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 However, the overall national picture remains unpublished.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.

Postgraduate cadaver surgery: An educational course which aims at improving surgical skills.

OBJECTIVE: To describe the postgraduate surgical skills training programme of the Flemish Society of Obstetrics and Gynaecology (VVOG*). Laparoscopic surgical techniques and indications have increased substantially during the past two decades. From surgeons it is expected that they keep up with all techniques and should be able to perform all relevant procedures. Learning new procedures in daily practice is hazardous and difficult to achieve. A training experience with cadaver surgery could improve the course and outcome of surgery on patients. We present the objective, structure, and outcome of the endoscopic postgraduate training course. STRUCTURE: The overall objective of the endoscopic postgraduate training course is to refresh anatomical knowledge and improve general gynaecological laparoscopic surgical skills. The VVOG endoscopic training programme is based on black box training, followed by pig surgery. New is the possibility to perform surgical procedures on specifically prepared human cadavers. The course consists of an anatomical teaching session followed by lectures with videotaped procedures on the anatomical exploration of the pelvis, laparoscopic hysterectomy and pelvic lymphadenectomy. During the hands-on session the participant performs the surgical procedures in a controlled, nonthreatening and interactive way under the guidance of an experienced trainer. CONCLUSIONS: All participants provided feedback on their experiences. The evaluation of the workshop revealed that this course is an opportunity to practise and improve clinical laparoscopic skills of gynaecological procedures and anatomy. Attending the course was regarded as of genuine additional value for surgical practice.

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Telerobotic-assisted laparoscopic hysterectomy for benign and oncologic pathologies: initial clinical experience with 30 patients.

BACKGROUND: Telerobotic-assisted laparoscopic attempts to provide technological solutions to the inherent limitations of traditional laparoscopic surgery. The aim of this study is to report the first experience of two teams concerning telerobotic-assisted laparoscopic hysterectomy for benign and malignant pathologies. METHODS: This study included 14 patients at the University Hospital Saint Pierre of Brussels (Belgium) and 16 patients at the Cancer Center of Nancy (France) from September 1999 to July 2003. RESULTS: The indications for surgery were uterine malignant diseases in 12 cases (stade I) (41%), and benign pathologies of the uterus in 18 cases (59%). Five postoperative complications (17%) occurred, none related to the robotic system. CONCLUSION: Robotic surgery can be safely performed in gynecologic and gynecologic-oncologic surgery with no increase in complication rates. A significant advance is represented by the surgeon's ergonomic improvement.

Return to fertility in nulliparous and parous women after removal of the GyneFix intrauterine contraceptive system.

OBJECTIVE: To evaluate the return to fertility following removal of the GyneFix intrauterine implant system in women wishing to conceive. STUDY DESIGN: A retrospective study was performed on a sample of healthy, sexually active nulligravid/nulliparous and parous women. The participants were 18-41 years of age, with no apparent infertility problem, living in a stable relationship and planning to become pregnant. Women who changed their mind and did not wish to become pregnant immediately after intrauterine device (IUD) removal were excluded from the study. Women were evaluated in terms of rates of conception and fertility outcome. A total of 128 women were evaluated. RESULTS: The study shows that 119 out of 128 (93%) past users of GyneFix have conceived, accounting for a net cumulative pregnancy rate of 88% at 12 months and 99% after 2 years' observation. No statistical differences in pregnancy rates were found for age and duration of use of the IUD. A strong significant difference in pregnancy rate was shown (p = 0.007) between parous and nulligravid/nulliparous women. Seventy-seven women (66.9%) gave birth to a term infant. There were no stillbirths. Twenty-five women (21.8%) are pregnant at the time of writing. Five (4.4%) spontaneous abortions occurred and in eight women (6.9%) the pregnancy was terminated. There were no ectopic pregnancies. CONCLUSION: The results obtained compare favorably with those obtained in previous studies conducted following the removal of copper IUDs. The use of the frameless IUD does not affect future fertility in nulligravid/nulliparous and parous women wishing to become pregnant following removal of the device. Nulliparous women conceive significantly earlier than parous women.

Feasibility of robotic laparoscopic surgery: 146 cases.

Theoretically, in laparoscopic surgery, a computer interface in command of a mechanical system (robot) allows the surgeon: (1) to recover a number a number of lost degrees of freedom, thanks to intraabdominal articulations; (2) to obtain better visual control of instrument manipulation, thanks to three-dimensional vision; (3) to modulate the amplitude of surgical motions by downscaling and stabilization; (4) to work at a distance from the patient. These advances improve the quality of surgical tasks in a perfect ergonomic position. The purpose of this paper is to evaluate the feasibility of utilizing a robot in laparoscopic surgery. The first robot-assisted procedure in humans was performed in March 1997 by our team. One hundred forty-six patients underwent robot-assisted laparoscopic surgery. Between March 1997 and February 2001 a nonconsecutive series was performed of 39 antireflux procedures, 48 cholecystectomies, 28 tubal reanastomoses, 10 gastroplasties for obesity, 3 inguinal hernias, 3 intrarectal procedures, 2 hysterectomies, 2 cardiac procedures, 2 prostactectomies, 2 arteriovenous fistulas, 1 lumbar sympathectomy, 1 appendectomy, 1 laryngeal exploration, 1 varicocele ligation, 1 endometriosis cure, 1 neosalpingostomy, 1 deferent canal. The robot (Da Vinci system, Intuitive Surgical, Mountain View, CA), consists of a console and a cart with three articulated robot arms. The surgeon sits in front of the console, manipulating joysticklike handles while observing the operative field through binoculars that provide a three-dimensional picture. This computer is capable of modulating these data by eliminating physiologic tremor and by downscaling the amplitude of motions by a factor 5 or 3 to one. This study has demonstrated the feasibility of several laparoscopic robotic procedures. There is no morbidity related to the system. Operating time and the hospital stay were within acceptable limits. The system seems most beneficial in intra-abdominal microsurgery or for manipulations in a very small space. Optimized ergonomics and increased mobility of the instrument tips are beneficial in many steps of abdominal surgical procedures.

Robotically assisted laparoscopic microsurgical tubal reanastomosis: a feasibility study.

OBJECTIVE: To assess the feasibility and reproducibility of laparoscopic microsurgical tubal anastomosis using a remote-controlled robot. DESIGN: Descriptive case study. SETTING: Academic medical center. PATIENT(S): Eight patients with previous laparoscopic tubal sterilization who requested tubal reanastomosis. INTERVENTION(S): Systematization of the operative steps for laparoscopic tubal reanastomosis using a remote-controlled robot. MAIN OUTCOME MEASURE(S): Primary outcome measures were feasibility and reproducibility; secondary measures were tubal patency, operative time, complications, and ergonomic qualities. RESULT(S): The 16 tubes were successfully reanastomosed and patency was confirmed. The mean time that the robotic system was in use was 140 minutes, and mean surgical time was 52 minutes per tube. CONCLUSION(S): Laparoscopic microsurgical tubal reanastomosis after tubal sterilization can be performed using a remote-controlled robotic system. The robot, which has three-dimensional vision, allows the surgeon to perform ultraprecise manipulations with intraabdominal articulated instruments while providing the necessary degrees of freedom. Systematization of the operative steps allowed performance of the operation at a speed that compares favorably with the time needed for open microsurgical techniques. Larger series are needed to assess postoperative pregnancy rates.

The place of Zoladex in deferred surgery for uterine fibroids. Zoladex Myoma Study Group.

Two hundred and forty-seven patients with uterine fibroids were randomized to surgery alone or 3 months' Zoladex (Zeneca, Macclesfield, Ches., UK) followed by surgery. Zoladex significantly reduced uterine and fibroid volumes (p = 0.0001). There was a significantly (p = 0.002) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group (1 g/dl) compared with the surgery-alone group (0.3 g/dl) as well as a tendency towards easier surgery, and reduced operative blood loss. Zoladex-treated patients had a significantly (p = 0.016) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly (p < 0.0001) reduced in this group. Zoladex was well tolerated.

[Obstetrical and perinatal outcome of patients not covered by medical insurance]. / Devenir obstétrical et périnatal des patientes sans couverture sociale.

The number of pregnant women uncovered by medical insurance is increasing in the maternity of Saint-Pierre Hospital (44% increase over a 3 year period). During the academic year 92-93, this situation was present in 9.8% of the mothers; 98% of these patients were foreigners. The majority of pregnancies were not or poorly followed. Admissions occurred very often in emergency situations. The lack of prenatal care in this population with a very low socio-economic level led to a six-fold increase in perinatal mortality after exclusion of congenital malformations (58.4% versus 8.7%). This high mortality rate was mainly due to extreme prematurity (birthweight between 500 and 1500 g).

Osteoporosis prevention with sex hormone replacement therapy.

It was suggested as long ago as 1941 that there might be a connection between the menopause and osteoporosis. Since then, abundant data have confirmed that hypothesis as well as showing that such osteoporosis may be prevented by estrogen supplementation (ERT--estrogen replacement therapy). In estrogen deficiency, increased bone resorption takes place in the process of bone remodeling, leading to bone loss. The bone loss occurs universally but to the greatest extent at sites rich in trabecular bone. There are uncertainties concerning extent of bone loss at various sites at different ages, effect of ERT at varying sites and different ages, degree of fracture prevention, and relationship between duration of therapy and fracture risk. That optimal fracture risk is not being attained now on a population basis is due to apparently low acceptance of ERT by patients and lack of strenuous effort in that direction by physicians.

Bone mineral content of women with uterine fibromyomas.

OBJECTIVE: To determine if the bone mineral content (BMC) of women suffering from fibroids is different from that of the reference population. DESIGN: Cross-sectional retrospective study. PARTICIPANTS: Fifty-nine women suffering from fibroids, compared to the reference population. OUTCOME MEASURES: BMC was measured at the vertebral L2-L4 site (BMC-1) and at the midradius site (BMC-r). RESULTS: The patients with fibroids exhibited no significant difference in BMC-r). RESULTS: The patients with fibroids exhibited no significant difference in BMC-r, but had a significantly higher (P < or = .001) BMC-1 than the reference population. CONCLUSION: Since BMC-1 is mainly constituted by trabecular bone and BMC-r by cortical bone, and since trabecular bone is more sensitive to estrogens than cortical bone, it is suggested that a hyper-estrogenic state co-existing with fibroids may induce a slight protective factor against osteoporosis of the vertebral skeleton.

Modulation of the growth of hematopoietic human stem cells by growth factors: comparison of umbilical cord blood with bone marrow.

The growth of cord blood and bone marrow myeloid mononuclear cells in response to single and multiple growth factors has been examined. Single factors such as IL-3, IL-6, GM-CSF, and stem cell factor did not optimally stimulate growth of cord blood CFU-GM. However a synergistic stimulation was observed when the factors were combined. This effect was seen in both the presence and absence of added fetal calf serum.

Early pregnancy loss and obstetrical risk after in-vitro fertilization and embryo replacement.

Between March 1983 and March 1986, 108 pregnancies were obtained at the IVF clinic of St Pierre Hospital in Brussels. There were 29 chemical pregnancies (26.8%), five ectopic pregnancies (4.6%), 15 abortions (14%) and 59 ongoing pregnancies of over 20 weeks (54%). Patients who had experienced a chemical pregnancy at first trial displayed a significantly higher rate of ongoing pregnancy at their second attempt. Among the 15 cases of abortion, a chromosomal anomaly was detected in two cases and suspected in a third. Four of the five ectopic pregnancies occurred in patients with previously documented tubal pathology. The ongoing pregnancies were distributed as 44 singletons, 13 pairs of twins, one set of triplets and one set of quadruplets. The Caesarian section rates were 21 and 40% for single and multiple pregnancies, respectively. The prematurity rate was low for singletons (4.5%) but reached 46.6% in multiple pregnancies. Two minor malformations were observed and five perinatal deaths occurred; among these latter, four cases were twins. It appears that perinatal pathology is substantially higher among IVF pregnancies than in the normal population. It is clear, however, that most of this difference is accounted for by the considerably higher rate of twin pregnancy displayed by the former group.

Higher pregnancy rates after in vitro fertilization and embryo transfer in cases with sperm defects.

One hundred thirty-three couples were classified into four groups according to previous sperm analyses. These couples underwent 237 in vitro fertilization trials that led to 46 clinical pregnancies (19.4%/trial). Clinical pregnancy rate per laparoscopy of the group with male defects was significantly higher than that of the normospermic couples (25 versus 14%, P less than 0.05). The fertilization rate was significantly reduced only if two sperm anomalies were present (P less than 0.05). However, the mean number of embryos transferred did not differ significantly among the four groups, but the proportion of trials without transfer was increased with regard to the severity of sperm defect. Implantation rate per embryo in cases of triple transfer was significantly higher in the group with sperm anomalies as compared with the normospermic cases (18 versus 10%, P less than 0.02). Correction of the male problem through IVF treatment allows higher female fertility to be disclosed in these cases.

In vitro fertilization and embryo transfer as related to endogenous luteinizing hormone rise or human chorionic gonadotropin administration.

After ovarian stimulation with clomiphene citrate combined with human menopausal gonadotropin for in vitro fertilization, the appearance of a spontaneous luteinizing hormone (LH) surge before fulfillment of the minimal criteria of follicular maturity (at least one follicle greater than 19 mm and serum estradiol [E2] greater than 400 pg/ml/follicle greater than 17 mm) is associated with reduced pregnancy rates. In these cases, follicles are smaller and serum E2 values are lower at the time of the LH surge. Oocyte recovery rate is reduced, embryonic anucleate fragments are more frequently observed, and the level of luteal progesterone on day 4 after oocyte retrieval is lower. Hyperandrogenic patients are more prone to display such premature spontaneous LH surge. We concluded that in case of an untimely LH rise, laparoscopy for oocyte retrieval should be cancelled.

Factors leading to tripronucleate eggs during human in-vitro fertilization.

Four-hundred-and-ninety-one oocytes were collected from 142 successive patients attending for in-vitro fertilization. The systematic observation of pronuclei between 14 and 18 h after insemination revealed 27 cases of tripronucleate eggs among 391 fertilized eggs (6.9%), which corresponds to rates generally reported in the literature. The following parameters were analysed in relation to the incidence of these eggs: aetiology of infertility, follicular response to hormonal stimulation, type of ovulatory stimulus, sperm count and motility and the incidence of fertilization. Only fertilization rates and concentration of motile spermatozoa in the insemination medium were found to be correlated with tripronucleate eggs, confirming that the condition is predominantly due to polyspermy. Comparisons with data from animals, and measures aimed at preventing polyspermy are suggested.