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The influence of advanced age on the outcome of assisted reproduction.

PURPOSE: Our purpose was to determine the influence of age on the outcome of assisted reproduction, with particular interest in women aged 40 years or older. METHODS: A retrospective review of the 779 patients enrolled in the Royal Hospital for Women Fertility Group fertility program between 1987 and 1994 was performed. The results for women aged 40 years or older were compared with those for women between 36 and 39 years and those younger than 36 years. The main outcome measures were pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response. RESULTS: Compared with those in younger women, pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response to controlled ovarian stimulation were significantly worse in women aged 40 years or older. CONCLUSIONS: The outcome of assisted reproduction in women of 40 years of age or older was extremely poor. Compared with those in younger women, pregnancy outcome and ovarian response to controlled ovarian stimulation were significantly worse in women of 40 years or more.

Adult↗

Current technology of oocyte retrieval.

Transvaginal follicle puncture under sonographic control has become the method of choice for ovum retrieval worldwide. Because it is the current technology of the 1990s, there are very few reports in the literature on other methods of oocyte retrieval. Furthermore, perhaps because of the simplicity of transvaginal follicle puncture under sonographic control, there are only a few reports on the technique itself in the current literature. This review classifies the papers on hand according to general studies of the subject, appropriate anesthesia, necessity of follicle flushing for oocyte retrieval, vaginal disinfection and the evaluation of the risk following transvaginal oocyte retrieval, and new techniques in connection with the harvesting of oocytes.

Anesthesia↗

Gamete intrafallopian transfer. An overview.

Gamete intrafallopian transfer involves a direct transfer of both human gametes, sperm and oocytes, into the fallopian tube. Since the first report of a successful pregnancy following the use of this technique by Asch et al in 1984, its role in the treatment of infertile women with patent tubes has been established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the highest pregnancy rate achieved in infertile women due to endometriosis or unexplained infertility.

Aftercare↗

Recurrent cervical pregnancy after assisted reproduction by intrafallopian transfer.

BACKGROUND: Cervical pregnancy is an uncommon, yet potentially catastrophic form of ectopic pregnancy. Early diagnosis and intervention are important in avoiding short-term and long-term morbidity. Although transcervical embryo transfer is thought to increase the incidence of this phenomenon in patients undergoing in vitro fertilization, its occurrence after intrafallopian transfer is rarely seen. CASE: A 43-year-old nulliparous white female with a history of unexplained infertility experienced recurrent cervical pregnancy after two consecutive gamete/zygote intrafallopian transfer cycles. Abnormally rising beta-hCG levels combined with transvaginal sonography helped establish the diagnosis in each case. Intramuscular (IM) methotrexate combined with intra-amniotic potassium chloride successfully treated this condition initially, and IM methotrexate alone was sufficient for successful treatment in the second case. CONCLUSION: Cervical pregnancy may occur with assisted reproductive techniques involving intrafallopian transfer. Early diagnosis may be important for successful treatment of cervical pregnancy with conservative measures. Even in the case of recurrence, prompt intervention may allow for preservation of a patient's future fertility potential.

Adult↗

Intrafallopian transfer of gametes and early stage embryos for in vivo culture in cattle.

It may be possible to avoid inadequate in vitro culture conditions by incubating gametes or embryos in the oviducts for a short time. Ideally, an optimized procedure should be devised, combining in vitro and in vivo systems, in order to achieve synchronization in cattle. We transferred gametes as well as embryos in various stages of development and placed them into the oviducts. Embryos were recovered on Day 7 by flushing of oviducts and uterine horns. Blastocyst rates were determined on Day 7 and on Day 8. Experimental designs included transfer of in vitro matured cumulus oocyte complexes into previously inseminated heifers (COCs group), transfer of in vitro matured COCs simultaneously with capacitated spermatozoa (GIFTs group), transfer of four to eight cell stage embryos developed in vitro after IVM/IVF (Cleaved Stages group) and a group of solely in vitro produced embryos (IVP control group). Our results indicate that in vivo culture of IVM/IVF embryos in the homologous bovine oviduct has a positive influence on subsequent pre-implantation development. In addition, we have evidence that in vitro maturation and in vivo fertilization cannot be synchronized.

Animals↗

Evaluation of the significance of the estradiol response during the clomiphene citrate challenge test.

OBJECTIVE: To evaluate the relationship between the E2 response during the clomiphene citrate (CC) challenge test and ovarian responsiveness to exogenous gonadotropins. DESIGN: Performance of a CC challenge test followed by ovulation induction with exogenous gonadotropins as part of participation in an assisted reproduction program. SETTING: Assisted reproduction program in a large military tertiary care center. PATIENTS: Two hundred forty-seven women between the ages of 24 and 39 years with normal CC challenge tests within 1 year of their assisted reproduction cycle. INTERVENTIONS: Performance of CC challenge tests and ovulation induction with exogenous gonadotropins as a component of an assisted reproduction cycle. MAIN OUTCOME MEASURES: Correlation of the E2 response during the CC challenge test and peak E2, the duration of stimulation, number of ampules of exogenous gonadotropins, number of mature follicles, number of mature oocytes recovered, and fertilization and pregnancy rates in an assisted reproduction program. RESULTS: No correlation exists between the E2 response during the CC challenge test and any of the parameters evaluated. CONCLUSION: Monitoring of the E2 response during the CC challenge test did not predict ovarian responsiveness or pregnancy rates in patients participating in an assisted reproduction program and one may choose not to include it in routine testing.

Adult↗

[A randomized prospective study comparing supplementation of the luteal phase and early pregnancy by natural progesterone administered by intramuscular or vaginal route].

Deficiency in the luteal phase has been shown during stimulated cycles using a protocol involving a GnRH agonist. The authors undertook a randomised prospective trial of supplementation by progesterone of the luteal phase and of early pregnancy in two hundred and seventy two patients requiring fertilisation in vitro (FIV), gamete inter-fallopian transfer (GIFT) or zygote inter-fallopian transfer (ZIFT). Either progesterone in solution in oil (50 mg/day) administered by intramuscular injection or micronized progesterone administered intra-vaginally (600 mg/d) were used as support for the luteal phase. Administration of progesterone in association with estradiol valerate was started on the day prior to oocyte puncture and was continued until the 12th week of pregnancy. The implantation rate was very close to the threshold of significance (P = 0.07) in favour of the patients given vaginal progesterone. There was a higher rate of clinical pregnancies (33.6 versus 26.7 p. cent) in the latter group, though this was not significant. While plasma progesterone (Pg) levels were lower in patients using vaginal progesterone, the abortion rate during the first three months was lower in this group (P < 0.05). Micronized progesterone administered vaginally was well tolerated by all patients. During stimulated cycles, notably by GnRHa, it thus proved to be more effective than Pg administered by intramuscular injection with regard to implantation and abortion rates.

Administration, Intravaginal↗

Comparison of pronuclear stage embryo transfer and in vitro fertilization-embryo transfer following intracytoplasmic sperm injection.

To determine whether the mode of embryo transfer (PROST vs IVF) affected the outcome in intracytoplasmic sperm injection (ICSI) cycles, 237 ICSI cycles (106 PROST and 131 IVF) were analyzed. Several parameters, including patient age, duration of infertility, amounts of hMG used, number of mature eggs retrieved and injected, fertilization rate, number of embryos transferred, and clinical pregnancy rate, were compared. Most of the variable factors were not significantly different, except the mean numbers of transferred embryos which were significantly higher in the PROST group. The clinical pregnancy rate showed no statistical difference between PROST and IVF cycles (25.5 and 16.8%; p = 0.139). This study suggests that even the pregnancy rate in PROST cycles was slightly higher than IVF cycles, but there was no statistically significant difference between the two groups.

Adult↗

Analysis of the risk factors with regard to the occurrence of ectopic pregnancy after medically assisted procreation.

In a retrospective study (1985-1989) based on data from the Centre for Reproductive Medicine in Brussels, a total of 23 ectopic pregnancies (2.24%) occurred after 3800 embryo, zygote or gamete transfers. This number was low compared with the data published elsewhere. Tubal damage was a major risk factor towards developing an ectopic pregnancy after in-vitro fertilization and embryo transfer. The number of ectopic pregnancies after the association of clomiphene citrate and human menopausal gonadotrophin (HMG) was significantly higher in patients with tubal (7.8%) and non-tubal indications (2.1%) compared with those stimulated with gonadotrophin-releasing hormone (GnRH) and HMG (2.18% and 0.84%, respectively). The number of replaced embryos was not associated with the rate of ectopic pregnancy and neither did transfer technique (intra-uterine or intra-Fallopian transfer) influence the ectopic pregnancy rate.

Adult↗

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles.

OBJECTIVE: To determine if the level of serum P drawn on the day of hCG administration predicts assisted reproductive technology (ART) outcome in patients undergoing stimulation with hMG under GnRH agonist (GnRH-a) suppression. DESIGN: Retrospective P assay of stored serum. PATIENTS: One hundred seventy-one patients (189 cycles) who had undergone GnRH-a suppression (leuprolide acetate or nafarelin) and stimulation with hMG for an ART procedure. MAIN OUTCOME MEASURES: Progesterone RIA of serum obtained on the day of hCG administration. Measurement of sequential serum LH values by RIA in those patients with the highest P levels. RESULTS: Pregnancy rates per oocyte retrieval were not correlated with the P level before hCG administration. There were 18 of 54 (33.3%) clinical pregnancies in those cycles with P < 0.9 ng/mL (conversion factor to SI unit, 3.180) and 42 of 135 (31.1%) clinical pregnancies in cycles with a P > or = 0.9 ng/mL. Significantly higher serum E2 levels and numbers of of follicles and oocytes obtained were observed in the high P cycles. There were no differences in the number of oocytes fertilized, the number of embryos transferred, or the implantation rate. However, a significantly higher percentage of mature oocytes were fertilized in the low P cycles (73%), as compared with the high P cycles (60%). CONCLUSIONS: Serum P levels before hCG administration do not predict the outcome of ART cycles in patients suppressed with GnRH-a before hMG stimulation. Lower fertilization rates observed in the high P cycles did not have an effect on clinical outcome.

Chorionic Gonadotropin↗

Pregnancy and implantation rates in normal replacement versus stimulated cycles.

The relative importance that endometrial development and embryo quality have on implantation rates achieved with assisted reproductive technology (ART) is the subject of controversy. Ovarian stimulation has been repeatedly mentioned as having a detrimental effect on endometrial receptivity (Paulson et al., 1990, Fertil. Steril., 53, 870-874). We compared pregnancy and implantation rates achieved with ART during stimulated cycles and hormonal replacement cycles, in patients matched for the following criteria: age < 35 years for the patient donating oocytes; transfer of at least two good quality embryos/oocytes and good quality transfer. All transfer cases performed during hormonal replacement cycles were done with donated oocytes. Comparison of results between techniques was not attempted due to potential differences in populations. The pregnancy and implantation rates achieved with each technique during stimulated and hormonal replacement cycles were not statistically different. In contradiction to previous results, our data suggest that differences in uterine receptivity between stimulated and hormonal replacement cycles in the age group studied are not of critical importance in embryo implantation. Good embryo quality appears to be the dominant factor in determining the success of ART.

Adult↗

Operative laparoscopy in assisted reproduction.

After the introduction of transvaginal ultrasound guided recovery of oocyte, the use of laparoscopy in Assisted Reproductive Technology is limited to GIFT and ZIFT or TET method and to the selection of patients. In this paper the Authors discuss about these methods, the advantages of tubal gametes or embryos transfer versus uterine transfer.

Embryo Transfer↗

Establishment of an assisted reproduction program in the Armed Forces.

Approximately one in seven couples are infertile. Half of these couples fail to conceive following conventional therapies. Recently, technologies have evolved which provide hope to these couples and lead to cumulative pregnancy rates of 65%. An assisted reproduction (AR) program has recently been established at Wilford Hall Medical Center. The reproductive endocrinologists, on-service residents, and clinic support staff are responsible for all aspects of care including stimulation, retrieval, andrology, embryology, and transfer. To date, there have been 104 transfers with 28 pregnancies. In summary, AR is available in the Armed Forces and allows infertile couples to receive state-of-the-art health care.

Appointments and Schedules↗

Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis.

The objective of our study was to establish the most adequate ovarian stimulation regimen for assisted procreation in endometriotic patients. It consisted of a retrospective analysis comparing the use of the gonadotrophin-releasing hormone analogue (GnRHa) buserelin either for 3 months or for 3 weeks and continued with ovarian stimulation with human menopausal gonadotrophin (HMG), and the use of clomiphene citrate in association with HMG for in-vitro fertilization (IVF) and embryo transfer, gamete intra-Fallopian transfer (GIFT) and zygote intra-Fallopian transfer (ZIFT). A total of 145 patients with endometriosis in 174 cycles were divided into two groups according to the revised American Fertility Society staging of the disease (group A, stages 1 and 2; group B, stages 3 and 4). The use of GnRHa significantly increased the number of oocytes retrieved. GnRH analogues for 3 months gave the highest fertilization rate for groups A and B. The cleavage, pregnancy and delivery rates, although higher in the groups treated with analogues, did not reach statistical significance. A higher number of patients had an embryo transfer in the groups treated with GnRHa (P < 0.05). Treatment with GnRHa for either 3 months or for 3 weeks proved to be more efficient than clomiphene citrate-HMG for assisted procreation procedures in patients with endometriosis.

Adult↗

Assisted reproductive technology in the United States and Canada: 1993 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.

OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive technology (ART) initiated in the United States in 1993. DESIGN: Data were collected on an annual summary form and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANTS: Two hundred sixty-seven programs submitted data on procedures performed in 1993. Data were collected in October 1994 so that outcome of all pregnancies established would be known. MAIN OUTCOME MEASURES: The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, and congenital abnormality. RESULTS: Programs reported initiations of 41,209 cycles of ART treatment, excluding frozen embryo and donor oocyte cycles. Of these, 33,543 cycles initiated were IVF (standard, with micromanipulation, and for host uterus transfer) with 18.3% deliveries per retrieval; 4,992 were cycles of GIFT with 28.1% deliveries per retrieval; 1,792 were cycles of ZIFT with 24.4% deliveries per retrieval; and 882 were combination cycles, combining IVF and one of the tubal transfer techniques, resulting in 27.8% deliveries per retrieval. In addition to these cycles initiated in 1993, 6,869 frozen ET procedures were reported, either as separate procedures or in combination with another ART procedure with 13.3% deliveries per procedure, and 2,766 donor oocyte cycles were initiated with an overall success of 30.2% deliveries per retrieval. As a result of all procedures, a total of 8,741 deliveries were reported. CONCLUSIONS: In 1993, there were more programs offering more treatment cycles of ART. Overall average success rates (deliveries per procedures) exhibited only a small increase compared with previously reported summaries.

Adult↗

[Programmed pre-embryonic freezing in the pronuclear stage].

The authors discuss about freezing procedure of surplus pronuclear stage praeembryos in six cases. The total amount of praeembryos were 36. From these nine were thawing and were cultured further. The surviving rate was 88.8%, the development to blastocysts rate was 77.7%. The freezing procedure in pronuclear stage needs some extra methodological force. The success, increasing influence on pregnancy rate and the benefit that reduces the IVF-ET patient's intolerance procedure is also an important factor. Beneath the cost saving effect of this intervention, the cryopreservation technique for the institutes performing this way of assisted reproduction is highly suggested.

Cryopreservation↗