A uterine ultrasonographic scoring system as a method for the prognosis of embryo implantation

Purpose : The objective of the present study was to evaluate an ultrasonographic uterine scoring system as a method for the prognosis of embryo implantation in patients submitted to ICSI. Methods : A total of 562 patients submitted to an ICSI program were prospectively evaluated on the day of hCG administration in terms of the following ultrasonographic uterine parameters: A. Endometrial thickness (<7.0 mm = 0; 7 a 14 mm = 3; 14 mm = 1); B. Endometrial layering (three lines = 2; absence of three lines = 0); C. Myometrial contractions in 2 min (<3 = 0; 3 = 3); D. Uterine artery Doppler flow (>3 = 0; 2.2 a 3 = 2; 2.19 = 3); E. Endometrial power Doppler (The endometrium was divided into four equal quadrants and classified as grade I = 1; II = 2; III = 3; IV = 4, according to the visualization of the power Doppler in the quadrants). The colour Doppler signal was considered to be positive when it reached at least the basal layer of the endometrium; F. Myometrial power Doppler (absent = 0; weakly present = 2; strongly present = 3); G. Myometrial echogenicity (homogeneous = 2; inhomogeneous = 0). The patients were divided into 4 groups according to total score: Group I, score <10; Group II, score 10–14, Group III, score 15–17 and Group IV, score 18–20. Results : The uterine parameters using an ultrasonographic scoring system are inversely correlated with patient age (p < 0.0001). The number of days of stimulation with FSH did not differ (p = 0.10) between groups. The number of follicles measuring 16 mm was different (p = 0.01) between groups. The number of metaphase II oocytes also did not differ significantly between groups (p = 0.45). The fertilization rate was also similar (p = 0.10) for all groups. The number of transferred embryos was different between groups (p = 0.02). The rate of embryo implantation did not differ (p = 0.60) between groups. Finally, the pregnancy rates did not differ significantly (p = 0.93) between groups. Conclusions : The ultrasonographic evaluation of uterine parameters on the day of hCG administration using a scoring system is inversely correlated with patient age. In the present study, the use of this ultrasonographic score method could not identify a population with greater uterine receptivity.     

Clinical experiences of ICSI-ET thawing cycles with embryos cryopreserved at different developmental stages

Purpose: The aim of our study was to analyze factors including survival, implantation and pregnancy rate, patients’ age and BMI, abortions and extra uterine pregnancies that might influence the outcome of ICSI-ET thawing cycles.Methods: A total of 147 cycles with embryos cryopreserved at different developmental stages were retrospectively evaluated.Results: No difference was found in the survival, implantation and pregnancy rates of embryos cryopreserved on Day 2–3 and 5. However, in the pregnant group significantly higher implantation rate was observed with Day 5 blastocysts then with Day 2 or 3 early embryos. We found no difference in the number of abortions and extra uterine pregnancies between fresh and frozen ICSI-ET cycles. Higher BMI was found in the pregnant than in the non-pregnant group. However, the age of patient had no effect on the results.Conclusions: Developmental stage of embryo and patients’ BMI influences the success of ICSI-ET thawing cycles.     

A prospective randomized study to compare four different mineral oils used to culture human embryos in IVF/ICSI treatments

Objective(s)

We aimed to evaluate and compare the embryo quality at early cleavage stages using different oils overlaying media to culture human embryos during IVF/ICSI treatments.

Study design

A total of 500 IVF/ICSI treatments from 500 women were analyzed in a prospective randomized study. Oocytes/embryos were treated into microdroplets of appropriate media overlaid with (i) Mineral Oil (CryoBioSystem, L’Aigle, France) (group 1, n = 129), (ii) Liquid Paraffin (Medicult, Lyon, France) (group 2, n = 126), (iii) Nidoil (Nidacon International, Guthenburg, Sweden) (group 3, n = 126) and (iv) Ovoil (Vitrolife, Kungsbacka, Sweden) (group 4, n = 119). Comparisons between groups were done using two by two post hoc tests, with 5% significance. The primary endpoint was the embryo quality, defined as good or top quality when embryos were with (i) less than 20% of fragmentation and (ii) 3–5/4 cells at day 2 or 6–10/8 cells at day 3, respectively.

Results

At day 2, the embryo quality was similar in all groups. However, the mean number of top quality embryos at day 3 was statistically higher into the group 4 (1.4 ± 1.8) compared to the group 1 (0.9 ± 1.0; p = 0.03) and 2 (0.8 ± 1.3; p = 0.05). Furthermore, a significant increase of the mean number of good quality embryos was observed at day 3 into the group 4 (2.6 ± 2.6) compared to the group 1 (1.6 ± 1.6; p = 0.02).

Conclusion(s)

The embryo quality could be modified according to commercial oils used to overlay culture media.     

Elevated basal FSH and embryo quality: lessons from extended culture embryos

Background  The relationship between elevated basal FSH and embryo quality remains a topic of heated discussion among practitioners of ART. Some authors suggest a negative effect of raised FSH on the quality of embryos and therefore on IVF treatment outcome. We postulate that women with elevated FSH who respond well to ovarian stimulation and have embryos to transfer, have the same chance of conceiving like women of a similar age with normal FSH. To test this hypothesis, we studied women with elevated basal FSH who made enough embryos to qualify for blastocyst culture and day 5 embryo transfer. Methods  Analysis of data collected prospectively, on women age 25–43 years, who underwent IVF between January 2005 and December 2006. The women were divided into: those with high FSH (≥10 IU/L) and women with normal FSH (<10 IU/L). We analysed data to show treatment outcome in the two groups, following embryo transfer on day 3 and after transfer on day 5. Outcome measures include number of oocytes retrieved, number of embryos available, implantation rate, pregnancy and live birth rate. Results  Among the 1,858 women who under-went a day 3 transfer, 1,368 had basal FSH ≤ 10 IU/L, and in 492 basal FSH was above 10 IU/L. The average number of oocytes retrieved was lower among women with elevated FSH (10.12 ± 5.6 Vs 6.16 ± 3.9). Women with a normal FSH, had a higher pregnant and live birth rate than those with elevated FSH (43.3% vs 27.9% p = 0.021) and (30.8% vs 17.6% p = 0.028) respectively. 398 women made enough embryos to qualify for extended embryo culture to blastocysts. Of these 366 had an FSH ≤ 10 IU/L and 32 had FSH > 10 IU/L. In this group, there was no significant difference in the pregnancy and live birth rates between women with elevated and those with normal FSH, (67.2% vs 65.6%) and (51.9% vs 43.8%) respectively. In this selected group of women where quantity is not an issue, the quality of embryos was same irrespective of whether the basal FSH was low or high. Conclusion  Women with elevated basal FSH who respond well to stimulation and generate a good number of oocytes / embryos have a chance of becoming pregnant and having a live birth similar to that of women of their age. Women should therefore not be denied the benefits of IVF based solely on the basal FSH level as a subset may respond well and therefore have a good chance of taking home a baby.     

A closed system supports the developmental competence of human embryos after vitrification

Purpose

Closed-system vitrification may enable the risk of contamination to be minimised. We performed three studies to compare the developmental competence of human embryos vitrified using either a closed vitrification system (CVS; Rapid-i®) or an open vitrification system (OVS; Cryo-top®).

Methods

The first study was performed in vitro using 66 zygotes previously vitrified at pronuclear stage. These were warmed and randomised 1:1 to revitrification using either the OVS or the CVS. After re-warming, embryo development and blastocyst cell number were assessed. For the second study, also performed in vitro, 60 vitrified–warmed blastocysts were randomised 1:1:1 into three groups (OVS or CVS revitrification, or no revitrification). The proportion of dead cells was assessed by staining. The third study was performed in vivo, using 263 high-grade blastocysts randomly assigned to vitrification using either the CVS (n = 100) or the OVS (n = 163). After warming, single blastocyst transfer was performed.

Results

There were no differences between the CVS and the OVS in survival rate (100 % vs. 97 %), blastulation rate (96 h: 50 % vs. 50 %; 120 h: 68 % vs. 56 %), proportion of good blastocysts (96 h: 32 % vs. 22 %, 120 h: 47 % vs. 41 %), or mean number of cells (137 vs. 138). The proportion of dead cells in blastocysts re-vitrified by CVS (31 %) was similar to that for OVS (38 %) and non-revitrification (32 %). In vivo, the implantation rate for blastocysts vitrified using the CVS (54 %) was similar to that with the OVS (53 %).

Conclusion

Our studies consistently indicate that human embryos may be vitrified using a CVS without impairment of developmental competence.     

Pregnancy outcome and live birth after IVF and ICSI according to embryo quality

Purpose: The pregnancy outcome and the chances of birth were assessed according to embryo quality after IVF or ICSI. Methods: The implantation rate (IR), the loss of gestational sacs rate (LGSR), and birth rate (BR) were determined according to the cleavage stage and the integrity of blastomeres after day-2 homogeneous embryo transfers (n = 1812). Results: The LGSR was higher after transfers of 2–3-cell or 5–6-cell embryos and was significantly increased when more than 20% of the embryo volume was fragmented in 4-cell embryos. After transfers of 4-cell embryos without fragmentation, the BR was significantly higher than the BR after transfers of 4-cell embryos with 1–20% fragmentation (16.6% vs 13.1%). The difference was the consequence of a higher IR (20.4% vs 17.3%) but also of a lower LGSR (18.9% vs 24.2%). Conclusions: Not only implantation and the ability to give a pregnancy, but also the capacity to give a live birth are dependent on the embryo quality.     

Transfer of nonselected transferable day 3 embryos in low embryo producers

OBJECTIVE: To examine the implantation potential of embryos from assisted reproductive technology cycles with low embryo production and to assess the effects of clinical variables and embryo scores (ES) on pregnancy outcome. DESIGN: Prospective clinical study. SETTING: Assisted reproductive technology unit in a tertiary medical center. PATIENT(S): From July 1998 to December 2001, 280 cycles in 229 infertile couples produced a limited number of one, two, or three embryos 3 days after oocyte retrieval and underwent fresh embryo transfer (ET). INTERVENTION(S): Embryos with two or more blastomeres were scored and transferred. MAIN OUTCOME MEASURE(S): ES and implantation rate per ET. RESULT(S): Of 863 fresh ET cycles during the study period, 32.4% (280) were low embryo producers. Among them, there were no significant differences in average ES of individual embryos in single, dual, or triple ET or in embryos obtained from patients with low or high E2 responses, or young or old age. Embryos derived from conventional IVF had a better ES than those derived from intracytoplasmic sperm injection. The clinical pregnancy rate was strongly correlated with the cumulative ES. Implantation rates were similar among and between groups, with an average rate of 15.9%. CONCLUSION(S): Embryos of low embryo producers had an inherently low implantation potential that appeared to be unrelated to the number of embryos transferred, female age, ovarian E2 genesis, or fertilization method. The cumulative ES can serve as a predictor of pregnancy.     

A scoring system for predicting recurrence of cervical cancer

An evaluation was made of factors that affect the recurrence of cervical cancer after primary surgery, these including age, clinical stage, histology, grade, involvement of uterine body, parametrium or vagina and lymph node metastases. During a period of at least 3 years, 702 of 1508 patients who underwent radical hysterectomy and pelvic lymph node dissection were studied by using a scoring system. A comparison between the group of women scored at or greater than 13 that scored less than 13 revealed that the risk of recurrence was higher in the former group. One hundred and twenty five of 702 patients found to have positive pelvic node involvement scored greater than 13, which rendered them eligible for further mangement as follows: the recurrence rate in 99 patients receiving multi-agent chemotherapy was 34.4%, compared with 65.4% in 26 patients receiving no treatment ( P < 0.01). Applying this score to other patients in planning adjuvant therapy, the recurrence rate may be reduced further. The number of patients needlessly exposed to the toxic effects of multi-agent chemotherapy may be reduced also.     

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles

ObjectiveEmbryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET).Materials and methodsThis retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis.ResultsTop-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33–1.89) and pregnancy complications (95% CI 0.12–7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05–1.22) and pregnancy complication (95% CI 1.01–1.29), respectively.ConclusionClinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.     

Vitrification of blastocysts derived from fair to poor quality cleavage stage embryos can produce high pregnancy rates after warming

Purpose

This study investigates whether certain embryos considered unsuitable for cryopreservation on day 3 might nevertheless have the potential to develop into worthwhile blastocysts that could be vitrified in the same cycle.

Methods

Retrospective study: between 2010 and 2011, embryo transfers and cryopreservation took place mainly on day 3 in our centre. Supernumerary embryos of intermediate to poor quality were reassessed on days 5/6 and any good quality blastocysts were vitrified.

Results

Out of 914 cleavage stage (day 3) embryos left in culture, 16 % were vitrified on days 5/6. Fifty blastocyst warming cycles resulted in a 76 % survival rate, 44 % clinical pregnancy rate and 39 % implantation rate. During the same time period, 213 warming cycles of good quality cleavage stage embryos rendered survival rates, clinical pregnancy and implantation rates of 97 %, 23 % and 16 % respectively.

Conclusions

Supernumerary average quality day 3 embryos should be given a second chance to be selected for cryopreservation. If blastocysts are obtained and survive vitrification, there is a good chance of implantation thus reducing embryo waste.     

The influence of early cleavage on embryo developmental potential and IVF/ICSI outcome

Purpose  

To observe whether early cleavage can be a predictor of embryo developmental potential, pregnancy and implantation rates.     

Preferable correlation to blastocyst development and pregnancy rates with a new embryo grading system specific for day 3 embryos

Purpose: To investigate the cleavage stage embryo quality by the correlation between the morphological features and blastocyst development rate to develop a new embryo grading system. Methods: A retrospective analysis, including 216 cycles of cleavage stage embryo transfer and 251 cycles of blastocyst transfer. The correlation with blastocyst development of the embryo cleavage stage, fragmentation and uniformity of blastomeres was evaluated. Results: There were significant differences in the blastocyst development rate between ≥7 cells and ≤6 cells (68.8% vs. 30.7%), <50% fragmentation and ≥50% fragmentation (51.9% vs. 25.7%), and evenly sized blastomeres and unevenly sized blastomeres (48.7% vs. 30.1%) on day 3. The new grading system defined by these 3 parameters showed a preferable correlation to the pregnancy rate. Conclusions: The new grading system specific for day 3 embryos is useful for the selection of good quality embryos and may improve the pregnancy rate.     

Effects of embryo transfer quality on pregnancy and live birth delivery rates

Background  

To analyze the effects of embryo transfer (ET) quality on clinical pregnancy (CPR) and live birth delivery rates (LBDR).     

The effects of different laser pulse lengths on the embryo biopsy procedure and embryo development to the blastocyst stage

Purpose  

A laser is commonly used to remove a blastomere from an embryo for genetic testing. The laser uses intense heat which could possibly disrupt embryo development. It is the goal of this study to test the effects of different laser pulse lengths (and consequently heat) on the embryo biopsy procedure and embryo development.     

Pathogenesis, developmental consequences, and clinical correlations of human embryo fragmentation

This narrative review summarizes the current state of knowledge about human embryo fragmentation during IVF. The clinical relevance of fragmentation is discussed and evidence supporting a central role for the oocyte in the pathogenesis of fragmentation is presented. A mechanism of fragmentation as aberrant cell division involving the cytoskeleton is described along with the novel concept of membrane instability in relation to follicular high-density lipoprotein metabolism and cholesterol transport.     

Sperm quality may adversely affect the chromosome constitution of embryos that result from intracytoplasmic sperm injection

Objective: To determine whether the high rate of chromosomal abnormalities in the embryos of an infertile couple were caused by a paternal factor that may have involved the sperm centriole.

Design: Case report.

Setting: Private IVF program.

Patient(s): An infertile couple who underwent IVF-ET because of severe male factor infertility and endometriosis.

Intervention(s): Preimplantation genetic diagnosis of chromosomal abnormalities in embryos derived from two cycles of ICSI in which the husband’s sperm was used and one in which donor sperm was used.

Main Outcome Measure(s): Preimplantation genetic diagnosis with fluorescence in situ hybridization using probes for chromosomes X, Y, 13, 16, 18, and 21, and determination of hCG levels.

Result(s): Most of the embryos derived from the cycles in which the husband’s sperm was used were chromosomally abnormal (82%), whereas all the embryos derived from the cycle in which donor sperm was used were chromosomally normal. The cycle in which donor sperm was used resulted in an ongoing pregnancy.

Conclusion(s): Paternal factors, which most likely derive from the centrosome, can contribute to numerical chromosomal abnormalities, which in turn may predispose to implantation failure.     

Choriocarcinoma diagnostic score: A scoring system to differentiate choriocarcinoma from invasive mole

Okamoto T, Nomura S, Nakanishi T, Goto S, Tomoda Y, Mizutani M. Choriocarcinoma diagnostic score: A scoring system to differentiate choriocarcinoma from invasive mole. Int J Gynecol Cancer 1998; 8 : 128–132.
The histologic diagnosis of choriocarcinoma has been reported to be one of the prognostic factors for the treatment outcome of gestational trophoblastic tumors (GTT). A scoring system, called the choriocarcinoma diagnostic score (CD score), which had been devised to differentiate choriocarcinoma from invasive mole, was reevaluated in patients with GTT treated at Nagoya University Hospital from 1964 to 1996. There were 134 cases with pathologic documentation of choriocarcinoma and 155 cases of invasive mole. Sensitivity of the CD score (ie the true positive rate for the histologic diagnosis of choriocarcinoma) was 94.0%, and specificity of the score (ie true positive rate for the histologic diagnosis of invasive mole) was 97.4%. Thus, the accuracy of the score was very high (95.8%). Seventy-two (91.2%) of 79 cases with high CD scores (10 points or more) were categorized into high-risk or very high-risk groups according to the World Health Organization (WHO) prognostic index score. This unique scoring system should be included in the management of patients with GTT.