Uncomplicated pregnancy and normal singleton delivery after surgical excision of heterotopic (cornual) pregnancy following in vitro fertilization/embryo transfer.

A 39 year-old woman with previous salpingectomy developed a symptomatic heterotopic right cornual pregnancy identified by transvaginal ultrasonography at six weeks' gestation. The patient had previously undergone an ipsilateral partial salpingectomy, and the conception was established four months later after one cycle of controlled ovarian hyperstimulation, in vitro fertilization (IVF) and embryo transfer. We performed immediate surgical excision of the ectopic implantation with conservation of the intrauterine pregnancy. Progesterone was administered as 200 mg/d lozenge (troche) plus 200 mg/d rectal suppository, maintained from day of embryo transfer through the perioperative period and until 11th gestational week. Following an uneventful obstetrical course, a healthy male infant was delivered by cesarean at term. In this report, we review the incidence and significance of heterotopic gestation in the context of IVF/embryo transfer. Risk factors for complex intra- and extra-uterine pregnancies are also outlined. Additionally, the clinical management of heterotopic pregnancy, including a novel approach to progesterone supplementation, is discussed.

Clinical application of human egg cryopreservation.

Clinical egg cryopreservation has been applied during a 4-year period with some limited success. Mostly mature and a few immature eggs were frozen slowly and thawed rapidly in 1,2-propanediol and sucrose, and subsequently inseminated by intracytoplasmic sperm injection (ICSI). Three studies were performed in which: (i) it was established that 55% of aged unfertilized mature eggs survive freezing; (ii) in 22 cycles of thawed donated eggs cryosurvival was 24% with 15 cycles reaching transfer, and five pregnancies were initiated, one of which went to term at 39 weeks with fraternal twin boys, and one remains ongoing at 37 weeks; and (iii) in five cycles, where in-vitro fertilization patients had some of their own eggs frozen/ thawed, cryosurvival of mature eggs was poor at only 2.2%, although 44% sibling germinal vesicle (GV) stage eggs survived. A normal female infant delivered at 40 weeks arose from transfer of two embryos where GV eggs underwent in-vitro maturation post-thaw and were fertilized by ICSI. Pregnancies reported here and by others indicate a burgeoning awareness of the potential benefits of egg cryopreservation, prompting cautious optimism for the future of this technology.

Multiple pregnancy rate and embryo number transferred during in vitro fertilization.

OBJECTIVE: Our goal was to achieve a good pregnancy rate after in vitro fertilization; more than one embryo, if available, is transferred to the uterine cavity. This is a recognition of the low implantation rates of embryos from in vitro fertilization. A consequence of this can be high-order multiple implantation with obstetric complications. STUDY DESIGN: Retrospectively, we reviewed 42 months' in vitro fertilization experience; we related the number of embryos transferred and the pregnancy outcome. During this period 2173 fresh and frozen-thawed embryo transfers were performed. One to six embryos were transferred to women whose average age was 34.4 years (range 21 to 49). RESULTS: A total of 734 delivered pregnancies (33.8% per embryo transfer) was analyzed according to whether they were single or multiple, and this was related to the original number of embryos transferred. The overall multiple pregnancy rate was 31.3% (24.7% twins, 5.8% triplets, 0.8% quadruplets). CONCLUSIONS: There was a trend toward a higher pregnancy rate with more embryos transferred. The embryonic implantation rate, which reflects the number of embryos that implant per total transferred, was not significantly different in any one group, except in older women in whom more than one embryo was transferred. Whereas greater numbers of embryos (more than three) were transferred in couples with a poorer prognosis for successful in vitro fertilization (e.g., older women [> 36 years old], previous failure of in vitro fertilization, poor embryo quality, or severe male factor causing infertility), there still remained a significant trend toward a higher pregnancy rate when more embryos were transferred. The embryonic implantation rate did not decline in the poorer-prognosis groups (more than three embryos transferred), yet the multiple pregnancy rate was increased. Technologic procedures such as embryo biopsy for aneuploidy screening are proposed as one means to reduce embryo numbers transferred without decreasing the overall pregnancy rate.

Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates?

In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.

Effect of coculture on subsequent survival and implantation of cryopreserved human embryos.

PURPOSE: This retrospective analysis was designed to assess the performance of human embryos following cryopreservation based on whether they were originally developed in standard culture medium (65 cycles, 223 embryos) or cocultured on partial monolayers of bovine oviductal epithelial cells (63 cycles, 198 embryos). Embryo cryosurvival and implantation were compared between the study group and the contemporaneously match controls. RESULTS: During a 2-year period when no factors of the cryopreservation program were altered, 63 transfers of 159 surviving thawed control cleavage-stage embryos (71.3% survival) that were 54% intact gave rise to 11 viable pregnancies (17.5%/ET), to yield an implantation rate of 6.9% per embryo. Sixty-three transfers of 147 thawed cocultured embryos (74.2% survival) that were 61% intact gave an implantation rate of 13.6% per embryo that was significantly higher than the control group (P < 0.05). CONCLUSION: Coculture of embryos prior to cryopreservation does not appear to improve cryosurvival; however, it does improve implantation postthaw compared with embryos following standard culture prior to cryopreservation.

Cryopreservation of human embryos and oocytes.

Human embryo cryopreservation is now a fully established adjunct to assisted reproduction, with thawed embryos implanting at a rate approaching that of fresh embryos. As with fresh embryos, the quality of frozen-thawed embryos is affected by patient age at the time of oocyte retrieval, and by culture conditions. Ovarian stimulation incorporating gonadotropin-releasing hormone analogs does not appear to be detrimental to cryopreservation success, and natural or artificial thaw cycles seem equally effective. Successful cryopreservation seems feasible for one- to eight-cell embryos and blastocysts using a variety of protocols. Selection criteria for embryos to be frozen can vary, and embryo quality has the most significant impact on post-cryopreservation viability. Unfertilized oocyte cryopreservation is coming closer to routine clinical application.

Factors affecting success with intracytoplasmic sperm injection.

In this study, 141 couples underwent 163 cycles of in vitro fertilization (IVF) and embryo transfer in which the eggs were inseminated by intracytoplasmic sperm injection (ICSI). Overall, 41% of the injected eggs were normally fertilized and 81% of the resulting embryos were suitable for cryopreservation (91 embryos) or uterine transfer. From 153 fresh embryo transfers, 45 ongoing or delivered pregnancies (27.6% per cycle) were achieved, and of the 507 embryos transferred, 54 successfully implanted giving an implantation rate per embryo of 10.7%. Five additional pregnancies did not yield a viable fetus or underwent a spontaneous abortion, giving a miscarriage rate of 10% (5/50). Increased maternal age or a prior diagnosis of failed fertilization after conventional IVF had a significantly negative impact on success. Sperm from the testis and epididymis, those retrieved by electro-ejaculation, and completely immotile ejaculated sperm all gave rise to pregnancies. ICSI reinsemination was used with limited success to rescue failed fertilization cycles, although the implantation rate per embryo was poor (5%). ICSI has greatly improved the ability to use IVF for treating couples with a poor fertilization potential.