[Monoclonal gammopathy of undetermined significance : when and why to look for them ?] / Les gammapathies monoclonales de signification indéterminée : quand et pourquoi les chercher ?

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder. MGUS is a common disorder and the diagnosis is often made accidentally when a protein electrophoresis is performed in a routine blood test or during a biological assessment for other conditions. In the absence of biological abnormalities or clinical symptoms suggesting a plasma or lymphoplasma-cell disorder, there is no indication for routine screening of the monoclonal protein. When MGUS is diagnosed, the risk of transformation into myeloma or other lymphoproliferative disorders is estimated at 1 % per year. MGUS can also be associated with diseases that are not malignant disorders and in some cases, the monoclonal gammopathy is the witness of another rare but severe disorder wich will be critical not to be missdiagnosed.

La gammapathie monoclonale de signification indéterminée (MGUS) est une anomalie biologique asymptomatique dont le diagnostic est souvent posé lors d'un bilan réalisé en routine ou pour d'autres symptômes que ceux requérant cette analyse. L'incidence des MGUS est évaluée à au moins 3 % au-dessus de 50 ans et sa fréquence continue à augmenter avec l'âge. La majorité des patients avec une MGUS n'évoluera jamais vers une hémopathie et en l'absence d'anomalies biologiques ou de symptômes évoquant une maladie associée à une immunoglobuline monoclonale, il n'y a pas d'indication d'effectuer une électrophorèse des protéines. Si le diagnostic de MGUS est posé, le risque d'évolution vers un myélome ou une autre hémopathie maligne est de 1 % par an. Une MGUS peut aussi être associée à des pathologies non malignes ou être le reflet d'autres maladies rares et graves dont il est capital de ne pas rater le diagnostic.

[Diagnostic approach of an IgM monoclonal gammopathy and clinical importance of gene MYD88 L265P mutation]. / Approche diagnostique d'une gammapathie monoclonale à IgM et intérêt clinique de la recherche de la mutation L265P du gène MYD88.

INTRODUCTION: An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. POPULATION AND METHODS: 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics. We checked if the MYD88 mutation had been detected. The overall survival rate was studied. RESULTS: 5 histological groups were identified: Waldenstrom's Macroglobulinemia (MW, N = 27), lymphoplasmacytic lymphoma (LLP, N = 10), marginal zone lymphoma (LMZ, N = 7), monoclonal gammopathy of unknown significance and multiple myeloma (MGUS/MM, N = 5). The MW group was compared to the other groups. Regarding biological characteristics, the IgM level upon diagnosis was statistically higher in the MW group with a median level at 19.5 g/L (2.3-101 g/L) (p-value = 0,0001). Concerning the clinical characteristics, a splenomegaly was more frequent in the LMZ group (p-value = 0,04). The L265P mutation of the MYD88 gene was found in 77 % of patients in the MW group, 60 % of patients in the LLP group and 67 % in the LMZ group (p-value = 0,38). For the 49 patients, the 10-yearoverall survival was 85 % (CI 95 %, 67 % to 94 %) and the 15-year-overall survival was 65 % (CI 95 %, 41 % to 81 %). CONCLUSION: A monoclonal IgM peak suggests a MW but other B lymphoproliferatives disorders should be excluded. Even if the L265P mutation is frequent in the LLP/MW, it is not specific. A precise diagnosis requires collating clinical, histological, immunophenotypical and genetical data.

INTRODUCTION: Une gammapathie monoclonale à IgM évoque généralement le diagnostic de maladie de Waldenström. D'autres syndromes lymphoprolifératifs B doivent être exclus mais les " frontières " entre les différentes entités sont parfois mal définies. La découverte de la mutation L265P du gène MYD88 a potentiellement simplifié cette situation. Population et méthodes : 383 patients de l'Institut Jules Bordet présentant un taux d'IgM supérieur à 2 g/L ont été étudiés. 49 d'entre eux présentaient un pic monoclonal pour lesquels nous avons réalisé l'analyse de la pathologie sous-jacente en terme de caractéristiques générales, cliniques et biologiques et avons identifié si une recherche de mutation MYD88 avait été réalisée. La survie globale a également été étudiée. Résultats : 5 groupes histologiques ont été identifiés : maladie de Waldenström (MW, N = 27), lymphome lymphoplasmocytaire (LLP, N = 10), lymphomes de la zone marginale (LMZ ; tous types confondus, N = 7), gammapathie monoclonale de signification indéterminée et myélome multiple (MGUS/MM, N = 5). Le groupe MW a été comparé aux autres groupes. En terme de caractéristiques biologiques, c'est le taux d'IgM au diagnostic qui est statistiquement plus élevé dans le groupe MW avec un taux médian de 19,5 g/L (2,3-101 g/L) (p-valeur = 0,001). Concernant les caractéristiques cliniques, une splénomégalie est plus souvent présente dans le groupe LMZ (p-valeur = 0,04). La mutation L265P du gène MYD88 est retrouvée chez 77 % des patients du groupe MW, 60 % des patients du groupe LLP et 67 % des patients du groupe LMZ (p-valeur = 0,38). La survie globale des 49 patients est de 85 % à 10 ans (IC 95 %, 67 % à 94 %) et de 65 % à 15 ans (IC 95 %, 41 % à 81 %). CONCLUSION: Un pic d'IgM monoclonal évoque généralement une MW, mais il faut toujours exclure d'autres syndromes lymphoprolifératifs B. Alors que la mutation L265P du gène MYD88 est fortement exprimée chez les patients porteurs d'un LLP/MW, elle n'en est pas pour autant spécifique. Un diagnostic précis nécessite aujourd'hui d'intégrer les données cliniques, histologiques, immunophénotypiques et génétiques.

Depth and lateral deviations in guided implant surgery: an RCT comparing guided surgery with mental navigation or the use of a pilot-drill template.

AIM: To assess the accuracy of guided surgery compared with mental navigation or the use of a pilot-drill template in fully edentulous patients. MATERIAL AND METHODS: Sixty consecutive patients (72 jaws), requiring four to six implants (maxilla or mandible), were randomly assigned to one of the following treatment modalities: Materialise Universal(®) mucosa, Materialise Universal(®) bone, Facilitate(™) mucosa, Facilitate(™) bone, mental navigation, or a pilot-drill template. Accuracy was assessed by matching the planning CT with a postoperative CBCT. Deviations were registered in a vertical (depth) and horizontal (lateral) plane. The latter further subdivided into BL (bucco-lingual) and MD (mesio-distal) deviations. RESULTS: The overall mean vertical deviation for the guided surgery groups was 0.9 mm ± 0.8 (range: 0.0-3.7) and 0.9 mm ± 0.6 (range: 0.0-2.9) in a horizontal direction. For the non-guided groups, this was 1.7 mm ± 1.3 (range: 0.0-6.4) and 2.1 mm ± 1.4 (range 0.0-8.5), respectively (P < 0.05). The overall mean deviation for the guided surgery groups in MD direction was 0.6 mm ± 0.5 (range: 0.0-2.5) and 0.5 mm ± 0.5 (range: 0.0-2.9) in BL direction. For the non-guided groups, this was 1.8 mm ± 1.4 (range: 0.0-8.3) and 0.7 mm ± 0.6 (range 0.0-2.9), respectively. The deviation in MD direction was significantly higher in the non-guided groups (P = 0.0002). CONCLUSION: The most important inaccuracy with guided surgery is in vertical direction (depth). The inaccuracy in MD or BL direction is clearly less. For non-guided surgery, the inaccuracy is significantly higher.

Accuracy of computer-aided implant placement.

AIM: To assess the accuracy of static computer-guided implant placement. MATERIAL AND METHODS: Electronic and manual literature searches were conducted to collect information on the accuracy of static computer-guided implant placement and meta-regression analyses were performed to summarize and analyse the overall accuracy. The latter included a search for correlations between factors such as: support (teeth/mucosa/bone), number of templates, use of fixation pins, jaw, template production, guiding system, guided implant placement. RESULTS: Nineteen accuracy studies met the inclusion criteria. Meta analysis revealed a mean error of 0.99 mm (ranging from 0 to 6.5 mm) at the entry point and of 1.24 mm (ranging from 0 to 6.9 mm) at the apex. The mean angular deviation was 3.81° (ranging from 0 to 24.9°). Significant differences for all deviation parameters was found for implant-guided placement compared to placement without guidance. Number of templates used was significant, influencing the apical and angular deviation in favour for the single template. Study design and jaw location had no significant effect. Less deviation was found when more fixation pins were used (significant for entry). CONCLUSION: Computer-guided implant placement can be accurate, but significant deviations have to be taken into account. Randomized studies are needed to analyse the impact of individual parameters in order to allow optimization of this technique. Moreover, a clear overview on indications and benefits would help the clinicians to find the right candidates.

Sleeping vs. loaded implants, long-term observations via a retrospective analysis.

OBJECTIVE: Several theories have been presented to explain initial and secondary marginal bone loss around dental implants (e.g. microbial load, adverse loading, microbial leakage, compromised healing/adaptation of host-implant interface). MATERIAL AND METHODS: This study compared the long-term outcome (up to 12 years) of sleeping with loaded implants in the mandible via a split-mouth concept. Fourteen patients with overdentures were enrolled (10 women, mean age at implant insertion: 56 years [range: 33-71]). They presented with 28 loaded (position 33/43) and 14 sleeping implants (mostly position 31/41). At several follow-up visits, intra-oral radiographs (long-cone principle) were taken to observe marginal bone level changes. RESULTS: At each observation, compared with abutment connection, the submerged non-loaded implants showed less bone loss (P-values: 1st year 0.007, 3 years 0.000, 5 years 0.002, 8 years 0.007, 12 years 0.000) than their neighbouring functional implants. This difference was primarily due to a more significant bone loss during the first year of loading (0.8 vs. 0.1 mm respectively), since afterwards, the bone level changes remained quite similar for both implant types. CONCLUSIONS: Our data suggest that the first months of loading have a significant impact on the bone level (initial difference sleeping vs. loaded implants), followed by a more physiological bone level change afterwards. This initial difference might be explained by the adaptation of the surrounding bone to the loaded implant.

Model-based guided implant insertion for solitary tooth replacement: a pilot study.

OBJECTIVE: The impact of the implant position on the restorative outcome could justify guided surgery even for the single implants particularly in the aesthetic zone and especially when a simplified concept is available. MATERIAL AND METHODS: Based on a plaster model, on which the soft tissues were mimicked (according to the thickness measured on a Cone-Beam CT), a tooth-supported, surgical template was prepared. The latter guided all drills so that even flapless implant insertion became possible. All implants were placed by students of the master-after-master training program in Periodontology. RESULTS: The prospective cohort included a total of 34 implants, all of AstraTech (Osteospeed(®)) type, which were successfully inserted in 29 patients, 16 flapless, 32 onestage. The marginal bone along the integrated implants remained stable over time, with 0.13 mm loss during the first year. The aesthetic parameters were reassuring. CONCLUSIONS: This simple model-based concept seems to be reliable for the guided placement of single implants and the pre-operative preparation of their restorations.

Management of rectal foreign bodies.

The presence of foreign bodies inserted into the rectum is not an uncommon situation. Precise guidelines for the management and extraction of these foreign bodies are not frequently described in the literature. Anal access, whether endoscopic or surgical, varies depending on the type of foreign bodies, their size and morphology, and their location in the lower digestive tract In this report, we describe a case of three rectal foreign bodies that necessitated a mixed endoscopic and surgical approach, and provide a review of the literature.

Long-term, retrospective evaluation (implant and patient-centred outcome) of the two-implant-supported overdenture in the mandible. Part 2: marginal bone loss.

OBJECTIVE: In part 2 of this long-term, retrospective study on the two-implant-supported overdenture in the mandible, the annual marginal bone loss was evaluated in detail and parameters, with a significant effect on the annual bone loss, were verified. MATERIAL AND METHODS: For all 495 patients with an overdenture in the mandible at least 5 years in function, data up to their last follow-up visit had been collected, including long-cone radiographs (taken at the abutment connection and after years 1, 3, 5, 8, 12 and 16 of loading) and probing data at their last evaluation. General information (medical history, implant data, report on surgery) was retrieved from the patient's file. Two hundred and forty-eight patients had been clinically examined recently. For the others, information on bone level and probing depths were retrieved from the patient's files, as all patients had been enrolled in our annual follow-up schedule. RESULTS: The mean annual bone loss on a site level (without considering the first year of bone remodelling) after 3 years of loading was 0.08 mm/year (SD=0.22, n=1105), after 5 years of loading 0.07 mm/year (SD=0.14, n=892), after 8 years of loading 0.06 mm/year (SD=0.12, n=598), after 12 years 0.04 mm/year (SD=0.07, n=370) and 0.05 mm/year (SD=0.05, n=154) after 16 years of loading. Ongoing bone loss was seen in a number of implants (n=26) with the annual bone loss exceeding 0.2 mm. Some factors clearly showed a significant impact on bone loss: smoking (> or =10 cigarettes/day), GBR, the presence of dehiscence and bone quantity(the latter only during the first year). The probing data showed a favourable condition, with <1.2% of the approximal pockets being > or =6 mm, and 4.1%=5 mm. CONCLUSIONS: The mean annual bone loss over the study period was <0.1 mm/year after the first year of loading. However, a small number (2.5%) of the implants showed continuing bone loss.

Cumulative live-birth delivery after IVF/ICSI since the progressive introduction of single-embryo transfer.

The only way to decrease the incidence of multiple pregnancies in the IVF/intracytoplasmic sperm injection (ICSI) population is to introduce single-embryo transfer (SET). This study investigated the impact of the progressive introduction of SET for the whole IVF/ICSI population from the patients' point of view by calculating the cumulative live-birth delivery rate. During a 5-year period (2001-2005), the outcome of 2164 cycles with oocyte aspiration in 1047 patients was analysed. A subanalysis was made to calculate the additional effect of frozen-thawed cycles. Survival analysis was performed with the Kaplan-Meier method and the endpoint was live-birth delivery. In this 5-year period, the cumulative live-birth delivery rate per patient was 51% after three IVF/ICSI cycles and 58% after six cycles. With a more permissive method of survival analysis, these results were 64% and 85%, respectively. The additional effect of the frozen-thawed cycles since reimbursement was only 5%. SET was progressively introduced in this period leading to a twin live-birth delivery rate of only 6.7%. It is concluded that a favourable outcome was observed for the cumulative live-birth delivery rate since the introduction of SET but with a disappointing additional effect of the frozen-thawed cycles.

Long-term, retrospective evaluation (implant and patient-centred outcome) of the two-implants-supported overdenture in the mandible. Part 1: survival rate.

OBJECTIVE: This retrospective analysis evaluated the long-term outcome of two implants supporting an overdenture in the mandible, as well as the significance of some confounding factors (smoking, implant length, bone quality). MATERIAL AND METHODS: All mandibular overdenture cases (n=495) treated during the past 25 years in our centre (with > or = 5 years loading of the implants) were included in this study. General information (medical history, implant data, report on surgery) was retrieved from the patient's file. A large number of patients (n=248) were willing to visit the clinic for an additional follow-up visit. For the others, information on implant survival was collected by phone (n=121), or contact was impossible (57 had died, three were hospitalized and 66 could not be reached). In the latter group, information was used, up to their last visit to the clinic. An implant was considered as surviving if it was still in function in the mouth, without clear adverse effects (pain, swelling, mobility). A failure was defined as early if it occurred within the window, insertion-final prosthesis placement; afterwards, it was considered as late. RESULTS: Most of the inserted implants (Brånemark type) were of the turned (machined) type (95.5%), the remainder was anodized (TiUnite). The anchoring system was either a bar (86.3%), ball attachments (11.7%) or magnets (1.6%), and only some patients changed from one to the other (0.4%). Kaplan-Meier analyses showed a survival rate of 95.5% after 20 years of loading. Factors that influenced the outcome included smoking (90% rate for smokers) and the surgical protocol (reduced survival rate for one-stage-placed implants). Implant length and bone quality had no impact. CONCLUSIONS: These results fully support the two-implant overdenture concept in the mandible even in the long run.

The use of CT scan based planning for oral rehabilitation by means of implants and its transfer to the surgical field: a critical review on accuracy.

The purpose of the present paper is to review the literature on the use of CT scan based planning for oral rehabilitation and its transfer to the surgical field by means of a surgical guide. The first part will deal with surgical guides based on tomographies or CT scan data often using dedicated software, but manually fabricated. In the second part, CT-derived drill guides are discussed, which are fabricated by means of CAD/CAM technology or other computer-controlled technology. The deviations between the position of the implants at the planning stage and after the surgery are of utmost importance, especially when flapless procedures are applied. The maximal deviations are often not stated in the literature. This should be taken into account when a system is applied clinically.

The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies.

BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538 SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.

Single top quality embryo transfer as a model for prediction of early pregnancy outcome.

BACKGROUND: Single embryo transfer (particularly of a top quality embryo) is an excellent model to correlate embryo quality in terms of morphological criteria to early pregnancy. We investigated whether this model could provide us with more information on what happens after implantation in the first trimester of pregnancy. METHODS: The outcome of 370 consecutive single top quality embryo transfers in patients younger than 38 years was analysed for pregnancy and first-trimester pregnancy loss (FTPL) before 13 weeks of gestation. Analysis was done on each cohort of embryos from which the transferred top quality embryo was selected. Serum HCG levels were measured on day 8 and day 12 after day 3 embryo transfer. The HCG index was calculated as the level of HCG on day 12/HCG on day 8. RESULTS: The pregnancy rate after single top quality embryo transfer was 51.9%. This was independent of the patients' age. FTPL, however, appeared to be age dependent: 15.4% for the whole group, 9% in patients younger than 30 years and 19% in patients above 30 years. The pregnancy rate was 50% in IVF cycles and 52% in ICSI cycles; FTPL was 19% in IVF cycles and 10% in ICSI cycles. Multiple regression analysis showed that these differences originated from age differences between both populations rather than from technique-related factors. An HCG level >or=45 IU/l on day 12 was predictive for ongoing pregnancy with 75.6% sensitivity and 100% specificity; an HCG index >or=3.5 similarly predicted ongoing pregnancy with 72.3% sensitivity and 100% specificity. CONCLUSIONS: These data show that embryo selection for transfer on day 3 can be used as an excellent tool for prediction of pregnancy but not for prediction of FTPL. The pregnancy rate of a single top quality embryo is not related to age, whereas FTPL is age dependent.

A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles.

BACKGROUND: We analysed the difference in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). METHODS: We performed a two-centre prospective study of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. RESULTS: In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). CONCLUSIONS: This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.

Cryopreservation as a tool to reduce multiple birth.

The potential role of embryo cryopreservation from the point of view of prevention of multiple pregnancies is analysed. Cryopreservation is an unavoidable option in stimulated IVF/intracytoplasmic sperm injection (ICSI), but at the same time an underestimated tool in the prevention of twins. There is a need for an evaluation system not only of the cryotechnology process per se, but also of the true augmenting effect of cryopreservation on the total reproductive potential of a single oocyte harvest. Only cryopregnancies occurring after an unsuccessful fresh cycle (possibly followed by one or more unsuccessful freeze-thaw cycles with embryos from the same harvest) truly reflect the augmentation potential of cryopreservation. This potential is greater than generally thought. First, the efficacy of cryopreservation is suboptimal with survival rates between 30 and 70%. Second, if single-embryo transfer were applied in a much larger proportion of cycles than is presently the case, more embryos would be available for cryopreservation, resulting in more and more successful freeze-thaw cycles. In the future, the combination of elective single-embryo transfer with an optimized cryopreservation programme is likely to become the standard of care for routine IVF/ICSI treatment.

Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle.

BACKGROUND: The aim of this study was to evaluate the impact of transferring a single top quality embryo in the first IVF/ICSI cycle of patients <38 years old who chose to have one or two embryos transferred. METHODS: A total of 262 patients participated in the study, and 243 transfers were performed: 156 (64%) patients chose the transfer of a single top quality embryo, if available, and two non-top quality embryos if not available; 87 (36%) patients chose to have a double embryo transfer regardless of embryo quality. RESULTS: In the first group an ongoing pregnancy rate of 40% (63/156) with a twin pregnancy rate of 2% (1/63) was achieved. In the second group the ongoing pregnancy rate was 44% (38/87) with 26% (10/38) twin pregnancies. In the patient group with only one embryo transferred, irrespective of the patient's choice, the ongoing pregnancy rate was 43% (54/127) with no twin pregnancies. For the study population as a whole, the ongoing pregnancy rate was 42% (101/243) with 11% (11/101) twins. CONCLUSION: We conclude that the introduction of single embryo transfer in the first IVF/ICSI cycle is highly acceptable in women <38 years old.

Intracytoplasmic sperm injection in the treatment of male subfertility.

OBJECTIVE: To evaluate the results obtained after intracytoplasmic sperm injection (ICSI) in couples with male factor subfertility. DESIGN: Retrospective analysis of results obtained after ICSI in the unit of in vitro fertilisation in a private centre for infertility. RESULTS: Application of ICSI in treatment cycles for male subfertility resulted in a fertilisation rate of 62%. An embryo transfer was done in 98% of the cycles, resulting in a 24% pregnancy rate/ET or 22% per cycle. CONCLUSION: ICSI is the first microfertilisation technique with reproducible high fertilisation rates in different centres and the method of choice in the treatment of severely impaired sperm quality. Although, up to now, no higher incidence of congenital malformations has been reported, except for sex chromosomal anomalies, careful genetic counselling is mandatory because of the risk of transmitting genetically defined male subfertility to the next generation.

Mitochondrial distribution after fast embryo freezing.

Mitochondrial distribution pattern after ultrarapid freezing in dimethylsulphoxide was assessed in human multipronucleate zygotes, 2-cell and 4-cell stage embryos using rhodamine 123. The mitochondrial distribution pattern was evaluated at 37 degrees C after a 30 min incubation in rhodamine 123 solution, 4 h and 24 h after thawing. Non-frozen human unfertilized oocytes, 2-cell and 4-cell embryos used as a control showed a homogeneous distribution of mitochondria throughout the cytoplasm, while there was sequestration of mitochondria from the cortex to the region surrounding the pronuclei in multipronucleate zygotes. Morphologically intact multipronucleate zygotes, 2-cell and 4-cell stage embryos after quick freeze-thawing showed the same mitochondrial distribution pattern found in the unfrozen controls. Mitochondria exhibited a typical severe aggregation (clumping) throughout the cytoplasm when non-viable single blastomeres or embryos at thawing were exposed to rhodamine 123. Our study indicates that quick freezing does not affect subcellular structures. The well-organized and specific mitochondrial distribution appeared still to be present after frozen storage, and subcellular structures seemed to be rather resistant targets for cryo-injury.