect, but the ML Cu 250 was significantly better retained and the T Cu 200 was significantly better tolerated. Both the T Cu 200 and the ML Cu 250 were more often expelled by the younger recipients. Performance of the devices was influenced by the woman's gravidity/parity. No significant difference in performance was found between the 2 IUDs after immediate postpartum insertion. This procedure is effective, well tolerated and safe. For both IUD types, the pregnancy and expulsion rates are significantly higher after immediate postpartum placement than after interval insertion. Due to the fact that the majority of the expulsions occur early, close follow-up of acceptors is essential.^ieng