Influence of advanced age on the blastocyst development rate and pregnancy rate in assisted reproductive technology

Objective: To evaluate the percentage of blastocysts developing, the pregnancy rate, the implantation rate, and the abortion rate in women >40 years of age using a cell-free culture system for the development of viable human blastocysts.

Design: Retrospective clinical study.

Setting: Private IVF units.

Patient(s): Two hundred ninety-three cycles in patients undergoing IVF treatment for infertility. Sixty-two cycles were in patients ≥40 years of age, and 231 cycles were in patients <40 years of age.

Intervention(s): Pronucleate oocytes obtained from IVF were cultured in vitro for 5–6 days. One to four embryos were transferred.

Main Outcome Measure(s): Blastocyst development rate, pregnancy rate, implantation rate, and abortion rate.

Result(s): From 293 cycles, 3,115 pronucleate oocytes were cultured, producing 1,175 blastocysts. In the women >40 years of age, the blastocyst development rate was 22.2%, and in the younger group, the rate was 40.5%. The pregnancy rate and implantation rate in the ≥40-year age group were 21.1% and 8.9%, respectively; corresponding rates in the younger group were 44.6% and 19.9%. The abortion rate was increased for the ≥40-year age group (25% versus 13.3%).

Conclusion(s): Success rates for the development of viable human blastocysts, pregnancy, and implantation decline significantly in women ≥40 years old.     

Two-blastocyst transfer has similar pregnancy rates and a decreased multiple gestation rate compared with three-blastocyst transfer.

OBJECTIVE: To examine the effect of the number of blastocysts transferred on pregnancy and multiple gestation rates. DESIGN: Retrospective study. SETTING: Academic infertility center. PATIENT(S): Patients < 40 years undergoing IVF, with FSH levels of < 15 mIU/mL and more than three eight-cell embryos. INTERVENTION(S): Embryos were cultured in P1 until day 3 and then transferred to blastocyst medium. A maximum of three blastocysts were transferred. MAIN OUTCOME MEASURE(S): Pregnancy, multiple gestation, and implantation rates. RESULT(S): All 55 patients developed blastocysts and underwent ET. Twenty-four patients had three embryos transferred and 29 patients had two embryos transferred. Two patients had only one embryo each for transfer. There was no difference in the viable pregnancy rate between the two-blastocyst transfer and three-blastocyst transfer groups (62% vs. 58%). In the two-blastocyst transfer group, 39% of pregnancies were multiple gestations (all twin gestations), compared with 79% of pregnancies in the three-blastocyst transfer group (50% twin gestations, 29% triplet gestations). The implantation rate was 47% in both groups. CONCLUSION(S): A commercially available, sequential culture system is highly effective for producing viable blastocysts. Two-blastocyst transfer eliminated the risk of triplets while maintaining the same high success rates seen with three-blastocyst ET.     

The successful use of hatched blastocysts in assisted reproductive technology

This retrospective study was undertaken to determine the value of blastocyst culture and transfer as a tool in assisted reproductive technology. Six hundred and fifty-five cycles in patients undergoing IVF treatment for infertility were involved. All patients were aged < 40 years. Day-2 embryos were transferred to 427 (group 1) and day-6 embryos (blastocysts) were transferred to 228 patients (group 2). Pronucleate oocytes obtained from IVF were cultured in vitro for 2 or 6 days. One to five embryos were transferred. A total of 10,146 oocytes were retrieved, 6,105 oocytes were fertilized, 2,222 embryos were transferred and 197 clinical pregnancies were achieved in all groups. Blastocystes were transferred to almost 90% of group 2 patients. The pregnancy rate per cycle and implantation rate per transferred embryo was 42.1% and 19.4%, respectively, in the blastocyst group compared to 23.6% and 8.6%, respectively, when embryos were transferred on day 2. Even though in the blastocyst group there was an increased number of oocytes fertilized at the same time there was a significant reduction in the number of embryos being replaced (3.2 vs 3.8). This study demonstrate that transfer of blastocysts increases the success of IVF when compared with day-2 transfers and reduces the number of embryos to be transferred.     

Predictive value of 72-hour blastomere cell number on blastocyst development and success of subsequent transfer based on the degree of blastocyst development

OBJECTIVE: To determine the predictive value of 72-hour blastomere cell number on blastocyst development and to compare success rates of subsequent transfer based on the degree of blastocyst development. DESIGN: Retrospective clinical study. SETTING: Private assisted reproductive technology center. PATIENT(s): Ninety-three women aged 32.0 +/- 5.1 years undergoing oocyte retrieval for IVF. INTERVENTION(s): Bipronucleate oocytes obtained from IVF were grown for up to 168 hours after fertilization and subsequently transferred at the blastocyst stage. MAIN OUTCOME MEASURE(s): Percentages of embryos developing to blastocyst from 72-hour embryos by blastomere cell number and subsequent implantation and pregnancy rates of transferred blastocysts. RESULT(s): Rates of blastocyst formation and expansion increased as cell numbers at 72 hours increased. Implantation rates were 43% for embryos transferred to women receiving only expanded blastocysts and 17% for embryos transferred to women receiving one or more less developed blastocysts. Pregnancy rates were higher for women receiving only expanded blastocysts than for women receiving one or more less developed blastocysts, although the difference was not significant. CONCLUSION(s): More developed 72-hour embryos are more likely to become blastocysts and expand. Implantation rates are greater for the transfer of expanded rather than unexpanded blastocysts.     

A comparison of day 5 and day 6 blastocyst transfers

Objective: To compare implantation and pregnancy rates according to the day of embryo transfer (day 5 or 6 after oocyte retrieval) when transfer was postponed until expanded blastocysts developed.

Design: Retrospective clinical study.

Setting: Private ART center.

Patient(s): One-hundred and eighty-three women undergoing blastocyst-stage embryo transfer following in vitro fertilization.

Intervention(s): Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred only when at least one embryo attained the expanded blastocyst stage.

Main Outcome Measure(s): Implantation and pregnancy rates.

Result(s): Blastocysts transferred on day 5 implanted at nearly twice the rate of blastocysts transferred on day 6 (36.3% vs. 19.0%). Pregnancy rates were also almost twice as high among the day 5 transfer patients (59.3% vs. 32.3%). In addition, more blastocysts developed (3.6 vs. 2.4), and more were transferred (2.7 vs. 2.3) to the day 5 transfer patients, although the proportion of expanded blastocysts among the blastocysts that were transferred was the same for the two groups (91.7% vs. 93.6%).

Conclusion(s): Embryos that develop to the expanded blastocyst stage and are transferred on day 5 after retrieval are approximately twice as likely to implant compared to those for which expansion and transfer are delayed until day 6.     

First experiences with human blastocyst culture after IVF/ICSI under the conditions of the German embryo protection law

OBJECTIVE: Due to the improvements in human embryo culture in the recent years, it is now possible to transfer embryos five days after oocyte retrieval and IVF or ICSI at the blastocyst stage with favorable implantation rates. In Germany it is illegal to cultivate more than 3 embryos, therefore the selection has to be done at the pronuclear stage. There we report our experiences of human blastocyst culture in a routine IVF/ICSI programme under the conditions of the German Embryo Protection Law. MATERIALS AND METHODS: The data of 100 couples undergoing the IVF-ICSI programme at the University Clinic of Würzburg were analysed prospectively. 14-18 hours after insemination or micro-injection two or three zygotes with the best pronuclear development were selected for further cultivation. Fertilized oocytes were cultured in sequential media and were then transferred into the uterus 5 days after oocyte recovery. The blastocysts were graded from 1-8. RESULTS: In 100 cycles a total of 859 oocytes were collected, of whom 663 were fertilized and reached the pronuclear stage (median fertilization rate 88.9 %). 251 zygotes were selected at the PN stage. 51 % of the selected zygotes achieved the blastocyst stage after 5 days (grade 1-5), 28 % were morulae (grade 6-7) and 21 % of the embryos arrested in their development (grade 8). The clinical pregnancy rate was 26 %. Women who conceived had a significant better development of blastocysts on day 5 (grade 4 versus grade 6, P < 0.01) than those not achieving pregnancy. CONCLUSIONS: In summary, under the current legal conditions in Germany, blastocyst culture cannot improve pregnancy rates as the rate of arrested embryos of over 20 % limits the chances of implantation.     

Rate of blastocyst development from excess embryos remaining in culture after day 3 embryo transfer

OBJECTIVE: To assess the rate of blastocyst development (BDR) from embryos remaining in culture after day-3 embryo transfer (ET), and its relationship to cause of infertility. STUDY DESIGN: Retrospective cohort study in tertiary-care IVF Center. Blastocyst development rate (BDR) after day-3 ET was assessed in 126 women who underwent either conventional IVF or ICSI. RESULTS: Mean age, early follicular FSH levels, number of 2PN zygotes, number of excess embryos, and number of ET were similar between patients that underwent IVF and ICSI. Overall, 20% of extra embryos from conventional IVF patients developed into blastocysts compared to 14% of embryos obtained from ICSI. Cause of infertility did not affect BDR, even in patients who required ICSI due to male factors. CONCLUSIONS: Low rates of blastocyst development from excess embryos are similar between IVF and ICSI patients. Only 15 to 25% of excess embryos left in culture develop into blastocysts, regardless of cause of infertility. Physicians and patients can use this information to adjust both AR treatment protocols and patient expectations.     

Effect of ICSI on subsequent blastocyst development and pregnancy rates

Purpose: To investigate whether ICSI (intracytoplasmic sperm injection)results in decreased blastocyst formation and pregnancy compared to IVF (in vitro fertilization). Methods: We performed a retrospective analysis of blastocyst transfer (BT)offered routinely to patients under age 40 with three 8-cell embryos on day 3 and compared IVF to ICSI cycles. Sequential media were used with P1 until day 3, then Blastocyst Medium until day 5/6. Results: There were 131 IVF and 75 ICSI cycles. There was no difference in age, number of oocytes, zygotes, 8-cell embryos, blastocysts on days 5 and 6, or embryos transferred. Progression to blastocyst was similar (78% for IVF and 73% for ICSI) as was the viable pregnancy rate (51.4% for IVF and 55% for ICSI). No cycles failed to form blastocysts. Conclusions: The progression to blastocyst and the likelihood of conceiving aviable pregnancy were unaltered by ICSI. Thus it seems appropriate for programs to offer BT to patients undergoing ICSI using the same inclusion criteria applied to their IVF patients.     

Comparison of blastocyst transfer with day 3 embryo transfer in similar patient populations

OBJECTIVE: To compare implantation and pregnancy rates (PRs) achieved with blastocyst transfer (BT) and day 3 ET in similar patient populations. DESIGN: Retrospective analysis. SETTING: Academic infertility center. PATIENT(S): One hundred consecutive patients <40 years undergoing IVF, each with more than three eight-cell embryos on day 3. INTERVENTION(S): Patients used their own eggs for IVF or IVF and intracytoplasmic sperm injection. Embryos were cultured in P1 medium (Irvine Scientific, Santa Ana, CA) until day 3, when they were either transferred or, in the case of embryos for BT, incubated in Blastocyst Medium (Irvine Scientific), followed by transferring on day 5. MAIN OUTCOME MEASURE(S): Implantation and PRs. RESULT(S): There were no statistically significant differences in patient age, FSH level, or number of oocytes or zygotes. The BT group had fewer embryos transferred (mean, 2.4) compared with the day 3-ET group (mean, 4.6). The viable PR (cardiac activity at 6-7 weeks was considered indicative of a viable pregnancy) was higher with BT (68%, 34/50) than with day 3 ET (46%, 23/50). The implantation rate was increased with BT (47%, 56 sacs/120 embryos) compared with day 3 ET (20%, 46 sacs/231 embryos). CONCLUSION(S): The BT group in our study had higher implantation and PRs compared with the day 3-ET group. Better embryo selection, improved embryo-uterine synchrony, and decreased cervical mucus on day 5 may have accounted for the enhanced outcome. Our data support the use of BT to limit the number of embryos transferred while improving PRs.     

Basal 17β-estradiol did not correlate with ovarian response and in vitro fertilization treatment outcome

Objective: To verify the correlation of basal 17β-E₂ with ovarian response to stimulation and outcome of in vitro fertilization (IVF).

Design: Retrospective observational study.

Setting: The Assisted Conception Unit, University College London Hospitals.

Patient(s): Three hundred five women undergoing IVF and IVF with intracytoplasmic sperm injection.

Intervention(s): Basal follicle-stimulating hormone (FSH) and 17β-E₂ were assessed. The cutoff level for day 2 E₂ established was 250 pmol/L. Each patient was noted for below (group A) or above (group B) the cutoff point according to her basal E₂ level.

Main Outcome Measure(s): Basal E₂, age, duration of infertility, cycle day 2 FSH, number of ampules of gonadotropin used, number of days of stimulation, number of retrieved oocytes, fertilization rate, number of embryos transferred, number of cycles with embryo freezing, cancellation rate, clinical pregnancy rate, and implantation rate were compared between the two groups.

Result(s): No differences were found between group A and group B in the number of oocytes retrieved (8.8 ± 4.2 vs. 9.3 ± 4.8), embryos transferred (2.5 ± 0.8 vs. 2.7 ± 0.7), cancellation (9.1% vs. 6.9%), pregnancy (24.8% vs. 30%), and implantation rate (12.3% vs. 15.6%). Correlation coefficient and coefficient of determination showed no significant correlation between basal E₂ and the number of oocytes retrieved, age, and basal FSH.

Conclusion(s): In our study population, basal E₂ was not a sensitive predictor of ovarian response to stimulation and did not correlate with IVF outcome.     

Sibling embryo blastocyst development correlates with the in vitro fertilization day 3 embryo transfer pregnancy rate in patients under age 40

OBJECTIVE: To examine the IVF day 3-ET pregnancy rate in patients under 40 with sibling embryo blastocyst development, compared with similar patients without blastocyst formation. DESIGN: Retrospective analysis. SETTING: Academic infertility center. PATIENT(S): One hundred twenty-five IVF day 3-ET patients under 40 with sibling embryos for extended culture. INTERVENTION(S): Extended culture of nontransferred sibling embryos for blastocyst development. MAIN OUTCOME MEASURE(S): Pregnancy and multiple gestation rates, number of oocytes, embryos formed, and embryos transferred. RESULT(S): Thirty-eight percent of patients became pregnant. Forty-eight percent of patients had sibling embryos develop to blastocyst. The blastocyst group had more oocytes retrieved (17.4+/-6.6 versus 14.4+/-5.6), more embryos formed (11.2+/-4.2 versus 8.8+/-3.2), and a higher clinical pregnancy rate (60% versus 18%) than the group without blastocyst development. CONCLUSION(S): Blastocyst transfer has been shown to improve implantation rates and reduce the risk of multiple gestations from assisted reproductive technology. Sibling embryo blastocyst development may reflect superior embryo quality, as manifested by increased IVF-ET pregnancy rates. In addition to predicting pregnancy in the current cycle, sibling embryo blastocyst development may provide information about the potential for fresh blastocyst transfer in subsequent cycles and help to identify patients at risk for multiple gestations.     

The Well-of-the-Well system: an efficient approach to improve embryo development

Transfer of human embryos at the blastocyst stage may offer considerable benefits including an increased implantation rate and a decreased risk of multiple pregnancies; however, blastocyst culture requires an efficient and reliable in-vitro embryo culture system. In this study, the effect of the Well-of-the-Well (WOW) system consisting of microwells formed on the bottom of the culture dish was tested in three mammalian species, including humans. The WOW system resulted in significant improvement when comparing the drops for culture of in-vitro-matured and parthenogenetically activated porcine oocytes, and in-vivo-derived mouse zygotes. In human embryos, using a sibling oocyte design, embryos cultured in WOW developed to the blastocyst stage in a significantly higher proportion than did embryos cultured traditionally (55% in WOW and 37% in conventional culture; P < 0.05). In a separate study, also in human, a total of 48 patients with a cumulative 214 unsuccessful previous IVF cycles were selected for the trials. In subsequent intracytoplasmic sperm injection cycles, oocytes/embryos were cultured individually in the WOW system or in microdrops. Transferable quality blastocyst development (48.9% of cultured zygotes) was observed in the WOW system. Ninety-four blastocysts transferred to 45 patients resulted in clinical pregnancy rates of 48.9%, including nine twin pregnancies, seven single pregnancies, five miscarriages and one ectopic pregnancy. The results indicate that the WOW system provides a promising alternative for microdrop culture of mammalian embryos, including human embryos.     

Birth after the injection of sperm and the cytoplasm of tripronucleate zygotes into metaphase II oocytes in patients with repeated implantation failure after assisted fertilization procedures.

OBJECTIVE: To assess the technique of injecting a single sperm and cytoplasm obtained from tripronucleate zygotes into metaphase II oocytes for the treatment of patients with repeated implantation failure after intracytoplasmic sperm injection or IVF. DESIGN: Clinical study. SETTING: Private infertility clinic. PATIENT(S): Patients with repeated implantation failure after intracytoplasmic sperm injection or IVF. INTERVENTION(S): The metaphase II oocytes of recipients were injected with their husbands' spermatozoa and cytoplasm aspirated from the tripronucleate zygotes of donors. MAIN OUTCOME MEASURE(S): Fertilization after cytoplasm and sperm injection, embryo development, and successful pregnancy. RESULT(S): In total, 62 metaphase II oocytes from nine recipients were injected. Of the 62 injected oocytes, 3 (5%) degenerated and 43 (69%) had two pronuclei 18 hours after injection. Thirty-nine oocytes with two pronuclei cleaved to the two-cell to six-cell stage after another 24 hours of culture. All cleaved embryos were transferred into the uteruses of recipients. Four clinical pregnancies occurred in four recipients. No abnormal chromosomes were observed after amniocentesis and karyotyping in all pregnancies. Five healthy infants were born. CONCLUSION(S): Injection of the cytoplasm of tripronucleate zygotes may enhance the clinical pregnancy rate in patients with repeated implantation failure after intracytoplasmic sperm injection or IVF.     

Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer

Objective: To determine the relationship between blastocyst score and pregnancy outcome.

Design: Retrospective review of blastocyst transfer in an IVF clinic.

Setting: Private assisted reproductive technology unit.

Patient(s): 107 patients undergoing blastocyst culture and transfer of two embryos.

Intervention(s): Culture of all pronucleate embryos in sequential media to the blastocyst stage (day 5), followed by transfer of two blastocysts.

Main Outcome Measure(s): Implantation rates, pregnancy rates, and twinning were analyzed.

Result(s): When a patient received two top-scoring blastocysts (64% of patients), implantation and pregnancy rates were 70% and 87%, respectively. The twinning rate in this group was 61%. When only one top-quality blastocyst was available for transfer (21% of patients), the implantation and pregnancy rates were 50% and 70%. The twinning rate for this group was 50%. In contrast, when only low-scoring blastocysts were available for transfer (15% of patients), implantation and pregnancy rates were 28% and 44%, and the twinning rate was 29%. No monozygotic twins were observed in this group of patients.

Conclusion(s): The ability to transfer one high-scoring blastocyst should lead to pregnancy rates greater than 60%, without the complication of twins.     

移植无原核胚胎出生健康子代

目的:观察无原核(PN)胚胎的发生率、影响因素及移植0PN胚胎周期的临床治疗结局。方法:回顾性分析4 424个IVF-ET周期移植0PN来源胚胎的结局。结果:0PN胚胎的发生率为11.3%。女方的年龄、获卵数及优质胚胎率与0PN的发生率相关。70个周期移植了112个0PN来源的卵裂期胚胎,获得的临床妊娠率为24.3%(17/70),植入率为17.0%(19/112),流产率为11.8%(2/17)。1例死产。13个周期活产13个健康子代,未见畸形的发生。对0PN来源的囊胚进行复苏周期移植,可获得与2PN囊胚相似的临床妊娠率及植入率,但流产率较高,差异有统计学意义。结论:IVF周期中,含有0PN优质胚胎的周期可能有较好的临床治疗结局。形态正常的0PN胚胎有较好的胚胎发育潜能,在无2PN胚胎的情况下,可考虑移植0PN来源胚胎。     

Blastocyst culture and transfer: analysis of results and parameters affecting outcome in two in vitro fertilization programs.

OBJECTIVE: To determine whether previously described advanced blastocyst development and high implantation rates are confirmed in an expanded multicenter trial. DESIGN: Retrospective review. SETTING: Two private assisted reproductive technology units. PATIENT(S): One hundred seventy-four patients who underwent blastocyst culture and transfer. INTERVENTION(S): Culture of all pronucleate embryos in sequential media to the blastocyst stage (day 5) followed by ET. MAIN OUTCOME MEASURE(S): The number and percentage of blastocysts developed, implantation rates, pregnancy rates, and parameters that affected outcome were analyzed. RESULT(S): Only 3 of 174 patients failed to achieve blastocyst-stage ET. The mean blastocyst development rate was 48%. The ongoing pregnancy rate was 66.3% per oocyte retrieval, with a mean (+/-SE) of 2.2 +/- 0.05 blastocysts transferred and an implantation rate of 48% per blastocyst transferred. CONCLUSION(S): Blastocyst culture and transfer is an effective means of treating patients who respond well to gonadotropins. High pregnancy rates can be accomplished with low numbers of embryos transferred. Patients who failed to achieve ET were rare.     

Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study

OBJECTIVE: To evaluate the reproductive and neonatal outcome of blastocyst transfer after coculture with human endometrial epithelial cells in IVF and oocyte donation. DESIGN: Retrospective study.Private assisted reproductive center. PATIENTS(S): Two hundred sixty women undergoing IVF and 469 oocyte recipients. INTERVENTION(S): IVF or intracytoplasmic sperm injection (ICSI) and transfer of at least one blastocyst after coculture with human endometrial epithelial cells. MAIN OUTCOME MEASURE(S): Blastocyst formation rate, implantation and pregnancy rates, neonatal outcome, and congenital birth defects. RESULT(S): Among patients who had transfer with their own oocytes, 1193 of 2349 cocultured embryos developed up to the blastocyst stage (50.8%), and pregnancy and implantation rates of 33.9% and 19.2%, respectively, were achieved. In the oocyte donation program, 1819 blastocysts were obtained from 3127 embryos (58.2%), with subsequent pregnancy and implantation rates of 57.0% and 31.0%, respectively. The blastocyst rate remained stable throughout the 5 years of the study, but the pregnancy and implantation rates increased dramatically. Of 139 deliveries, 57 (41.0%) were multiple pregnancies and 1 (0.7%) was a multifetal birth (four live born infants). Out of 200 children born, 59% were male, and congenital birth defects were observed in 2.5%. CONCLUSION(S): Coculture of human embryos with endometrial epithelial cells yields a blastocyst formation rate of 50.8% to 58.2% and encouraging implantation and pregnancy rates. This technique reduces the mean number of embryos transferred in each patient. The number of embryos implanted is more relevant to neonatal outcome than is the coculture system and blastocyst transfer used. The risk of congenital birth defects associated with this program is similar to that recorded in early ET in IVF or ICSI.     

Oocyte quality in patients with severe ovarian hyperstimulation syndrome

Objective: To study the oocyte quality in patients with ovarian hyperstimulation syndrome (OHSS).

Design: Retrospective study.

Setting: The Egyptian IVF-ET Center.

Patient(s): Forty-two patients who developed severe OHSS (group A) were studied for the mean number of oocytes retrieved, percentage of high-quality oocytes, embryo quality, and fertilization, implantation, and pregnancy rates; these patients were compared with an agematched control group who did not develop OHSS (group B; n = 183) after superstimulation for IVF or intracytoplasmic sperm injection.

Intervention(s): In vitro fertilization and ICSI.

Main Outcome Measure(s): Fertilization and pregnancy rates.

Result(s): In group A, the mean number of oocytes retrieved was significantly higher, whereas the percentage of high-quality oocytes and the fertilization rate were significantly lower than that in group B. There were no statistically significant differences in the quality of embryos transferred or the implantation or pregnancy rate between the groups. The percentage of high-quality oocytes and the fertilization rate were significantly lower in patients with polycystic ovaries (PCO) in both groups.

Conclusion(s): The inferior quality and maturity of oocytes in OHSS reduced the fertilization rate but did not affect the quality or the number of embryos transferred or the pregnancy rate. The effect on oocyte quality could be due to the prevalence of PCO in this group of patients.     

Introduction of blastocyst culture and transfer for all patients in an in vitro fertilization program

Objective: To evaluate the nonselective application of extended embryo culture on the outcome of IVF.

Design: Retrospective analysis.

Setting: Private practice assisted reproductive technology center.

Patient(s): Seven hundred ninety nonselected patients undergoing IVF with controlled ovarian stimulation.

Intervention(s): For day 3 ET, multicell embryos were cultured in human tubal fluid medium and 12% synthetic serum substitute. For day 5 ET, embryos were cultured for 48 hours in S1 medium and then for 48 hours in S2 medium.

Main Outcome Measure(s): Implantation rate (determined by total no. of visualized gestational sacs), ongoing pregnancy rate, and number of embryos available for ET.

Result(s): Respective day 3 and day 5 implantation rates for patients aged <35 years (29.5% and 38.9%), patients aged 35–39 years (20.7% and 28.2%), and all patients combined (23.3% and 32.4%) were statistically significantly different. Significantly more embryos were transferred on day 3 than on day 5 for patients aged <35 years (2.9 vs 2.4), patients aged 35–39 years (3.1 vs 2.6), and all patients combined (3.0 vs 2.5). The difference in ongoing pregnancy rates per retrieval was statistically significant for day 3 compared with day 5 transfers for all patients combined (35.9% vs 43.8%). Cancellation rates for transfer after retrieval increased significantly for day 3 compared with day 5 transfer (2.9% vs 6.7%).

Conclusion(s): These results demonstrate the feasibility of using extended embryo culture in a nonselective manner for couples undergoing IVF. Overall, extended embryo culture was associated with a significant increase in pregnancy rates and implantation rates and a significant decrease in the number of embryos transferred. The rate of multiple implantation among patients aged <35 years warrants consideration of single blastocyst transfers for this group.     

"Smart asses"--and spectrum bias

Objective: To report improved follicular cohort development and a healthy ongoing pregnancy after midcycle aspiration of a single dominant ovarian follicle in a patient with poor response to IVF treatment.

Design: Case report.

Setting: University-based infertility center.

Patient(s): A 39-year-old woman (gravida 1, para 0) with a borderline FSH level and four previous unsuccessful IVF attempts.

Intervention(s): A single 27-mm follicular cyst was aspirated after 13 days of treatment, while controlled ovarian hyperstimulation was continued.

Main Outcome Measure(s): Number of follicles developed, number of oocytes retrieved, development of a clinical pregnancy.

Result(s): In previous attempts, the patient had no more than two dominant follicles and a maximum of three oocytes retrieved. After midcycle aspiration of the single lead follicle, a new cohort of seven follicles developed and seven oocytes were recovered. Six embryos were replaced by tubal ET and an ongoing singleton gestation resulted.

Conclusion(s): Midcycle aspiration of a single lead follicle in a patient with poor response to IVF treatment allowed the development of a larger secondary cohort of follicles during the same cycle and ultimately led to a viable pregnancy. This intervention may have future implications for the treatment of poor responders.