Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial

This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52–0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46–0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day     

Live birth rates with a freeze-only strategy versus fresh embryo transfer: secondary analysis of a randomized clinical trial

Research question

What are the roles of serum progesterone and endometrial thickness as biomarkers in the decision between a freeze-only and fresh embryo transfer in IVF for women without polycystic ovary syndrome (PCOS)?

Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials

Purpose

To examine available data from randomized controlled trials to assess if the freeze-all embryo and subsequent frozen-thawed embryo transfer (FET) results in better clinical outcomes than fresh embryo transfer (ET).

Methods

Meta-analysis.

Results

We conducted an electronic literature search on PubMed and Embase databases and manually supplemented another 2 articles from relevant citations. Seven studies were finally included in the meta-analysis,including 1141 women who underwent fresh embryo transfer and 1079 who underwent frozen embryo transfer. The results of the meta-analysis suggested that the live birth rate [RR (95% CI) 1.18 (1.08–1.30), P?=?0.0003] and clinical pregnancy rate [RR (95% CI) 1.10 (1.02–1.19), P?=?0.02] were significantly higher in FET group. Miscarriage rate [RR (95% CI) 0.62 (0.48–0.80), P?=?0.0002], and moderate to severe OHSS occurrence rate [RR (95% CI) 0.22 (0.12 to 0.39), P?<?0.00001] were significantly lower in FET group. Differences of biochemical pregnancy rate, ongoing pregnancy rate and implantation rate between the two groups did not reach the statistical significance.

Conclusions

Our results suggest that the IVF/ICSI with FET is more efficient and less risky for OHSS compared with ET. However, we should comprehensively inform patients with advantages, disadvantages and potential risks related to embryo cryopreservation, and carefully assess their fertility conditions to make the most beneficial clinical decision.

     

Age-related normogram for antral follicle count in women with polycystic ovary syndrome

Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in infertile women with polycystic ovary syndrome (PCOS) and to compare age-related decline in AFC between infertile women with and without PCOS. A retrospective cohort study was conducted. Of a total of 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th and 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear, while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages of 18 and 30. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P < 0.001). This study concludes that age-related decline in AFC among women with PCOS is slower than in those without PCOS.Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in women with polycystic ovary syndrome (PCOS), and to compare age-related decline in AFC between women with and without PCOS. A retrospective cohort study was conducted. All patients underwent a baseline transvaginal ultrasound that was performed on day 2–4 of the menstrual cycle. The total number of antral follicles of 2–9 mm in diameter was recorded. Of total 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear; while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages 18–30 years. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P < 0.001). We have concluded that age-related decline in AFC among women with PCOS is slower than in those without PCOS. Further studies are needed to determine if the AFC normogram in women with PCOS could be clinically relevant to select the optimal gonadotrophin dose for ovulation induction.     

Electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas assessed by antral follicle count: preliminary results of randomized clinical trial

Purpose  

The assessment of ovarian reserve by antral follicle count (AFC) following electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas.     

No advantage of fresh blastocyst versus cleavage stage embryo transfer in women under the age of 39: a randomized controlled study

Purpose

Is there a difference in implantation and pregnancy rates between embryos transferred electively at cleavage or blastocyst stage in infertile women ≤?38 years with at least four zygotes on day 1 post retrieval?

Methods

A randomized clinical trial was conducted in a single tertiary care hospital with a sample size of 194 patients in each arm for a total population of 388 women. Patients less than 39 years of age with more than three fertilized oocytes and less than four previous assisted reproductive technology (ART) attempts were inclusion criteria.

Results

The two groups were similar for age, years of infertility, indication to treatment, basal antimüllerian hormone and FSH, number of previous ART cycles, primary or secondary infertility, type of induction protocol, days of stimulation, total gonadotrophin dose, and estradiol (E2) and progesterone (P) levels at trigger. No statistically significant differences were found in terms of number of retrieved oocytes, inseminated oocytes, fertilization rate, canceled transfers (7.73% in blastocyst and 3.61% in cleavage stage group), and cycles with frozen embryos and/or oocytes. Although a higher number of fertilized oocytes were in the blastocyst stage group (6.18?±?1.46 vs 5.89?±?1.54, p?=?0.052), a statistically greater number of embryos/randomized cycle were transferred at cleavage stage (1.93?±?0.371) compared with the number of transferred blastocysts (1.80?±?0.56), probably due to the number of embryos not reaching blastocyst stage (3.09%). The implantation rate (28.37 vs 25.67%), pregnancy rate per cycle (36.06 vs38.66%), transfer (39.66 vs 40.11%), spontaneous abortions (19.72% vs 12.00%), delivery rate per cycle (27.84 vs 32.99%), and transfer (30.17 vs 34.22%) were not significantly different between the blastocyst and cleavage stage groups. The twin delivery rate was higher in the blastocyst stage group, although not significant (42.59 vs 28.12%). The mean numbers of frozen blastocyst (2.30?±?1.40 vs 2.02?±?1.00) and frozen oocytes (7.09?±?3.55vs 6.79?±?3.26) were not significantly different between the two groups.

Conclusions

Fresh blastocyst-stage transfer versus cleavage-stage transfer did not show any significant difference in terms of implantation and pregnancy rate in this selected group of patients. A high twin delivery rate in both groups (35.59%) was registered, and although not significant, they were higher in the blastocyst transfer group (42.59 vs 28.12%). Our conclusion supports considering single embryo transfer (SET) policy, even in cleavage stage in patients younger than 39 years with at least four zygotes.

Trial registration

ClinicalTrials.gov registration number NCT02639000

     

Ovarian stimulation for in vitro fertilization and embryo transfer, human menopausal gonadotropin versus pure human follicle stimulating hormone: a randomized prospective study

A randomized, prospective study was conducted to compare ovarian stimulation with human menopausal gonadotropin (hMG) and human follicle-stimulating hormone (hFSH) in an in vitro fertilization and embryo transfer (IVF-ET) program. Minimal inclusion criteria included age less than or equal to 37, tubal infertility, regular menstrual cycles before IVF, and a normal semen analysis. Equivalent doses (225 IU/day) of either hMG (N = 20) or hFSH (N = 20) were administered, and the patients followed by serum estradiol (E2) levels and pelvic ultrasound. Parameters related to the ovarian response to therapy, the number and quality of ova recovered, and the cycle outcome were compared in the two groups using the Student's t-test and chi-square analysis. No difference was detected between the groups in peak E2 levels (828 +/- 78 versus 819 +/- 79 in the hMG and hFSH groups, respectively), day of human chorionic gonadotropin (hCG) administration (9.3 +/- 0.3 versus 9.7 +/- 1.01), occurrence of spontaneous luteinizing hormone (LH) surge (44% versus 27%, P greater than 0.05, chi square analysis), average number of ova recovered (5.0 +/- 0.7 versus 5.6 +/- 1), ova maturation (7.5% versus 12.7% rate of immature ova), rate of normal and abnormal fertilization (9.2% versus 8.1% polyspermic fertilization), cleavage stage at transfer (3.6 +/- 0.4 versus 3.4 +/- 0.7 cells per embryos), the number of embryos transferred (2.5 +/- 0.3 versus 2.6 +/- 0.3), or the occurrence of pregnancy (1 in the hMG group and 2 in the hFSH group).(ABSTRACT TRUNCATED AT 250 WORDS)     

Day 3 versus day 5 embryo transfer: a prospective randomized study

Transfer of embryos at the blastocyst stage has been associated with exceptionally high implantation rates. There are, however, only a few prospective randomized studies comparing day 3 versus day 5 embryo transfer. Furthermore, the number of embryos replaced in the day 3 group transfer is often higher than the number of blastocysts replaced, thereby affecting implantation rates. A total of 118 patients undergoing standard IVF/intracytoplasmic sperm injection who had developed at least three 8-cell embryos showing <20% extracellular fragmentation on day 3 were randomized for day 3 or day 5 transfer. A maximum of two embryos were replaced. In this prospective, randomized study the implantation and pregnancy potential of embryos transferred on day 3 or day 5 were compared. Equal numbers of embryos were replaced in the two groups. There was no statistically significant difference between day 3 and day 5 transfer regarding positive human chorionic gonadotrophin rates (70 versus 67%), clinical pregnancy rates (61 versus 51%), implantation rates (44 versus 37%), twinning rates (42 versus 41%) and rates of early pregnancy loss (15 versus 29%). Transfer of embryos on day 3 or 5 showed similar implantation rates when equal numbers of embryos were transferred. Embryo transfer at the blastocyst stage seems to have no advantage over day 3 transfer in patients with more than two 8-cell embryos showing less than 20% fragmentation on day 3.     

Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled trials

OBJECTIVE: To conduct a meta-analysis of randomized controlled studies to evaluate abdominal ultrasound-guided embryo transfer compared to the clinical touch method. DESIGN: Meta-analysis. SETTING: Four studies performed in academic research centers in Barcelona, Vizcaya, Hong Kong, and Madrid. PATIENT(S): A total of 2,051 patients: 1,024 received ultrasound-guided embryo transfers and 1,027 received clinical touch method transfers. INTERVENTION(S): Fourteen studies were retrieved from the literature, but only four of them fitted our selection criteria. The meta-analysis was conducted using the RevMan software with the Peto-modified Mantel-Haenszel method and the fixed effect model. MAIN OUTCOME MEASURE(S): The primary outcome measures were the clinical pregnancy and ongoing pregnancy rates. The secondary outcome measures were the incidences of ectopic pregnancies, miscarriage rate, multiple pregnancies, and difficult transfers. RESULT(S): Compared to the clinical touch method, abdominal ultrasound-guided transfer significantly increased the clinical pregnancy rate and the ongoing pregnancy rate. There was no effect on the incidence of ectopic pregnancy, multiple pregnancy, or miscarriage rate. CONCLSUION(S): Ultrasound-guided embryo transfer increases the clinical pregnancy and ongoing pregnancy rates significantly compared to the clinical touch method.     

Live births after oocyte in vitro maturation with a prematuration step in women with polycystic ovary syndrome

Standard oocyte in vitro maturation (IVM) usually results in lower pregnancy rates than in vitro fertilization (IVF). IVM preceded by a prematuration step improves the acquisition of oocyte developmental competence and can enhance embryo quality (EQ). This study evaluated the effectiveness of a biphasic culture system incorporating prematuration and IVM steps (CAPA-IVM) versus standard IVM in women with polycystic ovarian morphology (PCOM). Eighty women (age < 38 years, ≥ 25 follicles of 2–9 mm in both ovaries, no major uterine abnormalities) were randomized to undergo CAPA-IVM (n = 40) or standard IVM (n = 40). CAPA-IVM uses two steps: a 24-h prematuration step with C-type natriuretic peptide-supplemented medium, then 30 h of culture in IVM media supplemented with follicle-stimulating hormone and amphiregulin. Standard IVM was performed using routine protocols. A significantly higher proportion of oocytes reached metaphase II at 30 h after CAPA-IVM versus standard IVM (63.6 vs 49.0; p < 0.001) and the number of good quality embryos per cumulus-oocyte complex tended to be higher (18.9 vs 12.7; p = 0.11). Clinical pregnancy rate per embryo transfer was 63.2% in the CAPA-IVM versus 38.5% in the standard IVM group (p = 0.04). Live birth rate per embryo transfer was not statistically different between the CAPA-IVM and standard IVM groups (50.0 vs 33.3% [p = 0.17]). No malformations were reported and birth weight was similar in the two treatment groups. Use of the CAPA-IVM system significantly improved maturation and clinical pregnancy rates versus standard IVM in patients with PCOM. Furthermore, live births after CAPA-IVM are reported for the first time.     

Zygote versus embryo transfer: a prospective randomized multicenter trial

Purpose : To determine the efficiency of transferring human zygotes as opposed to human day 2 or 3 embryos. Methods : A prospective, randomized, Multicenter trial. Patients were randomized into zygote or embryo transfer. Patients were prepared for oocyte retrieval using standardized protocols. Oocyte retrieval was performed under general anesthesia. Oocytes and spermatozoa were treated using standard laboratory techniques. All protocols were coordinated by the coordinating center. Results : A total of 386 patients were included in the trial. Pregnancy rates were 36.5% after zygote transfer and 42% after embryo transfer. Implantation rates were equivalent (17%) in both groups. Conclusions : No general difference was observed for zygote or embryo transfer. The results suggest that zygote transfer is a valid alternative to embryo transfer.     

Low versus high volume of culture medium during embryo transfer: a randomized clinical trial

Purpose

The aim of this prospective randomized control trial was to evaluate if the use of two different volumes (20–25 vs 40–45 μl) of media used for embryo transfer affects the clinical outcomes in fresh in vitro fertilization (IVF) cycles.

Methods

In total, 236 patients were randomized in two groups, i.e., “low volume” group (n?=?118) transferring the embryos with 20–25 μl of medium and “high volume” group (n?=?118) transferring the embryos with 40–45 μl of medium. The clinical pregnancy, implantation, and ongoing pregnancy rates were compared between the two groups.

Results

No statistically significant differences were observed in clinical pregnancy (46.8 vs 54.3%, p?=?0.27), implantation (23.7 vs 27.8%, p?=?0.30), and ongoing pregnancy (33.3 vs 40.0%, p?=?0.31) rates between low and high volume group, respectively.

Conclusion

Higher volume of culture medium to load the embryo into the catheter during embryo transfer does not influence the clinical outcome in fresh IVF cycles.Trial registration number: NCT03350646

     

Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey

Purpose

The purpose of the present study was to identify trends in the therapeutic approaches used to measure antral follicle count (AFC) in patients undergoing in vitro fertilization (IVF) treatment worldwide.

Methods

A retrospective evaluation utilizing the results of a web-based survey, IVF-Worldwide (www.IVF-Worldwide.com), was performed.

Results

Responses from 796 centers representing 593,200 cycles were evaluated. The majority of respondents (71.2 %) considered antral follicle count as a mandatory part of their practice with most (69.0 %) measuring AFC in the follicular phase. Most respondents (89.7 %) reported that they would modify the IVF stimulation protocol based on the AFC. There was considerable variation regarding a limit for the number of antral follicles required to initiate an IVF cycle with 46.1 % designating three antral follicles as their limit, 39.9 % selecting either four or five follicles as their limit, and 14.0 % reporting a higher cutoff criteria. With respect to antral follicle size, 61.5 % included follicles ranging between 2 and 10 mm in the AFC. When asked to identify the best predictor of ovarian hyper-response during IVF cycles, AFC was selected most frequently (49.4 %), followed by anti-Mullerian hormone level (42.7 %). Age was selected as the best predictor of ongoing pregnancy rate in 81.7 % of respondents.

Conclusions

While a large proportion of respondents utilized AFC as part of their daily practice and modified IVF protocol based on the measurement, the majority did not consider AFC as the best predictor of ongoing pregnancy rate.     

Endometrial advancement after triggering with recombinant or urinary HCG: a randomized controlled pilot study

More than 3 days’ luteal endometrial advancement in IVF has been related with no pregnancies. This study assessed the effect of recombinant and urinary human chorionic gonadotrophin (recHCG and uHCG) when administered for final oocyte maturation on the advancement of endometrial histology. Thirty patients were randomized to receive either 250 μg recHCG or 10,000 IU uHCG in an antagonist/recombinant FSH protocol. Endometrial biopsy was performed on the day of oocyte retrieval. All specimens were evaluated according to Noyes’ criteria by one pathologist blinded to the allocation treatment groups. Single blastocyst transfer was performed. Overall, 13 patients in recHCG group and 14 patients in uHCG group underwent endometrial biopsy. The mean days of histological endometrial advancement were comparable between the two groups: 2.03 versus 2.17 days, respectively. Nevertheless more patients (69%, 9/13) had less than 3 days’ advanced endometrium in the recHCG arm as compared with 43% (6/14) patients in the uHCG group (OR 3.00, 95% CI 0.4–16.3). The delivery rate per patient was higher, although not significantly, in the recHCG group (38.5% versus 28.6%). Both recHCG and uHCG preparations induce advancement of endometrial maturation. Whether a subtle difference in endometrial maturation affects the reproductive outcome remains to be proven.