Does the freeze-all strategy improve the cumulative live birth rate and the time to become pregnant in IVF cycles?

PURPOSE: The freeze-all strategy is widely used for ovarian hyperstimulation syndrome (OHSS) prevention. Indeed, it increases live birth rates among high responders and prevents preterm birth and small for gestational age. Why should not we extend it to all? METHODS: A retrospective and monocentric study was conducted between January 2008 and January 2018 comparing the cumulative live birth rates (CLBR) between patients having undergone FAS and a control group using fresh embryo transfer (FET) and having at least one frozen embryo available. Analyses were made for the entire cohort (population 1) and for different subgroups according to confounding factors selected by a logistic regression (population 3), and to the BELRAP (Belgian Register for Assisted Procreation) criteria (population 2). RESULTS: 2216 patients were divided into two groups: Freeze all (FA), 233 patients and control (C), 1983 patients. The CLBR was 50.2% vs 58.1% P = 0.021 for population 1 and 53.2% vs 63.3% P = 0.023 for population 2, including 124 cases and 1241 controls. The CLBR stayed in favour of the C group: 70.1% vs 55.9% P = 0.03 even when confounding variables were excluded (FA and C group, respectively, 109 and 770 patients). The median time to become pregnant was equally in favour of the C group with a median of 5 days against 61 days. CONCLUSION: CLBR is significantly lower in the FA group compared to the C group with a longer time to become pregnant. Nevertheless, the CLBR in the FA group remains superior to that observed in previous studies.

Impact of ARTs on oncological outcomes in young breast cancer survivors.

STUDY QUESTION: What is the risk of recurrence in young breast cancer survivors who undergo ARTs following completion of anticancer treatment? SUMMARY ANSWER: ART in breast cancer survivors does not appear to have a negative impact on disease-free survival. WHAT IS KNOWN ALREADY: In healthy women, fertility treatment does not increase the risk of developing breast cancer. At the time of breast cancer diagnosis and before starting anticancer treatments, several studies have shown the safety of performing ART. However, the safety of ART in breast cancer survivors following completion of anticancer treatment remains under-investigated. In general, breast cancer survivors are counselled to avoid any hormonal treatment but there are limited data available on the effect of short exposure to high oestradiol levels during ART. The largest study in this regard included 25 breast cancer survivors exposed to ART and did not show a detrimental effect of ART on patient survival. Hence, taking into account that pregnancy after breast cancer does not affect cancer prognosis, defining the safety of ART in breast cancer survivors remains a priority. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective multicentric matched cohort study including a cohort of breast cancer survivors who underwent ART (exposed patients) between January 2006 and December 2016. Exposed patients who were eligible for the study were matched according to known breast cancer prognostic factors. Matched breast cancer survivors did not undergo ART (non-exposed patients) and were disease-free for a minimum time that was not less than the time elapsed between breast cancer diagnosis and first ART for the matched ART-exposed patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were retrieved from all survivors who had been diagnosed with breast cancer in eight participating centres at an age of ≤40 years, without metastasis, ongoing pregnancy, pre-existing neoplasia or ovarian failure. ART included ovarian stimulation for IVF/ICSI, clomiphene citrate treatment and hormone replacement therapy for embryo transfer. Data were collected from an oncological database for the selection of breast cancer patients in the non-exposed group. Exposed patients were matched (1:2) for germline BRCA status, tumour stage, anticancer treatment and age, whenever feasible. Matched groups were compared at baseline according to characteristics using conditional logistic regression. Kaplan-Meier curves were constructed to compare time to recurrence between groups, with the time of ART as starting point that has been adjusted in the non-exposed group. The analyses were performed using Stata IC/15.1. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 39 breast cancer patients in the ART group were eligible for the analysis and were matched with 73 controls. There was no statistical difference between the two groups for the presence of BRCA mutation, tumour characteristics, use of (neo)adjuvant chemotherapy and of adjuvant endocrine therapy. Exposed patients were younger than non-exposed patients (mean age 31.8 vs 34.3 years, respectively; P < 0.001). In the ART group, 89.7% were nulliparous at diagnosis compared to 46.6% of controls (P < 0.001). ART was performed at a mean age of 37.1 years old, after a median time of 4.1 years following breast cancer diagnosis (range: 1.5-12.5). Median anti-Müllerian hormone at the time of ART was 0.28 ng/ml (range: 0-4.4) and median serum oestradiol peak level was 696.5 pg/ml (range: 139.7-4130). Median follow-up time from first attempt of ART was 4.6 years (range: 2.4-12.5) in the ART group. Adjusted follow-up time for the non-exposed group was 6.9 years (range: 1.1-16.5 years) (P = 0.004). In the ART group, 59% of patients had a pregnancy after breast cancer compared to 26% in the non-exposed patients (P = 0.001). Breast cancer relapsed in 7.7% versus 20.5% women in the ART and non-exposed groups, respectively (hazard ratio 0.46, 95% CI 0.13-1.62, P = 0.23). Median time to relapse was 1.3 (range: 0.3-2.7) years versus 4.5 (range: 0.4-11.1) years after ART and adjusted time in the ART and non-exposed groups, respectively (P = 0.14). LIMITATIONS, REASONS FOR CAUTION: Although this is the first and largest multicentric study addressing the impact of ART on breast cancer recurrence to provide data on oestrogen exposure, only a small number of patients could be included. This reflects the reluctance of breast cancer survivors and/or oncologists to perform ART, and highlights the need for a prospective data registry to confirm the safety of this approach. This would offer the possibility for these patients, who are at a high risk of infertility, to fully benefit from ART. WIDER IMPLICATIONS OF THE FINDINGS: Although recent studies have proven that pregnancy after breast cancer has no detrimental impact on prognosis, counselling patients about the safety of ART remains challenging. Our study provides reassuring data on the use of ART in breast cancer survivors with favourable prognostic factors, for when natural conception fails. STUDY FUNDING/COMPETING INTEREST(S): M.C. and I.D. are funded by FNRS, Télévie-FNRS and Fonds Erasme. M.D.V. is a CooperSurgical scientific advisory board member and receives lecture fees for MSD, Gedeon-Richter and Ferring, outside the submitted work. M.L. has acted as a consultant for Roche and Novartis and has received honoraria from Theramex, Roche, Lilly, Pfizer, Novartis and Takeda, outside the submitted work. I.D. has acted as a consultant for ROCHE and has received speaker's fees from Novartis, outside the submitted work. E.d.A. has received honoraria and is a Roche/GNE, Novartis, SeaGen and Zodiac scientific advisory board member, has received travel grants from Roche/GNE and GSK/Novartis, and has received research grants from Roche/GNE, Astra-Zeneca, GSK/Novartis and Servier, outside the submitted work. A.D. is a recipient of a research grant from Ferring Pharmaceuticals and receives lecture and/or consultancy fees from Merck, Gedeon-Richter and Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

[Favorable impact of left antegrade sclerotherapy of clinical left varicocele on spermogram]. / Impact de la sclérothérapie antégrade de varicocèle gauche clinique sur le spermogramme.

OBJECTIVES: Study the early postoperative course of sperm parameters after antegrade sclerotherapy (AS) of clinical left varicocele (CLV) in men consulting for infertility with sperm disruption, and to validate the efficacy and safety of treatment. MATERIALS AND METHODS: Monocentric retrospective observational study of men with CLV, consultant in medically assisted procreation center for primary or secondary infertility of the couple. All patients were operated by SA via scrotal approach. After clinical and ultrasound checks at 6 weeks, a control spermogram was performed at 3-6 months of surgery. The following parameters were analyzed: sperm count, motility, percent of normal form, and total number of motile sperm ("total motile sperm count" [TMSC]). RESULTS: The study involved 138 men (median age 33 years) with sperm alteration. All patients benefited from AS of their CLV. No Clavian complication > 1 was observed. Postoperative control demonstrated a significant improvement in all spermogram parameters, with a median progression of 40% of the count (55 vs 32×106), 80% of the concentration (20.3 vs 11.1×106/ml), 30% of the motility (34.7% vs 26.5%), 60% of the normal form percentage (4.0 vs 2.5%) and the 75% TMSC (41.5 vs 23%), 7×106) (p<0.005). CONCLUSIONS: SA is an effective and safe technique for treating CLV and improving sperm parameters fertility indicators. Our results suggest that this treatment may be recommended to infertile men with CLV in the management of infertility of the couple. LEVEL OF EVIDENCE: 3.

How do cumulative live birth rates and cumulative multiple live birth rates over complete courses of assisted reproductive technology treatment per woman compare among registries?

STUDY QUESTION: How do the national cumulative (multiple) live birth rates over complete assisted reproduction technology (ART) courses of treatment per woman in Belgium compare to those in other registries? SUMMARY ANSWER: Cumulative live birth rates (CLBRs) remain high with a low cumulative multiple live birth rate when compared with other registries and publications. WHAT IS KNOWN ALREADY: In ART, a reduction in the multiple live birth rate could be achieved by reducing the number of embryos transferred. It has been shown that by doing so, live birth rates per cycle were maintained, particularly when the augmentation effect of attached frozen-thawed cycles was considered. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study included all patients with a Belgian national insurance number who were registered in the national ART registry (Belrap) and who started a first fresh ART cycle between 1 July 2009 until 31 December 2011 with follow up until 31 December 2012. We analysed 12 869 patients and 38 008 cycles (both fresh and attached frozen cycles). PARTICIPANTS, MATERIALS, SETTINGS, METHODS: CLBRs per patient who started a first ART cycle including fresh and consecutive frozen cycles leading to a live birth. Conservative estimates of cumulative live birth assumed that patients who did not return for treatment had no chance of achieving an ART-related live birth, whereas optimal estimates assumed that women discontinuing treatment would have the same chance of achieving a live birth as those continuing treatment. A maximum of six fresh ART cycles with corresponding frozen cycles was investigated and compared with other registries and publications. MAIN RESULTS AND ROLE OF CHANCE: The CLBR was age dependent and declined from 62.9% for women <35 years, to 51.4% for women 35-37 years, to 34.1% for women 38-40 years and 17.7% for women 41-42 years in the conservative analysis after six cycles. In the optimal estimate, the CLBR declined from 85.9% for women <35 years, to 72.0% for women 35-37 years, to 50.4% for women 38-40 years and 36.4% for women 41-42 years. The cumulative multiple live birth rates for the whole population were 5.1 and 8.6% for the conservative and optimal estimate, respectively. LIMITATIONS, REASONS FOR CAUTION: Conservative and optimal estimates use assumptions for the whole ART population and do not take the individual patient into account. WIDER IMPLICATIONS OF THE FINDINGS: These data reinforce the validity of the Belgian model of coupling reimbursement of ART costs to a restriction in the number of embryos transferred. Our data can improve decision-making in medical ART practice both on the patient level and for society at large and could provide health care takers and insurance companies with a valid model. STUDY FUNDING COMPETING INTERESTS: none.

The history of Belgian assisted reproduction technology cycle registration and control: a case study in reducing the incidence of multiple pregnancy.

STUDY QUESTION: What is the effect of a legal limitation of the number of embryos that can be transferred in an assisted reproductive technology (ART) cycle on the multiple delivery rate? SUMMARY ANSWER: The Belgian national register shows that the introduction of reimbursement of ART laboratory costs in July 2003, and the imposition of a legal limitation of the number of embryos transferred in the same year, were associated with a >50% reduction of the multiple pregnancy rate from 27 to 11% between 2003 and the last assessment in 2010, without any reduction of the pregnancy rate per cycle. WHAT IS KNOWN ALREADY: Individual Belgian IVF centres have published their results since the implementation of the law, and these show a decrease in the multiple pregnancy rate on a centre by centre basis. However, the overall national picture remains unpublished. STUDY DESIGN, SIZE, DURATION: Cohort study from 1990 to 2010 of all ART cycles in Belgium (2685 cycles in 1990 evolving to 19 110 cycles in 2010), with a retrospective analysis from 1990 to 2000 and prospective online data collection since 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS: Registration evolved from paper written reports per centre to a compulsory online registration of all ART cycles. From 2001 up to mid-2009, data were collected from Excel spread sheets or MS Access files into an MS Access database. Since mid-2009, data collection is done via a remote and secured web-based system (www.belrap.be) where centres can upload their data and get immediate feedback about missing data, errors and inconsistencies. MAIN RESULTS AND THE ROLE OF CHANCE: National Belgian registration data show that reimbursement of IVF laboratory costs in July 2003, coupled to a legal limitation in the number of embryos transferred in utero, were associated with a 50% reduction of the multiple pregnancy rate from 27 to 11% without reduction of the pregnancy rate per cycle, and with an increase in the number of fresh and frozen ART cycles due to improved access to treatment. LIMITATIONS, REASONS FOR CAUTION: There is potential underreporting of complications of ART treatment, pregnancy outcome and neonatal health. WIDER IMPLICATIONS OF THE FINDINGS: Over the 20 years of registration, the pregnancy rate has remained constant, despite the reduction in the number of embryos transferred, optimization of laboratory procedures and stimulation protocols, introduction of quality systems and implementation of the EU Tissue Directive over the period 2004-2010. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. None of the authors has any conflict of interest to declare.

[Evaluation of the male of the infertile couple]. / L'exploration de l'homme du couple infécond.

The exploration of male infertility combines clinical examination and complementary analysis, including biology and ultrasonography. The purpose of this review is to analyze the data available on the accuracy of interview, testicular ultrasonography, sperm analysis and post-coital test. Medical history and patient's interview remain central in the exploration of the infertile man. Despite some limitations, studies on testicular sonography confirm the high prevalence of testicular lesions in infertile men. Up to now, sperm analysis remains the pivotal element of the exploration of male fertility. The new WHO manual for semen analysis published in 2010 should help in redefining its place in the global exploration of male infertility. Despite its statutory character in France, the interest of systematic sperm bacterial examination remains to be demonstrated. Concerning sperm DNA fragmentation, its use as a first-line test should not be recommended. Finally, high levels of evidence do not exist concerning the use of post-coital test as a predictor of pregnancy in infertile couples.

[Preservation of fertility in case of sterilizing treatment]. / Préservation de la fertilité en cas de traitement stérilisant.

The different options of fertility preservation must be approached with all patients before initiating any cancer therapy and physicians should refer each patient treated during their reproductive years to specialists in a specialized center that will evaluate the best available alternatives to preserve male and female fertility.The only efficiently proven ways of fertility preservation are sperm cryopreservation for men and embryo cryopreservation to preserve couple fertility. However, the recent progress observed with oocyte cryopreservation (in particular the oocyte vitrification) may change our practices in the future if vitrification is allowed in France. Although the law of Bioethics of 2004 authorizes the ovarian cryopreservation today, its modalities of use stay at present at the stage of the research. But in spite of the low number of published births today in France and in the world, the ovarian tissue cryopreservation is a promising technique. It remains the last possible alternative to protect fertility of prepubertal girls. The sperm cryopreservation must be systematically proposed to all men (even teenagers) undergoing a treatment for cancer potentially harmful for their fertility whatever their sperm quality. The testicular tissue cryopreservation is also a method to be discussed for adults, teenagers in case of failure of sperm banking or for prepubertal boys.

Acceptance of HIV-infected patients in assisted reproductive technique protocols.

OBJECTIVE: To assess the adequacy of a multidisciplinary approach providing information to couples affected by HIV before ART. DESIGN: Prospective observational study. SETTING: RT centre and infectious disease clinic, public university hospital. PATIENTS: 50 couples with at least one HIV-infected partner. INTERVENTIONS: Multidisciplinary approach towards ART by various intervening physicians (specialist in fertility, infectious diseases, paediatrics, obstetrics, psychiatry). MAIN OUTCOME MEASURED: We analysed specifically the cases in which the staff did not accept and the patient's compliance to the counselling procedures. RESULTS: Among the 150 couples, 30 did not complete the procedure and were lost to follow-up. The remaining 120 couples were evaluated: 89 couples were accepted, 5 were temporarily refused and 26 were refused definitively. The major reasons for refusal were medical reasons (n=13). CONCLUSION: Because of the high refusal rate and the drop of rate, a multidisciplinary approach is mandatory before initiating ART in seropositive couples.

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.

ART outcome in HIV-infected patients.

BACKGROUND: To assess assisted reproductive technique (ART) outcome in couples affected by human immunodeficiency virus (HIV). METHODS: Intrauterine insemination (IUI), IVF and ICSI were performed in 85 couples affected by HIV between January 2000 and June 2005. RESULTS: In 33 of the 85 couples, women were HIV positive-the clinical pregnancy rate (CPR) and cancellation rate (CR) after 34 IUI cycles were, respectively, 25 and 18%. The CPR after 26 IVF and 30 ICSI cycles were, respectively, 37.5 and 18.8% with CRs of 38.5 and 46.7%, respectively. In 38 couples, men were infected-the CPR and CR after 85 IUI cycles were, respectively, 14.7 and 20%; 62 ICSI cycles were performed leading to CPR of 23.4% with a CR of 25%. In 14 couples, the two partners were infected: none of the four IUI cycles carried out was successful (CR, 20%); the CPR and CR after 35 ICSI cycles were, respectively, 12.5% with 31%. All children born had a negative HIV test. CONCLUSION: In couples affected by HIV, an acceptable pregnancy rate was obtained. The worst results were obtained when both partners were infected. The CR was elevated among HIV-infected couples.

Preventive attitude of physicians to avoid OHSS in IVF patients.

The ovarian hyperstimulation syndrome (OHSS) is a dramatic iatrogenic complication of fertility treatment. There is no consensus about its prevention strategies. We assessed whether physicians modify their preventive attitude in relation to clinical risk factors and to the oestradiol response chart. Three case scenarios with three levels of risk factors for OHSS were constructed. For each case scenario, four different charts of the oestradiol curve were described (peak serum oestradiol of 3590 or 6590 pg/ml obtained after a shorter or longer period). At random, we sent three out of the 12 artificially constructed case scenarios to 573 physicians who are members of the European Society of Human Reproduction and Embryology (ESHRE). They were asked whether they would cancel the cycle, take preventive measures or proceed to a regular IVF. A total of 389 cases from 130 different physicians was analysed. Globally, in 23% of the cases the physicians would proceed to a regular IVF. This decision varied significantly according to the risk level (between 38% in low risk to 8% in high risk cases; P < 0.01) and in relation to the oestradiol curve (P < 0.01). In 11% of the cases they would cancel the cycle and in 66% take some preventive measures. Among the selected preventive measures, coasting was by far the most popular choice (60%), followed by the use of i.v. albumin or hydroxyaethyl starch solution (36%) and cryo-preservation of all embryos (33%). In view of the sparse data as to whether coasting is really an effective method, and on how it should be carried out, we suggest that there is an urgent need to evaluate coasting as a preventive method in a large randomized trial in order to properly assess its efficiency and to provide precise guidelines for its use.

Is coasting effective for preventing ovarian hyperstimulation syndrome in patients receiving a gonadotropin-releasing hormone antagonist during an in vitro fertilization cycle?

OBJECTIVE: To report two cases of coasting during receipt of GnRH antagonists. DESIGN: Case report. SETTING: University hospital. PATIENT(S): One 27-year-old and one 28-year-old woman, both with risk factors for the ovarian hyperstimulation syndrome (OHSS). INTERVENTION(S): Two IVF treatments during which hMG treatment was stopped until E2 decreased to a safer level during receipt of GnRH antagonist. MAIN OUTCOME MEASURE(S): Development of OHSS and pregnancy. RESULT(S): Embryos were transferred in both women. Neither woman developed OHSS and one ongoing pregnancy was obtained. CONCLUSION(S): Coasting is feasible when a GnRH antagonist is used during IVF. Further studies are needed to evaluate its preventive role in OHSS.

Acne neonatorum and familial hyperandrogenism.

We report a case of acne neonatorum developed in a boy since birth. His mother and his aunt had different signs of hyperandrogenism including acne and hirsutism. This case illustrates the correlation between acne neonatorum and familial hyperandrogenism. It shows the importance of the family history and the eventual clinical and serological presence of hyperandrogenism in the mother when confronted with acne neonatorum.

Relationship of human follicular diameter with oocyte fertilization and development after in-vitro fertilization or intracytoplasmic sperm injection.

The aim of this work was to evaluate the relationship between follicular size at the time of oocyte retrieval, and the subsequent oocyte competence to be fertilized and to develop in vitro. All the obtained oocytes were classified according to the corresponding volume of aspirated follicular fluid. Aspirated volume of follicular fluid <2 ml corresponded to a follicular diameter <16 mm and constituted the small size group. Volume of follicular fluid from 2 to 6 ml corresponded to a diameter from 16 to 23 mm and constituted the medium size group. The large size group contained follicles with diameter >23 mm and corresponded to an aspirated volume of follicular fluid of >6 ml. A progressive and significant increase in the rates of oocytes with a first polar body was observed from the small size group to the other groups and from the medium to the large size group: 75.3, 85.9 and 95.3% respectively. After classical in-vitro fertilization (IVF), significantly better rates of fertilization and development were obtained in the medium size group compared to the two other groups. Moreover, a positive relationship was observed between follicular diameter and rates of embryos scored as 'good' when oocytes were fertilized by intracytoplasmic sperm injection (ICSI). These results demonstrated that follicular size is positively related to the oocyte ability to be fertilized and to develop. Although oocytes from small follicles gave lower percentages of development probably due to partial oocyte incompetence, they allowed an increase in the total number of embryos scored as 'good'.

Unpredictable cases of complicated ovarian hyperstimulation in IVF.

OBJECTIVE: To characterize a subpopulation of complicated cases of ovarian hyperstimulation syndrome (OHSS). METHOD: Descriptive retrospective study. RESULTS: 0.75% of our IVF-ET population suffered from OHSS. Among this group, 33% did not exhibit any recognized risk criteria of OHSS in terms of infertility characteristics and ovarian response to exogenous gonadotrophins. Only severe (ascites) OHSS cases were considered (n = 5) in this study. Previous IVF-ET attempts had been uneventful and during the complicated trial, estradiol peak levels and numbers of oocytes retrieved remained below 2,500 pg/mL (conversion factor to SI unit, 3.671) and 10, respectively. In all cases, the luteal phase was supplemented by hCG and all patients became pregnant. A threshold level of exogenous and/or endogenous hCG seems to be responsible for the occurrence of OHSS. CONCLUSION: One-third of the patients developing an ovarian hyperstimulation syndrome after IVF-ET had not previously shown risk criteria. A causal role of exogenous and/or endogenous hCG is suggested.

Continuation rates with a levonorgestrel-releasing contraceptive implant (Norplant). A prospective study in Belgium.

Contraceptive protection offered by a method depends on its duration of use, which reflects costs, side effects, and relatives' opinions. This study investigated in Norplant implants users the continuation rates, some of their determinants, and the motives for removals. Since 1988, 612 Norplant implants sets, designed to protect for 5 years, have been inserted. Observing 13,907 months of use, we determined over time the continuation rates and how age, parity, circumstances at insertion (postpartum, postabortum, others), and patronymic origins (surrogate for sociocultural factors) influenced them. Statistics included Kaplan-Meier's method and log rank tests, and uni- and multivariate Cox models. Continuation increased with age and depended on sociocultural factors. Parity exerted influence only in younger women. Median duration of use was 3 years 11 months. Removals before 5 years related almost equally to irregular bleeding, other side effects, and pregnancy wish. The cumulative 5-year failure rate was 1.5%. Unsatisfied users returned earlier, distorting the first results. A literature search showed that implants yield, in the mean, slightly better continuation figures than do intrauterine devices, and clearly higher than those obtained with pills and injectables. To optimize costs and counseling, warnings about the risk of short duration of use in young nullipara, especially if negative sociocultural influences prevail, are recommended. In no category are the implants absolutely to be avoided. Individual and programmatic contraceptive choice should take into account the expected continuation of use.

[Continuity of utilization of a levonorgestrel releasing contraceptive implant: prospective study in Belgium]. / Continuité d'utilisation d'un implant contraceptif au lévonorgestrel: étude prospective en Belgique.

Since 1988 we inserted 760 sets of a subcutaneous hormonal contraceptive releasing levonorgestrel active for 5 years. The aim of the study was to investigate the continuation rates. We considered our first 612 insertions. The 5-year cumulative pregnancy rate was 3.7%. The continuation rates were high (50% of the implants remained in situ after 3 1/2 years). These rates increased with age, and were better with European than with non-European subjects (mainly Moroccan and Turkish women). Parity didn't influence. The rates increased over time, because more unhappy women soon came back compared to satisfied users. Removals were related to pregnancy wish, irregular blood loss, end of action, and various side effects. In a few cases untrained physicians removed the implants.

Vimentin expression in cervical carcinomas: association with invasive and migratory potential.

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines. In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.