Fernand Leroy

Clinical Study on Embryo Transfer After Human in Vitro Fertilization

One hundred forty-six embryo transfers were carried out in the In Vitro Fertilization (IVF) Clinic at St. Pierre Hospital, Brussels, between November 1983 and February 1985. In each of these cases a series of characteristics of the replacement procedure was systematically rates indicated that (i) no significant differences appeared among three different operators, (ii) the absence or occurrence of cervical bleeding and subjective evaluation of the procedure were related to the chances of establishing a pregnancy, and (iii) the duration of replacement had no influence on the outcome of trials. A prospeative randomized study of 100 replacements showed that (i) no better pregnancy rate was obtained by placing patients in the knee-to-chest rather than the dorsal position and (ii) the addition of a rigid external sleeve to the catheter did not provide any advantage. A simplified method of replacement is thus advocated.

Pathologic examination of placentas from singleton and twin pregnancies obtained after in vitro fertilization and embryo transfer.

A pathologic investigation was conducted on 100 placentas collected from pregnancies resulting from in vitro fertilization (IVF) and intrauterine embryo transfer (ET), including 70 singleton pregnancies, 20 twin pregnancies, and 10 multiple pregnancies complicated by the vanishing twin (VT) phenomenon (n = 5) or artificially reduced (n = 5). These results were compared with those for 70 spontaneous spontaneous singleton and 20 spontaneous twin pregnancies. In cases of singleton pregnancies, the incidence of abnormal placental shapes was significantly different (P < .025) in the IVF group compared to controls. A significant (P < .005) difference was also observed between these groups in terms of umbilical cord insertion. The mean distance between the cord insertion and the closest placental margin was significantly (P < .001) shorter among IVF singleton pregnancies (3.19 +/- 1.83 versus 4.62 +/- 2.23 cm). In cases of twin pregnancy, no difference was found between IVF and spontaneous pregnancy in the incidence of pregnancy complications and distribution of cord insertion. First-trimester bleeding was the only clinical sign of the disappearance of an embryo in multiple pregnancies complicated by the VT phenomenon and was not observed in multiple pregnancies artificially reduced. The present findings support the hypothesis that marginal cord insertion is secondary to oblique orientation of the blastocyst at the nidation. A larger trial is now required, analyzing the placental features from IVF pregnancies in relation to the etiology of infertility.

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.

Radioautographic evaluation of the estrogen-dependent proliferative pool in the stem cell compartment of the mouse uterine and vaginal epithelia

Abstract The proliferative pool in the generative compartment of the vaginal and uterine epithelia of spayed mice has been evaluated. Continuous exposure to 3 H-thymidine has been performed by hourly injections of the precursor during 98 hr. This procedure proved to be sufficient to attain a total labelling of the cell populations under study. It is thus clear from our data that homogeneous population of cells continuously proliferate in the basal layer of the vagina, and in the uterine epithelium of the mouse. The proliferation rate of those cells depends on the presence of estrogen, the action of which is to reduce the generative cycle time. In the extreme case of high estrogen doses this accelerating effect of the hormone is accompanied by a marked decrease of the S phase duration. Hence it appears unnecessary to consider, as suggested earlier [2], a stimulative action of estrogen via the awaking of a dormant reserve of cells, whose existence is excluded by our results.

Effect of stage of development on survival of mouse embryos frozen-thawed rapidly

Embryos were recovered on Day 4 of pregnancy from superovulated random-bred OF1 Swiss albino mice. They were classified into four categories based on their stage of development: expanding blastocyst, blastocyst, early blastocyst, and compacted morula. They were then cooled at 2 degrees C/min from -7 to -25 degrees C in a freezing medium containing 1.36 M glycerol and 0.25 M sucrose in phosphate-buffered saline (PBS). At -25 degrees C, they were plunged into LN2 and thawed a few hours later in water at 20 degrees C. After washing in PBS, recovered embryos were cultured for 20 to 24 hr and the number of embryos that had developed normally was recorded. The results showed a clear effect of the stage of development on survival. Survival of expanding blastocysts and blastocysts was very low (1.4 and 21.8%, respectively) compared to that of early blastocysts and compacted morulae (69.4 and 73.5%). The more differentiated stage of the blastocyst (two kinds of cells) and the presence of a blastocoelic cavity may explain the differences observed under our cooling conditions. As a further test of viability, 93 blastocysts that had developed in culture for 20 hr from 153 frozen-thawed early blastocysts and compacted morulae (60.8%) were transferred to 8 recipient mice. Seven became pregnant, yielding 38/82 normal live young (46.3%).

Use of buserelin acetate in an in vitro fertilization program: a comparison with classical clomiphene citrate-human menopausal gonadotropin treatment

A comparison has been established retrospectively between clomiphene citrate-human menopausal gonadotropin (CC-hMG) and buserelin acetate-hMG treatments in in vitro fertilization trials performed over a 3-year period. The analysis of 466 CC-hMG and 319 buserelin acetate-hMG trials shows that buserelin acetate-hMG stimulation generates a greater ovarian response resulting in higher numbers of oocytes being retrieved (6.2 + 3.8 versus 9.3 + 5.2) and fertilized (2.8 + 2.7 versus 4.3 + 3.8). More embryos are thus obtained, allowing a wider choice for intrauterine replacement and cryopreservation. Mean embryonic vitality scores do not differ (4.33 + 1.51 versus 4.44 + 1.54), implying that the embryonic quality remains similar in both treatments. A premature demise of the corpus luteum occurs in a large proportion of buserelin acetate-hMG cycles. However, when suppletive progesterone treatment is given, there is a trend toward a better implantation rate per embryo, and a significantly higher ongoing pregnancy rate is observed in relation to buserelin acetate-hMG treatment (20%) as compared with CC-hMG cycles (14%).

A reappraisal of perinatal mortality factors in twins

During the last 33 years, the perinatal mortality of twins has decreased regularly in our department. When examined by duration of pregnancy, mortality was lowest at 37-38 weeks. Below 38 weeks, fetal loss was paradoxically higher in twins born from multiparae. When delivery occurred beyond 38 weeks, mortality rates were increased, but only differences for primiparous group showed statistical significance. Near-term fetal loss was predominantly due to antepartal intrauterine deaths. Analysis of individual cases indicated that early termination of pregnancy might help prevent near-term stillbirths in twins delivered by primiparae. Efforts should be directed at specific detection of twins threatened by antepartum death.

Experimental study on local factors in the process of ova implantation in the rat.

Abstract 1. 1. The athrocytic phenomenon has been used to determine the general hormonal properties and local conditions governing the implantation of the egg in the uterine horn of the rat. 2. 2. Athrocytosis has been found to be under control of the corpus luteum of pseudogestation or gestation. 3. 3. In the uterine horn, athrocytosis may be obtained by simple trauma, provoking liberation of histamine. 4. 4. The evident correlation between this occurrence and nidation has been considered.

Altered Duration of DNA Synthesis and Cell Cycle in Non-target Tissues of Mice treated with Oestrogen

THE effects of ovarian hormones on the cell cycle of target tissues have been extensively studied. It has been shown that high doses of oestrogens of exogenous origin can alter the duration of DNA synthesis (S phase) in target tissues when administered alone1,2 or in association with progesterone3.

Oxytocin treatment in twin pregnancy labour

A continuous series of 483 twin deliveries was studied. In 30% of cases, intravenous oxytocic treatment was given for labour induction or to accelerate the first stage. In 13% of twin deliveries this treatment was applied only after the first twins birth. In the group perfused during cervix dilatation, foetal mortality rate was significantly lower than in the nontreated group. In order to understand the reason(s) for this difference, the following factors were studied in relation to oxytocic treatment: parity, obstetrical complications, second stage duration, abnormal presentations, obstetrical maneuvers, and birth weight. Contrasting with mortality data, Apgar scores of first twins were significantly lower in the oxytocin-treated group. In summary, several variables indirectly linked to oxytocic treatment could have favoured or hampered foetal outcome in the treated group. Therefore, it is difficult to ascertain if the use of oxytocics is helpful in twin pregnancy management. In the majority of cases, however, it may at least be considered harmless.