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What are the main risk factors associated with ectopic pregnancy and what is the true incidence of ectopic pregnancies in an IVF programme?Retrospective single-centre study of 12,429 blastocyst transfers (8182 fresh and 4247 frozen embryo transfers) conducted between January 2010 and December 2017. IVF outcome was analysed, and ectopic pregnancy risk evaluated according to patient's characteristics and assisted reproductive technology treatment factors.Of 5061 patients reporting a positive pregnancy test, 43 were diagnosed with ectopic pregnancy (0.85%). Neither female age (36.7 versus 35.8 years), body mass index, quality of transfer nor stimulation protocol affected the ectopic pregnancy rate, but history of previous ectopic pregnancy (OR 3.26; P = 0.0080), tubal surgery, or both (OR 6.20; P0.0001) did. The incidence of ectopic pregnancy was increased in women with uterine malformations (OR 3.85; P = 0.0052), uterine pathologies (OR 5.35; P = 0.0001), uterine surgeries (OR 2.29; P = 0.0154) or sub-optimal endometrial build-up (OR 4.46 to 5.31; P0.0001). Transfer of slow-developing blastocysts (expressed by expansion) significantly increased the risk of ectopic pregnancy (OR 2.59; P = 0.0102).Unfavourable uterine environment, including uterine pathologies, uterine or tubal surgery and suboptimal endometrial build-up were related to ectopic pregnancy. Low expansion grade of blastocysts was identified as an additional putative risk factor for ectopic pregnancy, indicating the importance of proper embryonal-maternal synchronization. The overall ectopic pregnancy rate after blastocyst transfer was low, comparable with reported ectopic pregnancy rates in spontaneous conceptions. Proper evaluation of tubal and uterine pathologies, optimizing endometrial preparation and the transfer of expanded blastocysts in a frozen embryo transfer cycle, might be beneficial.

Das „preimplantation genetic screening“ (PGS)/„preimplantation genetic testing for aneuploidies“ (PGT-A) ist ein Teil der Praimplantationsdiagnostik (PID). Der Begriff umfasst eine Vielzahl von Methoden, die angewandt werden, um die chromosomale Konstitution eines Embryos vor dessen Transfer in die Gebarmutter zu erfassen. Dabei geht es nicht etwa darum, die Weitergabe (mono‑)genetisch bedingter Erbkrankheiten zu verhindern, sondern rein um den Ausschluss von Aneuploidien. Mit der Anwendung eines PGS sollten die Implantationschancen sowie die Lebendgeburtenraten steigen und die Abortraten sinken, da euploide Embryonen fur den Transfer ausgewahlt werden, so die klinische Hypothese. In den letzten Jahren erfuhr diese Technik nicht nur eine rasante technische Entwicklung, sondern erfreut sich international auch einer zunehmenden Beliebtheit. Was dabei haufig nicht beachtet wird, ist die Tatsache, dass nach wie vor die klinische Evidenz fehlt, die den postulierten „benefit“ des PGS beweist. Selbst neueste Techniken, wie das „next generation sequencing“ (NGS), konnten bisher daran nichts andern. Im Gegenteil, diese hochsensitiven Analyseplattformen haben zu neuen Erkenntnissen uber den chromosomalen Status des Praimplantationsembryos gefuhrt und damit auch zu einem fundamentalen Problem, das das PGS allgemein infrage stellen konnte – namlich die Tatsache, dass ein nicht unwesentlicher Teil der menschlichen Embryonen nicht uniform euploid oder aneuploid ist, sondern als ein chromosomales Mosaik (CM) mit numerischen und/oder strukturellen Aberrationen vorliegt. Diese Ubersichtsarbeit fasst die aktuelle Literatur zusammen und durchleuchtet die Kernprobleme des PGS aus biologisch-medizinischer, juristischer und ethischer Sicht.

STUDY QUESTION How do live birth rates (LBRs), following fresh and vitrified/warmed embryo transfer, compare according to morphological grade, developmental stage and culturing strategy of human blastocysts in vitro? SUMMARY ANSWER Equivalent LBRs were obtained after fresh embryo transfer and after vitrified/warmed embryo transfer of blastocysts of top or non-top quality, while vitrification after prolonged embryo culture of blastocysts with delayed development had a positive impact on LBR. WHAT IS KNOWN ALREADY Blastocyst morphology correlates with clinical outcome; however, few data are available on vitrified/warmed embryo transfer using non-top quality blastocysts. The aim of this study was to determine clinical outcomes of non-top quality blastocysts and blastocysts with delayed development that underwent vitrified/warmed embryo transfer. STUDY DESIGN, SIZE, DURATION This retrospective, single-centre study (conducted January 2009 to June 2013) compared 1010 fresh embryo transfer and 1270 vitrified/warmed embryo transfer of blastocysts originating from the same stimulation cycle. Furthermore, 636 fresh embryo transfers and 304 vitrified/warmed embryo transfer after delayed expansion or blastulation in the same period were also analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS Clinical outcomes after fresh and vitrified/warmed embryo transfer according to blastocyst morphology were compared in both groups. MAIN RESULTS AND THE ROLE OF CHANCE Similar LBRs after fresh embryo transfer or after vitrified/warmed embryo transfer of top or non-top quality blastocysts were observed. A statistically significant improvement in clinical outcomes was obtained after vitrified/warmed embryo transfer of Day 5 embryos with delayed expansion or blastulation when applying prolonged culture. Our study suggests that vitrification of non-top quality blastocysts as well as delayed cavitating and blastulating Day 5 embryos should be considered in autologous IVF cycles. LIMITATIONS AND REASONS FOR CAUTION Given that the present retrospective study used aseptic vitrification of blastocysts, the results, particularly the survival rates, may not be fully applicable to other vitrification protocols. The retrospective nature of the study has to be mentioned. WIDER IMPLICATIONS OF THE FINDINGS Restriction of vitrification to top quality blastocysts may result in discarding potentially viable embryos. STUDY FUNDING AND COMPETING INTERESTS This study was not externally funded. There are no conflicts of interest to declare.

Intracytoplasmic sperm injection (ICSI) was introduced in the clinical practice in 1992, to overcome male-factor infertility and in failed conventional IVF cases. Today ICSI is used across the world in most IVF cases, for almost all indications of infertility and it provides consistently high pregnancy rates.

Does the storage time of vitrified human blastocysts negatively impact their survival, the implantation potential of embryos or the malformation rate of babies born?There was no evidence that storage times of up to 6 years after vitrification (VIT) had a negative impact on blastocyst survival, the implantation potential of embryos or the malformation rate of babies born.Although several thousand children have been born after blastocyst VIT, many aspects of this technique remain to be elucidated. New applications, such as fertility preservation, lead to long storage times of vitrified gametes or embryos but it remains to be determined if these vitrified embryos are stable over time.A retrospective study including 603 transfers was conducted between January 2009 and April 2012. Blastocysts were vitrified using a closed system.All patients underwent the transfer of aseptically vitrified/warmed blastocysts in a cryo-cycle. A total of 1077 blastocysts were transferred. Survival rates (SRs), implantation potential, birth rates and characteristics of the children born were evaluated.We found that the storage of vitrified blastocysts in aseptic conditions neither impaired blastocyst viability (SR after warming during the first year of storage was 83.0% compared with 83.1% after 5-6 years of storage: NS) nor decreased pregnancy rates (clinical pregnancy rate after 1 year of storage was 40.0 versus 38.5% after 6 years: NS). In addition, no increase in the malformation rate over time was observed.Our study only included the transfer of blastocysts which had been vitrified aseptically (i.e. using a closed system). Therefore, our results might not be applicable to 'open' VIT systems. The long-term follow-up of children born will be necessary to confirm our findings.The results suggest that vitrified human blastocysts can be stored for long periods of time without significant negative consequences for the offspring. Therefore, the method should be of benefit to those patients who need to consider taking measures for fertility preservation.No external funding was sought for this study and the authors have no conflict of interest to declare.

Vitrification has been successfully applied in the cryopreservation of oocytes and embryos. It can be achieved either by direct (open system) or indirect (closed system) contact with liquid nitrogen. Unlike embryo vitrification, few reports have been published regarding oocyte vitrification in closed systems. In order to validate the effectiveness of a closed and aseptic vitrification approach for oocyte cryopreservation, a prospective, randomized study was performed. Sibling oocytes donated from the same donor were randomly and equally assigned into closed or open vitrification groups. A total of 75 vitrification-warming cycles were performed in each group. Apart from the survival rate (82.9% versus 91.0%, P

In some IVF cycles, no fresh embryo transfer in the stimulated cycle is advisable. The cryopreservation of zygotes and the transfer of blastocysts in a cryo-embryo transfer is an option to circumvent an inadequate uterine environment due to risk of ovarian hyperstimulation syndrome, inappropriate endometrium build up, endometrial polyps or uterine myomas. For this strategy, highly secure and safe cryopreservation protocols are advisable. This study describes a protocol for aseptic vitrification of zygotes that results in high survival rates and minimizes the potential risk of contamination in liquid nitrogen during cooling and long-term storage. In mouse zygotes, there was no difference in efficiency as compared with a conventional open vitrification system. In IVF patients, aseptically vitrified zygotes showed no difference in blastocyst formation rate as compared with sibling zygotes kept in fresh culture. A clinical study comprising 173 cryo-cycles with a transfer of blastocysts originating from vitrified zygotes showed an ongoing pregnancy rate of 40.9%. The live birth rate per patient was 36.8%. A combination of good clinical results and increased safety conditions due to aseptic vitrification encourages the use of cryo-embryo transfer for patients with a suboptimal uterine environment in a fresh cycle. In stimulated IVF cycles, high doses of hormones are given to stimulate multifollicular growth. One drawback of the hormonal substitution is that the uterine environment is not at the same time optimally prepared for embryo implantation. A solution, which is increasingly under discussion, is to cryopreserve the embryos obtained in the stimulated cycle and to transfer them back into the optimal uterine environment in a subsequent cryo-cycle. This procedure requires highly secure and safe cryopreservation protocols in order to ensure benefits for both pregnancy and birth rates. We have established a protocol for the vitrification of zygote-stage embryos in aseptic devices, which minimize the potential risk of contamination during cooling and storage. The vitrified zygotes showed the same blastocyst development as compared with sibling zygotes in fresh culture. A clinical study comprising 173 cryo-cycles with transfer of blastocysts originating from vitrified zygotes shows an ongoing pregnancy rate of 40.9%. The live birth rate per patient was 36.8%. A combination of good clinical results and increased safety conditions due to aseptic vitrification conditions contributes to a change in transfer strategy and encourages us to increase the cryo-embryo transfer rate for an optimal uterine environment.

Although some post-thaw morphological predictors of pregnancy have been investigated in slow freezing of blastocysts, no such data have been published for vitrified and warmed blastocysts. Therefore, a prospective four-part score was applied to vitrified/warmed day-5 embryos to evaluate whether certain morphological parameters could serve as predictors of implantation, pregnancy and live birth. All morulae/blastocysts that were considered to be viable after warming were scored according to a previously unpublished grading system based on re-expansion, hatching (out of an artificial gap in the zona pellucida), extensive cytoplasmic granulation and presence of necrotic foci. Overall, 74% (202/273) of the vitrified concepti were found to be viable after warming. Early blastocysts showed better survival versus extended/hatching blastocysts (P < 0.01). Of the morphological parameters analysed, immediate re-expansion (P < 0.05) and hatching (P < 0.001) were positive predictors of the rates of implantation, pregnancy and live birth. The opposite holds for extensive cytoplasmic granulation (P < 0.05), which was negatively related. Accurate scoring of warmed blastocysts (within the first 2 h) allows for prediction of pregnancy outcome, and thus will help to further reduce the number of transferred embryos.

Objective To evaluate whether is possible to vitrify oocytes in an aseptic (hermetically closed) fashion and maintain clinical results comparable with those of fresh oocytes. Design Prospective, observational, cohort, noninferiority trial. Setting Private in vitro fertilization center. Patient(s) One hundred eighty-four recipients of donated vitrified oocytes. Intervention(s) Closed system vitrification. Main Outcome Measure(s) Pregnancy rate per cycle and clinical pregnancy rate per cycle. Result(s) No statistically significant differences were observed between two groups regarding the pregnancy rate per cycle (63.1% vs. 60.9%) or the clinical pregnancy rate per cycle (55.4% vs. 58.7%). Biochemical pregnancy rate was statistically significantly higher in the fresh group (7.6% vs. 2.2%). The mean number of embryos transferred was similar (2.0 ± 0.0 vs. 1.97 ± 0.3). Concerning embryologic data, there were no statistically significant differences regarding the fertilization, cleavage, top quality day-3 embryo, or blastocyst rates, whereas the top quality blastocyst rate on day 5 was statistically significantly higher in the fresh oocyte group (31.7% vs. 26.1%). Conclusion(s) Aseptically (in a closed system) vitrified oocytes show similar clinical efficiency compared with their sibling fresh oocytes.

Resume La vitrification est un processus par lequel un liquide se solidifie sans formation de cristaux. Cette technique de cryopreservation consiste a exposer pour de courtes durees les embryons a des concentrations elevees en cryoprotecteurs puis de les refroidir ultrarapidement, ce qui induit une augmentation de la viscosite favorisant la formation d'un etat vitreux intra- et extracellulaire. Malgre l'obtention de taux de survie et de grossesse respectivement de l'ordre de 80 et 30 % accompagnes de la naissance d'enfants en parfaite sante, apres vitrification de zygotes, d'embryons segmentes, de morulae et de blastocystes, une apprehension subsiste quant a son application dans les centres d'Assistance medicale a la procreation. L'utilisation de concentration elevee de cryoprotecteurs et de technique de refroidissement et de stockage des embryons dans des conditions non steriles sont des arguments qui discreditent la technique. Le but de cet article est de repondre dans la premiere partie a differentes questions concernant la technique et les apprehensions qu'elle suscite. Dans une deuxieme partie seront presentes les resultats de la vitrification des embryons, et analysees les raisons liees a la difficulte de cryopreserver les blastocystes.

To determine the best day for the selection and transfer of a single embryo, a prospective, randomized study was undertaken that compared the ongoing pregnancy rate (PR) after single embryo transfer (SET) on day 3 with that after single blastocyst transfer (SBT) on day 5. Our results show an overall significantly higher PR after SBT (32.8%) compared with SET (23.2%), and a PR of 40.8% after SBT versus 25.6% after excellent-quality embryos became available.

Les auteurs rapportent les tentatives de micro-insemination de spermatides dans des programmes TESE au cours desquels il n'etait pas possible de recueillir des spermatozoides matures. Des spermatides de divers types ont ete utilisees. La technicite de la micro-insemination est detaillee, de meme que les indications du recours a des spermatides. Les resultats concernent tant des cas d'azoospermie secretoire qu'excretoire

Objective To limit the high number of multiple pregnancies in an IVF program. Setting In Vitro Fertilization Laboratory, Fertility Department, Public Hospital. Interventions The number of embryos transferred was limited to two instead of three. Results Limiting the number of embryos transferred to only two did not influence the take home baby rate but eliminated triplet and quadruplet gestations. Moreover, the number of patients with good quality supernumerary embryos available for cryopreservation increased. Conclusions To reduce the high frequency of multiple gestations in an IVF program, the number of embryos replaced should be limited to a maximum of two.

During embryo vitrification, it is advisable that cooling and storage should occur in a carrier device in which there is complete separation of the embryos from liquid nitrogen to ensure asepsis. The consequence of a reduction in the cooling rate resulting from the heat-insulating barrier aseptic devices has to be counteracted by gradually increasing intracellular concentrations of cryoprotectants without inducing a toxic effect. Blastocysts originating from couples with male and/or female factor infertility (group 1) or from oocyte donors (group 2) or from in-vitro matured oocytes (group 3) were gradually exposed to increasing concentrations of dimethylsulphoxide/ethylene glycol (5/5%, 10/10% and 20/20%) before aseptic vitrification using a specially designed carrier (VitriSafe), a modification of the open hemi-straw plug device. A total of 120 aseptic vitrification/warming cycles were performed in group 1, 91 in group 2 and 22 in group 3. Survival rates before embryo transfer, ongoing pregnancy and implantation rates were as follows: for group 1, 73, 43 and 26%; for group 2, 88, 53 and 34%; and for group 3, 69, 50 and 38%, respectively. In spite of reduced cooling rates due to aseptic vitrification conditions, a three-step exposure to cryoprotectant solutions protects the embryos effectively from cryo-injuries and guaranties high survival rates.

Objective To understand the correlation between normalcy of the sperm, fertilization, and early embryo development, and to establish a detailed classification scoring scale for the individual spermatozoon with the highest predictive fertilizing potential in real time during intracytoplasmic sperm injection (ICSI). Design A retrospective and analysis. Setting Laboratory Drouot. Patient(s) 27 couples with male factor infertility referred for ICSI treatment. Intervention(s) Before ICSI, motile spermatozoa were scored after aspiration. Main Outcome Measure(s) Oocyte fertilization, embryo development and morphology, outcome of scored motile injected spermatozoa. Result(s) Our suggested formula is (Normal head score=2) + (Lack of vacuole score=3) + (Normal base score=1) = (Total score=6) for a morphologic "normal top" spermatozoon, calculated with the major criteria affecting the outcome of ICSI. We take into account the normalcy of head size and shape, the base of the head, and the lack of vacuoles. Our scoring of three classes of injected spermatozoa revealed a statistically significant difference in fertilization rate: 39 out of 46 (84%), 94 out of 128 (73%), and 27 out of 44 (61%), respectively. Our examination of the contribution of maternal age in correlation to sperm score revealed a distinction between oocytes originating from women younger than 30 years and oocytes from women aged 30 years and older. Conclusion(s) Our suggested classification provides allows the best spermatozoon to be chosen for ICSI, particularly for oocytes from women aged 30 years and older.

Although its occurrence is rare, the presence of large headed or macrocephalic spermatozoa and increased chromosomal abnormality has recently been reported by several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was performed with samples containing macrocephalic spermatozoa, lower fertilization and implantation rates result in poor clinical outcome. In order to evaluate the impact of preimplantation genetic diagnosis (PGD) on implantation and ongoing pregnancy rates in these couples, the results of 23 PGD cycles were compared with non-PGD cycles (n = 60) as well as cycles with absolute teratozoospermia (having zero normal morphology) with (n = 14) or without PGD (n = 66). Out of 82 embryos biopsied in the macrocephalic sperm group, abnormalities were detected in 46.4% of the embryos analysed. Most of the abnormalities were trisomies (37.0%) and complex aneuploidies (51.9%). A 33.3% pregnancy rate was achieved by selectively transferring euploid embryos after PGD with the statistically higher implantation rate of 25.0% compared with non-PGD cycles (IR: 12.3%, P < 0.01). Moreover, only one missed abortion (14.3%) was observed in the PGD group, whereas seven of the 15 pregnancies resulted in abortion in the non-PGD group (46.7%). Preliminary results indicate that patients should be counselled for increased chromosomal abnormality and a possible beneficial effect of eliminating chromosomally abnormal embryos with PGD on a bortion rates.

BACKGROUND: Retrospective cohort study to evaluate differences in outcome when embryo transfer was performed either on day 2– 3 (cleavage stage, CS-group) or on day 4– 5 (blastocyst stage, BS-group). METHODS: A total of 1259 consecutive cycles yielding 500 live born babies performed at a single centre in Bregenz, Austria, were included. Main outcome measures were implantation and (multiple) pregnancy rates and neonatal outcome including birth defects. RESULTS: Total Pregnancy rate was 44% vs 28% ( P< 0.001) and the total ‘take home baby rate’ was 37% vs 22% in the BS-group and the CS-group, respectively. Rate of multiple gestations (34% vs 17%, P 5 0.001) was significantly higher among the BS-group, resulting in a higher rate of preterm deliveries