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Assisted reproductive technology in the United States: 1998 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.

OBJECTIVE: To summarize the procedures and outcomes of ART initiated in the United States in 1998. DESIGN: Data were collected electronically by using the SART Clinical Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANT(S): Three hundred and sixty programs submitted data on procedures performed in 1998. Data were collated after November 1999 so that the outcome of all pregnancies established would be known. MAIN OUTCOME MEASURE(S): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. RESULTS: Programs reported initiating 81,899 cycles of ART treatment. Of these, 58,937 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 29.1%; 1,293 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 27.4%; 1,054 were cycles of zygote intrafallopian transfer with a delivery rate per retrieval of 29.6%. The following additional ART procedures were also initiated: 5,273 fresh donor oocyte cycles, with a delivery rate per transfer of 41.2%; 11,228 frozen embryo transfer procedures, with a delivery rate per transfer of 19.3%; 1,913 frozen embryo transfers using donated oocytes or embryos, with a delivery rate per transfer of 23.5%, and 809 cycles using a host uterus, with a delivery rate per transfer of 31.6%. In addition, 969 cycles were reported as combinations or more than one treatment type, 25 cycles as research, and 398 as embryo banking. As a result of all procedures, 20,241 deliveries were reported, resulting in 29,128 neonates. CONCLUSIONS: In 1998, there were more programs reporting ART treatment and a significant (12.1%) increase in reported cycles compared with 1997. In comparable cycle types, the actual increase in overall success rate (deliveries per retrieval) was 1.4%, which represents an increase of 4.7% compared with the success rate in 1997.

Adult↗

Laser-assisted hatching of embryos is better than the chemical method for enhancing the pregnancy rate in women with advanced age.

OBJECTIVE: Assisted hatching may enhance embryo implantation. This study was conducted to examine the efficacy of the laser- and chemical-assisted hatching for promotion of implantation (IR), pregnancy (PR), and delivery rate (DR) in older women undergoing IVF cycles. DESIGN: Prospective study. SETTING: An IVF unit of a medical center. PATIENT(S): A total of 601 embryos from 141 women aged > or =38 years underwent controlled ovarian hyperstimulation (COH) and assisted hatching. INTERVENTION(S): The study population was divided into two groups: group 1 had laser-assisted hatching (n = 85) and group 2 had chemical-assisted hatching (n = 56). Before the transfer, the day 3 embryos were hatched by using a 1.48-microm noncontact diode laser or acid Tyrode's solution. MAIN OUTCOME MEASUREMENT(S): The IR, PR, and DR between the groups were compared. RESULT(S): There were no statistical differences between groups in age, E2 concentrations during hCG administration, gonadotrophin dosage, embryo grade, the numbers of oocytes retrieved, oocytes fertilized, and embryos transferred. Higher IR, PR, and DR were noted in the laser-assisted hatching group. The IR, PR, and DR were: group 1, 8.2%/31.8%/24.7% and group 2, 3.8%/16.1%/10.7%, respectively. CONCLUSION(S): Laser-assisted hatching of embryos is more effective than the chemical method in enhancing the IR and PR of women with advanced age. The laser system allows an easier, faster, and safer micromanipulation of the zona pellucida, which provided a better method in zona drilling.

Adult↗

Assisted reproductive technology in the United States: 1999 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.

OBJECTIVE: To summarize the procedures and outcomes of ART initiated in the United States in 1999. DESIGN: Data were collected electronically by using the SART Clinical Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANT(S): Three hundred sixty programs submitted data on procedures performed in 1999. Data were collated after November 2000 so that the outcome of all pregnancies established would be known. MAIN OUTCOME MEASURE(S): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. RESULT(S): Programs reported initiating 88,077 cycles of ART treatment. Of these, 63,639 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 29.4%; 838 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 27.9%; 945 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 29.8%. The following additional ART procedures were also initiated: 6,509 fresh donor oocyte cycles, with a delivery rate per transfer of 41.8%; 12,005 frozen embryo transfer procedures, with a delivery rate per transfer of 18.6%; 2,488 frozen embryo transfers using donated oocytes or embryos, with a delivery rate per transfer of 23.6%, and 821 cycles using a host uterus, with a delivery rate per transfer of 33.6%. In addition, 398 cycles were reported as combinations of more than one treatment type, 18 cycles as research, and 416 as embryo banking. As a result of all procedures, 21,904 deliveries were reported, resulting in 30,967 neonates. CONCLUSION(S): In 1999, more programs reported ART treatment and reported cycles increased significantly (7.5%) compared to 1998. In comparable cycle types, the overall success rate (deliveries per retrieval) increased by 0.4%, which represents an increase of 1.2% compared to the success rate for 1998.

Adult↗

A flexible CO2 laser fiber for operative laparoscopy.

A flexible, hollow fiber measuring 1.5 mm diameter was used in conjunction with the laparoscope to deliver a CO2 laser beam to the rabbit uterine horn. The fibers tested consistently transmitted 5 to 15 W of laser power without loss of input mode. Several fiber-to-target distances were evaluated from the standpoint of crater characteristics. Microscopic sections were studied, and crater heights and widths were quantified. All lesions produced by the CO2 laser fiber closely mimicked those delivered by the free-hand piece or micromanipulator. In two chronic experiments, rapid fibrosis and "filling in" of the craters was evident at 5 days. No adhesions were observed. The CO2 laser fiber has several advantages over current techniques for the performance of laser laparoscopy as well as over alternative systems, e.g., neodymium:yttrium-aluminum-garnet(ND:YAG) and argon-coupled fibers. The CO2 laser fiber will further increase the options available to the gynecologist for operative endoscopy.

Animals↗

Immunosuppression supports implantation of zona pellucida dissected human embryos.

The effect of low dose immunosuppression with methylprednisolone during the first 4 days after oocyte retrieval on potential immune cell invasion of partially zona dissected embryos in utero was investigated in alternate in vitro fertilization patients (n = 32). The incidence of pregnancy was significantly higher in patients receiving methylprednisolone (7 of 18, 39%) than in control patients (1 of 14, 7%). Twenty-eight percent (11 of 39) of the embryos replaced in the corticosteroid treated patients implanted, whereas only 7% (2 of 31) of embryos in control patients had a fetal heart beat. There were no side effects reported in any of the patients receiving corticosteroids. It can be concluded that methylprednisolone supports implantation of embryos with small holes in their zonae. However, the actual mechanisms of corticosteroid support on the interaction between immune cells and micromanipulated embryos are not well understood.

Clinical Trials as Topic↗

Preclinical models for human pre-embryo biopsy and genetic diagnosis. I. Efficiency and normalcy of mouse pre-embryo development after different biopsy techniques.

OBJECTIVE: To compare the usefulness of three micromanipulative methods at two different stages of pre-embryo development and to assess possible effects on postbiopsy survival and development. DESIGN: Four-cell and eight-cell mouse pre-embryos were biopsied using enucleation, aspiration, or extrusion of single blastomeres. After biopsy, pre-embryos were observed for in vitro and in vivo development. SETTING: Laboratories of The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. PATIENTS, PARTICIPANTS: Only mice were used. INTERVENTIONS: Pre-embryo biopsy, developmental normalcy and pre-embryo transfer were studied. MAIN OUTCOME MEASURE(S): Few pre-embryos died as a result of biopsy trauma. High postbiopsy survival rates were associated with normal intrauterine and postnatal development. RESULTS: Expanded blastocyst formation rates from four-cell and eight-cell pre-embryos were 94.6%, 96.7% (controls); 80.7%, 89.1% (enucleation); 90.1%, 91.7% (aspiration); 83.1%, 91.5% (extrusion), respectively. Live birth rates at the four-cell stage were slightly lower in the enucleation group than in the blastomere aspiration and extrusion groups or controls (49.2% versus 58.8%, 56.3% and 66.7%, respectively). For the eight-cell stage, there were no differences between the groups. No developmental abnormalities were found in body or organ weights, in neonates or at 3 weeks of age, or in their subsequent ability to reproduce a second generation. CONCLUSIONS: Biopsy of mouse pre-embryos produces only a small loss of viability because of trauma and permits normal prenatal and postnatal development among surviving pre-embryos.

Animals↗

Failure to fertilize in vitro in couples with male factor infertility: what next?

OBJECTIVE: To assess the predictive value of a failure to fertilize in vitro in couples with sperm abnormalities on future fertility. DESIGN: Retrospective file review. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program in the Sheba Medical Center during the years 1983 to 1990. PATIENTS: Seventy-six couples with sperm abnormalities who had at least one IVF cycle during which fertilization did not occur. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Occurrence of fertilization, percentage of fertilization, and pregnancies in additional IVF-ET cycles. RESULTS: Of 44 couples who underwent an additional IVF attempt with husband's sperm, 36 (81.2%) fertilized, with a mean fertilization rate of 47.7% +/- 26.6%. Of 17 couples who failed twice, 11 attempted IVF again with husband's sperm and 7 fertilized, with a median rate of 33%. A higher sperm concentration was found on the cycles during which fertilization occurred. Men with single parameter abnormalities did not fertilize better than those with two or three defective parameters. CONCLUSIONS: Failure to fertilize in vitro in couples with male factor infertility does not seem to predict future fertilization in IVF. At least two cycles of IVF should be tried before reverting to other options such as insemination by donor sperm or gamete micromanipulation.

Embryo Transfer↗

Human embryo biopsy on the 2nd day after insemination for preimplantation diagnosis: removal of a quarter of embryo retards cleavage.

OBJECTIVE: To assess any reduction in viability and development in vitro after biopsy of a quarter of the cells of human embryos on day 2 after insemination. DESIGN: A prospective study in which normally fertilized surplus embryos of good morphology with two to eight cells approximately 48 hours after insemination were randomly allocated to a control or biopsied group, respectively. SETTING: In vitro fertilization (IVF) unit and laboratories of the Hammersmith Hospital, Institute of Obstetrics and Gynaecology, London University. PATIENTS, PARTICIPANTS: One hundred twenty-nine embryos from 28 infertile IVF patients. INTERVENTIONS: Follicular aspiration by ultrasound-guided transvaginal puncture and embryo biopsy by micromanipulative procedures. MAIN OUTCOME MEASURE(S): Pyruvate uptake and cell number at the blastocyst stage. RESULTS: Embryo biopsy did not have an adverse effect on either the proportion developing to the blastocyst stage (50% [32 of 64] and 47.7% [31 of 65] for the control and biopsied groups, respectively) or embryo viability, measured indirectly through pyruvate uptake. However, the proportion of embryos that reached the morula stage after day 4 (retarded embryos) was significantly higher (44%, 11 of 25 versus 8.7%, 2 of 23) in the biopsied group. The total number of cells (29.6 +/- 3.1 versus 62.4 +/- 4.7), numbers of inner cell mass (7.7 +/- 2.2 versus 24.5 +/- 1.4) and trophectoderm (24.0 +/- 5.2 versus 45.0 +/- 6.4) cells, and the inner cell mass:trophectoderm ratio (34.7 +/- 7.9 versus 59.5 +/- 11.7) were strikingly reduced at the blastocyst stage in the biopsied group. This reduction was greater in embryos that reached the morula stage after day 4. CONCLUSIONS: More investigation is needed to assess whether the detrimental effects observed were because of the biopsy method used in this study or to a high sensitivity of human embryos at early stages to manipulation in vitro.

Biopsy↗

Two years of assisted fertilization by partial zona dissection in male factor infertility patients.

OBJECTIVE: To assess partial zona dissection in our routine IVF-ET program over a 2-year period. DESIGN: Partial zona dissection before insemination on the day of oocyte collection or 24 hours after unsuccessful conventional IVF. In a subgroup of patients, oocytes were randomized to either partial zona dissection before insemination or IVF. SETTING: University infertility clinic. PATIENTS: Couples who suffered principally from male factor infertility or who had failed fertilization previously. INTERVENTIONS: Micromanipulation of oocytes with partial zona dissection. MAIN OUTCOME MEASURES: Comparison of fertilization rate, embryo morphology, and implantation rate between partial zona dissection inseminated oocytes and conventional IVF inseminated oocytes (controls). RESULTS: Five pregnancies were established in 199 patients. The incidence of polyspermy was significantly higher in the partial zona dissection group than in conventional IVF (4.8% versus 1.3%). There were no significant differences in the remaining parameters. The fertilization rate of partial zona dissection and reinsemination was significantly higher than conventional IVF insemination (13.6% versus 4.5%) but similar to the rate obtained when partial zona dissection was applied before insemination (13.6% versus 15.7%). CONCLUSIONS: Oocytes treated by partial zona dissection did not exhibit a greater fertilization rate than conventional IVF inseminated oocytes. Partial zona dissection may not be a useful technique for treating severe male factor infertility.

Adult↗

Clinical outcomes of pregnancies achieved by microinsemination by sperm transfer.

Micromanipulative techniques such as microinsemination by sperm transfer are evolving as treatment for couples suffering from some forms of male factor infertility where previously donor insemination was the only option. Being a relatively new technology, the numbers of microinsemination by sperm transfer pregnancies that have progressed to term are still small. However, at this time, it would seem that outcome in terms of antenatal complications, gestation length, and birth weight is no different from that seen with conventional IVF. Continuing review of the rate of congenital malformation in microinsemination by sperm transfer progeny seems warranted.

Abortion, Induced↗

Most living acrosome-reacted spermatozoa do not fuse with the oocyte when inserted into the perivitelline space.

OBJECTIVE: To evaluate the frequency with which acrosome-reacted spermatozoa fuse with the oocyte after subzonal insemination (SUZI). DESIGN: The acrosome reaction frequency determined in sperm suspensions used for SUZI was related with the frequency of sperm-oocyte fusion after the microinsemination procedure. In some experiments, the acrosome reaction frequency was compared in sperm suspensions aspirated into the microinjection needle and in those leaving the needle. SETTING: Private hospital, public research center, and university-based laboratory. PATIENTS, PARTICIPANTS: Patients involved in a program of micromanipulation-assisted fertilization and healthy sperm donors. INTERVENTIONS: IVF-ET. MAIN OUTCOME MEASURES: Frequency of the acrosome reaction, frequency of sperm-oocyte fusion. RESULTS: The procedure of sperm aspiration to the microinjection needle followed by active swim-out of motile spermatozoa did not change the overall percentage of acrosome-reacted spermatozoa even though the subpopulation of acrosome-reacted spermatozoa leaving the needle was enriched in recently reacted cells. The frequency of sperm-oocyte fusion was considerably lower than the frequency of the acrosome reaction in both patient and donor sperm samples, irrespective of the number of spermatozoa inserted per egg. CONCLUSIONS: A spontaneous acrosome reaction does not necessarily predispose a spermatozoon to fuse with the oocyte after SUZI. It remains to be elucidated whether this relative inefficiency of acrosome-reacted spermatozoa is related to technical aspects of SUZI or whether, in a more general sense, the acrosomal exocytosis and the development of sperm-oocyte fusion capacity are distinctly regulated, though closely related, phenomena.

Acrosome↗

Factors of importance for the establishment of a successful program of intracytoplasmic sperm injection treatment for male infertility.

OBJECTIVE: To establish an intracytoplasmic sperm injection treatment program for couples with male infertility and to determine those factors important for success. DESIGN: A retrospective analysis of 171 consecutive cycles of intracytoplasmic sperm injection concerning 145 infertile couples. SETTING: Infertility clinic in a private hospital associated with a university hospital. PATIENTS: Couples with infertility in the male partner whose sperm parameters were unacceptable for conventional IVF or in whom fertilization by conventional IVF failed repeatedly. INTERVENTIONS: One hundred seventy-one transvaginal oocyte retrievals were completed after superovulation with GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: The parameters evaluated included fertilization, cleavage, implantation, pregnancy, and spontaneous abortion in relation to patient indications and improved procedures. RESULTS: After intracytoplasmic sperm injection, normal fertilization occurred in 45% of the oocytes (n = 1,499). Of 171 treatment cycles, 93% of the couples had fertilization and 86% had ET. Thirty-six pregnancies were achieved. During the period studied, the mean fertilization rate increased from 21.3% during the first 17 weeks to 67.8% during the last 13 weeks, and the pregnancy rate (PR) per started cycle increased from 12.8% to 31.3%. CONCLUSIONS: Technical factors critical for achieving high rates of fertilization and pregnancy were the use of standardized intracytoplasmic sperm injection pipettes, the immobilization of sperm before injection, and the aspiration of a minimal amount of ooplasm before reinjection with the sperm. Intracytoplasmic sperm injection appears to be superior to other micromanipulation methods for alleviating male infertility.

Adult↗

Use of a specific zona pellucida (ZP) protein 3 antiserum as a clinical marker for human ZP integrity and function.

OBJECTIVE: To evaluate binding characteristics of a specific zona pellucida (ZP) protein 3 (ZP3) antiserum to human oocytes in order to determine its usefulness as a clinical marker for human ZP integrity and function and its correlation with IVF outcome. DESIGN: Prospectively designed, blinded, internally controlled study. SETTING: Tertiary care academic center. PATIENTS: Patients undergoing IVF therapy who had either total failed fertilization or partial fertilization were studied. INTERVENTIONS: Metaphase II oocytes showing absence of pronuclear formation were salt stored 48 hours after insemination and bisected into matching hemizonae using micromanipulation. One hemizona was incubated with AS ZP3-6 (an antiserum generated against a synthetic ZP3 peptide derived from an amino acid sequence that is highly conserved in the structure of ZP3), whereas the matching hemizona was incubated with AS ZP3-7, an antiserum detecting exclusively mouse ZP3 (internal, negative control). Antibody binding was visualized using the peroxidase-antiperoxidase method and diaminobenzidine as color reagent. RESULTS: A total of 104 unfertilized oocytes were evaluated. Analysis of variance showed a significant interaction between gamete factor groups (sperm and oocyte) and antiserum factor. Patients with oocyte factor had significantly lower mean staining scores for the AS ZP3-6-treated hemizonae than patients with sperm factor. CONCLUSIONS: These results demonstrate that anomalies of human ZP3 can be identified with AS ZP3-6 and that these ZP abnormalities correlate with fertilization failure during IVF treatment. Thus, this newly developed biomarker may be of clinical significance in the identification of oocyte defects that are associated with fertilization disorders and may help in the decision-making process in the IVF-assisted fertilization setting.

Adult↗

Intracytoplasmic sperm injection: a powerful tool to overcome fertilization failure.

OBJECTIVE: To describe the novel micromanipulation technique known as intracytoplasmic sperm injection (ICSI), which has been applied successfully to treat male factor infertility, even in patients with severely impaired sperm characteristics. This paper reviews the historical aspects that led to the development of ICSI in the animal model as well as the current experience in the human. DESIGN: Before using assisted fertilization techniques to enhance fertilization of human gametes, it is imperative that practitioners gain extensive experience in the animal model. In addition, criteria for accepting individuals for treatment with ICSI are discussed along with other applications of the procedure in infertile couples who do not benefit from standard IVF. RESULTS: Because ICSI resulted in limited success in animal models, it seemed unlikely that it would be successful in humans. Yet, ICSI now appears to be the most successful and significant innovation developed for dealing with male factor infertility since the emergence of IVF itself. To date, a relatively large group of healthy children have been born from this technology and there appears to be no increased incidence of congenital malformations. CONCLUSIONS: The consistently high success rate resulting from the application of ICSI to treat couples with male factor infertility is comparable to the results obtained using standard IVF techniques performed in nonmale factor couples. This finding indicates that spermatozoa obtained from subfertile men selected for intracytoplasmic injection are usually genotypically normal.

Animals↗

Assisted reproductive technology in the United States and Canada: 1994 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 1994. DESIGN: Data were collected on the Society for Assisted Reproductive Technology (SART) Database program and submitted to KMPG Peat Marwick, who served as the 1994 collection center for the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. PARTICIPANT(S): Two hundred forty-nine programs submitted data on procedures performed in 1994. Data were collected after October 1995 so that outcome of all pregnancies established would be known. MAIN OUTCOME MEASURE(S): The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, and congenital abnormality. RESULT(S): Programs reported initiations of 39,390 cycles of ART treatment, excluding frozen embryo and donor oocyte cycles. Of these, 33,700 cycles initiated were IVF (standard, with micromanipulation, and for host uterus transfer) with 20.7% deliveries per retrieval; 4,214 were cycles of GIFT with 28.4% deliveries per retrieval; 926 were cycles of zygote intrafallopian transfer with 29.1% deliveries per retrieval; and 550 were combination cycles, combining IVF and one of the tubal transfer techniques, resulting in 29.7% deliveries per retrieval. In addition to these cycles initiated in 1994, 7,046 frozen ET procedures were reported, either as separate procedures or in combination with another ART procedure with 15.4% deliveries per procedure, and 3,119 donor oocyte cycles were initiated with an overall success of 46.8% deliveries per retrieval. As a result of all procedures, a total of 9,573 deliveries were reported. CONCLUSION(S): In 1994, there were fewer programs reporting a similar number of treatment cycles of ART as in 1993. Overall average success rates (deliveries per procedures) exhibited only a small increase compared with previously reported summaries.

Adult↗

Fertilization of human oocytes by microinjection of a single spermatozoon under the zona pellucida.

The authors report a method of micromanipulation for the insertion of a single spermatozoon under the zona pellucida of human oocytes that results in a high rate of fertilization without damage to the oocyte. Spermatozoa were exposed to calcium-depleted medium containing strontium chloride for 20 to 24 hours before resuspension in medium containing calcium to induce capacitation. Single spermatozoa treated in this way were injected under the zona pellucida of morphologically mature oocytes and fertilization was confirmed by electron-microscopy. Five of seven oocytes manipulated within 9 hours of aspiration from the follicle and 3 of 12 oocytes manipulated 23 to 28 hours after recovery from the follicle fertilized. This technique has profound implications for the possible treatment of severe male infertility.

Cell Nucleus↗