Jeffrey D Fisch

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.

Blastocyst-ET and Monozygotic Twinning

AbstractPurpose: To examine the rate of monozygotic twinning associatedwith blastocyst transfer using commercially available,cell-free culture systems with unmanipulated blastocysts. Methods: A retrospective analysis was conducted in multipleprivate and academic infertility centers throughout theUnited States, of 199 pregnant patients following in vitrofertilization (IVF) blastocyst embryo transfer (ET). Humanembryos obtained through standard IVF stimulation protocolswere cultured in commercially available, cell-free mediasystems and transferred as blastocysts. The main outcomemeasure was the rate of monozygotic twinning. Results: A total of 199 blastocyst-ET pregnancies wereachieved during the study period at the fertility centersexamined. Monozygotic twinning was noted in 10/199 (5;pc)of these pregnancies. All were monochorionic diamnionic. Conclusions: Monozygotic twinning previously has beenreported following IVF, especially in relation to assistedhatching. While blastocyst transfer has been available formany years using coculture, there have been no publishedmulticenter reports of monozygotic twinning associated withunmanipulated blastocysts. In a multicenter analysis, a definiteincrease in monozygotic twinning was seen followingblastocyst-ET. We believe this phenomenon is real and thatthis information should be considered when counselingpatients for treatment.

Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development

OBJECTIVE To evaluate the effects of vaginally administered sildenafil on endometrial thickness and IVF outcome in a large cohort of infertile women with poor endometrial development. DESIGN Retrospective cohort analysis. SETTING Private practice setting. PATIENT(S) A cohort of 105 infertile women aged <40 years, with normal ovarian reserve and at least two consecutive prior IVF failures attributed to inadequate endometrial development. INTERVENTION(S) Patients underwent IVF using a long GnRH-a protocol with the addition of sildenafil vaginal suppositories (25 mg, 4 times per day) for 3-10 days. MAIN OUTCOME MEASURE(S) Peak endometrial development, pregnancy, and implantation rates. RESULT(S) Of 105 patients, 73 (70%; Group A), attained an endometrial thickness of >/=9 mm, whereas 32 (30%; Group B) did not. Implantation and ongoing pregnancy rates were significantly higher for Group A (29% and 45%) than for Group B (2% and 0). Of 11 women in Group B who had embryos transferred in that cycle, only one conception occurred, which resulted in a miscarriage. In Group B, 59% of women had a history of endometritis, compared with 44% in Group A. CONCLUSION(S) Vaginal administration of sildenafil enhanced endometrial development in 70% of patients studied. High implantation and ongoing pregnancy rates were achieved in a cohort with a poor prognosis for success. Previous endometritis may decrease the response to sildenafil.

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.

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.

Timing of blastocyst transfer relative to the thaw: a critical factor in outcome following FET

Objective: To evaluate effects of different blastocyst freezing and thawing protocols on pregnancy and implantation rate. Design: Retrospective cohort study. Setting: Multi-site, private practice. Patients: Infertile women ages between 27-51 years (n 95) undergoing IVF. Interventions: Women undergoing in vitro fertilization (IVF) between January and December 2002 had surviving expanded supernumerary blastocysts cryopreserved 5 and 6 days following fertilization. All embryos were cultured in P1 (Irvine Scientific) medium until day 3 and thereupon in Blastocyst medium (Irvine Scientific) until day 5 or 6. Patients were allocated to Group 1 or Group 2 based on the method of cryopreservation and the time interval between the thawing process and the frozen embryo transfer (FET). In Group 1, the cryopreservation process involved treatment with 5% and 9% Glycerol 0.2 M sucrose for 10 minutes followed by freezing through exposure of the blastocysts to 7°C for 17 min, and thereupon lowering the temperature by 0.3°C/min to 38°C. Prior to the FET the embryos were thawed in a water bath at 33°C, treated with 0.5 M and 0.2 M sucrose for 10 min and then immediately transferred to the uterine cavity. In Group 2, the same method of exposure of the blastocysts to glycerol and sucrose as described above was employed at 20°C. Thereupon the temperature was progressively reduced by 2°C/min to 6.5°C and maintained at this point for 17 min. Thereafter the temperature was lowered at a rate of 0.3°C/min to 38°C. However, in contrast with Group 1 patients whose blastocysts were transferred immediately upon thawing, the timing of FET’s in Group 2 was predicated upon whether day 5 or day 6 blastocysts were being thawed; whereas day 5 blastocysts were thawed, then treated with 0.5 and 0.2 M sucrose for 10 min, cultured overnight and transferred the following afternoon. Blastocysts frozen on day 6 were thawed similarly on the morning of the scheduled FET, cultured for at least 4 hours and then transferred. Primary measures of outcome: Ongoing pregnancy rate (beyond 12 weeks) and implantation rate (number of viable gestations per transferred blastocyst). Results: The ongoing pregnancy and implantation rates were 16% and 11% for Group 1 as compared to 32% and 20% for Group 2 (P 0.05). Conclusions: Blastocyst transfer has been shown to be associated with improved pregnancy and implantation rates. Recent advances in embryo culture media and techniques have brought about improved embryo quality and survival to the blastocyst stage in the IVF setting. The resulting increase in availability of blastocysts has allowed for an ever increasing degree of discretion in the selection of only the best quality supernumerary blastocysts for cryopreservation. Our data strongly suggests that while the protocol of blastocyst cryopreservation does not affect FET outcome, the timing of the thaw, relative to the transfer could be a critical consideration.

Aspiration of a single dominant follicle leads to improved cohort development and pregnancy in a patient with poor response to in vitro fertilization treatment

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.