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Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer.

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.

Adult↗

Comparative analysis of in vitro fertilization methods for establishing successful embryo transfer clinics.

A review of the laboratory methods and embryo transfer procedures used by seven of the foremost clinics in the world are discussed and evaluated in this article. Based on these facts an in vitro fertilization clinic was launched in 1983. In the second part of the paper the latest laboratory methods, i.e. ovulation induction plans and the embryo transfer technique of Tygerberg Hospital, are described. One hundred and thirty laparoscopies were performed since 1 May 1984-30 November 1984. Six hundred and one follicles were aspirated, 482 oocytes were obtained, 84% of all oocytes were fertilized, 112 patients reached the transfer stage and 28 pregnancies resulted. A clinical pregnancy rate of 21,4% per transfer and 18,5% per laparoscopy resulted.

Blood↗

The incidence of multiple gestations after in vitro fertilization is dependent on the number of embryos transferred and maternal age.

OBJECTIVE: To determine if the incidence of multiple gestations after IVF differs significantly depending on the number of embryos transferred and maternal age. DESIGN: Retrospective analysis of IVF database. SETTING: Tertiary care academic center. PATIENTS: One thousand eight hundred sixty-seven patients undergoing IVF with up to four embryos transferred during 1986 through 1993. MAIN OUTCOME MEASURES: The rate of singleton and multiple gestations > 20 weeks estimated gestational age (EGA). RESULTS: The incidence of triplet gestations > 20 weeks EGA among patients < or = 34 years of age with three versus four embryos transferred was 0.3% (1/335) versus 2.4% (15/662), respectively. The incidence of twin gestations > 20 weeks EGA among patients < or = 34 years of age with two versus four embryos transferred was 1.3% (3/234) versus 7.4% (46/622), respectively. Also among patients < or = 34 years of age, the incidence of singleton gestations > 20 weeks EGA with two versus three embryos transferred was 12.8% (30/234) versus 15.8% (53/335); with two versus four embryos was 12.8% (30/234) versus 17.2% (107/622); and with three versus four embryos was 15.8% (53/335) versus 17.2% (107/622), respectively. CONCLUSIONS: In women < or = 34 years of age undergoing IVF-ET, the transfer of four versus three and four versus two embryos significantly increased the incidence of triplet and twin gestations, respectively, without significantly improving the chance of singleton conception. This implies that a policy of transferring only three embryos should be considered in this age group (realizing that such a policy may merit modulation if pretransfer embryo selection is used.).

Adult↗

A postal survey of embryo transfer practice in the UK.

In this postal survey a questionnaire was sent to all unit directors in the UK to determine their attitudes to the factors influencing embryo transfer practice. They were requested to rate each step on a scale of 1-10, where 1 was irrelevant and 10 very important. A total of 80 practitioners from 40 units replied. Over 50% of the corresponding practitioners were consultants, 33% were middle-grade clinicians, and 12% were infertility nurse specialists. The factor that got the highest rating was the need for a standardized protocol for all unit staff regarding embryo transfer technique. The second critical factor voted by the respondents was the presence of blood on the embryo transfer catheter. Not touching the uterine fundus was deemed to be the third most important factor while the type of embryo transfer catheter used was a very close fourth. Prolonged bed rest following embryo transfer was voted the least important factor to influence the outcome. The wide variations in practice and choice of catheters encountered in this survey are indications of the divided opinion and lack of concrete evidence on which to base any firm decisions. The need for large clinical studies to assess clearly whether higher pregnancy rates will result from modifications in embryo transfer practice is highlighted.

Data Collection↗

Multiple attempts at embryo transfer: does this affect in-vitro fertilization treatment outcome?

In this study, we retrospectively analysed data from 877 patients who had 1204 embryo transfer procedures following in-vitro fertilization (IVF) at Midland Fertility Services, UK, between January 1991 and December 1995 to investigate the factors contributing to failure of embryo transfer at first attempt and the impact of immediate retransfer of retained embryos on the treatment outcome. Embryos were significantly more likely to be retained when the embryo transfer catheter was contaminated with mucus (3.3 versus 17.8%, P = 0.000001) or blood (3.3 versus 12%, P = 0.00001) and when the transfer procedure was difficult compared with when it was easy (20.3 versus 0.8%, P = 0.00001). There was no significant difference in the clinical pregnancy rate between those who had all their embryos transferred at the first attempt (24.7%) and those who required more than one attempt (23.2%). The types of embryo transfer catheter used in the unit did not show any difference in terms of embryo retention. Although we recommend aspiration of cervical mucus in order to reduce the rate of retained embryos, there is no evidence from our study to suggest that pregnancy rate is compromised when embryos are retained, provided they are discovered and immediately retransferred into the uterine cavity. Immediate retransfer is more convenient to the patients and reduces the laboratory workload without compromising the treatment outcome.

Adult↗

Analysis of the incidence and risk factors associated with ectopic pregnancy following in-vitro fertilization and embryo transfer.

Ectopic pregnancy is a well known complication of in-vitro fertilization (IVF) and embryo transfer. From March 1983 to December 1993, 3000 clinical pregnancies were achieved at Bourn Hall Clinic, including 135 ectopic pregnancies (4.5%). Of these ectopics 20 were heterotopic, eight ovarian, six bilateral tubal and the remainder were singleton tubal pregnancies. The main risk factor identified in the series was a history of pelvic inflammatory disease (P < 0.001). The data also showed that ectopic pregnancy is at present more prevalent among patients in whom tubal damage is the reason for treatment. There was slight statistical evidence (P = 0.05) that patients having ectopic pregnancies received a higher volume of culture medium than those having normal deliveries. There was also an apparent trend (P = 0.07, not significant) that high progesterone/oestradiol ratio on the day of embryo transfer was associated with ectopic pregnancy. There was no statistical evidence of association between ectopic pregnancy and a history of ectopic pregnancy, abortion, still birth, termination of pregnancy, neonatal death, tubal surgery, ovarian stimulation protocol, plasma concentration of oestradiol, luteinizing hormone and progesterone, number of oocytes retrieved, number or quality of embryos transferred, administration of general anaesthesia for embryo transfer, and the number of patent Fallopian tubes. Awareness of the risk factors associated with ectopic pregnancy plays an important part in the early diagnosis of this potentially fatal condition.

Adult↗

Cumulus coculture and cumulus-aided embryo transfer increases pregnancy rates in patients undergoing in vitro fertilization.

OBJECTIVE: To evaluate the effect of the use of cumulus-aided embryo transfer on pregnancy rates. To study the proximity of expanded cumulus cells to the developing embryo. To document by light microscopy the anchoring of day 3 to day 4 embryos by the expanded cumulus cells. To demonstrate by transmission electron microscopy the cellular activity of the expanded cumulus cells. To evaluate the expression of growth factors (vascular endothelial growth factor, interleukin-6, insulin-like growth factor I) that are secreted by the cumulus cells. DESIGN: A comparative study of a group of women undergoing cumulus coculture and cumulus-aided embryo transfer, with those who underwent cumulus coculture but did not undergo cumulus-aided embryo transfer. The endpoint was the achievement of pregnancy. SETTING: Department of Infertility Management and Assisted Reproduction, Jaslok Hospital and Research Centre, Mumbai, India. PATIENT(S): Five hundred seventeen women undergoing treatment for infertility using intracytoplasmic sperm injection and embryo transfer and fulfilling set criteria. To validate our initial results, we conducted a similar study on 208 women where randomization was performed. INTERVENTION(S): Embryos were cocultured with the patient's own cumulus cells and were transferred into the uterus with approximately 30 microL of the expanded cumulus cells. MAIN OUTCOME MEASURE(S): Pregnancy, implantation, and multiple gestation rates. RESULT(S): Our study demonstrated a significant increase in the implantation rate in the study group (group A) of 25.6% versus 14.5% in the control group (group B) and a significant increase in the pregnancy rate in the study group (group A) of 47.6% versus 34% achieved in the control group (group B). Although the incidence of multiple gestation was similar (38.6% in the study group and 32.9% in the control group), the higher-order multiple gestation rate was significantly more in the study group as compared with the control group (18.1% vs. 2.4%). Similar pregnancy and implantation rates were observed in the randomized study. CONCLUSION(S): This study demonstrates the efficacy of cumulus-aided embryo transfer, using autologous cumulus cells. It indicates a significant increase in implantation and pregnancy rates. The results suggest that cumulus cells play an important role in embryonic development, and that they may provide a mechanism to improve embryo-uterine adhesion by physical proximity, and by secreting cytokines and growth factors required to aid the implantation process.

Adult↗

Risks of transmissible diseases in relation to embryo transfer.

Realizing the potential of Embryo transfer (ET) for rapid, cheap and widespread dissemination of genetic material, the risk of transmission disease through the embryos must be considered. The aim of this paper is to evaluate theses risks at each step of production, storage and transfer. The pathogen agent may potentially originate from the donor male (semen) or the donor female (oocytes, embryos) and finally from the environmental conditions. As the differences between in vivo and in vitro derived embryos have been well described, evaluation of the potential risks should be assessed separately for in vivo and in vitro produced embryos. Even if this paper insist on the diseases or diseases agents that are more questionable, it clearly appears that ET remains the more safety way to transfer gene, provided prevention measures are properly handled (use of donor that are specific pathogen free, washing of embryos, additional treatment...) and furthermore it can be easily seen as the best way to prevent some disease transmissions (TSEs, leukosis, foot-and-mouth disease...).

Animal Diseases↗

Rederivation of transgenic and gene-targeted mice by embryo transfer.

Research on genetically engineered mice provides insights into the etiology, therapy, and genetic basis of human diseases. An important variable that affects the results of mouse studies is the health status of the animals. Pathogen burdens may confound observations and obscure underlying mechanisms. Mouse resource centers frequently rederive infected mouse strains. We review our experience on the use of a well-established technique, embryo transfer to rederive infected mouse strains. The following mouse pathogens were eliminated by embryo transfer: Mouse Parvovirus, Mouse Hepatitis Virus, Mouse Rotavirus, Mouse Encephalomyelitis Virus, Mouse Adenovirus, Helicobacter species, endoparasites, and ectoparasites. We rederived transgenic mouse lines, gene-targeted mouse lines, and lines with spontaneous mutations. In the majority of strains, fertilized eggs for embryo transfer were obtained by mating superovulated egg donors with males of the desired genotype. A total of 309 embryo transfers were performed to rederive 96 mouse strains. The pregnancy rate was 76%; 1996 pups were born, of which 43% carried the desired genotype. We performed 44 additional embryo transfers to rederive 15 other strains. The pregnancy rate was lower (45%) and none of the 135 pups carried the desired genotype. Although we successfully eliminated the pathogens in all transfers, we were unable to obtain pups with the desired genotype in 15 of 111 mouse lines. Multiple factors affect the efficiency of rederivation by embryo transfer. They include the response to superovulation by embryo donors, the number and age of stud males, the yield of fertilized eggs, the number of embryo transfers, and genotyping.

Animals↗

Assessment of hamster blastocysts derived from eight-cell embryos cultured in hamster embryo culture medium-2 (HECM-2): cell numbers and viability following embryo transfer.

The viability of hamster blastocysts, cultured from the eight-cell stage using hamster embryo culture medium-2, was examined by embryo transfer. Approximately 15-20 cultured hamster blastocysts were surgically transferred unilaterally to uterine horns of pseudopregnant recipient hamsters that had been mated to vasectomized males 3 days previously. Control recipients received in vivo developed, freshly recovered eight-cell embryos or blastocysts on day 2 or 3 of pseudopregnancy, respectively. Of the successful embryo transfers, the experimental group (receiving cultured blastocyts; n = 10) gave 51.8% implantations and 28.2% live pups. These values were closely similar to those of the controls; the percentages of control implantations and offspring were 51.1 and 34.0%, respectively, for eight-cell embryo transfer (n = 7, P greater than 0.69) and 48.5 and 28.9% for blastocyst transfer (n = 6, P greater than 0.52). To evaluate the quality of cultured hamster blastocysts, the following two parameters were examined. (1) The mean number of cells per blastocyst was 24.4 +/- 0.7 for cultured blastocysts. This value was similar to that (range, 14-24) obtained in this laboratory for in vivo developed freshly recovered blastocysts. (2) Oxygen consumption analysis revealed that cultured blastocysts actively respired at a level close to that observed with freshly recovered eight-cell embryos (slopes of oxygrams: 0.25 and 0.26, respectively). From these results, it is concluded that hamster blastocysts, cultured from the eight-cell stage, are (a) qualitatively similar to freshly recovered in vivo developed blastocysts and (b) biologically viable as revealed by the production of live offspring upon embryo transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Embryo transfer under ultrasound guidance improves pregnancy rates after in-vitro fertilization.

Between October 1998 and January 1999, we examined the influence of ultrasound guidance in embryo transfer on pregnancy rate in 362 patients from our in-vitro fertilization (IVF)-embryo transfer programme. These patients were prospectively randomized into two groups: 182 had ultrasound-guided embryo replacement, and 180 had clinical touch embryo transfer. There were no statistically significant differences between the two groups with respect to age, cause of infertility and in the characteristics of the IVF cycle. The pregnancy rate was significantly higher among the ultrasound-guided embryo transfer group (50%) compared with the clinical touch group (33.7%) (P < 0.002). Furthermore, there was also a significant increase in the implantation rate: 25.3% in the ultrasound group compared with 18.1% in the clinical touch group (P < 0.05). In conclusion, ultrasound assistance in embryo transfer significantly improved pregnancy and implantation rates in IVF.

Adult↗

Abdominal ultrasound-guided embryo transfer improves clinical pregnancy rates after in vitro fertilization: experiences from 330 clinical investigations.

PURPOSE: To investigate the effect of ultrasound-guided embryo transfer on the rate of implantation and clinical pregnancy. METHODS: A prospective randomized trial was performed to compare ultrasound-guided embryo transfer with the traditional method. A total of 330 patients were randomly divided into two groups on the day of embryo transfer. For the cases (n = 178), ultrasound-guided was used; controls (n = 152) was performed using routine methods. RESULTS: The rate of implantation and clinical pregnancy for the cases (19.6 and 37.1%, respectively) was significantly higher than for the controls (12.6 and 25%, respectively; p < 0.05). CONCLUSION: Ultrasound-guided embryo transfer can significantly increase the rate of implantation and clinical pregnancy, and should be recommended as a routine procedure in the process of in vitro fertilization and embryo transfer (IVF-ET).

Abdomen↗

Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers.

BACKGROUND: To reduce the twin pregnancy rate, elective single embryo transfer (eSET) is increasingly implemented. Improvement of the results obtained with eSET can be achieved by better selection of the most viable embryo. This study investigated the predictive value of early cleavage (EC) as an additional parameter for selecting the embryo with the highest implantation potential by using data from SET's. METHODS: Data from 165 SET's were retrospectively evaluated. Cleavage to the 2-cell stage was determined 23-26 h after injection or 25-28 h after insemination. Selection of the embryo to be transferred was based on cell morphology and cell number on the day of transfer, not on the EC status. Additional information on the predictive value of EC on developmental potential was obtained by analysing 253 transfers with two embryos (double embryo transfer, DET) and blastocyst formation of 1160 surplus embryos. Logistic regression was used to determine the predictors of pregnancy or blastocyst development. RESULTS: A significantly higher pregnancy rate was observed after transfer of single EC embryos compared to single non-EC embryos (46 versus 18%). This result was confirmed by the significantly higher pregnancy rate after DET with two EC embryos as compared to DET with two non-EC embryos (45 versus 25%) and the blastocyst formation of EC embryos compared to non-EC embryos (66 versus 40%). Logistic regression showed that EC is an independent predictor for both pregnancy and blastocyst development in addition to cell morphology and cell number. CONCLUSIONS: In order to improve the selection of the embryo with the highest implantation potential, selection for transfer should not be based on cell number and morphology on the day of transfer alone, but also on early cleavage status.

Adult↗

Transvaginal intratubal embryo transfer: a new treatment of male infertility.

Intratubal embryo transfer is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in-vitro fertilization (IVF) is performed and embryos are transferred into the Fallopian tube transvaginally. In comparison with gamete intra-Fallopian transfer (GIFT), fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information, especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube, embryonic development occurs in the physiological milieu of the oviduct. Transvaginal intratubal embryo transfer was performed in 95 patients with male factor infertility. In 29 cases (31%), a pregnancy was achieved. One abortion, but no ectopic pregnancy was observed. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility.

Embryo Transfer↗

Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.

OBJECTIVE: To evaluate the use of maximal implantation potential (MIP) point in conjunction with a 3D/4D ultrasound in order to facilitate embryo transfers and potentially improve pregnancy rate. DESIGN: Retrospective, observational study. SETTING: IVF Center. PATIENT(S): Between October 1, 2002, and August 27, 2004, 1,222 patients who underwent 3D/4D-ultrasound guided embryo transfers. INTERVENTION(S): Ultrasound-guided embryo transfer using a 3D/4D ultrasound machine and the MIP point. MAIN OUTCOME MEASURE(S): Procedure feasibility with improved visibility. RESULT(S): Embryo transfers were performed at the MIP point and the pregnancy rate was 36.66% (average patient age, 37.6 years). Physicians reported improved visualization and a greater accuracy in the placement of embryos within the uterine cavity. CONCLUSION(S): The MIP point can be immediately identified and individualized for each patient. Embryo transfers at the MIP were associated with good implantation and pregnancy rates.

Embryo Implantation↗

Autoimmune disorders: another possible cause for in-vitro fertilization and embryo transfer failure.

This study was undertaken to investigate the role of autoantibodies in association with in-vitro fertilization (IVF) and embryo transfer failure. Anticardiolipin, lupus anticoagulant, anti-deoxyribonucleic acid and antinuclear antibody, rheumatoid factor and antithyroid antibody concentrations were measured. The study group comprised 50 IVF patients with three or more previously failed cycles after embryo transfer. The control group comprised 80 computer-matched women: 40 who had conceived and delivered following three or less IVF and embryo transfer cycles, and 40 who were healthy nulligravidas. The incidence of autoantibodies in the study group was 22.0%, compared with 2.5% in the IVF control group (P < 0.05) and 7.5% in the nulligravida group (P < 0.05). In the study group, no statistical difference was found between the patients with unexplained infertility and those with mechanical infertility (23.0 and 20.8% respectively). The high occurrence of autoantibodies found in patients who failed at least three IVF and embryo transfer cycles could imply that these autoantibodies may be one of the possible causes of IVF failure in either mechanical or unexplained infertility. Further investigations are required to indicate the autoantibody profile as part of the work-up after three or more failed IVF and embryo transfer attempts.

Adult↗

Cleavage stage versus blastocyst stage embryo transfer in assisted conception.

BACKGROUND: Despite numerous advances in the field of in vitro fertilisation (IVF), many of the widely applied embryo culture techniques and resulting implantation rates have remained relatively unchanged since the first treatment was performed in the mid 1970's. Recent advances in the understanding of nutrient requirements of embryos, have led to a renaissance of extending their culture from the standard procedure of 2-3 days (early cleavage embryo transfer) to 5-6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Numerous reports on the clinical benefits of blastocyst culture have led to the worldwide introduction of this technique, despite a deficiency of conclusive evidence to do so. OBJECTIVES: Primary: To determine if blastocyst stage embryo transfers (ET's) result in higher success rates, than cleavage stage embryo transfers. Secondary: To assess the overall embryo utilisation rate of both techniques. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 29 trials that were identified, ten trials met the inclusion criteria and were reviewed. Primary outcomes were rates of; live birth, clinical pregnancy and implantation per woman. Secondary outcomes were rates of; miscarriage, monozygotic twinning, embryo freezing, embryo utilisation, cancellation, multiple pregnancy and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: There was no significant difference between the two treatment groups in live birth rate, although this was reported by only one quasi-random trial (Peto OR 1.59, 95% CI 0.80, 3.15). There was also no evidence of a difference in pregnancy rate (both overall and subgroups) between the two groups for pregnancy rate per couple randomised (4 RCTs: Peto OR 0.86, 95% CI 0.57, 1.29). There was also no suggestion of an overall difference in implantation rates per embryo's transferred although it was impossible to calculate valid confidence intervals from published data (Day 2/3 17.1% vs Day 5/6 18.9%). The subgroup of sequential media trials suggested higher implantation rate for blastocyst transfer (Day 2/3 22.6% vs Day 5/6 32%). The miscarriage rate was no different between the two groups (1 RCT, Peto OR 1.66, 95% CI 0.41, 6.81). The RCTs reporting embryo freezing showed no difference (Peto OR 1.71, 95% CI 1.00, 2.94), however the two quasi-random trials showed a significant difference in favour of the Day 2/3 group (Peto OR 2.99, 95% CI 1.88, 4.75). Embryo transfer cancellation rates were significantly higher in the Day 5/6 group (5 RCTs: Peto OR 0.57, 95% CI 0.40, 0.83). There was no significant difference in the rate of multiple pregnancies or the rate of high order pregnancies (3 RCTs, Peto OR 0.58, 95% CI 0.30, 1.12)(2 RCTs, Peto OR 7.88, 95% CI 0.49, 126.30 respectively). REVIEWER'S CONCLUSIONS: Overall this review of the best available evidence based on data from randomised controlled trials, suggests that to date little difference in the major outcome parameters has been demonstrated between early embryo transfer and blastocyst culture. Collectively, the increase in cancellation and the possible decrease in cryopreservation rates suggest that the routine practice of blastocyst culture should be offered to patients with caution. The subgroup of trials employing sequential media, did however demonstrate a substantial improvement in implantation rates and similar pregnancy rates, despite the transfer of less embryos. Whether this trend will culminate in convincing higher live birth rates per woman, has yet to be validated.

Blastocyst↗

Successful embryo transfer in a small dasyurid marsupial, Sminthopsis crassicaudata.

A technique for the transfer of early embryos from the uterus of donors to recipient females of a small dasyurid marsupial, Sminthopsis crassicaudata , is described. When the recipients were killed 3 to 5 d later, a few expanded blastocysts were found to be present in the uteri of most of the females provided that corpora lutea were present in the ovaries. This study demonstrates successful embryo transfer in a small marsupial species and supports the view that secretion of the endometrium due to luteal activity may be necessary for development of the expanded unilaminar blastocyst stage.

Journal Article↗