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Background Objective Materials and methods Results Discussion Conclusion Ejaculated spermatozoa are considered to possess a higher fertilisation potential than testicular spermatozoa. In selected cases, the use of testicular spermatozoa from non‐azoospermic infertile men resulted in a higher implantation and pregnancy rate than the use of ejaculated spermatozoa.The primary objective was to compare the live birth rate and cumulative live birth rate between couples with failed intracytoplasmic sperm injection procedure using ejaculated spermatozoa who subsequently had an intracytoplasmic sperm injection cycle with testicular spermatozoa and those who subsequently had an intracytoplasmic sperm injection cycle with ejaculated spermatozoa. The secondary objective was to determine the indications for the use of testicular spermatozoa after intracytoplasmic sperm injection failure with ejaculated spermatozoa.A retrospective study of matched couples using propensity score matching analysis was performed. After an intracytoplasmic sperm injection failure (cycle_1), intracytoplasmic sperm injection with either ejaculated spermatozoa (ejaculated sperm group), or testicular spermatozoa (testicular sperm group), was performed (cycle_2). The matching was on intracytoplasmic sperm injection performed in cycle_1 according to spermatozoa used (testicular or ejaculated) in cycle_2. Logistic regression was used to evaluate the influence of sperm origin on cumulative live birth rate. Univariate analysis on parameters of cycle_1 was used to identify the prognostic factors to propose an intracytoplasmic sperm injection with testicular spermatozoa in case of cycle_1 failure. The study outcomes were live birth rate and cumulative live birth rate.Among the 6034 couples available, 63 were selected to constitute the testicular sperm group and 63 were selected by propensity score matching to constitute the ejaculated sperm group. After matching, the DNA fragmentation index was higher in the testicular sperm group (13.43% ± 9.65% vs. 8.93% ± 4.47%, p = 0.013); no significant difference was observed for the fertilisation rate, the number of obtained embryos, blastulation rate and frozen embryo rate. In cycle_2, the live birth rate was higher in the testicular group (22.2% vs. 0.0%, p < 0.001), as was the cumulative live birth rate (25.4% vs. 6.3%, p = 0.065). The prognostic factors identified for the proposal of intracytoplasmic sperm injection procedure with testicular spermatozoa after intracytoplasmic sperm injection failure with ejaculated spermatozoa were: teratozoospermia, cryptozoospermia and high DNA fragmentation index.According to the present study and current knowledge, the use of testicular spermatozoa after failed intracytoplasmic sperm injection procedure in non‐azoospermic men could be proposed instead of sperm donation in case of high sperm DNA fragmentation index, cryptozoospermia and teratozoospermia. A good oocyte response to ovarian stimulation during the previous assisted reproductive technology attempt will increase the chance of success. Although the main limitation of the current study is its retrospective nature, the use of the propensity score matching to perform causal inference study increases its reliability.The present study supports that the use of testicular spermatozoa outside the classical indication of azoospermia is a good option when the indication is well established. However, before proposing a testicular biopsy, an improvement in sperm characteristics should be considered by treating the causes of sperm alteration. [ABSTRACT FROM AUTHOR]

Collaboration between doctors and psychologists in the psychological support of patients seems to be a natural process at the moment, and is particularly important in the context of Assisted Reproductive Technology (ART) with gamete donors. Indeed, the psychological stress felt by patients can have a negative impact on the ART outcome. Psychological support can help address issues that are not discussed during the medical consultation. Psychological support is all the more important in that patients need to be aware of the process they are embarking on and the consequences it will entail. The psychologist will be able to work on the mourning of the dream journey, and enable acceptance of this new mode of conception. Psychological support for patients undergoing ART with gamete donors brings added value to the medical process, and could improve the effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work was to construct shallow neural networks (SNN) using time‐lapse technology (TLT) from morphokinetic parameters coupled to assisted reproductive technology (ART) parameters in order to assist the choice of embryo(s) to be transferred with the highest probability of achieving a live birth (LB). Methods: A retrospective observational single‐center study was performed, 654 cycles were included. Three SNN: multilayers perceptron (MLP), simple recurrent neuronal network (simple RNN) and long short term memory RNN (LSTM‐RNN) were trained with K‐fold cross‐validation to avoid sampling bias. The predictive power of SNNs was measured using performance scores as AUC (area under curve), accuracy, precision, Recall and F1 score. Results: In the training data group, MLP and simple RNN provide the best performance scores; however, all AUCs were above 0.8. In the validating data group, all networks were equivalent with no performance scores difference and all AUC values were above 0.8. Conclusion: Coupling morphokinetic parameters with ART parameters allows to SNNs to predict the probability of LB, and all SNNs seems to be efficient according to the performance scores. An automatic time recognition system coupled to one of these SNNs could allow a complete automation to choose the blastocyst(s) to be transferred. [ABSTRACT FROM AUTHOR]

Objective: To assess human papillomavirus (HPV) prevalence and distribution among French women with normal and pathologic cytology findings.Methods: A genomic DNA microarray assay enabling the detection of 35 different HPV genotypes was used for in vitro diagnosis, as a complement to Papanicolaou screening, to test 785 women who attended the gynecology department of a hospital in Lyon, France.Results: Pathologic and normal cytology findings were obtained for 260 (33.1%) and 302 (38.5%) of the 785 women, respectively, whereas 223 (28.4%) results were inconclusive. HPV infection and multiple infection were significantly more prevalent (P<0.001) in the population with pathologic findings (90.0% and 41.9%, respectively) than in the population with normal cytology findings (48.3% and 20.2%, respectively). Overall, the 4 most frequent HPV genotypes were HPV-16 (14.8%), HPV-53 (9.0%), HPV-31 (8.7%), and HPV-51 (7.5%), whereas HPV-18 (3.8%), HPV-6 (2.9%), and HPV-11 (0.4%) were less common. The HPV genotypes included in the quadrivalent vaccination had a prevalence of 20.6% among all women and 30.4% among those with pathologic findings.Conclusion: The present data indicate a reduced direct impact of HPV vaccination in the study population owing to a low prevalence of HPV-18 and a high prevalence of HPV-53, HPV-31, and HPV-51. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of our study was to compare the results of radical trachelectomy (LARVT or Dargent’s operation) to radical vaginal hysterectomy (LARVH) in terms of intraoperative and postoperative morbidity and mainly in terms of risk of tumor recurrence. Each technique is associated with laparoscopic pelvic lymph node dissection. Our objective was to know if performing radical trachelectomy in order to preserve the fertility of a young patient with an early cervical cancer is associated or not with an increased risk of operative morbidity or tumor recurrence. Methods: Patient affected by early invasive cervical cancer who has been submitted to LARVT (n =118) in our Institute between December 1986 and December 2003 has been compared to patients treated by LARVH (n =139) in the same period. All patient’s information, surgical and pathological data and oncological results have been prospectively collected. The associations between the discrete variables were assessed using χ 2 test with Yate’s correction when appropriate. Fisher’s exact test was used when it was necessary. Continuous variables were compared by Student’s t test. p values less than 0.05 were considered statistically significant. Statistical analysis used the Kaplan–Meier method to calculate disease-free and overall survival. Results: Between December 1986 and December 2003, 118 and 139 patients have undergone LARVT and LARVH, respectively, for FIGO stage I–IIA carcinoma of the cervix. The two populations (LARVT and LARVH) are comparable in terms of the main prognostic factors of cervical cancer. The rate of intraoperative complications has been similar in the two groups (2.5% for LAVRT and 5.8% for LAVRH, p =NS). Also the rate of postoperative complications has been similar in the two groups (21.2% for LAVRT and 19.4% for LAVRH, p =NS). When considering the risk of recurrence, the results in the two groups are also identical: 7 cases (5.2%) in patients treated with LAVRT and 9 cases (8.5%) in patients treated with LAVRH (p =NS). Conclusion: Our data demonstrate that early cervical cancer (less than 2 cm diameter) can be treated successfully with LARVT with similar efficacy and recurrence rates to LARVH. In our experience radical trachelectomy is a safe treatment for young women affected by early cervical cancer who want to conserve their fertility. [Copyright &y& Elsevier]

Objective: To examine sperm DNA fragmentation in semen used for assisted reproduction procedures to establish this factor’s prognostic role in fertilization rate, embryo development, pregnancy rate, and outcome. Design: Prospective study. Setting: Department of Medicine and Biology of Reproduction of the Edouard Herriot Hospital in Lyon, France. Patient(s): 322 couples, divided into 88 cycles of in vitro fertilization (IVF) or 234 cycles of intracytoplasmic sperm injection (ICSI). Intervention(s): Sperm DNA fragmentation was detected in sperm obtained 2 to 5 months before the ART procedure. Main Outcome Measure(s): Sperm DNA fragmentation was measured with the terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) technique. Result(s): There was a negative statistical correlation between the rate of fragmentation and the semen characteristics. A statistically significant negative relationship was found for sperm DNA fragmentation and fertilization when ICSI and IVF were compared. With ICSI, a statistically significant negative relationship was found between fertilization rate and percentage of sperm DNA fragmentation (DNA fragmentation index, or DFI). The risk of nontransfer due to blocked embryo development increased when the DFI exceeded 15% (18.2% for ICSI vs 4.2% for IVF) with an odds ratio of 5.05. The miscarriage risk increased fourfold when the DFI exceeded 15% (37.5% for ICSI vs 8.8% for IVF). Conclusion(s): Sperm DNA fragmentation measured 2 to 5 months before the assisted reproduction procedure was a prognostic indicator of the fertilization, pregnancy, and miscarriage rates and the pregnancy outcome. [Copyright &y& Elsevier]

: Objective:To determine the relationship between sperm DNA methylation level and sperm characteristics and pregnancy rates.: Design:Prospective study. Quantitation by image analysis of DNA methylation in sperm nucleus.: Setting:Department of Reproduction Biology, Edouard Herriot Hospital, Lyon, France.: Patient(s):Infertile couples undergoing IVF-ET.: Intervention(s):The immunostaining of 5 methyl-cytosine was performed on the spare sperm suspension that was used for an assisted reproduction technology procedure.: Main outcome measure(s):Sperm characteristics according to World Health Organization criteria, sperm motility parameters with computer-assisted semen analysis, sperm DNA methylation level, and heterogeneity index (HI).: Result(s):Sperm DNA methylation level and HI are correlated with sperm DNA characteristics. HI is negatively correlated with fertilization rate; sperm DNA methylation level is correlated with pregnancy rate.: Conclusion(s):The DNA methylation level in human spermatozoa could be a new approach to evaluating the ability of spermatozoa to fertilize and lead to normal embryo development. [Copyright &y& Elsevier]

Presents a study which used laser scanning confocal microscopy (LSCM) to observe fluorescent-labeled human preimplantation embryos. Relation of the major application of LSCM; Findings of a high level of multinucleated blastomeres from the confocal microscopy; Analysis of fresh arrested preimplantation embryos.

Cryopreservation of ovarian tissue is one of the strategies offered to girls and women needing gonadotoxic treatment to preserve their fertility. The reference method to cryopreserve is slow freezing; vitrification is an alternative method. The aim was to evaluate which of the two is the best method for human ovarian tissue cryopreservation. Each ovary was divided into three groups: (i) fresh; (ii) slow freezing; and (iii) vitrification. An evaluation of the follicular density, quality and the expression six genes (CYP11A, STAR, GDF9, ZP3, CDK2, CDKN1A) were performed. We observed no significant difference in follicular density within these three groups. Slow freezing altered the primordial follicles compared to the fresh tissue (31.8% vs 55.9%, p = 0.046). The expression of genes involved in steroidogenesis varied after cryopreservation compared to the fresh group; CYP11A was under-expressed in slow freezing group (p = 0.01), STAR was under-expressed in the vitrification group (p = 0.01). Regarding the expression of genes involved in cell cycle regulation, CDKN1A was significantly under-expressed in both freezing groups (slow freezing: p = 0.0008; vitrification: p = 0.03). Vitrification had no effect on the histological quality of the follicles at any stage of development compared to fresh tissue. There was no significant difference in gene expression between the two techniques. [ABSTRACT FROM AUTHOR]

Study Question: Should testicular sperm extraction (TESE) in non-mosaic 47,XXY Klinefelter syndrome (KS) patients be performed soon after puberty or could it be delayed until adulthood?Summary Answer: The difference in sperm retrieval rate (SRR) in TESE was not significant between the 'Young' (15-22 years old) cohort and the 'Adult' (23-43 years old) cohort of non-mosaic KS patients recruited prospectively in parallel.What Is Known Already: Several studies have tried to define predictive factors for TESE outcome in non-mosaic KS patients, with very heterogeneous results. Some authors have found that age was a pejorative factor and recommended performing TESE soon after puberty. To date, no predictive factors have been unanimously recognized to guide clinicians in deciding to perform TESE in azoospermic KS patients.Study Design, Size, Duration: Two cohorts (Young: 15-22 years old; Adult: 23-43 years old) were included prospectively in parallel. A total of 157 non-mosaic 47,XXY KS patients were included between 2010 and 2020 in the reproductive medicine department of the University Hospital of Lyon, France. However 31 patients gave up before TESE, four had cryptozoospermia and three did not have a valid hormone assessment; these were excluded from this study.Participants/materials, Setting, Methods: Data for 119 patients (61 Young and 58 Adult) were analyzed. All of these patients had clinical, hormonal and seminal evaluation before conventional TESE (c-TESE).Main Results and the Role Of Chance: The global SRR was 45.4%. SRRs were not significantly different between the two age groups: Young SRR=49.2%, Adult SRR = 41.4%; P = 0.393. Anti-Müllerian hormone (AMH) and inhibin B were significantly higher in the Young group (AMH: P = 0.001, Inhibin B: P < 0.001), and also higher in patients with a positive TESE than in those with a negative TESE (AMH: P = 0.001, Inhibin B: P = 0.036). The other factors did not differ between age groups or according to TESE outcome. AMH had a better predictive value than inhibin B. SRRs were significantly higher in the upper quartile of AMH plasma levels than in the lower quartile (or in cases with AMH plasma level below the quantification limit): 67.7% versus 28.9% in the whole population (P = 0.001), 60% versus 20% in the Young group (P = 0.025) and 71.4% versus 33.3% in the Adult group (P = 0.018).Limitations, Reasons For Caution: c-TESE was performed in the whole study; we cannot rule out the possibility of different results if microsurgical TESE had been performed. Because of the limited sensitivity of inhibin B and AMH assays, a large number of patients had values lower than the quantification limits, preventing the definition a threshold below which negative TESE can be predicted.Wider Implications Of the Findings: In contrast to some studies, age did not appear as a pejorative factor when comparing patients 15-22 and 23-44 years of age. Improved accuracy of inhibin B and AMH assays in the future might still allow discrimination of patients with persistent foci of spermatogenesis and guide clinician decision-making and patient information.Study Funding/competing Interest(s): The study was supported by a grant from the French Ministry of Health D50621 (Programme Hospitalier de Recherche Clinical Régional 2008). The authors have no conflicts of interest to disclose.Trial Registration Number: NCT01918280. [ABSTRACT FROM AUTHOR]

Abstract: Objective : Several studies have shown that lympho vascular space involvement (LVSI) and lymph node micrometastases (LNmM) may be risk factors for recurrence in early-stage cervical cancer with no apparent lymph node metastases. We performed a retrospective case-control study to reassess whether the presence of lymph node micrometastases and LVSI is predictive of subsequent recurrence following surgical resection of early-stage cervical cancer. Methods : In a series of 292 patients diagnosed with early cervical cancer and treated by the same surgical procedure (laparoscopic-vaginal radical hysterectomy) during the same time period, two paired series were selected. The first series consisted of 26 cases who recurred in a median time of 36.8 months and the second series were 26 cases matched for age, histological sub-type, surgico-pathological stage and maximal tumor diameter, who did not recur after a median follow-up of 122 months. Sections taken from the hysterectomy specimens were reassessed for LVSI. All the lymph node blocks which have initially been considered as uninvolved were submitted to serial sectioning. Immunohistochemical staining using anti-cytokeratins AE1 and AE3 was used for identifying LNmM. Results : LVSI was twice more frequent and LNmM ten-fold more frequent in the group of patients who recurred: 20/26 (77%) versus 9/26 (35%) and 11/26 (42%) versus 1/26 (4%) respectively. The relative risk of recurrence is 2.64 (1.67–5.49, P &#60; 0.01) in the presence of LVSI and 2.44 (1.58–3.78, P &#60; 0.01) in the presence of LNmM. All the patients with LNmM were LVSI positive. At bivariate analysis, the true LNmM (deposits more than 200 um in size) was the only independent risk factor. Conclusions : LNmM is an important risk factor of tumor recurrence in patients with early cervical cancer with no apparent lymph node metastases. LNmM seems to occur only in LVSI positive tumors. These data may lead to improve management of early-stage cervical cancer to reduce the risk of recurrence in those cases. [Copyright &y& Elsevier]

: ObjectiveThe aim of this work was to study and compare the tocolytic effects of rofecoxib with indomethacin, ritodrine, nicardipine and atosiban. We also studied the combination of rofecoxib with each agent.: DesignIn vitro animal experimental study.: SettingNon-selective cyclo-oxygenase (COX) inhibitors have potent tocolytic effect. However, they also have major fetal side effects that seem to be due to COX-1 inhibition. A specific COX-2 inhibitor could be a potent tocolytic agent with less fetal toxicity.: SampleMyometrial strips from pregnant Wistar rats at 18 days of gestation.: MethodsIsometric tension was recorded from 112 pregnant rat myometrial strips in vitro. Strips were exposed to increase molar concentration of one drug or combination.: Main outcome measuresContractile activity was assessed by calculating the area under the curve, to obtain a dose–response curve of each drug. EC50 and mean maximal inhibiting concentration were compared using ANOVA. Chemical interaction was defined for each combination.: ResultsThe in vitro tocolytic effect of rofecoxib was demonstrated. Contractile activity stopped at a concentration of 1.6 × 10−7 M. Effective concentrations were 1000 times less than for indomethacin and significantly lower than ritodrine and atosiban. Rofecoxib combined with ritodrine had a synergic effect. Other combinations only had an additive effect.: ConclusionsRofecoxib has a potent tocolytic effect in vitro. The high specificity and low effective concentrations of COX-2 may result in low fetal toxicity. Animal fetal side effects need to be explored. [Copyright &y& Elsevier]

The aim of this work was to construct a score issued from a machine learning system with self-improvement capacity able to predict the fate of an ART embryo incubated in a time lapse monitoring (TLM) system. A retrospective study was performed. For the training data group, 110 couples were included and, 891 embryos were cultured. For the global setting data group, 201 couples were included, and 1186 embryos were cultured. No image analysis was used; morphokinetic parameters from the first three days of embryo culture were used to perform a logistic regression between the cell number and time. A score named DynScore was constructed, the prediction power of the DynScore on blastocyst formation and the baby delivery were tested via the area under the curve (AUC) obtained from the receiver operating characteristic (ROC). In the training data group, the DynScore allowed the blastocyst formation prediction (AUC = 0.634, p < 0.001), this approach was the higher among the set of the tested scores. Similar results were found with the global setting data group (AUC = 0.638, p < 0.001) and it was possible to increase the AUC of the DynScore with a regular update of the prediction system by reinforcement, with an AUC able to reach a value above 0.9. As only the best blastocysts were transferred, none of the tested scores was able to predict delivery. In conclusion, the DynScore seems to be able to predict the fate of an embryo. The reinforcement of the prediction system allows maintaining the predictive capacity of DynScore irrespective of the various events that may occur during the ART process. The DynScore could be implemented in any TLM system and adapted by itself to the data of any ART center. Abbreviations: ART: assisted reproduction technology; TLM: time lapse monitoring system; AUC: area under the curve; ROC: receiver operating characteristic; eSET: elective single embryo transfer; AIS: artificial intelligence system; KID: known implantation data; AMH: anti-Müllerian hormone; BMI: body mass index; WHO: World Health Organization; c-IVF: conventional in-vitro fertilization; ICSI: intracytoplasmic sperm injection; PNf: pronuclear formation; D3: day 3; D5: day 5; D6: day 6; GnRH: gonadotrophin releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; hCG: human chorionic gonadotropin; PVP: polyvinyl pyrrolidone; PNf: time of pronuclear fading; tx: time of cleavage to x blastomeres embryo; ICM: inner cell mass; TE: trophectoderm; NbCellt: number of cells at t time; FIFO: first in first out; TD: training data group; SD: setting data group; R: real world [ABSTRACT FROM AUTHOR]

Background: Our study defines the clinical role of sperm DNA damage in the assisted reproductive technology procedure. Aim: To investigate if the compaction of chromatin explored added to the analysis of the sperm DNA fragmentation allows obtaining a new indicator for sperm genome quality linked to live birth rate (LBR). Design: This was a prospective study, undergoing 101 cycles in the intracytoplasmic sperm injection (ICSI) program. Materials and Methods: The sperm DNA fragmentation index (DFI) has been measured with sperm chromatin dispersion examination. The sperm decondensation index (SDI) of chromatin has been measured with aniline blue procedure; with these indexes, a new parameter has been created: DFI × SDI. Statistical Analysis: Pearson's correlation coefficient, Student's t-test, and Chi-square test were used. The quantitative variables were described as mean ± standard deviation. Multivariate logistic regressions were performed with live birth as outcome. Results: The sperm concentration, motility, and normal morphology were lower when the DFI was high (P = 0.001). The fertilization rates and the number of obtained embryos were not statistically significant different according to the DFI groups. The SDI does not appear to be linked either with the spermatic parameters or with the ICSI parameters. A low DFI seems to be a beneficial factor to obtain a live birth in ICSI procedure (P = 0.064). In case of high DFI, a high SDI allows to obtain a higher LBR than a low SDI. Conclusion: The DFI is a good prognostic for a delivery rate in ICSI procedure, and the SDI could be added to DFI to create a new parameter of sperm nuclear quality. This new parameter seems to be linked to LBR. [ABSTRACT FROM AUTHOR]

The purpose of the present multicenter study was to investigate whether an artificial insemination with donor sperm (AID) procedure after intra-couple intracytoplasmic sperm injection (ICSI) failure offers a significant chance of pregnancy and to identify prognostic factors for pregnancy after an AID procedure. An eleven-year retrospective multicenter study was conducted among 13 Centre d’Etude et de Conservation des Oeufs et du Sperme (CECOS) centers. A total of 319 couples having undergone an AID procedure after intra-conjugal ICSI failure were included in this study; a total of 1,159 AID and 1,011 intra-conjugal ICSI cycles were performed. Among the prognostics parameters, the parity and the embryo quality could not be adequately addressed, therefore the parity was not included in the statistical analysis and the embryo quality has been presented as preliminary observations. The pregnancy rate per cycle was 12.0% (139/1,159) and the overall AID pregnancy rate per couple was 43.6% (139/319). Normal or oligoasthenoteratozoospermia (OAT) semen and women aged 34 years or above at the time of AID procedure obtained the lowest AID clinical pregnancy rate. Azoospermia or cryptozoospermia semen and women aged below 34 years obtained the highest AID clinical pregnancy rate. In conclusion, the transition to the AID procedure after intra-conjugal ICSI failure allows such couples to obtain a pregnancy, however after each ART failure AID transition should be proposed according to the woman’s age and sperm characteristics.Abbreviations: AID: artificial insemination with donor sperm; ICSI: intracytoplasmic sperm injection; CECOS: Centre d’Etude et de Conservation des Oeufs et du Sperme; OAT: oligoasthenoteratozoospermia; IVF: in vitro fertilization; ART: artificial reproductive technology; β hCG: beta human chorionic gonadotrophin; SD: standard deviation; OR: Odds ratio [ABSTRACT FROM AUTHOR]

Objective: To construct an ART score to evaluate an ART procedure before the result (pregnancy or not), and to provide objective data in discussions with couples in the decision to discontinue further attempts.Study Design: A retrospective multicentrique study was performed. The ART score was constructed using data from the MediFirst© database used in our center. The development of the score was conducted on a sample of 507 in vitro fertilization cycles carried out between January 2011 and July 2011. Model calibration and determination of the discrimination capacity of the ART score were performed with 4463 cycles in our center and 1369 cycles from an external ART center. The ART score was validated temporally and geographically with clinical pregnancy and take home baby rate.Results: The ART score was obtained from data from both partners and ART procedure. The ART score was segmented into four classes depending on the clinical pregnancy rate. There was a linear relationship between the ART score and clinical pregnancy rate (r = 1.0, p < 0.001). The ART score was validated temporally and geographically.Conclusion: An objective ART score has been constructed and validated. It will be of help to ART teams and it is an objective tool to explain to a couple the choices for the next ART attempt. [ABSTRACT FROM AUTHOR]

: ObjectiveTo compare the tocolytic potency of ritodrine, nicardipine and atosiban, used alone and in dual combinations, to see whether combinations of these drugs, which act via different pathways, could improve inhibition of uterine contractility.: DesignStudy on myometrial contractility in vitro.: SettingLaboratory of physiology, Lyon, France.: SampleLongitudinal myometrial strips from non-labouring timed pregnant Wistar rats (18 gestational days).: MethodsStrips were simultaneously exposed to EC25, EC50 or EC75 of dual combinations of either ritodrine and nicardipine, ritodrine and atosiban or nicardipine and atosiban (n = 10/group). Basal contractile activity and contractile activity after addition of each combination was measured using the 10 min integral of activity. Changes were expressed as percentage from the basal 10 min integral activity. The observed percentage inhibition of activity was compared with the expected percentage inhibition in an additive pharmacological model. When no significant difference occurred, the combination was deemed simply to have an additive tocolytic effect. When inhibition of activity was significantly greater compared with the expected percentage inhibition, the combination was deemed to have a synergistic effect.: Main outcome measureChanges in integral contractile activity in response to tocolytic combinations.: ResultsRitodrine and atosiban inhibited integral activity to a greater extent than expected [e.g. using EC50: observed inhibition 88.9% (13.8%) vs expected inhibition 75%; P < 0.015]. Actual inhibition by nicardipine/ritodrine [78.55% (20.4%) vs 75%; P = n.s.] and nicardipine/atosiban [78.94% (17.8%) vs 75%; P = n.s.] was not significantly different from expected.: ConclusionsA combination of ritodrine plus atosiban exhibits a synergistic inhibition for myometrial activity, thus allowing the use of lower concentrations of each drug to achieve the same effect compared with each drug used alone. Combination of nicardipine plus ritodrine and nicardipine plus atosiban achieves only an additive effect. The potential for decreasing side effects (beta-mimetics) and costs (atosiban) when using a combination in clinical practice needs to be evaluated. [Copyright &y& Elsevier]